Category Archives: Depression

KETAMINE CENTER NORTHERN VIRGINIA | 703-844-0184 | NOVA HEALTH RECOVERY | SPRAVATO KETAMINE NASAL SPRAY CENTER |ALEXANDRIA, VA 22306 | KETAMINE FOR DEPRESSION AND PTSD | 22304 |20176 | 703-844-0184 | 22101 | 22102 | FAIRFAX KETAMINE INFUSION CENTER 22304 | DR. SENDI | Ketamine and OCD, PTSD, Depression, Anxiety



Call NOVA Health Recovery at 703-844-0184 for a free consultation for a Ketamine infusion. No referral needed. We offer intranasal Ketamine follow up therapy as well. Alexandria, Va 22306.

Call NOVA Health Recovery at 703-844-0184 for a free consultation for a Ketamine infusion. No referral needed. We offer intranasal Ketamine follow up therapy as well. Alexandria, Va 22306.

Ketamine: A Promising Novel Therapy for Anxiety and PTSD

Ketamine was originally approved by the US Food and Drug Administration (FDA) as an anesthetic, but is increasingly being used to treat mood disorders, such as treatment-resistant depression, anxiety disorders, and post-traumatic stress disorder (PTSD).1,2 Several studies have also found it to be effective for treating suicidal ideation.3,4

“Ketamine can play an important role in the treatment of anxiety disorders,” according to Prakash Masand, MD, co-founder, chairman, and CEO of Centers of Psychiatric Excellence (COPE) (https://www.copepsychiatry.com) and adjunct professor at the Academic Medicine Education Institute, Duke-National University of Singapore Medical School (Duke-NUS).

“Nowadays, people with anxiety disorders are treated either with a generic antidepressant, such as an SSRI (selective serotonin reuptake inhibitor), an SNRI (selective norepinephrine reuptake inhibitor), or a benzodiazepine and if they don’t respond to one of these, they get a trial of another or several more,” Dr Masand said.

However, between 30% and 40% of these patients will not achieve remission, despite 3 or 4 different traditional agents, and even with evidence-based nonpharmacologic therapies, such as cognitive behavioral therapy (CBT) or mentalization-based therapy (MBT), he noted.

“No good current strategies are available for these non-responders, so novel agents are being studied — including ketamine, which is accumulating an evidence base as [being] rapidly effective for an array of anxiety disorders, including social anxiety disorder (SAD) and PTSD,” he said.

How Does Ketamine Work?

A growing body of evidence points to the role of glutamate, a widely distributed excitatory neurotransmitter, in mediating response to stress and the formation of traumatic memories.2 Ketamine is an ionotropic glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist. Its antidepressant and anti-anxiety effects are presumed to occur through activating synaptic plasticity by increasing brain-derived neutrophic factor translation and secretion and also by inhibiting glycogen synthase kinase-3 and activating mammalian target of rapamycin signaling.5

Brain-derived neutrophic factor plays a role in behavioral responses to classical antidepressants, but the impact on synaptic plasticity may take several weeks to manifest. In contrast, ketamine-mediated synaptic plasticity changes appear to occur within a matter of hours after ketamine administration.5

“The current thinking is that eventually, 6 to 12 weeks after initiating treatment with traditional antidepressants, dendritic growth and increased synaptic connections occur but with ketamine, these can occur within 24 hours of the infusion,” Dr Masand said.

Ketamine and Anxiety: An Increasing Evidence Base

“Ketamine has been studied and shown [to be] effective with an array of anxiety disorders, including SAD, general anxiety disorder (GAD), and PTSD, although the data on its effectiveness in obsessive compulsive disorder (OCD) are more mixed,” Dr Masand observed.

GAD/SAD

  • A small study of patients with GAD and/or SAD (n=12) compared 3 ascending ketamine doses to midazolam. Each was given at 1-week intervals, with midazolam counterbalanced in dosing position across patients. Ketamine was found to dose-dependently improve scores on the Fear Questionnaire. Moreover, it’s impact on decreasing theta frequency in the right frontal sites assessed via  electroencelphalogram (EEG) was comparable to that of conventional anxiolytics.6
  • Glue et al evaluated the efficacy and safety of ketamine in 12 patients with refractory GAD and/or SAD who were not currently depressed using an ascending single-dose at weekly intervals study design. Within 1 hour of dosing, patients reported reduced anxiety, which persisted for up to 7 days.7
  • A continuation of that study evaluated the impact of maintenance treatment ketamine in patients with GAD and/or SAD (n=20) and found that 18 of the 20 patients reported ongoing improvements in social functioning and/or work functioning during maintenance treatment. The researchers concluded that maintenance therapy ”may be a therapeutic alternative for patients with treatment-refractory GAD/SAD.”8

“What is interesting about this study is that the impact of just one infusion lasted for 14 weeks, suggesting that patient[s] with anxiety disorders might have longer maintenance of response than patients with major depression, where the response has been maintained for only one week,” Dr Masand commented.

Anxious Depression

  • A study of patients with anxious and non-anxious bipolar depression (n=21 for both groups) found that both anxious and non-anxious patients with bipolar depression had significant antidepressant responses to ketamine, although the anxious depressed group did not show a clear antidepressant response disadvantage over the non-anxious group.9 “Given that anxiety has been shown to be a predictor of poor treatment response in bipolar depression when traditional treatments are used, our findings suggest the need for further investigations into ketamine’s novel role in the treatment of anxious bipolar depression.,” the investigators concluded.9

Related Articles

OCD

  • An open-label trial of ketamine in 10 patients with treatment-refractory OCD found that ketamine’s effects on OCD symptoms, in contrast to depressive symptoms, did not seem to persist or progress after the acute effects of ketamine had dissipated.10
  • On the other hand, another randomized controlled trial (RCT) of 15 patients with OCD found that anti-OCD effects from a single intravenous dose of ketamine persisted for more than 1 week in some patients with OCD with constant intrusive thoughts, demonstrating that “a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an [SSRI].”11

PTSD

In PTSD, there is “mounting evidence for a role of the excitatory neurotransmitter glutamate in stress responsiveness, the formation of traumatic memories, and the pathophysiology of PTSD, raising the possibility of identifying novel glutamatergic interventions for this disorder.”12

  • One double-blind study demonstrated that infusion of ketamine rapidly and significantly reduces symptom severity in patients with  PTSD compared with midazolam.2
  • Another study found that administration of ketamine immediately after witnessing a traumatic event has been shown to prevent the enhancement of passive avoidance learning in mice.13Ketamine may thus target the mechanisms involved in the consolidation of traumatic memory and may enable the brain to reconsolidate memory and release trauma.14
  • A case study of a child with PTSD reported remission from behavioral dysregulation after receiving procedural ketamine.15

Drawbacks and Potential Adverse Effects

The main concern regarding the use of ketamine for anxiety disorders is the lack of a road map regarding maintenance, Dr Masand noted.

“At COPE, we have found that roughly 30% to 40% of our patients being treated with ketamine require maintenance infusions, and we highly personalize this approach so that patients can identify early signs of recurrence or relapse and we can devise a treatment schedule to prevent them,” he said.

Some patients continue treatment with pharmacotherapy, including standard antidepressants, benzodiazepines, or a mood stabilizer such as valproate and some patients become more receptive to psychotherapies such as CBT,” he stated.

However, “there is very little data regarding what happens long-term in this patient population.”

“Most side effects are mild and transient,” Dr Masand reported. “Patients must be monitored because of potential increases in blood pressure and pulse.”

Additional adverse events include nausea or vomiting, which are also mild and transient. Patients may be pre-treated with prophylactic anti-nausea medication, such as ondansetron, to pre-empt these symptoms, he said.

Some patients experience dissociation, or an out-of-body experience, which is also usually transient but seen by some patients as “annoying,” he noted. “Dissociative experiences are sometimes seen as a biomarker for insufficient response and suggest that the dose should be increased.”

Providers should be aware that cystitis and lower urinary tract pathologies (eg, detrusor over-activity) have been reported in long-term ketamine users, but typically only at high doses.16

Ketamine’s psychedelic effects make it a” popular recreational drug.”16 At lower doses, the predominant effects are stimulating, and users experience mild dissociation with hallucinations and a distortion of time and space. However, higher doses can induce more severe, schizophrenia-like symptoms and perceptions.16 Although these effects resolve rapidly, long-term use “can cause more pronounced and persistent neuropsychiatric symptoms. For this reason, ketamine should be “used cautiously with other drugs that alter mood and perception, including alcohol, opioids, benzodiazepines and cannabis.”16

Promising Role

“Ketamine for treatment-resistant depression has a robust evidence base and a rapidly-growing evidence base for its use in anxiety disorders,” Dr Masand said.

“Given the gaps in current treatment, this promising agent is occupying a more promising role in treatment of anxiety disorders, such as PTSD. Considering how common PTSD is, ketamine can make an important difference for a large number of people who suffer from this debilitating condition,” he concluded.

First Person Account of Ketamine Therapy: An Interview with Kimberly Palmer

To gain insight into the experience of ketamine treatment in a person with depression and anxiety, Psychiatry Advisor interviewed Kimberly Palmer of Los Angeles, California. Ms Palmer received treatment at the Ketamine Clinics of Los Angeles (https://www.ketamineclinics.com). Ms Palmer works as a program manager for a consulting company where she organizes and runs corporate events for small groups.

Psychiatry Advisor: What made you decide to pursue ketamine treatment?

Ms Palmer: I was raised in an abusive home, and as an adult I had severe major depression, as well as anxiety. I was treated with medications, such as antidepressants, but they had many adverse events and they ended up making me feel like a zombie, so I discontinued them. I managed okay for a while, but then I had another major depressive episode.

I was receiving psychotherapy at the time and it was only moderately helpful — not enough to stop the episode. Fortunately, I knew someone who works at a ketamine clinic. She told me how many patients had been helped by ketamine and I was interested, mostly because the adverse events of ketamine seemed mild and are not long-term.

Psychiatry Advisor: What were your experiences during your infusion?

Ms Palmer: I felt incredible during the infusion. The best way I can describe it is by referring to the movie Avatar, specifically the scene in which the protagonist is walking through a jungle at night for the first time and touching all the plants, which light up with pretty colors—very vivid, colorful, and not linear. There was the sensation of being on a sort of roller coaster, riding through different scenes.

At one point, it felt as though my chair was on a cloud. Then suddenly, the chair disappeared and I was floating on the cloud. It was a wonderful experience.

Psychiatry Advisor: How did the ketamine treatment affect you afterwards?

Ms Palmer: After only one treatment, it was as if a switch had flipped in my brain that allowed me to digest things and move beyond my trauma. Before the infusion, a lot of what was going on with me had to do with self-esteem issues and negative self-talk. These were behaviors learned over many years. After the infusion, the negative self-talk immediately disappeared. All of those thoughts — such as telling myself I am not good enough — that were preventing me from working through emotional issues, were resolved. I was able to start looking at things more objectively rather than taking them personally, and not take on responsibility for other people’s emotions and reactions.

I am currently working with a therapist and a life coach to help me feel more comfortable with communication because I was raised not to ask for things and to put up with anything I’m asked to do. As a result, I have developed a much more positive outlook of myself and the world.

Psychiatry Advisor: How many ketamine treatments have you had?

Ms Palmer: Over a 6-month period I had 6 treatments, which were all very helpful. Then, 6 months after the conclusion of this first series of treatments, some new issues came up, so I received 2 more — one regular 60-minute treatment and one extended 90-minute treatment.

Recently, with the holidays coming up, I decided to pre-empt the effect of some stressors and have another treatment. My most recent infusion took place the day after my father passed away. I noticed that during the infusion, I was able to steer myself away from negative thoughts about that issue. Although I cannot control what visions or experiences I might have, I do have some control over the direction of my thoughts and the after-effects have been positive and helpful.

Psychiatry Advisor: Did you have any adverse events from the treatments?

Ms Palmer: I had no negative physical effects. I had one mild bad reaction, when I came to the treatment session in an agitated state because I had gotten into a fight with someone right before. I was sad and crying  by the time I finished the infusion. But I was in a bad headspace before I even walked into the room. And my experience was not scary, only sad.

Psychiatry Advisor: What impact has your treatment had on your day-to-day life?

Ms Palmer: My depression had interrupted my schooling. I was in school for 3 and a half years and then I hit a roadblock. After the treatments, I was able to complete my studies and graduated with a BA in business administration and management.

My job is stressful. I counterbalance the stress with hobbies like surfing and photography. But there are still stressors, and I have a dog who is reaching the end of life, which is affecting me. The ketamine treatments have helped me to manage those stressors. 

References

  1. Sanacora G, Frye MA, McDonald W, et al. A consensus statement on the use of ketamine in the treatment of mood disordersJAMA Psychiatry. 2017;74(4):399-405.
  2. Feder A, Parides M, Murrough JW, et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trialJAMA Psychiatry. 2014;71(6):681-688.
  3. Murrough JW, Soleimani L, DeWilde KE, et al. Ketamine for rapid reduction of suicidal ideation: a randomized controlled trialPsychol Med. 2015;45(16):3571-3580.
  4. Wilkinson ST, Ballard ED, Bloch MH, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysisAm J Psychiatry. 2018;175(2):150-158.
  5. Schwartz J, Murrough JW, Iosifescu DV. Ketamine for treatment-resistant depression: recent developments and clinical applicationsEvid Based Ment Health. 2016;19(2):35-38.
  6. Shadli SM, Kawe T, Martin D, McNaughton N, Neehoff S, Glue P. Ketamine effects on EEG during therapy of treatment-resistant generalized anxiety and social anxiety [published online April 24,2018]. Int J Neuropsychopharmacology. doi:10.1093/ijnp/pyy032
  7. Glue P, Medlicott NJ, Harland S, et al. Ketamine’s dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders. J Psychopharmacol. 2017;31(10):1302-1305.
  8. Glue P, Neehoff SM, Medlicott NJ, Gray A, Kibby G, McNaughton N. Safety and efficacy of maintenance ketamine treatment in patients with treatment-refractory generalised anxiety and social anxiety disordersJ Psychopharmacol. 2018;32(6):663-667.
  9. Ionescu DF, Luckenbaugh DA, Niciu MJ, Richards EM, Zarate CA. A single infusion of ketamine improves depression scores in patients with anxious bipolar depressionBipolar Disord. 2014;17(4):438-443.
  10. Bloch MH, Wasylink S, Landeros-Weisenberger A, et al. Effects of ketamine in treatment-refractory obsessive-compulsive disorderBiol Psychiatry. 2012;72(11):964-970.
  11. Rodriguez CI, Kegeles LS, Levinson A, et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013;38(12):2475-2483.
  12. Girgenti MJ, Ghosal S, LoPresto D, Taylor JR, Duman RS. Ketamine accelerates fear extinction via mTORC1 signalingNeurobiol Dis. 2016;100:1-8.
  13. Ito W, Erisir A, Morozov AObservation of distressed conspecific as a model of emotional trauma generates silent synapses in the prefrontal-amygdala pathway and enhances fear learning, but ketamine abolishes those effects. Neuropsychopharmacology. 2015; 40(11):2536-2545.
  14. Fattore L, Piva A, Zanda MT, Fumagalli G, Chiamulera C. Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketaminePsychopharmacology (Berl). 2018;235(2):433-445.
  15. Donoghue AC, Roback MG, Cullen KR. Remission from behavioral dysregulation in a child with PTSD after receiving procedural ketaminePediatrics. 2015;136(3):e694-e696.
  16. Li L, Vlisides PE. Ketamine: 50 years of modulating the mindFront Hum Neurosci. 2016;10:612.

Recommended For You



Ketamine Center Northern Virginia | 703-844-0184 | NOVA Health Recovery | Spravato Ketamine nasal spray Center |Alexandria, Va 22306 | Ketamine for depression and PTSD | 22304 |20176 | 703-844-0184 | 22101 | Arlington, Va Ketamine Infusion Center



Call NOVA Health Recovery at 703-844-0184 for a free consultation for a Ketamine infusion. No referral needed. We offer intranasal Ketamine follow up therapy as well. Alexandria, Va 22306.

Call NOVA Health Recovery at 703-844-0184 for a free consultation for a Ketamine infusion. No referral needed. We offer intranasal Ketamine follow up therapy as well. Alexandria, Va 22306.

VA to offer new ketamine-based nasal spray to help combat depression

The newest FDA-approved medication to treat severe depression, a nasal spray based on the anesthetic (and misused hallucinogenic party drug) ketamine, will soon be available to veterans treated within the Department of Veterans Affairs.

In a move that may help thousands of former service members with depression that has not improved with other treatments, VA officials announced Tuesday that the department’s doctors are now authorized to prescribe Spravato, the brand name for esketamine, a molecular variation of ketamine.

The decision to offer a drug hailed by many as a breakthrough in treatment for its speedy results — often relieving symptoms in hours and days, not weeks — shows the VA’s “commitment to seek new ways to provide the best health care available for our nation’s veterans,” Secretary Robert Wilkie said in a release.

“We’re pleased to be able to expand options for Veterans with depression who have not responded to other treatments,” Wilkie added.

The treatment will be available to veterans based on a physician’s assessment and only will be administered to patients who have tried at least two antidepressant medications and continue to have symptoms of major depressive disorder.

An estimated 16 million Americans have had at least one major episode of depression, and of those, 1 in 3 are considered treatment-resistant. In the veteran population of 20 million, the estimated diagnosis rate of depression is 14 percent — up to 2.8 million veterans. Between one-third and half of those veterans may be treatment-resistant.

The lack of effective medications for difficult-to-treat patients prompted the Food and Drug Administration to place esketamine on a fast track, expediting its review of the drug to ensure that it went to patent as soon as safely possible, according to administration officials.

“Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process, including a robust discussion with our external advisory committees, were important in our decision to approve this treatment,” said Dr. Tiffany Farchione, acting director of the FDA’s Center for Drug Evaluation and Research Division of Psychiatry Products, in a release.

As with any other medication, there are risks. Spravato carries a boxed warning for side effects that include misuse, the reason it is administered under a doctor’s supervision. The list of side effects includes sedation and blood pressure spikes and disassociation, such as feelings of physical paralysis and out-of-body experiences. It also can cause suicidal thoughts and behaviors.

Acknowledging the dangers, FDA made esketamine available only through a restricted distribution system.

A veteran prescribed Spravato would inhale the nasal spray at a medical facility while under supervision of a medical provider, and would be monitored for at least two hours after receiving the dose. A typical prescription includes twice-weekly doses the first month, followed by a single dose weekly or biweekly as needed. Spravato cannot be dispensed for home use.

Spravato is made by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson. It is the first major antidepressant medication to hit the market in 30 years.



KETAMINE INFUSION CENTER VIRGINIA| 703-844-0184 | NOVA HEALTH RECOVERY | FAIRFAX, VA 22101 | Loudon County, Va 20176 | Dr. Send | 703-844-0184 | ESKETAMINE PROVIDER VIRGINIA | ESKETAMINE CENTER | ESKETAMINE DOCTOR | 703-844-0184 | ARLINGTON, VIRGINIA 22207 22213 | NASAL SPRAY KETAMINE AND THE FDA APPROVAL| DR. SENDI | ESKETAMINE PROVIDER | NASAL SPRY KETAMINE THERAPY | KETAMINE FOR TREATMENT OF DEPRESSION, PTSD, ANXIETY | KETAMINE INFUSION CENTER | KETAMINE DEPRESSION | KETAMINE PTSD | EMAIL@NOVAHEALTHRECOVERY.COM | 2220 22182 23103 22039 20197 20184 22101 22102 22066 | CBD DOCTOR CBD CENTER | 703-844-0184 | FAIRFAX, VA 22034 | 22308 | ESKETAMINE LOUDON COUNTY, VA | ESKETAMINE ANNANDALE, VA | ESKETAMINE RICHMOND | ESKETAMINE VIRGINIA | KETAMINE SPRAY PROVIDER IN NORTHERN VIRGINIA 22308 | KETAMINE INFUSION CENTER | KETAMINE VIRGINIA | ESKETAMINE VIRGINIA | 703-844-0184 FOR AN APPOINTMENT | CBD PROVIDER | CBD CENTER | CBD VIRGINIA | DR. SENDI | NORTHERN VIRGINIA KETAMINE | KETAMINE CENTER |MAGNESIUM AND COPPER AND DEPRESSION | NEW TREATMENTS FOR DEPRESSION | LOUDON COUNTY KETAMINE 703-844-0184 NORTHERN VIRGINIA | Arlington, Va Ketamine Infusion Center



NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link

Ketamine Virginia Link

NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link

Ketamine Virginia Link

Ketamine Works as a Fast-Acting Antidepressant, But the Full Effects Are Still Unknown

Ketamine Works as a Fast-Acting Antidepressant, But the Full Effects Are Still Unknown

etamine leads something of a double life, straddling the line between medical science and party drug. Since it’s invention in the early 1960s, ketamine has enjoyed a quiet existence as a veterinary and pediatric anesthetic given in high doses. But in a second, wilder life, ketamine’s effects at lower doses—a profound sense of dissociation from self and body—became an illicit favorite among psychedelic enthusiasts. Pioneering neuroscientist John Lilly, who famously attempted to facilitate communication between humans and dolphins, used the drug in the late 1970s during experiments in sensory deprivation tanks. By the 1990s, the drug had made its way to the dance floor as “special K.”

More recently, ketamine has taken on a third, wholly unexpected role. Since the early 2000s, the drug has been studied as a uniquely powerful medication for treating severe depression and obsessive-compulsive disorder (OCD). When given as an intravenous infusion, ketamine can lift symptoms of depression and OCD from patients who fail to respond to common antidepressants like Prozac and even resist treatments like electroconvulsive therapy (ECT).

Exactly how ketamine produces antidepressant effects remains unclear, however. Antidepressants like Prozac are Serotonin Reuptake Inhibitors (SSRIs) that increase levels of the neurotransmitter serotonin in the brain, which is believed to boost mood. Ketamine’s main mechanism of action to produce dissociative anesthetic effects, on the other hand, depends on another neurotransmitter, glutamate.

“The prevailing hypothesis for ketamine’s antidepressant effect is that it blocks a receptor (or docking port) for glutamate,” says Carolyn Rodriguez, a professor of psychiatry at Stanford who has conducted some of the pioneering research into ketamine as an OCD treatment.

However, new research suggests that ketamine’s influence on glutamate receptors, and specifically the NMDA receptor, may not be the sole cause of its antidepressant effects. According to a recent study in the American Journal of Psychiatry by Rodriguez and her Stanford colleagues, ketamine might also activate a third system in the brain: opioid receptors.

Ketamine is known to bind weakly to the mu opioid receptor, acting as an agonist to produce a physiological response at the same site in the brain where narcotics like morphine exert their influence. It’s also known that opioids can have antidepressant effects, says Alan Schatzberg, a professor of psychiatry at Stanford and co-author of the new study.

It never made sense to Schatzberg that ketamine’s antidepressant effects were a result of blocking the glutamate receptors, as attempts to use other glutamate-blocking drugs as antidepressants have largely failed. The Stanford psychiatrist, who has spent his career studying depression, wondered if researchers were unknowingly activating opioid receptors with ketamine.

“You could test this by using an antagonist of the opioid system to see if you blocked the effect in people who are ketamine responders,” he says. “And that’s what we did.”

The researchers enlisted 12 subjects with treatment-resistant depression and gave them either an infusion of ketamine preceded by a placebo, or ketamine preceded by a dose of naltrexone, an opioid receptor blocker. Of those, seven subjects responded to the ketamine with placebo, “and it was very dramatic,” Schatzberg says, with depression lifting by the next day. “But in the other condition, they showed no effect,” suggesting it was the opioid receptor activity, not blocking glutamate receptors, that was responsible.

While opioid blockers prevented ketamine from activating the associated receptors, it did not block the drugs dissociative effects, suggesting dissociation alone won’t affect depression. “It’s not that, ‘hey, we’ll get you a little weird and you’ll get the effect,’” Schatzberg says.

The appeal of ketamine’s use as an antidepressant is clear enough. While more typical antidepressants may require six to eight weeks to produce benefits, ketamine works within hours.

“Our patients are asked to hang in there until the medication and talk therapy takes effect,” says Carlos Zarate, chief of the experimental therapeutics and pathophysiology branch of the National Institute of Mental Health (NIMH) who was not associated with the new study. While waiting for traditional treatments to kick in, patients “may lose their friends or even attempt suicide.”

But the study linking ketamine to opioid activity means an extra dose of caution is required. While ketamine acts quickly, the anti-depressive effects of the drug only last for a few days to a week, meaning repeat doses would be needed in practice. Researchers and clinicians should consider the risk of addiction in long-term use, Schatzberg says. “You’re going to eventually get into some form of tolerance I think, and that’s not good.”

However, the new finding is based on just seven subjects, and it still needs to be replicated by other scientists, says Yale professor of psychiatry Greg Sanacora, who was not involved in the new study. And even if the trial is replicated, it would not prove ketamine’s opioid activity is responsible for its antidepressant effects.

“It doesn’t show that at all,” says Sanacora, who studies glutamate, mood disorders and ketamine. “It shows that the opioid system needs to be functioning in order to get this response.”

Sanacora compares the new study to using antibiotics to treat an ear infection. If you administered an additional drug that blocks absorption of antibiotics in the stomach, you would block treatment of the ear infection, but you wouldn’t conclude that antibiotics fight ear infections through stomach absorption—you just need a normally functioning stomach to allow the antibiotic to do its job. Similarly, opioid receptors might need to be functioning normally for ketamine to produce antidepressant effects, even if opioid activity is not directly responsible for those effects.

Complicating matters further, placebos often cause patients to experience less pain, but opioid blockers like naltrexone have been shown to prevent this response, according to Sanacora. It could be, he suggests, that all the apparatus of the clinic—the nursing staff, the equipment—exerted a placebo effect that is mediated by the brain’s opioid system, and the patients who received naltrexone simply did not respond to that placebo effect

“That’s a very important and powerful tool that is in all of medicine, not just in psychiatry,” Sanacora says. “And we know that the opiate system is involved, to some extent, in that type of response.”

It’s also possible, the researchers note in the paper, that ketamine’s action at the glutamate receptor is still important. “Ketamine acts in three distinct phases—rapid effects, sustained effects and return to baseline,” Rodriguez says. Opioid signaling may turn out to mediate ketamine’s rapid effects, while “the glutamate system may be responsible for the sustaining effects after ketamine is metabolized.”

One interpretation is that ketamine blocks glutamate receptors on neurons that are inhibitory, meaning they signal other neurons to fire fewer signals. By blocking these neurons from firing, ketamine may enhance glutamate activity in the rest of the brain, producing anti-depressive effects that persist after the opioid activity dies down.

“The reality is it’s in a gray zone,” Sanacora says. “This is just one small piece of a very large puzzle or concern that we really need to look at the data in total.”

That data is forthcoming. Results from a Janssen Pharmaceuticals clinical trial using esketamine, an isomer of ketamine, and involving hundreds of subjects will soon become public, according to Sanacora, who has consulted for the company. And at NIMH, Zarate and colleagues are studying hydroxynorketamine, a metabolite of ketamine that may provide the same benefits but without the dissociative side effects

Ketamine Works as a Fast-Acting Antidepressant, But the Full Effects Are Still Unknown

A new study suggests that ketamine activates the brain’s opioid receptors, complicating its use to treat clinical depression

Ketamine Syringe
Ketamine syringe, 10mg held by a healthcare professional. (Peter Cripps / Alamy Stock Photo)

By Jon KelveySEPTEMBER 11, 2018777110231.1K

Ketamine leads something of a double life, straddling the line between medical science and party drug. Since it’s invention in the early 1960s, ketamine has enjoyed a quiet existence as a veterinary and pediatric anesthetic given in high doses. But in a second, wilder life, ketamine’s effects at lower doses—a profound sense of dissociation from self and body—became an illicit favorite among psychedelic enthusiasts. Pioneering neuroscientist John Lilly, who famously attempted to facilitate communication between humans and dolphins, used the drug in the late 1970s during experiments in sensory deprivation tanks. By the 1990s, the drug had made its way to the dance floor as “special K.”

More recently, ketamine has taken on a third, wholly unexpected role. Since the early 2000s, the drug has been studied as a uniquely powerful medication for treating severe depression and obsessive-compulsive disorder (OCD). When given as an intravenous infusion, ketamine can lift symptoms of depression and OCD from patients who fail to respond to common antidepressants like Prozac and even resist treatments like electroconvulsive therapy (ECT).

Exactly how ketamine produces antidepressant effects remains unclear, however. Antidepressants like Prozac are Serotonin Reuptake Inhibitors (SSRIs) that increase levels of the neurotransmitter serotonin in the brain, which is believed to boost mood. Ketamine’s main mechanism of action to produce dissociative anesthetic effects, on the other hand, depends on another neurotransmitter, glutamate.

“The prevailing hypothesis for ketamine’s antidepressant effect is that it blocks a receptor (or docking port) for glutamate,” says Carolyn Rodriguez, a professor of psychiatry at Stanford who has conducted some of the pioneering research into ketamine as an OCD treatment.

However, new research suggests that ketamine’s influence on glutamate receptors, and specifically the NMDA receptor, may not be the sole cause of its antidepressant effects. According to a recent study in the American Journal of Psychiatry by Rodriguez and her Stanford colleagues, ketamine might also activate a third system in the brain: opioid receptors.

Ketamine is known to bind weakly to the mu opioid receptor, acting as an agonist to produce a physiological response at the same site in the brain where narcotics like morphine exert their influence. It’s also known that opioids can have antidepressant effects, says Alan Schatzberg, a professor of psychiatry at Stanford and co-author of the new study.

It never made sense to Schatzberg that ketamine’s antidepressant effects were a result of blocking the glutamate receptors, as attempts to use other glutamate-blocking drugs as antidepressants have largely failed. The Stanford psychiatrist, who has spent his career studying depression, wondered if researchers were unknowingly activating opioid receptors with ketamine.

“You could test this by using an antagonist of the opioid system to see if you blocked the effect in people who are ketamine responders,” he says. “And that’s what we did.”

The researchers enlisted 12 subjects with treatment-resistant depression and gave them either an infusion of ketamine preceded by a placebo, or ketamine preceded by a dose of naltrexone, an opioid receptor blocker. Of those, seven subjects responded to the ketamine with placebo, “and it was very dramatic,” Schatzberg says, with depression lifting by the next day. “But in the other condition, they showed no effect,” suggesting it was the opioid receptor activity, not blocking glutamate receptors, that was responsible.

While opioid blockers prevented ketamine from activating the associated receptors, it did not block the drugs dissociative effects, suggesting dissociation alone won’t affect depression. “It’s not that, ‘hey, we’ll get you a little weird and you’ll get the effect,’” Schatzberg says.

The appeal of ketamine’s use as an antidepressant is clear enough. While more typical antidepressants may require six to eight weeks to produce benefits, ketamine works within hours.

“Our patients are asked to hang in there until the medication and talk therapy takes effect,” says Carlos Zarate, chief of the experimental therapeutics and pathophysiology branch of the National Institute of Mental Health (NIMH) who was not associated with the new study. While waiting for traditional treatments to kick in, patients “may lose their friends or even attempt suicide.”

<

A treatment that works within 24 hours? “That’s huge.”

A vial of ketamine. The drug is used primarily as an anesthetic but is gaining popularity as an effective antidepressant.
A vial of ketamine. The drug is used primarily as an anesthetic but is gaining popularity as an effective antidepressant. (Wikimedia Commons)

But the study linking ketamine to opioid activity means an extra dose of caution is required. While ketamine acts quickly, the anti-depressive effects of the drug only last for a few days to a week, meaning repeat doses would be needed in practice. Researchers and clinicians should consider the risk of addiction in long-term use, Schatzberg says. “You’re going to eventually get into some form of tolerance I think, and that’s not good.”

However, the new finding is based on just seven subjects, and it still needs to be replicated by other scientists, says Yale professor of psychiatry Greg Sanacora, who was not involved in the new study. And even if the trial is replicated, it would not prove ketamine’s opioid activity is responsible for its antidepressant effects.

“It doesn’t show that at all,” says Sanacora, who studies glutamate, mood disorders and ketamine. “It shows that the opioid system needs to be functioning in order to get this response.”

Sanacora compares the new study to using antibiotics to treat an ear infection. If you administered an additional drug that blocks absorption of antibiotics in the stomach, you would block treatment of the ear infection, but you wouldn’t conclude that antibiotics fight ear infections through stomach absorption—you just need a normally functioning stomach to allow the antibiotic to do its job. Similarly, opioid receptors might need to be functioning normally for ketamine to produce antidepressant effects, even if opioid activity is not directly responsible for those effects.

Complicating matters further, placebos often cause patients to experience less pain, but opioid blockers like naltrexone have been shown to prevent this response, according to Sanacora. It could be, he suggests, that all the apparatus of the clinic—the nursing staff, the equipment—exerted a placebo effect that is mediated by the brain’s opioid system, and the patients who received naltrexone simply did not respond to that placebo effect.

“That’s a very important and powerful tool that is in all of medicine, not just in psychiatry,” Sanacora says. “And we know that the opiate system is involved, to some extent, in that type of response.”

It’s also possible, the researchers note in the paper, that ketamine’s action at the glutamate receptor is still important. “Ketamine acts in three distinct phases—rapid effects, sustained effects and return to baseline,” Rodriguez says. Opioid signaling may turn out to mediate ketamine’s rapid effects, while “the glutamate system may be responsible for the sustaining effects after ketamine is metabolized.”

One interpretation is that ketamine blocks glutamate receptors on neurons that are inhibitory, meaning they signal other neurons to fire fewer signals. By blocking these neurons from firing, ketamine may enhance glutamate activity in the rest of the brain, producing anti-depressive effects that persist after the opioid activity dies down.

“The reality is it’s in a gray zone,” Sanacora says. “This is just one small piece of a very large puzzle or concern that we really need to look at the data in total.”

That data is forthcoming. Results from a Janssen Pharmaceuticals clinical trial using esketamine, an isomer of ketamine, and involving hundreds of subjects will soon become public, according to Sanacora, who has consulted for the company. And at NIMH, Zarate and colleagues are studying hydroxynorketamine, a metabolite of ketamine that may provide the same benefits but without the dissociative side effects.

The ultimate goal of all this research is to find a ketamine-like drug with fewer liabilities, and that aim is bringing researchers back to the fundamentals of science.

“For me, one of the exciting parts of this study is that it suggests that ketamine’s mechanism is complicated, it acts on different receptors beyond glutamate and is the start of this exciting dialogue,” Rodriguez says. “Sometimes great science raises more questions than answers.”











KETAMINE INFUSION CENTER VIRGINIA| 703-844-0184 | NOVA HEALTH RECOVERY | ARLINGTON, VA 22101 | ESKETAMINE PROVIDER VIRGINIA | ESKETAMINE CENTER | ESKETAMINE DOCTOR | 703-844-0184 | ARLINGTON, VIRGINIA 22207 22213 | NASAL SPRAY KETAMINE AND THE FDA APPROVAL| DR. SENDI | ESKETAMINE PROVIDER | NASAL SPRY KETAMINE THERAPY | KETAMINE FOR TREATMENT OF DEPRESSION, PTSD, ANXIETY | KETAMINE INFUSION CENTER | KETAMINE DEPRESSION | KETAMINE PTSD | EMAIL@NOVAHEALTHRECOVERY.COM | 2220 22182 23103 22039 20197 20184 22101 22102 22066 | CBD DOCTOR CBD CENTER | 703-844-0184 | FAIRFAX, VA 22034 | 22308 | ESKETAMINE LOUDON COUNTY, VA | ESKETAMINE ANNANDALE, VA | ESKETAMINE RICHMOND | ESKETAMINE VIRGINIA | KETAMINE SPRAY PROVIDER IN NORTHERN VIRGINIA 22308 | KETAMINE INFUSION CENTER | KETAMINE VIRGINIA | ESKETAMINE VIRGINIA | 703-844-0184 FOR AN APPOINTMENT | CBD PROVIDER | CBD CENTER | CBD VIRGINIA | DR. SENDI | NORTHERN VIRGINIA KETAMINE | KETAMINE CENTER | Depression Nutrition

NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link

Ketamine Virginia Link

Do Adjunctive Neutraceuticals Help Relieve Depression?

Using adjunctive neutraceuticals together with antidepressants can be helpful in reducing depressive symptoms, according to a new systematic review and meta-analysis published in the June 1, 2016 issue of the American Journal of Psychiatry.

An Australian research team analyzed findings of 40 studies encompassing 14 different neutraceuticals and found evidence to support the use of adjunctive S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D in order to alleviate symptoms of depression.

Findings regarding omega-3 were particularly robust. Eight double blind RCTs of omega-3, varying in size (from 20 to 122 participants) and in duration (4 to 12 weeks), met inclusion criteria. Of these, 6 studies showed a statistically significant reduction in depression scores for the treatment group, compared to the placebo group, with a significant effect size of 0.61 (P=0.0009). Ten out of 15 datasets found an effect in favor of 1-carbon cycle neutraceuticals (which consist of SAMe, folic acid, methylfolate, B6, and B12).

Creatine and an amino acid combination yielded positive findings in “isolated studies,” and the researchers stated that these products should receive “tentative consideration.”

The investigators noted that further research is needed to clarify whether zinc, vitamin C, or tryptophan (more specifically, 5-HTP, the active precursor of serotonin) could be of value. They concluded that inositol is “unlikely to have any utility as an adjunctive antidepressant agent,” although some research has suggested it may have utility as depression monotherapy.

Studies were tabulated in 4 separate groups: 1-carbon cycle neutraceuticals (consisting of SAMe and folic acid or related forms, such as methylfolate, B6 and B12); omega-3; tryptophan; other neutraceuticals.

All of the investigated supplements have “mechanistic antidepressant activity underpinning their use,” the researchers emphasized. For example, 1-carbon cycle agents are critical in the methylation processes of monoamines. Omega-3 modulates norepinephrine, dopamine, and serotonin reuptake, degradation, synthesis, and receptor binding.

The study was undertaken in response to the “growing recognition that for many people with a depressive disorder, full remission is either short-lived or absent.” The researchers noted that augmentation and combination approaches with pharmaceuticals are often used in clinical practice. Coadministration of neutraceuticals may “provide an effective and safe approach to enhancing antidepressant effects” either by “synergistically augmenting an antidepressant agent” or by providing “a range of additional biological effects.”

Sarris J, Murphy J, Mischoulon D, et al. Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. Am J Psychiatry. 2016;173(6):575-87.

Natural Depression Remedies

Natural protocol for depression treatment that includes omega-3s, magnesium, B vitamins, vitamin D, St John’s wort, ginkgo, SAMe, 5-HTP, and ginseng

Depression is a common mental disorder that presents with some or all of the following symptoms: a depressed mood, a loss of interest in things that once brought pleasure, feelings of guilt or low self-worth, disturbed sleep patterns, changes in appetite, a lack of energy, and poor concentration. These symptoms lead to impairments in an individual’s ability to take care of his or her everyday responsibilities and can become chronic or recurrent.   According the World Health Organization (WHO), depression is common worldwide, affecting about 121 million people. Untreated depression can lead to suicide, and the WHO estimates that 850,000 people worldwide commit suicide every year. Depression is the leading cause of disability worldwide and was the 4th leading contributor to the global burden of disease for the year 2000, according to the WHO. Their estimates project that depression will rise to 2nd place in the global burden of disease listing by the year 2020.  In many patients, mild to moderate depression can be successfully treated with a variety of naturopathic and holistic options, such as dietary changes, dietary supplements, exercise, massage, herbs, and sunlight.  Naturopathic medicine is based on the philosophy of addressing the basic underlying cause of any health condition. Proper nutrition is a foundational component of any natural medicine program. Nutrition affects mood through the many substrates and nutrients needed for proper neurotransmitter synthesis and function. A healthy diet is not only essential for proper neurotransmitter balance, but it affects the immune system in ways that then affect neurotransmitter function. The inclusion of exercise is also of utmost importance in any program addressing mood disorders. In addition to nutritional intervention and exercise, there are many other therapies that may improve mood in patients with mild depression. Following are a number of evidence-based, effective alternative/naturopathic treatments for depression, including dietary supplements, massage, herbs, sunlight, and more.

Anthroposophic Therapy

Anthroposophy is a spiritual science whose practical applications include biodynamic agriculture, anthroposophical medicinal products, and eurhythmy (“movement as visible speech”). Anthroposophic therapy is rooted in a healing method known as anthroposophical medicine, a branch of anthroposophic philosophy founded by Austrian philosopher and social thinker Rudolph Steiner in the 1920s. It utilizes a holistic approach, endeavoring to restore the balance between the physical, mental, and emotional states of the patient. Anthroposophical practitioners use medicines based on homeopathic principles and physical therapies that call upon massage and artistic expression to trigger the patient’s self-healing capacity. Anthroposophic medicine uses the anthroposophic view of the human being as a blend of 3 interdependent aspects: the physical body; the life force, understood as the source of growth and regeneration and sometimes called the soul; and the “astral body,” which mediates between the body and the soul, also called the “ego” or “consciousness.”  A 4-year study of the effectiveness of anthroposophic therapies in the treatment of depression evaluated 97 outpatients from 42 medical practices in Germany. Patients ranged from 20 to 69 years old and were referred to anthroposophic therapies (art, eurhythmy movement exercises, or rhythmical massage) or started physician-provided anthroposophic therapy (counseling, medication) for depression. Participants had suffered from depressed mood and at least 2 of 6 further depressive symptoms for a minimum of 6 months. Data were collected from July 1998 to March 2005.  The authors concluded “in outpatients with chronic depression, anthroposophic therapies were followed by long-term clinical improvement. Although the pre-post design of the present study does not allow for conclusions about comparative effectiveness, study findings suggest that the anthroposophic approach, with its recourse to nonverbal and artistic exercising therapies can be useful for patients motivated for such therapies.”1

Aromatherapy Massage

Aromatherapy is the use of essential oils to treat a variety of conditions. Naturopathic physicians use aromatherapy to treat depression, anxiety, insomnia, and stress-related disorders and to manage chronic pain.  Essential oils have been used effectively for centuries as a traditional medicine, but they have been the subject of few studies. Even in the absence of sufficient studies to completely explain the pharmacological effects of many essential oils or their active chemical constituents, the studies that have been done show measurable pharmacological effects when essential oils enter the blood stream through either inhalation or topical application.  Researchers at the Medicinal Plant Research Centre, United Kingdom, reviewed the published clinical trials of “psychoaromatherapy” in relation to psychiatric disorders, as well as evidence from mechanistic, neuropharmacological studies of the effects of essential oils. The authors concluded that aromatherapy may offer effective treatment for a range of psychiatric disorders. They also found that it does not appear to pose the risk of adverse effects found with many conventional psychotropic drugs.2 Various aromatherapy oils, diluted in carrier oil like almond or olive oil, are massaged into the skin, where they are absorbed into the bloodstream. Below is a list of some of the essential oils used in the treatment of depression and anxiety.

  • Clary sage is used for treating insomnia, anxiety, and depression.
  • Basil lifts fatigue, anxiety, and depression.
  • Rose acts on the nervous system.
  • Ylang ylang is used for anxiety, depression, insomnia, and stress.
  • Sandalwood has sedative properties and is good for treating depression and tension.
  • Lavender is used for depression, headache, hypertension, insomnia, migraine, nervous tension, and other stress-related conditions.
  • Jasmine increases the beta waves in the frontal lobe, which can create a more alert and responsive state of mind.
  • Rosemary relieves headaches and aids clear thinking.
  • Patchouli has an uplifting effect for depression and anxiety.
  • Chamomile is very calming; it soothes nerves and helps insomnia.
  • Geranium is both sedative and uplifting and thus is used for treating nervous tension, depression, and hormonal and menstrual problems.

 A 2007 clinical study published in the Journal of Clinical Oncology looked at the effectiveness of aromatherapy massage in the management of anxiety and depression in patients with cancer. Two hundred eighty-eight cancer patients in the United Kingdom referred to complementary therapy services because of clinical anxiety and/or depression were randomized to a course of aromatherapy massage or usual supportive care alone. The authors concluded that aromatherapy massage does not appear to confer benefit on cancer patients’ anxiety and/or depression in the long term but is associated with clinically important benefit up to 2 weeks after the intervention.3 In other words, aromatherapy is not a cure for depression, but it may be an effective short-term aid in managing depression and anxiety when used with other treatment options. According the World Health Organization (WHO), depression is common worldwide, affecting about 121 million people.Another study was conducted with nursing students in Korea to test the effectiveness of lavender essential oil on insomnia and depression. In a 4-week-long, single-blind, repeated-measurements experiment, researchers studied 42 female students who complained of insomnia. The lavender fragrance had a beneficial effect on insomnia and depression in the students, though repeated studies would be needed to confirm effective proportions of lavender oil and carrier oil for insomnia and depression.4 A controlled trial conducted in Thailand tested the relaxation properties of ylang ylang oil. The oil caused a significant decrease in blood pressure, a significant increase in skin temperature, and a greater sense of calm and more relaxation. The authors conclude that there is evidence of the effectiveness of ylang ylang oil for relief of depression and stress in humans.5

Dietary Changes/Supplements

The first line of naturopathic treatment for almost every disease is improved patient nutrition. Nutrition plays a key role in the onset, severity, and duration of depression, including daily mood swings. Food patterns preceding the onset of depression and during a depressive episode are similar. These patterns may include skipping meals, poor appetite, and a desire for sweets. Depressive symptoms are exacerbated by nutritional imbalances, including 

  • frequent consumption of caffeine;
  • sucrose consumption;
  • deficiencies in vitamins and minerals (biotin, folic acid, and other B vitamins; vitamin C; calcium; copper; iron; magnesium; or potassium);
  • excesses of vanadium6,7;
  • imbalances in amino acids; and
  • food allergies.

A recent study published in Neuropharmocology demonstrates that physiologically relevant doses of caffeine can significantly depress adult hippocampal neurogenesis.8 (Adult neurogenesis has been associated with learning, memory, and depression). A review published by the Oklahoma State Medical Association finds that “caffeine is a widely used psychoactive substance that has the potential to contribute to many psychiatric symptoms.”9 Sugar intake has been linked to depression. In an article in the Journal of Depression and Anxiety, the national rate of sugar consumption was shown to directly affect the prevalence of major depression. The basis for this includes the relationship between sugar consumption, β-endorphins, and oxidative stress.10

Dietary Recommendations

The main dietary focus in treating depression is to ensure that the patient’s diet is rich in foods containing omega-3 fatty acids and those containing magnesium, vitamins B and D, and the antioxidant vitamins A, C, and E. Along with proper food, sufficient water intake plays a vital role in maintaining proper chemical balance in the body; even mild dehydration can cause fatigue. The Institute of Medicine advises that women should consume 2.7 Ls (91 oz) of total water (from all beverages and foods) each day, and men should average approximately 3.7 L (125 oz daily) of total water. The panel did not set an upper limit for water consumption.11

Omega-3 Fatty Acids

Foods that are rich in omega-3 fatty acids have been shown to reduce neuronal phospholipid turnover. In 1 study, registered difference images showed that the “omega-3 treatment was accompanied by structural brain changes including, in particular, a reduction in the lateral ventricular volume.”12 A 2007 meta-analysis of trials involving patients with major depressive disorder and bipolar disorder provided evidence that omega-3 PUFA supplementation reduces symptoms of depression.13 The foods with the highest amounts of omega 3 are flax seeds, Chia seeds, walnuts, baked/broiled salmon, soybeans, baked/broiled halibut, sardines, herring, tofu, and winter squash. Other foods containing omega-3s are canola oil, olive oil, broccoli, cantaloupe, kidney beans, spinach, grape leaves, Chinese cabbage, and cauliflower.

Dietary Magnesium

Studies have shown an inverse relationship between magnesium intake and depression and anxiety.14-16 Patients with depression should add foods that are high in magnesium to their diet, such as fish, barley, artichokes, buckwheat, oat bran, almonds, cashews, pine nuts, black beans, white beans, cornmeal, spinach, broccoli, tomatoes, pumpkin seeds, and soybeans. Whole-wheat flour contains magnesium, but the magnesium-rich germ and bran are removed in the process of making white flour. All green vegetables are sources of magnesium because the center of the chlorophyll molecule contains magnesium.

B Vitamins

The B-complex vitamins are water-soluble vitamins that are essential to mental and emotional well-being. B-vitamin deficiency is common because B vitamins are easily destroyed by common lifestyle behaviors such as drinking alcohol and caffeinated beverages, smoking, and eating foods rich in refined sugars. Studies have shown that vitamin-B deficiency can be a cause of both depression and epilepsy and that “preventive vitamin B supplementation and sufficient intake seem very important for secondary and primary prevention of neuropsychiatric disorders, especially in subjects with a low intake or status of the vitamins.”17 When advising patients to supplement with specific B vitamins, it must be remembered that the patient must also take a B-complex supplement to prevent imbalances. Nerve tissue requires vitamin B1 to utilize glucose to produce energy; this vitamin modulates cognitive performance, especially in the elderly. Folic acid preserves the brain during its development and preserves memory during aging. Vitamins B6 and B12, among others, are directly involved in the synthesis of some neurotransmitters. Vitamin B6 is likely to benefit the treatment of premenstrual depression. Good sources of B vitamins include the following.

  • Asparagus, broccoli, spinach, bananas, potatoes
  • Dried apricots, dates, and figs
  • Milk, eggs, cheese, yogurt
  • Nuts and legumes (includes rice, corn, soy beans, string beans, peas, lentils, mustard, sesame seeds, and poppy seeds)
  • Fish
  • Brown rice, wheat germ, whole grain cereals

Vitamin D

Seasonal affective disorder (SAD) is prevalent when vitamin D stores are typically low. Researchers note that people suffering from depression, particularly those with SAD, tend to improve as their levels of vitamin D in the body increase.18 It has been hypothesized that vitamin D increases levels of serotonin in the brain.19 There are individual differences in the amount of vitamin D needed daily based on geographical location, the time of year, skin type, and amount of sun exposure. Research is ongoing to establish new standards for recommended daily vitamin D intake for adults as the importance of proper vitamin D levels becomes more obvious; currently, tolerable upper intake levels for vitamin D according to the National Institutes of Health Office of Dietary Supplements is 2,000 IU for adults and children over the age of 13 and 1,000 IU for children under one year of age.20 In an experiment conducted in 1998, Australian researchers found that vitamin D3(cholecalciferol) given in doses of 400 IU and 800 IU had significant positive effects on the mood of healthy individuals. Forty-four people were given either 400 IU of vitamin D, 800 IU of vitamin D, or a placebo for 5 days during the late winter. Research subjects reported that vitamin D3 had the effect of enhancing a positive mood and also reducing a negative mood in some cases. The authors concluded, “Vitamin D3 deficiency provides a compelling and parsimonious explanation for seasonal variations in mood.”21 In 1999, a study done by Hollis, Gloth, and Alam showed that a one-time dose of 100,000 IU of vitamin D improved symptoms of depression better than light therapy in a small group of participants who suffered from SAD.22 All of the participants in the vitamin D group improved according to all depression scale measurements, and the increase of serum 25-hydroxyvitamin D [25-(OH)D] levels was strongly associated with the degree of improvement of SAD symptoms. A study at the Institute of Clinical Medicine in Norway examined the relationship between serum 25-(OH)D levels and depression in overweight and obese subjects and assessed the effect of vitamin D supplementation on depressive symptoms. Researchers found a significant improvement in Beck Depression Inventory scores after 1 year in the 2 groups given vitamin D but not in the placebo group. There was a significant decrease in serum parathyroid hormone in the 2 vitamin D groups without a concomitant increase in serum calcium. There are receptors for parathyroid hormone (PTH) and 1,25–dihydroxyvitamin D in the brain, and there are clinical and experimental data indicating that PTH and vitamin D may affect cerebral function.22 The authors concluded that there “appears to be a relation between serum levels of 25-(OH) D and symptoms of depression. Supplementation with high doses of vitamin D seems to ameliorate these symptoms indicating a possible causal relationship.”23  Dietary sources of vitamin D include milk, salmon, and tuna. The best food source of vitamin D is salmon, with 530 IU per 3 oz of canned salmon. Salmon is also rich in omega 3 fatty acids, making it a very important part of a depression prevention or treatment diet.

Exercise

Research has shown that exercise is an effective but often underused treatment for mild to moderate depression, even in elderly patients, and has virtually no side effects.24,25Researchers at Duke University demonstrated several years ago that exercise can be an effective antidepressant even for those patients with major depressive disorder.26 According to a report from the UK Mental Health Foundation, exercise may be just as effective at treating depression as antidepressant medicines, and they also claim that being physically active may help prevent depression in the first place. The UK report also states that exercise therapy should be used as a first-line treatment for mild depression because it may be just as effective as antidepressant medicines.27 Exercise has a number of beneficial physiological effects that make it ideal for treating depression. Exercise has been proven to increase activity in both the frontal lobe of the brain and the hippocampus. It also has been found to increase mood-enhancing brain-derived neurotrophic factor levels.28,29 Studies have also found that exercise increases levels of serotonin, dopamine, and norepinephrine.30-35 Physical activity should last at least 20 minutes a session for at least 10 weeks in order to help improve psychological well-being. Aerobic activities such as brisk walking, jogging, cycling, swimming, and dancing tend to be the most effective for treating depression.36

Natural Medicines

Several herbs have been proven to have a beneficial effect on depression and its symptoms of anxiety, sleeplessness, and inability to concentrate. Following are some of the most common herbs and supplements used for mild to moderate depression.

St John’s Wort (Hypericum perforatum

St John’s wort is a bushy plant with a turpentine-like odor and yellow flowers whose petals have black dots on the margins. Its extract has been used in various folk remedies and herbal tinctures since Roman times. It is used extensively in both the United States and Europe to treat mild to moderate depression. A German study compared the effectiveness of St John’s wort with imipramine, a well-known antidepressant. The trials involved 40 outpatient clinics in Germany with a total of 324 outpatients suffering mild to moderate depression. Participants were given either 75 mg imipramine twice daily or 250 mg Hyericum perforatum extract  ZE 117 twice daily for 6 weeks. The study concluded that H perforatum extract is therapeutically equivalent to imipramine in treating mild to moderate depression and is better tolerated.37 Another German review investigated the efficacy and side effects of H perforatum. This study looked at 27 trials that included a total of 2,291 patients who met inclusion criteria. Seventeen trials, with a total of 1,168 patients, were placebo-controlled (16 addressed single preparations, 1 a combination with 4 other plant extracts). Ten trials (8 single preparations, 2 combinations of Hypericum and Valeriana) with a total of 1,123 patients compared Hypericum with other antidepressant or sedative drugs. Most trials were 4 to 6 weeks long. Participants usually had “neurotic depression” or “mild to moderate severe depressive disorders.” The study concluded that “there is evidence that extracts of Hypericum are more effective than placebo for the short-term treatment of mild to moderately severe depressive disorders.” The proportions of patients reporting side effects were 26.3% for Hypericum single preparations vs 44.7% for standard antidepressants and 14.6% for combinations vs 26.5% with amitriptyline or desipramine. In other words, patients taking standard antidepressant medications were almost twice as likely to experience side effects as patients taking Hypericum.38 Until 2004, only 1 randomized controlled trial had been conducted using Hypericum in patients with severe depression, but it was underpowered and so its negative findings were questionable.39 With this in mind, German researchers conducted a study of acute treatment of moderate to severe depression with Hypericum extract WS 5570 vs paroxetine. The study involved 251 adult outpatients with acute major depression with total score ≥22 on the 17-item Hamilton Depression Scale from 21 psychiatric primary care practices in Germany. Patients were given either 900 mg/day Hypericum extract WS 5570 (300 mg 3 times/d) or 20 mg paroxetine once per day for 6 weeks. (In initial nonresponders, doses were increased to 1,800 mg/day Hypericum or 40 mg/day paroxetine after 2 weeks.) The study concluded that Hypericum extract WS 5570 is at least as effective as paroxetine in the treatment of moderate to severe major depression and is better tolerated.40 A comprehensive clinical review by British researchers supports the findings of the various studies above, and the authors note that all studies have found Hypericum to be less likely to cause side effects than standard pharmaceutical drugs used currently.41 The mechanism of action with St John’s wort is being investigated. Initial biochemical studies report that St John’s wort inhibits the uptake of serotonin, dopamine, and noradrenalin (norepinephrine). However, other in vitro binding assays carried out using St John’s wort extract demonstrate significant affinity for adenosine, GABA (A), GABA (B), and glutamate receptors. In vivo, St John’s wort extract leads to a decrease in the number of beta-adrenergic receptors and an increase in the number of serotonin 5-HT(2) receptors in the rat frontal cortex and causes changes in neurotransmitter concentrations in brain areas that are implicated in depression. However, there are reasons to be cautious when prescribing St John’s wort, as it has been found to have significant interactions with some other drugs. In a study done at the College of Pharmacy in Little Rock, Arkansas, comparisons of pre– and post–St John’s wort phenotypic ratios revealed significant induction of CYP3A4 and CYP2E1 activity.42 Because CYP3A4 is involved in the oxidative metabolism of more than 50% of all drugs, this suggests that Hypericum extracts are likely to interact with many more drugs than previously had been realized. Examples of medications that could be affected include carbamazepine (anticonvulsant and analgesic), cyclosporine (immunosuppressant), irinotecan (cancer drug), midazolam (anesthetic), nifedipine (calcium channel blocker), birth control pills, simvastatin (cholesterol-lowering drug), theophylline (bronchodilator), tricyclic antidepressants, warfarin (blood thinner), or HIV drugs such as nonnucleoside reverse transcriptase inhibitors or protease inhibitors. St John’s wort may also interact with digoxin or digitoxin (cardiac drug), resulting in a decrease in digoxin blood concentration. There may also be an interaction with triptan-type headache medications. Examples include naratriptan, rizatriptan, sumatriptan, and zolmitriptan. In theory, St John’s wort may also interact with certain chemotherapy drugs such as anthracyclines and may increase antiinflammatory effects of COX-2 inhibitor drugs or nonsteroidal antiiflammatories such as ibuprofen. 

Ginkgo Biloba

The Ginkgo biloba tree is an ancient species of tree native to the Asia. Chinese herbalists have used ginkgo for thousands of years, and it is one of the most widely studied botanical products. Ginkgo is widely used throughout both the United States and Europe. Since ginkgo nuts are mildly toxic, most of the ginkgo sold is in the form of a standardized extract of the leaves of the tree.  Ginkgo has a long history in traditional medicine for treating circulatory disorders and enhancing memory. Scientific studies throughout the years support the effectiveness of ginkgo for these problems.43-48 Evidence to date shows that ginkgo biloba extract (GBE) is primarily effective in the elderly and when treating disorders that are caused by diminished cerebral blood flow. Laboratory studies have shown that “GBE improves blood circulation by dilating blood vessels and reducing the stickiness of blood platelets.” Ginkgo leaves also contain flavonoids and terpenoids, which are powerful antioxidants.49,50Ginkgo biloba can be used to enhance other depression treatments and sometimes can be used alone instead of pharmaceutical treatments for mild cases of depression. Even in cases where ginkgo is used as an adjunct to other depression treatments, it can be helpful as an aid to improving short-term memory by improving cerebral circulation.

S-adenosylmethionine

S-adenosylmethionine is sold as a nutritional supplement under the marketing name SAMe. SAMe is also marketed as an approved prescription drug in Russia, Italy, and Germany. The supplement SAMe is a synthetic form of a compound formed naturally in the body from the essential amino acid methionine and adenosine triphosphate. It was first discovered in 1953. SAMe serves as a primary methyl group donor in various physiological reactions and is then converted to S-adenosyl-homocysteine.51-54 Clinical trials have shown that SAMe is effective in treating depression when taken on a regular basis. Other conditions that SAMe has been shown to help in clinical trials are liver disease and osteoarthritis. SAMe is required for the biosynthesis of the neurotransmitters dopamine and serotonin as well as for cellular growth and repair. Patients with bipolar disorder or anxiety disorders or other psychiatric disease must be closely monitored while taking SAMe as it has been associated with hypomania and mania. There are also concerns that SAMe could cause levodopa to be less effective when taken over a long period of time, so patients with Parkinson’s disease should be advised to avoid this supplement.55 There are a number of side effects associated with SAMe; the most commonly reported are nausea and other digestive disturbances. Less common side effects include anxiety, insomnia, increased thirst, increased urination, headache, hyperactivity, decreased blood glucose levels, skin rashes, dry mouth, and blood in the stool. Therapeutic doses range from 400 mg per day to 1,600 mg per day, although higher doses are used empirically in some cases. In contrast, some physicians recommend lower doses ranging from 50 to 200 mg per day to treat mild depression in an effort to lessen the risk of triggering the side effects mentioned above.

5-Hydroxytryptophan

5-Hydroxytryptophan (5-HTP) is a naturally occurring amino acid, a precursor to the neurotransmitter serotonin, and an intermediate in tryptophan metabolism. 5-HTP is effective in treating depression, suppressing appetite, and promoting sleep. 5-HTP increases serotonin synthesis and release, making it useful in the treatment of conditions thought to be caused or made worse by a lack of serotonin. Care must be used to avoid serotonin syndrome in patients taking antidepressant medications. 5-HTP is usually extracted from the seeds of Griffonia simplicifolia and sold in 50 mg or 100 mg gelatin or vegetarian capsules. 

Siberian ginseng (Eleutherococcus senticosus)

Siberian ginseng, also known as Eleuthero, is an adaptogen that has been used for centuries in eastern countries, including China and Russia. As an adaptogen, it helps to control excess cortisol levels and thereby reduces depression.56,57 Although a distant relative of American ginseng (Panax quinquefolius) and Asian ginseng (Panax ginseng) with some overlap in its uses, Siberian ginseng is a distinct plant with different active chemical components. Ten compounds have been isolated from Siberian ginseng. Its pharmacological activities are mainly due to lignans and iridoid glycosides, such as eleutherosides.58Prized for its ability to restore vigor, increase longevity, enhance overall health, and stimulate both a healthy appetite and a good memory, it is widely used in Russia to help the body adapt to stressful conditions and to enhance productivity.  Practitioners of Chinese medicine use Siberian ginseng to restore the balance of qi and to treat a deficiency of yang in the spleen and kidney. Siberian ginseng is also an antioxidant, a nervine, an anticholesteremic, and mildly antiinflammatory. Siberian ginseng is used to help the body deal with physical and mental stressors such as heat, cold, physical exhaustion, viruses, bacteria, chemicals, extreme working conditions, noise, and pollution. It works by strengthening the system, thereby helping to prevent illness. It has been shown to have significant antidepressant effects in rats that were subjected to the desperation test and neuropharmacological tests based on the antagonist activity with respect to reserpine clofelin, and L-DOPA,59 and a Chinese study has shown that Siberian ginseng exhibited antifatigue, antistress, immunoenhancing effect, central nervous system activity, and antidepressive effects.60

Phototherapy

Phototherapy is the use of light to treat disease and is a treatment of choice for SAD. Other indications for bright light therapy include nonseasonal depression, bipolar depression, chronic depressive disorder, antepartum and postpartum depression, late luteal phase dysphoric disorder, circadian phase sleep disorders, jet lag, shift work problems, and behavioral disturbance and insomnia in organic dementia. A 2004 study combining bright light exposure and physical exercise showed that this treatment may be an effective way of relieving depressive symptoms. The study concluded that “problems with sleep, especially initial insomnia, may predict a good response to treatment using combined light and exercise. Bright light exposure and physical exercise, even in combination, seem to be well tolerated and effective on depressive symptoms.”61 At the Be’er Ya’akov Mental Health Center associated with Tel Aviv University, Israel, a pilot study was conducted using partial sleep deprivation during the second half of the night, medium (green) wavelength light in combination with dawn simulation, bright light therapy, and sleep phase advance. The results showed the procedure to be effective and well tolerated. It affords many advantages, such as “the achievement of a rapid response, no extinction of the therapeutic effect after 4 weeks of follow-up, safety, high patient compliance, and cost effectiveness.”62

Energy Psychology

Many of the body’s electrical systems and energy fields are understood, readily verified, and a focus of established interventions. The application of lasers and magnetic pulsation, for example, can be described in terms of specific, measurable wavelengths and frequencies that have been found to be therapeutic.63 Other energies are considered to be of a more subtle nature and have not been directly measured by reproducible methods. While such subtle energies are generally not recognized in Western healthcare frameworks, they are at the root of numerous ancient systems of healing and spiritual development that are not only still in wide use throughout the world but increasingly being utilized in the West. Energy psychology has been referred to as “acupuncture without needles” in treating mental health disorders. More than two dozen variations of energy psychology can be identified, with the most well-known being Thought Field Therapy (TFT), the Tapas Acupressure Technique (TAT), and the Emotional Freedom Techniques (EFT). Many of these adapt practices and concepts from acupuncture and acupressure; others borrow from yoga, meditation, qigong, and other traditional practices. Some practitioners of these modalities describe their therapeutic mechanism as the activation of electrical signals that are said to influence brain activity64; others as describe them as catalyzing shifts in putative energy fields, such as the body’s biofield.65TFT, TAT, and EFT, each utilizing techniques derived from acupuncture and acupressure, have received by far the most attention. But what is the proof that there is any real effectiveness to these methods? Evidence is still preliminary, but energy psychology is gaining credence as an evidence-based treatment. In fact, 1 form has met the American Psychological Association’s criteria as a “probably efficacious treatment” for specific phobias; another has met the criteria for maintaining weight loss.66 The limited scientific evidence, combined with extensive clinical reports, suggests that energy psychology holds promise as a rapid and potent treatment for a range of psychological conditions. 

Conclusion

A number of alternatives to standard antidepressant medications exist for patients with mild to moderate depression. An essential first step is to work with the patient to ensure proper diet and regular exercise. Once this has been done, nutritional supplementation, herbal medicines, phototherapy, and energy psychologies can be utilized according to patient needs as described above. 

About the Author

Rena Freedenberg, ND, graduated from Michlelet Eden College of Natural Medicine in Jerusalem, Israel, where she did 2 years of internship in internal medicine. Freedenberg’s practice is located in Beitar Illit, Israel, where she specializes in women’s and children’s healthcare. Her primary interest is in addressing the underlying causes of illness and improving the health and quality of life of women and their families.

References

  1. Hamre HJ, Witt CM, Glockmann A, et al. Anthroposophic therapy for chronic depression: a four-year prospective cohort study. BMC Psychiatry. 2006; 6:57. 
  2. Perry N, Perry E. Aromatherapy in the management of psychiatric disorders: clinical and neuropharmacological perspectives. CNS Drugs. 2006;20(4):257-280.
  3. Wilkinson SM, Love SB, Westcombe AM, et al. Effectiveness of aromatherapy massage in the management of anxiety and depression in patients with cancer: a multicenter randomized controlled trial. J Clin Oncol. 2007;25(5):532-539.
  4. Lee IS, Lee GJ. Effects of lavender aromatherapy on insomnia and depression in women college students. Taehan Kanho Hakhoe Chi. 2006;36(1):136-143.
  5. Hongratanaworakit T, Buchbauer G. Relaxing effect of ylang ylang oil on humans after transdermal absorption. Phytother Res. 2006;20(9):758-763.
  6. Naylor GJ, Smith AH. Vanadium: a possible aetiological factor in manic depressive illness. Psychol Med. 1981;11(2):249-256.
  7. Naylor GJ. Vanadium and manic depressive psychosis. Nutr Health. 1984;3(1-2):79-85.
  8. Wentz CT, Magavi SS. Caffeine alters proliferation of neuronal precursors in the adult hippocampus. Neuropharmacology. 2009; 56(6-7):994-1000. 
  9. Broderick P, Benjamin AB. Caffeine and psychiatric symptoms: a review. J Okla State Med Assoc. 2004;97(12):538-542
  10. Westover AN, Marangell LB. A cross-national relationship between sugar consumption and depression? J Depression Anxiety. 2002;16:118-120.
  11. Panel on Dietary Reference Intakes for Electrolytes and Water, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes: Water, Potassium, Sodium, Chloride, and Sulfate. Released February 11, 2004.
  12. Puri BK, Counsell SJ, Hamilton G, Richardson AJ, Horrobin DF. Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover. Int J Clin Pract. 2001;55(8):560-563.
  13. Ross BM, Seguin J, Sieswerda LE. Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid? Lipids Health Dis. 2007:6:21. 
  14. Jacka FN, Overland S, Stewart R, et al. Association between magnesium intake and depression and anxiety in community-dwelling adults: the Hordaland Health Study. Aust N Z J Psychiatry. 2009;43(1):45-52.
  15. Jung KI, Ock SM, Chung JH, Song CH. Associations of serum Ca and Mg levels with mental health in adult women without psychiatric disorders. Biol Trace Elem Res. 2009 Jun 19 [epub ahead of print].
  16. Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006;67(2):362-370.
  17. Herrmann W, Lorenzl S, Obeid R. Review of the role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric disorders—current evidence and preliminary recommendations. Fortschr Neurol Psychiatr. 2007;75(9):515-527.
  18. Gloth FM 3rd, Alam W, Hollis B. Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. J Nutr Health Aging. 1999;3(1):5-7.
  19. Partonen T. Vitamin D and serotonin in winter. Med Hypotheses. 1998;51(3):267-268.
  20. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press, 1997.
  21. Lansdowne AT, Provost SC. Vitamin D3 enhances mood in healthy subjects during winter. Psychopharmacology (Berl). 1998;135(4):319-323.
  22. Jorde R, Waterloo K, Saleh F, Haug E, Svartberg J. Neuropsychological function in relation to serum parathyroid hormone and serum 25-hydroxyvitamin D levels. The Tromsø study. J Neurol. 2006;253(4):464-470. 
  23. Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med. 2008;264(6):599-609. 
  24. Rethorst CD, Wipfli BM, Landers DM. The antidepressive effects of exercise: a meta-analysis of randomized trials. Sports Med. 2009;39(6):491-511.
  25. Blumenthal JA, et al. Effects of exercise training on older patients with major depression. Arch Intern Med. 1999;159:2349-2356.
  26. Babyak M, Blumenthal JA, Herman S, et al. Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months. Psychosom Med. 2000;62(5):633-638.
  27. Mental Health Foundation. Up and running: exercise therapy and the treatment of mild or moderate depression in primary care. 2005. http://www.google.com/url?sa=t&source=web&ct=res&cd=2&ved=0CA0QFjAB&url=http%3A%2F%2Fwww.mentalhealth.org.uk%2FEasySiteWeb%2Fgetresource.axd%3FAssetID%3D38661%26type%3Dfull%26servicetype%3DAttachment&ei=w-oGS-XYKdSvngfct8m2Cw&usg=AFQjCNGlkzsF2n7bYpQ_G-mcb3LTgLvsXQ&sig2=ovftEa4eXmjOnEIwHLGZmA.Accessed November 20, 2009.
  28. Ni H, Li C, Tao LY, Cen JN. Physical exercise improves learning by modulating hippocampal mossy fiber sprouting and related gene expression in a developmental rat model of penicillin-induced recurrent epilepticus. Toxicol Lett. 2009 1;191(1):26-32. 
  29. Helfer JL, Goodlett CR, Greenough WT, Klintsova AY. The effects of exercise on adolescent hippocampal neurogenesis in a rat model of binge alcohol exposure during the brain growth spurt. Brain Res. 2009;1294:1-11.
  30. Caperuto EC, dos Santos RV, Mello MT, Costa Rosa LF. Effect of endurance training on hypothalamic serotonin concentration and performance. Clin Exp Pharmacol Physiol. 2009;36(2):189-191.
  31. Pothakos K, Kurz MJ, Lau YS. Restorative effect of endurance exercise on behavioral deficits in the chronic mouse model of Parkinson’s disease with severe neurodegeneration. BMC Neurosci. 2009;10:6.
  32. Farrell PA, Gustafson AB, Morgan WP, Pert CB. Enkephalins, catecholamines, and psychological mood alterations: effects of prolonged exercise. Med Sci Sports Exerc. 1987;19(4):347-53. 
  33. Kotchen TA, Hartley LH, Rice TW, Mougey EH, Jones LG, Mason JW. Renin, norepinephrine, and epinephrine responses to graded exercise. J Appl Physiol. 1971;31(2):178-184.
  34. Rasmussen P, Brassard P, Adser H. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol. 2009;94(10):1062-1069. 
  35. BDNF brain-derived neurotrophic factor. www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&term=(bdnf[gene])%20AND%20(Homo%20sapiens[orgn])%20AND%20al
  36. Petruzzello SJ, Landers DM, et al. A meta-analysis on the anxiety-reducing effects of acute and chronic exercise. Outcomes and mechanisms. Sports Med.1991;11(3):143-182.
  37. Woelk H. Comparison of St. John’s wort and imipramine for treating depression: randomised controlled trial. BMJ. 2000;321(7260):536-539.
  38. Linde K, Mulrow CD. St. John’s wort for depression. Cochrane Database Syst Rev. 2000;(2):CD000448.
  39. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John’s wort) in major depressive disorder: a randomized controlled trial. JAMA. 2002;287(14):1807-1814. 
  40. Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John’s wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ. 2005;330(7490):503.
  41. Whiskey E, Werneke U, Taylor D. A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review. Int Clin Psychopharmacol. 2001;16(5):239-252.
  42. Gurley BJ, Gardner SF, Hubbard MA, et al. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St. John’s wort, garlic oil, Panax ginseng and Ginkgo bilobaDrugs Aging. 2005;22(6):525-539.
  43. Wu YZ, Li SQ, Zu XG, Du J, Wang FF. Ginkgo biloba extract improves coronary artery circulation in patients with coronary artery disease: contribution of plasma nitric oxide and endothelin-1. Phytother Res. 2008;22(6):734-739.
  44. Boelsma E, Lamers RJ, Hendriks HF, van Nesselrooij JH, Roza L. Evidence of the regulatory effect of Ginkgo biloba extract on skin blood flow and study of its effects on urinary metabolites in healthy humans. Planta Med. 2004;70(11):1052-1057.
  45. Kasper S, Schubert H. Ginkgo biloba extract EGb 761 in the treatment of dementia: evidence of efficacy and tolerability. Fortschr Neurol Psychiatr. 2009;77(9):494-506.
  46. Cho HJ, Shon YH, Nam KS. Ginkgolide C inhibits platelet aggregation in cAMP- and cGMP-dependent manner by activating MMP-9. Biol Pharm Bull. 2007;30(12):2340-2344.
  47. Pietta PG. Flavonoids as antioxidants. J Nat Prod. 2000;63(7):1035-1042.
  48. Grassmann J. Terpenoids as plant antioxidants. Vitam Horm. 2005;72:505-535.
  49. Blecharz-Klin K, Piechal A, Joniec I, Pyrzanowska J, Widy-Tyszkiewicz E. Pharmacological and biochemical effects of Ginkgo biloba extract on learning, memory consolidation and motor activity in old rats. Neurobiol Exp (Wars). 2009;69(2):217-231.
  50. Cho HJ, Shon YH, Nam KS. Ginkgolide C inhibits platelet aggregation in cAMP- and cGMP-dependent manner by activating MMP-9. Biol Pharm Bull. 2007;30(12):2340-2344. 
  51. Knowlton L. Investigating SAM-e. Geriatric Times. 2001:2(5). http://www.cmellc.com/geriatrictimes/g010923.html 2001. Accessed November 20, 2009.
  52. Kagan BL, Sultzer DL, Rosenlicht N, Gerner RH. Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 1990;147(5):591-595.
  53. Rosenbaum JF, Fava M, Falk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand. 1990;81(5):432-436. 
  54. Hardy ML, Coulter I, Morton SC, et al. S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease. Evid Rep Technol Assess (Summ). 2003;(64):1-3.
  55. Liu X, Lamango N, Charlton C. L-dopa depletes S-adenosylmethionine and increases S-adenosyl homocysteine: Relationship to the wearing off effects. Soc Neurosci. 1998;24:1469.
  56. Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009;4(3):198-219.
  57. Römer B, Lewicka S, Kopf D, et al. Cortisol metabolism in depressed patients and healthy controls. Neuroendocrinology. 2009;90(3):301-306.
  58. Deyama T, Nishibe S, Nakazawa Y. Constituents and pharmacological effects of Eucommia and Siberian ginseng. Acta Pharmacol Sin. 2001;22(12):1057-1070.
  59. Kurkin VA, Dubishchev AV, Ezhkov VN, et al. Antidepressant activity of some phytopharmaceuticals and phenylpropanoids. Pharmaceut Chem J. 2006. 40(11):33-38.
  60. Deyama T, Nishibe S, Nakazawa Y. Constituents and pharmacological effects of Eucommia and Siberian ginseng. Acta Pharmacol Sin. 2001;22(12):1057-1070.
  61. Leppämäki S, Haukka J, Lönnqvist J, Partonen T. Drop-out and mood improvement: a randomised controlled trial with light exposure and physical exercise. BMC Psychiatry. 2004;4:22. 
  62. Moscovici L, Kotler M. A multistage chronobiologic intervention for the treatment of depression: a pilot study. J Affect Disord. 2009;116(3):201-207.
  63. Oschman J. Energy Medicine in Therapeutics and Human Performance. New York: Elsevier; 2003.
  64. Ruden RA. A model for disrupting an encoded traumatic memory. Traumatology. 2007;13:71-75.
  65. Rubik B. The biofield hypothesis: its biophysical basis and role in medicine. J Altern Complement Med. 2002;8(6):703-717.
  66. Feinstein D. Energy psychology: a review of the preliminary evidence. Psychother Theor Res Pract Train. 2008;45(2):199-213.

KETAMINE INFUSION CENTER VIRGINIA| 703-844-0184 | NOVA HEALTH RECOVERY | ARLINGTON, VA 22101 | ESKETAMINE PROVIDER Virginia | ESKETAMINE CENTER | ESKETAMINE DOCTOR | 703-844-0184 | ARLINGTON, VIRGINIA 22207 22213 | Nasal Spray Ketamine and the FDA approval| DR. SENDI | ESKETAMINE PROVIDER | NASAL SPRY KETAMINE THERAPY | KETAMINE FOR TREATMENT OF DEPRESSION, PTSD, ANXIETY | KETAMINE INFUSION CENTER | KETAMINE DEPRESSION | KETAMINE PTSD | EMAIL@NOVAHEALTHRECOVERY.COM | 2220 22182 23103 22039 20197 20184 22101 22102 22066 | CBD DOCTOR CBD CENTER | 703-844-0184 | FAIRFAX, VA 22034 | 22308 | ESKETAMINE LOUDON COUNTY, VA | ESKETAMINE ANNANDALE, VA | ESKETAMINE RICHMOND | ESKETAMINE VIRGINIA | KETAMINE SPRAY PROVIDER IN NORTHERN VIRGINIA 22308 | KETAMINE INFUSION CENTER | KETAMINE VIRGINIA | ESKETAMINE VIRGINIA | 703-844-0184 FOR AN APPOINTMENT | CBD PROVIDER | CBD CENTER | CBD VIRGINIA | DR. SENDI

NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link

Ketamine Virginia Link

Ketamine-like depression treatment on track for FDA approval

CNN)A ketamine-like drug for treatment-resistant depression was backed by a US Food and Drug Administration advisory committee on Tuesday. If it is then approved by the FDA, the drug — called esketamine — may provide a new option for patients with major depressive disorder who have tried at least two other antidepressants without success.A panel of experts voted to endorse the drug, which is made in nasal spray form by the pharmaceutical company Janssen, a division of Johnson & Johnson. Fourteen members voted that the benefits outweighed the risk, with two opposed and one abstaining.

Ketamine offers lifeline for people with severe depression, suicidal thoughts
703-844-0184 | NOVA Health Recovery | Alexandria, Va 22306

Ketamine offers lifeline for people with severe depression, suicidal thoughtsThe drug is a close relative of ketamine, a powerful medication used in hospitals primarily as an anesthetic; recent scientific studies have also shown its potential with treatment-resistant depression and suicidal ideation. Ketamine is also used recreationally — and illegally — as a club drug known as Special K. It generates an intense high and dissociative effects.Esketamine, which is not FDA-approved for any conditions, targets a different brain pathway than approved antidepressants, many of which have been around for decades. It is expected to be used in combination with antidepressants, but the latter can take a month or two to take effect. Esketamine, on the other hand, might have an effect within hours or days, according to an FDA briefing document.The drug was designated as a breakthrough therapy in 2013, intending to “expedite the development and review of drugs for serious or life-threatening conditions,” the FDA says. First-line treatments don’t work for roughly 30% to 40% of patients with major depressive disorder, according to the briefing document.The FDA does not have to follow the recommendation of advisory committees, though it often does.

ERs 'flooded' with mentally ill patients with no place else to turn

ERs ‘flooded’ with mentally ill patients with no place else to turnHowever, the research behind esketamine has come under some criticism, with two of five key studies failing to meet their primary endpoints. Only one of these studies is a positive short-term trial, whereas most FDA-approved antidepressants are backed by at least two, according to the briefing document. But Janssen has maintained that the overall picture is positive.Adverse events tended to occur in the first two hours patients received the drug, including sedation, blood pressure increases and dissociation. For this reason, patients wouldn’t be able to pick it up at a local pharmacy; it would be given under the supervision of health care professionals who can keep an eye on the person during those first two hours.Because of the drug’s close relationship to ketamine, experts have also raised concerns about its potential for misuse and abuse. The clinical trials have not seen evidence of this risk, according to presentations made during the meeting.Advisory panelists also expressed concern that not enough long-term data was available to characterize the drug’s cognitive effects and other health impacts down the line.Get CNN Health’s weekly newsletter

There were six deaths of patients taking esketamine in trials, including three suicides, but FDA materials concluded “it is difficult to consider these deaths as drug-related.”The only current FDA-approved medication for treatment-resistant depression combines two other drugs already on the market. Other non-pharmaceutical treatments exist, such as electroconvulsive therapy.Janssen spokesman Greg Panico said no information about pricing would be available at this time. An FDA decision is expected in early March, he added.

Ketamine Infusion Center Virginia| 703-844-0184 | NOVA Health Recovery | Alexandria, Va 22101 | Esketamine Provider | ESKETAMINE CENTER | ESKETAMINE DOCTOR | 703-844-0184 | ARLINGTON, VIRGINIA 22207 22213 | NOVA HEALTH RECOVERY | DR. SENDI | ESKETAMINE PROVIDER | NASAL SPRY KETAMINE THERAPY | KETAMINE FOR TREATMENT OF DEPRESSION, PTSD, ANXIETY | KETAMINE INFUSION CENTER | KETAMINE DEPRESSION | KETAMINE PTSD | EMAIL@NOVAHEALTHRECOVERY.COM | 2220 22182 23103 22039 20197 20184 22101 22102 22066 | CBD DOCTOR CBD CENTER | 703-844-0184 | FAIRFAX, VA 22034 | 22308 | ESKETAMINE LOUDON COUNTY, VA | ESKETAMINE ANNANDALE, VA | ESKETAMINE RICHMOND | ESKETAMINE VIRGINIA | KETAMINE SPRAY PROVIDER IN NORTHERN VIRGINIA 22308 | KETAMINE INFUSION CENTER | KETAMINE VIRGINIA | ESKETAMINE VIRGINIA | 703-844-0184 FOR AN APPOINTMENT | CBD PROVIDER | CBD CENTER | CBD VIRGINIA | DR. SENDI

NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link



NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link

Ketamine Virginia Link

A Randomized Controlled Trial of Intranasal Ketamine in Major
Depressive Disorder

A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder

Abstract
Background—The N-methyl-d-aspartate glutamate receptor antagonist ketamine, delivered via
an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant
depression. The current study was designed to test the safety, tolerability and efficacy of intranasal
ketamine in patients with depression who had failed at least one prior antidepressant trial.
Methods—Twenty patients with major depression were randomized and 18 completed two
treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution in a randomized,
double-blind, crossover study. The primary efficacy outcome measure was change in depression
severity 24 hours following ketamine or placebo, measured using the Montgomery-Asberg
Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in selfreports of depression, changes in anxiety, and proportion of responders. Potential
psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with
ketamine were also measured.

Results—Patients showed significant improvement in depressive symptoms at 24 hours
following ketamine compared to placebo [t=4.39, p<0.001; estimated mean MADRS score
difference of 7.6 ± 3.7 (95% CI: 3.9 – 11.3)]. Eight of 18 patients (44%) met response criteria 24
hours following ketamine administration, compared to 1 of 18 (6%) following placebo (p=0.033).
Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and
was not associated with clinically significant changes in hemodynamic parameters.

Conclusions—This study provides the first controlled evidence for the rapid antidepressant
effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If
replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients
with major depression

Intranasal ketamine has shown safety and efficacy as an anesthetic and analgesic agent (16–
20). In particular, intranasal ketamine has been successfully used in the treatment of
headache and pain in ambulatory patients (21–23). In one study, 50 mg of ketamine
administered intranasally was well tolerated and led to symptomatic improvement in chronic
pain (23). The objective of the current proof of concept clinical trial was to test the rapid
antidepressant effect of a single 50 mg administration of ketamine via an intranasal route in
patients with major depression who had failed to respond to at least one prior antidepressant
trial. Based on accumulating evidence supporting the efficacy and tolerability of ketamine
administered IV in depression, and prior research examining intranasal ketamine in pain, we
hypothesized that a dose of 50 mg, administered via an intranasal route, would be safe, well
tolerated and lead to a rapid reduction in depressive symptoms.

DISCUSSION
In the current study we found that a single dose of 50 mg of ketamine administered via
intranasal route was associated with a rapid antidepressant response in patients with major
depression who had failed at least one prior antidepressant trial. A significant antidepressant
effect of ketamine was detected as early as 40 min following administration and there was a
large difference in depression severity between the treatment conditions at the 24-hour
primary outcome (mean difference in MADRS score of 7.6 ± 3.7). In aggregate, there was
significant antidepressant benefit following ketamine compared to placebo over the full 7-
day assessment period, although when comparing individual time points the treatment
conditions no longer separated at 72 hours or 7 days. Ketamine was associated with
significant improvement in anxiety symptoms and self-reports of depressive symptoms at 24
hours. Intranasal ketamine was well tolerated with only very minimal increases in
dissociation, psychosis-like symptoms or hemodynamic parameters. This study provides the
first randomized, controlled evidence that intranasal ketamine is safe, well tolerated, and
effective for rapid reduction of depressive symptoms in patients with MDD and at least mild
treatment resistance.
In comparison with prior studies of ketamine administered IV (at a dose of 0.5 mg/kg) in
depression, our observed magnitude of antidepressant effect with intranasal administration
may be somewhat reduced. Murrough et al. reported a mean ketamine-placebo difference of
7.95 points (95% CI: 3.20–12.71) on the MADRS 24 hours following a single IV infusion
and a response rate of 64% (15). Response rates as high as 70% following IV administration
have been reported in some studies (11, 15), though other studies have reported response
rates from 50% to as low as 30% following IV ketamine (28, 29). Our mean drug-placebo
difference is in line with what has been previously reported (7.6 ± 3.7 points on the
MADRS), although the proportion of responders in our study may be somewhat lower at
44%. This lower proportion of treatment responders may be consistent with the lower blood
ketamine levels achieved in our study compared to levels previously reported following IV
administration. In our sample, the mean ketamine blood level was 72 ng/mL at 20 min and
84 ng/mL at 40 min. In contrast, mean ketamine levels reported following IV infusion
(0.5mg/kg) are approximately 150 ng/mL at 30 min and 200 ng/mL at 40 min. (27, 30, 31).
It is currently not known if efficacy equivalent to IV administration can be obtained by
intranasal administration in the case that comparable blood levels can be achieved.

We report a significant improvement in anxiety symptoms at 24 hours, assessed with the
HAM-A. Two studies of IV ketamine for bipolar depression reported a significant
improvement in anxiety symptoms measured with the HAM-A and a visual analog scale(27,
32). However, previous studies of patients with unipolar TRD have not described effects of
IV ketamine on anxiety, with the exception of an early RCT (11) and an open label study
(33) reporting significant improvement in psychic anxiety measured as an individual
symptom on the Hamilton Depression Rating Scale, and another open-label study reporting
significant decrease in anxiety symptoms on the HAM-A at +230 minutes (34).
Previous studies of IV ketamine in depression have reported elevations in measures of
psychotomimetic, dissociative and hemodynamic parameters (11, 13, 35). In our study, the
ketamine group experienced a very limited increase in dissociation at +40 min as measured
by the CADSS (mean 1.4 points; scale range 0–92). In comparison, Murrough et al. reported
a larger dissociative effect 40 min following ketamine administered IV [mean CADSS score
of 14.7 points (95% CI: 10.6–18.8)] (15). A similar pattern was observed for psychotic-like
effects measured using the BPRS+ (11, 15). We also observed comparatively small changes
in hemodynamic parameters. No patient met protocol criteria for interventions. Studies of IV
ketamine in depression have reported relatively greater changes in hemodynamic parameters
(mean systolic BP increase of 19.0 versus our 7.6 mmHg at +40mins relative to baseline)
(15). The reduced magnitude of acute behavioral and hemodynamic changes observed in the
current study may be consistent with the lower blood levels achieved compared to prior
studies with ketamine administered IV, as discussed above.
The bioavailability of ketamine administered via an intranasal route has been reported to be
between 25–50% (36). A study in healthy volunteers comparing administration methods
found intranasal ketamine bioavailability of 45%, higher than subligual, oral, or rectal
administration and found no significant differences in pharmacokinetics between
preparations, including injection (37). Additionally, this study found conversion to
norketamine was more similar between intranasal and injection than the other administration
methods, suggesting that first-pass metabolism is relatively absent with intranasal
administration. The area under the ketamine and norketamine plasma concentration-time
curves in that study was lowest for intranasal administration but was found to increase
almost linearly with doses from 25 to 50mg (37). In previous studies of IV ketamine in
depression, peak norketamine blood levels of approximately 20–50 ng/mL have been
reported (30, 31). In line with these findings, the mean norketamine level in our study was
46 ng/mL at 40 min.
We selected our dose of 50 mg largely based on a previous study using a similar design and
the same dose in patients with a chronic pain disorder (23). Based on an expected
bioavailability of intranasal ketamine between 25–50% (36), our dose may be approximately
equivalent to 0.15 – 0.34 mg/kg administered IV. Although this is lower than the standard
0.5 mg/kg IV frequently used in ketamine depression studies, we reasoned that this dose was
appropriate from a safety perspective given that the administration period in the current
study is relatively short (20 min versus 40 min or longer in IV studies). Clearly, much more
research is required in order to determine the optimal dose, duration, frequency and route of
administration of ketamine for depression



Ketamine Center in Fairfax, Virginia | 703-844-0184 | Ketamine for PTSD | Depressipn | Ketamine Treatment Center | 22308 | Depression: Ketamine prevents loss of pleasure in primates | Ketamine for low mood and anhedonia | Brain area 25

Call 703-844-0184 for a consultation for a Ketamine treatment for depression or low mood | Alexandria, Va 22306 | Loudon County, Va | Fairfax, Va 22304

New research, which features in the journal Neuron, shows that primates lose excitement in anticipation of a reward when a specific area of their brain becomes overactive. The study also shows that ketamine affects this brain region and prevents the loss of pleasure.

woman sitting on the edge of the bed seen from behind
Ketamine Treatment Center | 703-844-0184 | Loudon County Virginia | 703-844-0184 | Ketamine Center for Depression

A loss of interest or pleasure in activities that were once exciting is one of the hallmarks of depression.

Depression is “the leading cause of disabilityworldwide” and one of the most commonmental health problems in the United States.

The symptoms of major depression include depressed mood and loss of interest or pleasure in daily activities. Some people may also experience difficulty sleeping, eating, and focusing or have intrusive thoughts of death or taking their own life.

The loss of interest, pleasure, or excitement in anticipation of activities that the individual once perceived as enjoyable is called anhedonia.

The brain mechanisms that underpin anhedonia in depression have remained unclear until now, and this lack of knowledge has hindered the success of many antidepressant treatments.

Now, a new study casts much-needed light on this symptom. Leading a team of researchers, professor Angela Roberts from the Department of Physiology, Development, and Neuroscience at the University of Cambridge, United Kingdom, and doctoral researcher and medical student Laith Alexander set out to study this phenomenon in marmosets.

Marmosets are a type of nonhuman primate with frontal lobes that are very similar to those of humans. This physical similarity means that the findings are more easily translatable to humans than they would be if the study involved rodents instead.

Prof. Roberts and colleagues tested the effects of ketamine, a hallucinogenic drug that has recently garnered interest as a potential treatment for depression, and found that it had a positive effect on the primates.

Studying anhedonia in primates

Prof. Roberts explains the motivation behind the study, saying, “Imaging studies of [people with depression] have given us a clue about some of the brain regions that may be involved in anhedonia, but we still don’t know which of these regions is causally responsible.”

“A second important issue,” she adds, “is that anhedonia is multi-faceted — it goes beyond a loss of pleasure and can involve a lack of anticipation and motivation, and it’s possible that these different aspects may have distinct underlying causes.”

To find out more about the brain mechanisms behind anhedonia, Prof. Roberts and her team devised an experiment in which they trained primates to react to two sounds. Sound A indicated that the marmosets would receive marshmallows as a treat while no treat followed sound B.

After the training, blood pressure measurements and head movements showed that the marmosets would get excited on hearing sound A but would not respond in this way to sound B.

Next, the scientists surgically implanted very thin metal tubes into the marmosets’ heads, through which they injected either a drug or a placebo into the brains of the primates.

The researchers targeted a specific brain region called “area 25,” which the drug made temporarily hyperactive. They used PET scans to study the primates’ brain activity.

Brain’s area 25 is key in anhedonia

The primates that received the drug showed increased activity in area 25 in the brain and also displayed significantly lower excitement in anticipation of the marshmallows.

In contrast, there was no change in either the brain activity or behavior of the primates that received the placebo.

In a second experiment, the primates had to work for their rewards. At first, they received a treat after touching a colored shape on a screen just once.

However, over the course of the experiment, the primates had to press the shape an increasing number of times before they received the marshmallow. Eventually, the animals would give up because the treat was no longer worth the effort.

The researchers found that the marmosets with a hyperactive area 25 gave up much more quickly. PET scans also revealed that abnormal activity in this brain area overflowed into other brain areas, which also became overactive when the anticipatory excitement dwindled.

How ketamine prevents the loss of pleasure

Finally, the researchers tested the effect that ketamine had on the primates. They gave the marmosets ketamine 24 hours before repeating the same experiments as before.

This time, ketamine blocked the activity of the drug that overactivated area 25. The brain activity of the primates that received ketamine looked normal in PET scans, and the primates continued to exhibit just as much excitement in anticipation of the marshmallow treats.

“Understanding the brain circuits that underlie specific aspects of anhedonia is of major importance,” says first author Laith Alexander, “not only because anhedonia is a core feature of depression but also because it is one of the most treatment-resistant symptoms.”

Studies show that as many as 30 percent of people living with depression have a form of the condition that does not respond to treatment.

“By revealing the specific symptoms and brain circuits that are sensitive to antidepressants like ketamine, this study moves us one step closer to understanding how and why patients may benefit from different treatments.”

Laith Alexander

Fractionating Blunted Reward ProcessingCharacteristic of Anhedonia by Over-ActivatingPrimate Subgenual Anterior Cingulate Cortex

Can we Stop Suicides | 703-844-0184 | Ketamine Treatment Center | Ketamine for depression, PTSD, Anxiety | Arlington, Va 22204 22205 22206 22207 22208 22209 22210 22211 22212 22213 22214 22304 22308 22306 | Fairfax Ketamine Treatment Center | 703-844-0184 | Loudon County, VA

703-844-0184 | Ketamine Treatment Center | Ketamine for depression, PTSD, Anxiety

Call for a free consultation for Ketamine | Alexandria, Virginia 22306 | 703-844-0184

 

Can We stop Suicides?

The link above attached to the New York Times article opinion section that discusses Ketamine and its transforming ability for depression and related mood  disorders. Below is the excerpt:

In May of 2017, Louise decided that her life was just too difficult, so she’d end it. In the previous four years, three siblings and a half-sibling had died, two from disease, one from fire and one from choking. Close friends had moved away. She felt painfully, unbearably alone. It would be the fourth time Louise (I’m using her middle name to protect her privacy), then 68, would attempt suicide, and she was determined to get it right.

She wrote a letter with instructions on where to find important documents and who should inherit what. She packed up her jewelry and artwork, addressing each box to particular friends and family members. Then she checked into a motel — homes where people have committed suicide lose value and she didn’t want hers to sell below market — put a plastic sheet on the bed, lay down and swallowed what she figured was an overdose of prescription pills with champagne.

A few days later, she woke up in a psychiatric ward in Albuquerque. The motel maid had found her. “I was very upset I had failed,” she told me recently. So she tried to cut her wrists with a bracelet she was wearing — unsuccessfully.

The suicide rate has been rising in the United States since the beginning of the century, and is now the 10th leading cause of death, according to the Centers for Disease Control and Prevention. It’s often called a public health crisis. And yet no new classes of drugs have been developed to treat depression (and by extension suicidality) in about 30 years, since the advent of selective serotonin reuptake inhibitors like Prozac.

The trend most likely has social causes — lack of access to mental health care, economic stress, loneliness and despair, the opioid epidemic, and the unique difficulties facing small-town America. These are serious problems that need long-term solutions. But in the meantime, the field of psychiatry desperately needs new treatment options for patients who show up with a stomach full of pills.

Now, scientists think that they may have found one — an old anesthetic called ketamine that, at low doses, can halt suicidal thoughts almost immediately

Depression ran in Louise’s family. It had afflicted all her siblings, both of her parents and her grandmother. Prozac had helped Louise for a time, but stopped working for her in the late 2000s, as it sometimes does. No other drug seemed able to lift her dark moods.

After her suicide attempt, Louise’s psychiatrist suggested she try ketamine. She agreed, and received an infusion intravenously. Within hours, her sense of well-being improved. The hospital discharged her. Back home, she discovered that going to the market was no longer a “herculean task.” Getting her car washed wasn’t an insurmountable chore. “Life was better,” she said. “Life was doable.”

Using ketamine to treat depression and suicidality is somewhat controversial. Numerous small studies suggest that it holds great promise, but it’s only now being tested in placebo-controlled trials with hundreds of patients. It is also popular as a club drug in some circles. Like morphine, it may operate on the opioid system, and it can induce feelings of euphoria. Occasionally ketamine abusers develop severe symptoms, including brain damage, persistent hallucinations and a painful inflammation of the bladder called cystitis.

Nonetheless, if proven safe and effective in small doses, ketamine stands to transform how doctors deal with suicidal patients and depression generally.

The drug seems to address a longstanding problem in emergency psychiatry. Sedation and physical restraint aside, doctors have few ways to quickly stop suicidal ideation, or thoughts of killing oneself. The current crop of anti-depressants can take weeks and sometimes months to work, if they work at all. They may also, paradoxically, increase suicidality in some patients. Talk therapy takes time to help as well (assuming it does). Here’s a sobering fact: Some studies indicate that suicide risk peaks soon after patients have been discharged from a medical facility.

Antidepressants and Suicide Risk A Comprehensive Overview

Antidepressants and Suicide Risk A Comprehensive Overview

Suicide risk peaks in first week of psychiatric hospitalisation and post discharge  <, See commentary excerpt at bottom of this page

 

Researchers at Yale discovered ketamine’s potential as an antidepressant in the late 1990s and scientists at the National Institute of Mental Health confirmed it the mid 2000s. Numerous studies followed suggesting that the drug helps precisely with that subset of depressive patients — about a third — for whom nothing else works. It doesn’t work for everyone in this group, but when it does, it works within hours, not weeks.

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression<<<Carlos Zarate

Suicidality doesn’t perfectly overlap with depression. Many people attempt suicide not because they’re clinically depressed, but rather impulsively, because they’ve been fired or they’ve broken up with girl- and boyfriends, or sometimes because they’re just really drunk. I’ve heard people who show up in the hospital in this state — despondent, angry and uninhibited more than depressed — described as “drunkicidal.”

Many are fine once they sober up. For those who aren’t, ketamine may help independent of its effect on depression. And because ketamine is already approved by the Food and Drug Administration, doctors can prescribe it off-label. Meaning that not only does a drug exist right now that could help with depression and suicidality, it’s theoretically available to patients.

I kept thinking about this during the recent spate of high-profile suicides: the chef Anthony Bourdain, the designer Kate Spade, the actress Margot Kidder. Could ketamine have saved any of them? Did they know about it? Did their psychiatrists?

Intranasal Ketamine | 703-844-0184 | Ketamine Treatment Provider | Alexandria, Va 22306| Ketamine for deprssion | Ketamine doctor | Loudon, Va 22043 22046 22101 22102 22107 22108 22109 | IV Ketamine for depression | Ketamine for PTSD , OCD | Bipolar | Ketamine Infusion Center | 703-844-0184 | Loudon, Va | Ketamine IV Treatment Center | Ketamine Doctor | Intranasal Ketamine |Alexandria, Va 22306 | Ketamine for Depression | Intranasal Ketamine | OCD| CBD Center | Medical CBD | Medical THC Center | THC Doctor | Ketamine for Alcoholism | Intranasal Ketamine | 22043 22046 22101 22102 22106 22107 22108 22109 20175 20176 20147 20148 20151 22030 22031 22032 22034 22038 | IV Vitamin Therapy

 

703-844-0184 | NOVA health Recovery Ketamine Treatment Center | Alexandria, Va 22306 | email@novahealthrecovery.com

 

Image result for intranasal ketamine |Ketamine Infusion Center | 703-844-0184 | Loudon, Va | Ketamine IV Treatment Center | Ketamine Doctor | Intranasal Ketamine |Alexandria, Va 22306 | Ketamine for Depression | Intranasal Ketamine | OCD| CBD Center | Medical CBD | Medical THC Center | THC Doctor | Ketamine for Alcoholism | Intranasal Ketamine | 22043 22046 22101 22102 22106 22107 22108 22109 20175 20176 20147 20148 20151 22030 22031 22032 22034 22038 | IV Vitamin Therapy
Ketamine Infusion Center | 703-844-0184 | Loudon, Va | Ketamine IV Treatment Center | Ketamine Doctor | Intranasal Ketamine |Alexandria, Va 22306 | Ketamine for Depression | Intranasal Ketamine | OCD| CBD Center | Medical CBD | Medical THC Center | THC Doctor | Ketamine for Alcoholism | Intranasal Ketamine | 22043 22046 22101 22102 22106 22107 22108 22109 20175 20176 20147 20148 20151 22030 22031 22032 22034 22038 | IV Vitamin Therapy

One more reason to treat your depression rapidly with Ketamine:

 

Depression Linked to Increased Risk of Developing Atrial Fibrillation

NEW YORK—Depression appears to be a risk factor for atrial fibrillation, the most common arrhythmia in the U.S., according to new observational data from the national Multi-Ethnic Study of Atherosclerosis (MESA) study.

Considering that 20% of U.S. adults report depressive symptoms, “our findings identify a large portion of the U.S. population that is potentially at an increased risk of developing atrial fibrillation and who may benefit from more targeted efforts to prevent atrial fibrillation,” Dr. Parveen Garg, from the Keck School of Medicine at the University of Southern California in Los Angeles, told Reuters Health by email.

He presented the study March 22 at the American Heart Association’s Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions in New Orleans.

The analysis included 6,644 adults (mean age, 62; 53% women, 38% white, 28% black, 22% Hispanic, 12% Chinese-American) with no known heart disease at baseline who were followed for a median of 13 years as part of the MESA study.

In the fully adjusted model, individuals with a Centers for Epidemiologic Studies Depression Scale (CES-D) score of 16 or higher (indicating clinically relevant depressive symptoms) had a 34% (P=0.039) higher risk of developing atrial fibrillation during follow-up compared with those with a CES-D score of less than 2. Similarly, individuals reporting antidepressant use had a significant 36% increase in their risk of developing atrial fibrillation compared with those not on the drugs.

“An important next step is to confirm these results in other studies, especially those with more comprehensive and clinically validated assessments of depression. If confirmed, then it will be important to determine if treating individuals with depression actually reduces their risk of atrial fibrillation,” Dr. Garg said.

Several mechanisms have been proposed to explain a possible link between depression and atrial fibrillation, Dr. Garg explained. Depression can increase systemic inflammation and activate the autonomic nervous system, which increases catecholamine levels, and the hypothalamic-pituitary-adrenal axis, which increases cortisol levels. Depression may also activate the renin-angiotensin-aldosterone system.

“Taken together, these changes may induce atrial fibrillation susceptibility either directly by disrupting the electrophysiologic properties of the atria or indirectly by promoting atrial fibrosis, increasing the atrial pressure,” Dr. Garg said, adding that further research is needed to fully understand the mechanisms involved.

Dr. Gordon Tomaselli, a spokesman for the American Heart Association, said this study “affirms the association between depression and atrial fibrillation in a population that I think is important because it’s a mixed population and not just the standard Caucasian population.”

“There are some associated risk factors in people with depression that might increase their risk of atrial fibrillation, including an increased incidence of hypertension in some patients who have depression as well as other disorders that might be driven by activation of the sympathetic nervous system like anxiety disorder. So there are several reasons why people might have depression and atrial fibrillation,” Dr. Tomaselli, who was not involved in the research, told Reuters Health by phone.

“One question is what should we do about it, and I’m not sure we have an answer from this study except to make sure that we are looking for symptoms of depression,” he said. “We don’t know whether treatment of depression will reduce the incidence of atrial fibrillation. There is some reason to think that it might, but there are other reasons to think that antidepressant drugs actually have some effects on the heart, the ion channels that determine the rhythm of the heart.”

The study had no commercial funding and the authors have no relevant disclosures.

SOURCE: https://bit.ly/2pCdkOA

AHA Epidemiology and Prevention – Lifestyle and Cardiometabolic Health Scientific Sessions 2018.

Ketamine Infusion Center | 703-844-0184 | Loudon, Va | Ketamine IV Treatment Center | Ketamine Doctor | Intranasal Ketamine |Alexandria, Va 22306 | Ketamine for Depression | Intranasal Ketamine | OCD| CBD Center | Medical CBD | Medical THC Center | THC Doctor | Ketamine for Alcoholism | Intranasal Ketamine | 22043 22046 22101 22102 22106 22107 22108 22109 20175 20176 20147 20148 20151 22030 22031 22032 22034 22038 | IV Vitamin Therapy

 

703-844-0184 | Ketamine Treatment Center | Alexandria, Va 22306 | Call for Ketamine Doctor | Ketamine for depression, OCD, Chronic Pain

 

Ketamine Nasal Sprays for Depression

What is ketamine?

Ketamine Nasal Spray
703-844-0184 | NOVA Health recovery | Fairfax, Va 22304

Ketamine is a drug currently approved by the FDA for use as a general anesthetic during minor surgical procedures such as biopsies. It is widely known as a recreational drug because of its ability to induce cognitive-dissociative, hallucinogenic, and euphoric states in humans. Recently, it has been implicated in research as a potential therapeutic agent in depression especially in patients who have failed previous standard therapies.

Why ketamine?

Standard pharmacologic therapies for depression take several weeks of treatment before patients experience relief. Ketamine is different in that it has been shown to reduce depression symptoms and suicidal ideation in as little as forty minutes. This is considered a potentially lifesaving breakthrough in the treatment of depression because ketamine can rapidly reduce symptoms especially in emergency situations.

How does it work?

The most common medications used in depression affect serotonin in the brain. Ketamine works by a different mechanism. It has been shown to block the glutamate receptors in the brain resulting in its famous hallucinogenic effects. Ketamine has been shown to act on several other receptors, but it is theorized that at low doses, blocking glutamate receptors in the brain may be the reason for its anti-depressive effects.

Who should (and shouldn’t) take ketamine?

Ketamine has not been approved by the FDA for treatment of depression. Although, because of new studies, psychiatrists have been prescribing ketamine “off-label” for patients who did not respond to selective serotonin reuptake inhibitors (SSRIs) such has Celexa (citalopram), Zoloft (sertraline), or Prozac (fluoxetine) for immediate treatment of symptoms.

Ketamine has been shown to transiently yet significantly increase blood pressure following administration. Patients with high blood pressure should use caution when using ketamine. Ketamine has also been shown to be associated with increases in psychosis or dissociative properties.

Ketamine nasal sprays offer a quick and convenient way to administer ketamine for patients who need immediate relief, although they are currently not available commercially, so you will not find them at your local community pharmacy. Compounding pharmacies have the proper experience, equipment, and personnel to safely compound and customize this medication for you.

References

  1. Ketalar [package insert]. Chestnut Ridge, NY 10977: Par pharmaceutical; 2017 https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016812s043lbl.pdf
  2. Browne CA, Lucki I. Antidepresssant effects of ketamine: mechanisms underlying fast-acting novel antidepressants. Front Pharmacol December 2013.
  3. Lapidus K, Levitch CF, Perez AM, et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychology 2014;76:970–976
  4. Sanacora G, Frye MA, McDonald W, et al. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry 2017;74(4):399-405.