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 peakssoon after patients have been discharged from a medical facility.
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?
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.
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.
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.
This study suggests that ketamine can safely be used to avoid intubation and may decrease length of intensive care unit stay.
Severe alcohol withdrawal, or delirium tremens (DT), is a life-threatening condition that can require massive doses of benzodiazepines or barbiturates (GABA agonists), which can require intubation and prolonged intensive care unit (ICU) care. These authors studied a retrospective sample of adult patients admitted to a single ICU with DT to determine whether adjunctive therapy with ketamine improved outcomes.
They compared outcomes in 29 patients who received symptom-triggered therapy with GABA agonists with outcomes in 34 patients who were treated after initiation of a guideline that added an intravenous ketamine infusion (0.15–0.3 mg/kg/hour) to GABA agonist therapy. Using multivariable modeling that accounted for initial ethanol level and the total amount of GABA agonist required for treatment, patients who received ketamine had significantly lower rates of intubation (29% vs. 76% for patients who did not receive ketamine) and shorter ICU stay (5.7 days vs. 11.2 for patients who did not receive ketamine). There were no reported adverse events.
Ketamine offers a new option for people with stubborn depression that doesn’t respond to other medications.
Many people know of ketamine as a hallucinogenic and addictive street drug, which, when abused, can put people in medical peril. But today, doctors are increasingly looking to ketamine as a potentially lifesaving treatment for people with severe, treatment-resistant depression, who may be at high risk for suicide.
“Ketamine has been shown to be effective in people who have not responded to antidepressant treatment,” says Dr. Cristina Cusin, an assistant professor of psychiatry at Harvard Medical School. The fast-acting treatment has shown promise — sometimes improving depressive symptoms within hours of the first intravenous treatment.
While ketamine can offer hope to some, it’s not for everyone. The use of ketamine to treat depression is still controversial in some circles. “Some prescribers would never consider the use of a controlled substance for this purpose, because of the potential for abuse,” says Dr. Cusin. “But as with opiates, a drug is not good or bad, per se.” Still, ketamine does need to be carefully matched to the right patient for the right use to avoid harm, and treatment should be closely monitored over time.
A variety of uses
The use of ketamine in medicine isn’t new. It’s routinely used in hospitals both for anesthesia and for pain relief.
Currently, the use of ketamine for depression is “off label.” This means that although ketamine is approved by the FDA for some medical purposes, it’s not approved specifically to treat depression. However, that may soon change. Under its “fast track” drug approval process, the FDA is reviewing the results of clinical trials of esketamine, a ketamine-based nasal spray, to treat depression, says Dr. Cusin.
For now, people who undergo ketamine treatment for depression typically receive the drug at specialized clinics, either intravenously or as a nasal spray. Effects from the nasal spray last for a single day or a few days, while the intravenous treatment may last for a few weeks to a month. In both instances the dose is significantly lower than would be used for anesthesia or when used illicitly.
How ketamine works
Studies have shown that ketamine is effective in treating people whose depression has not responded to other interventions, says Dr. Cusin. Such treatment-resistant depression is estimated to affect from 10% to 30% of people diagnosed with the condition.
Experts believe that ketamine works through a unique mechanism, directly modulating the activity of a brain chemical called glutamate. Glutamate is believed to play a role in stimulating the growth of new brain connections that may help alleviate depressive symptoms.
People who have taken ketamine to treat their depression experience varying success, depending on their personal history—how long they’ve been depressed, how severe their symptoms are, and how many drugs they’ve tried without seeing improvement, says Dr. Cusin.
For people with less severe depression, ketamine may be effective in as many as 60% of those who try it. Among those with more persistent and significant disease, a smaller number, 30% to 40%, may experience relief, says Dr. Cusin. “The expectation should not be that it will magically cure depression in everybody,” she says. “Ketamine is not a perfect fix. It’s like any other medication.” In other words, it works for some people, and it won’t work for others.
To be effective, treatment with ketamine must typically continue indefinitely and involve careful monitoring. Clinicians who prescribe ketamine for depression should screen patients carefully to ensure the drug is appropriate for the individual, says Dr. Cusin. “Not everybody who wishes to try ketamine will be a good candidate,” she says.
Among those who should not use ketamine are people with
a history of substance abuse
a history of psychosis
elevated blood pressure
an uncontrolled medical condition.
Who can benefit?
Because ketamine is a newer treatment, there are still a lot of questions surrounding its use, says Dr. Cusin. For instance:
Which people respond best to treatment?
How much should be given, and how often?
What are the long-term effects of treatment?
Because the medication is being used off label for depression, there are no clearly defined safety recommendations either for home use or for its use in specialized clinics, she says. This means that it’s up to individual providers to guide the patient in making informed decisions about treatment. Choosing a qualified provider is essential. JAMA Psychiatrypublished a statement in 2017 outlining best practices for doctors to follow in ketamine treatment, such as performing a comprehensive assessment, obtaining informed consent, and documenting the severity of depression before starting the medication. These guidelines are aimed at increasing the safe use of ketamine for depression, and providers can use them to help ensure that the treatment is a good match for your condition.
As with any other medical intervention, anyone considering ketamine should also consider the drawbacks of treatment along with the potential benefits. Ketamine’s drawbacks include these:
Cost. It’s expensive and not covered by insurance. “The cost ranges from $400 to $1,200 per dose for the intravenous drug, and you may need as many as 12 to 18 doses a year,” says Dr. Cusin.
Unknowns. Ketamine hasn’t been used to treat depression for long enough for doctors to know whether there are any harmful long-term consequences of taking the medication. More time and study are needed to truly understand how it affects people over the long term.
Treatment failure. Many people with treatment-resistant depression view ketamine treatment as their last option, so if this therapy fails to improve their depression, they can be emotionally devastated. Realistic expectations and follow-up support are essential.
Even if ketamine does produce results, it’s still important to understand what it can and can’t do. “-Ketamine isn’t going to eliminate all frustrations and stress from your life. While it may lift some symptoms of depression, the life stressors will still be there,” says Dr. Cusin. You’ll still need support to help you manage them.
Side effects. While ketamine is viewed as safe in a controlled setting, it can frequently increase blood pressure or produce psychotic-like behavior, which may result in delusions or hallucinations. Serious adverse events are rare because the drug is used at such low doses, says Dr. Cusin.
However, provided you are an appropriate candidate for the treatment and your doctor monitors you closely, you could find that it improves your mood. “Ketamine could make a huge difference in the quality and duration of life and can be very effective for people who are thinking about suicide,” says Dr. Cusin.
Seasonal Affective Disorder and Ketamine Infusions as a rapid treatment
Do you find yourself getting depressed and sad in the fall and wintertime despite your best efforts? Seasonal affective disorder is common and can disrupt your lifestyle and happiness. Consider Ketamine infusions as an option for immediate relief with follow through intranasal ketamine. We can provide these solutions for people suffering from this disorder. A series of 2- 6 infusions can manage the majority of patients with rapid recover, almost within a few days.
Seasonal Affective Disorder, or SAD, is a type of recurrent major depressive disorder in which episodes of depression occur during the same season each year. This condition is sometimes called the “winter blues.”
Seasonal affective disorder (also called SAD) is form of depression in which people experience depressive episodes during specific times of the year. The most common seasonal pattern is for depressive episodes to being in the fall or winter and diminish in the spring. A less common type of SAD, known as summer depression, usually begins in the late spring or early summer. SAD may be related to changes in the amount of daylight a person receives.
SAD is not considered as a separate disorder, but rather is a type of depression that has a recurring seasonal pattern. To be diagnosed with SAD, an individual must meet criteria for major depression coinciding with specific seasons for at least two years. The individual must experience seasonal depressions much more frequently than any non-seasonal depressions.
Seasonal affective disorder is estimated to affect 10 million Americans. Another 10 percent to 20 percent may have mild SAD. SAD is four times more common in women than in men. The age of onset is estimated to be between the age of 18 and 30. Some people experience symptoms severe enough to affect quality of life, and 6 percent require hospitalization. Many people with SAD report at least one close relative with a psychiatric disorder, most frequently a severe depressive disorder (55 percent) or alcohol abuse (34 percent).
Not everyone with SAD has the same symptoms, but symptoms commonly associated with the “winter blues” include the following:
Feelings of hopelessness and sadness
Thoughts of suicide
Hypersomnia or a tendency to oversleep
A change in appetite, especially a craving for sweet or starchy foods
A heavy feeling in the arms or legs
A drop in energy level
Decreased physical activity
Increased sensitivity to social rejection
Avoidance of social situations
Symptoms of summer SAD are:
Agitation and anxiety
Either type of SAD may also include some of the symptoms that are present in major depression, such as feelings of guilt, a loss of interest or pleasure in activities previously enjoyed, ongoing feelings of hopelessness or helplessness, or physical problems such as headaches and stomach aches.
Symptoms of SAD tend to reoccur at about the same time every year. To be diagnosed with SAD, the changes in mood should not be a direct result of obvious seasonal stressors (like being regularly unemployed during the winter). Usually, this form of depression is mild or moderate. However, some people experience severe symptoms that leave them unable to function in their daily lives.
Seasonal affective disorder can be misdiagnosed as hypothyroidyism, hypoglycemia, or a viral infection such as mononucleosis.
The cause for SAD is unknown. One theory is that it is related to the amount of melatonin in the body, a hormone secreted by the pineal gland. Darkness increases the body’s production of melatonin, which regulates sleep. As the winter days get shorter and darker, melatonin production in the body increases and people tend to feel sleepier and more lethargic.
Another theory is that people with SAD may have trouble regulating their levels of serotonin, which is a major neurotransmitter involved in mood. Finally, research has suggested that people with SAD also may produce less Vitamin D, which is believed to play a role in serotonin activity. Vitamin D insufficiency may be associated with clinically significant depression symptoms.
There are several known risk factors that increase an individuals chance of developing SAD. For example, SAD is more frequent in people who live far north or south of the equator. Additionally, people with a family history of other types of depression are more likely to develop SAD than people who do not have this family history.
Treatment approaches to alleviate the symptoms of SAD typically include combinations of antidepressant medication, light therapy, Vitamin D, and counseling.
Because winter depression may be caused by a reaction to a lack of sunlight, broad-band light therapy is frequently used as a treatment option. This therapy requires a light box or a light visor worn on the head like a cap. The individual either sits in front of the light box or wears light visor for a certain length of time each day. Generally, light therapy takes between 30 and 60 minutes each day throughout the fall and winter. The amount of time required varies with each individual. When light therapy is sufficient to reduce symptoms and to increase energy level, the individual continues to use it until enough daylight is available, typically in the springtime. Stopping light therapy too soon can result in a return of symptoms.
When used properly, light therapy seems to have few side effects. The side effects that do arise include eyestrain, headache, fatigue, irritability, and inability to sleep (when light therapy is used too late in the day). People with manic depressive disorders, skin that is sensitive to light, or medical conditions that make their eyes vulnerable to light damage may not be good candidates for light therapy.
When light therapy does not improve symptoms within a few days, then medication and behavioral therapies such as CBT should be introduced. In some cases, light therapy can be used in combination with one or all of these therapies.
Monitor your mood and energy level
Take advantage of available sunlight
Plan pleasurable activities for the winter season
Plan physical activities
Approach the winter season with a positive attitude
When symptoms develop seek help sooner rather than later
Ketamine is emerging as a popular treatment for depression. New research suggests the drug acts like an opioid
Ketamine is emerging as a way to treat depression, but it appears to act like an opioid, Stanford researchers found.
Clinics are cropping up around the country where people receive ketamine infusions.
A handful of pharmaceutical companies, including Johnson & Johnson and Allergan, are using ketamine as inspiration for new prescription drugs to treat depression.
This is a vial of the animal tranquilizing drug ketamine hydrochloride, better known in the drug culture as “Special K.”
Ketamine is emerging as a way to treat depression, but it appears to act like an opioid — and it may carry similar risks, Stanford researchers found.
Clinics are cropping up around the country where people receive ketamine infusions. A handful of pharmaceutical companies are using ketamine as inspiration for new prescription drugs to treat depression. Yet the new research questions whether scientists know enough about chronic ketamine use to introduce it broadly.
The drug blocks NMDA receptors, which scientists think may treat depressive symptoms. Researchers wanted to test whether it was possible to elicit this reaction without activating the brain’s opioid receptors.
To block an opioid response, they gave participants naltrexone then infused them with ketamine. To compare that response with the normal response, they also gave participants a placebo before giving them the treatment.
Naltrexone so successfully blocked the anti-depressant effects of ketamine that researchers cancelled the study after the first interval because they felt it wasn’t ethical to continue it, said Dr. Nolan Williams, one of the study’s authors and a clinical assistant professor of psychiatry and behavioral sciences at Stanford University.
When patients took naltrexone, the opioid blocker, their symptoms did not improve, suggesting ketamine must first activate opioid receptors in order to treat depression, according to the study, published Wednesday in the American Journal of Psychiatry.
That’s not to say ketamine cannot be used occasionally, but it does raise questions about using it repeatedly over time, said Dr. Alan F. Schatzberg, co-author of the study and Stanford’s Kenneth T. Norris, Jr., professor of psychiatry and behavioral sciences. He likens it to opioid painkillers being an appropriate pain treatment when used once in the emergency room but posing problems, such as the risk of dependence, when used chronically.
“More studies need to be done to fully understand ketamine before it’s widely rolled out for long-term chronic use,” Schatzberg said.
Researchers planned on studying 30 adults but stopped enrolling patients once they decided combining ketamine and naltrexone was not only ineffective but also “noxious” for many participants. They tested a total of 12 people with both naltrexone and the placebo.
Of those 12, seven who received naltrexone experienced nausea after the ketamine infusion, compared to three in the placebo group. Two participants in each group also experienced vomiting.
Participants who received the placebo and ketamine treatment reported reduced depression symptoms. But those same participants did not see a decrease in depression symptoms after receiving ketamine and opioid-blocker naltrexone.
“We essentially blocked the mechanism for producing the anti-depressant effect, which were opioids,” said Williams.
The findings may have implications for clinics offering ketamine infusions and drug manufacturers trying to commercialize ketamine-like drugs.
Ketamine is meant to be used as an anesthetic. Since ketamine is currently not indicated to treat depression, insurance typically doesn’t cover the cost of infusions, so people tend to pay out of their own pocket. One session can run more than $500.
Meanwhile, drug giant Johnson & Johnson plans to seek approval from the Food and Drug Administration for its nasal spray esketamine this year after reporting positive results from a Phase 3 trial. Allergan plans to file its drug Rapastinel, which targets the NMDA receptors like ketamine, within the next two years. VistaGen Therapeutics is working on a similar drug.
In a statement, J&J said while the study reviewed ketamine and not esketamine, the findings “are difficult to interpret because of the study’s design.”
Now that the days are getting shorter, the air is getting cooler, Virginians have had the first glimpse of cold for the season, some of us begin to feel the winter blues. These feelings of low energy and sleepiness may actually be Seasonal Affective Disorder, or SAD.
SAD is a form of depression related to the changing seasons. It usually starts in the late fall, especially in our northern climes. The decreasing hours of sunlight, along with the cold and snow, cause our bodies to retreat into the warmth and coziness of our homes. We tend to crave carbohydrates, eat comfort foods, and socially withdraw as we sleep more, and move less; much like we are hibernating!
Those most at risk for SAD are people already suffering from major depression or bipolar disorder. Risk factors include being female, family history, young age, and the further you live from the equator, the higher your risk. However, there are ways to decrease your risk, and increase your mood.
What can you do to improve your mood? Soak up the sun! When the weather allows, go for a walk on those bright, crisp sunny days. If the temperature or the ice and snow don’t allow you to venture outside, open the curtains and let the sun shine in. Exercise and eating healthy are both options to make you feel better. Vitamins, especially vitamin D, the sunshine vitamin can help with mood. Be social, visit with friends. A phone call, visit, or even a vacation to visit your “snowbird” friends will keep you socially involved.
So, if these options aren’t working or you just need something more to improve your mood, your healthcare provider may recommend seeking help from a psychotherapist. They may offer medications, light box therapy, or talk therapy.
Ketamine therapy is an option to help make it through dark times when nothing else seems to work. Contact 703-844-0184 for a consultation.
Seasonal Affective Disorder
Seasonal Affective Disorder (SAD) is a type of depression that comes and goes with the seasons, typically starting in the late fall and early winter and going away during the spring and summer. Depressive episodes linked to the summer can occur, but are much less common than winter episodes of SAD.
Signs and Symptoms
Seasonal Affective Disorder (SAD) is not considered as a separate disorder. It is a type of depression displaying a recurring seasonal pattern. To be diagnosed with SAD, people must meet full criteria for major depression coinciding with specific seasons (appearing in the winter or summer months) for at least 2 years. Seasonal depressions must be much more frequent than any non-seasonal depressions.
Symptoms of Major Depression
Feeling depressed most of the day, nearly every day
Feeling hopeless or worthless
Having low energy
Losing interest in activities you once enjoyed
Having problems with sleep
Experiencing changes in your appetite or weight
Feeling sluggish or agitated
Having difficulty concentrating
Having frequent thoughts of death or suicide.
Symptoms of the Winter Pattern of SAD include:
Having low energy
Craving for carbohydrates
Social withdrawal (feel like “hibernating”)
Symptoms of the less frequently occurring summer seasonal affective disorder include:
Poor appetite with associated weight loss
Episodes of violent behavior
Attributes that may increase your risk of SAD include:
Being female. SAD is diagnosed four times more often in women than men.
Family history. People with a family history of other types of depression are more likely to develop SAD than people who do not have a family history of depression.
Having depression or bipolar disorder. The symptoms of depression may worsen with the seasons if you have one of these conditions (but SAD is diagnosed only if seasonal depressions are the most common).
Younger Age. Younger adults have a higher risk of SAD than older adults. SAD has been reported even in children and teens.
The causes of SAD are unknown, but research has found some biological clues:
People with SAD may have trouble regulating one of the key neurotransmitters involved in mood, serotonin. One study found that people with SAD have 5 percent more serotonin transporter protein in winter months than summer months. Higher serotonin transporter protein leaves less serotonin available at the synapse because the function of the transporter is to recycle neurotransmitter back into the pre-synaptic neuron.
People with SAD may overproduce the hormone melatonin.Darkness increases production of melatonin, which regulates sleep. As winter days become shorter, melatonin production increases, leaving people with SAD to feel sleepier and more lethargic, often with delayed circadian rhythms.
People with SAD also may produce less Vitamin D. Vitamin D is believed to play a role in serotonin activity. Vitamin D insufficiency may be associated with clinically significant depression symptoms.
Treatments and Therapies
There are four major types of treatment for SAD:
These may be used alone or in combination.
Selective Serotonin Reuptake Inhibitors (SSRIs) are used to treat SAD. The FDA has also approved the use of bupropion, another type of antidepressant, for treating SAD.
Light therapy has been a mainstay of treatment for SAD since the 1980s. The idea behind light therapy is to replace the diminished sunshine of the fall and winter months using daily exposure to bright, artificial light. Symptoms of SAD may be relieved by sitting in front of a light box first thing in the morning, on a daily basis from the early fall until spring. Most typically, light boxes filter out the ultraviolet rays and require 20-60 minutes of exposure to 10,000 lux of cool-white fluorescent light, an amount that is about 20 times greater than ordinary indoor lighting.
Cognitive behavioral therapy (CBT) is type of psychotherapy that is effective for SAD. Traditional cognitive behavioral therapy has been adapted for use with SAD (CBT-SAD). CBT-SAD relies on basic techniques of CBT such as identifying negative thoughts and replacing them with more positive thoughts along with a technique called behavioral activation. Behavioral activation seeks to help the person identify activities that are engaging and pleasurable, whether indoors or outdoors, to improve coping with winter.
At present, vitamin D supplementation by itself is not regarded as an effective SAD treatment. The reason behind its use is that low blood levels of vitamin D were found in people with SAD. The low levels are usually due to insufficient dietary intake or insufficient exposure to sunshine. However, the evidence for its use has been mixed. While some studies suggest vitamin D supplementation may be as effective as light therapy, others found vitamin D had no effect.
Everyone occasionally feels blue or sad. But these feelings are usually short-lived and pass within a couple of days. When you have depression, it interferes with daily life and causes pain for both you and those who care about you. Depression is a common but serious illness.
Many people with a depressive illness never seek treatment. But the majority, even those with the most severe depression, can get better with treatment. Medications, psychotherapies, and other methods can effectively treat people with depression.
There are several forms of depressive disorders.
Major depression,—severe symptoms that interfere with your ability to work, sleep, study, eat, and enjoy life. An episode can occur only once in a person’s lifetime, but more often, a person has several episodes.
Persistent depressive disorder—depressed mood that lasts for at least 2 years. A person diagnosed with persistent depressive disorder may have episodes of major depression along with periods of less severe symptoms, but symptoms must last for 2 years.
Some forms of depression are slightly different, or they may develop under unique circumstances. They include:
Psychotic depression, which occurs when a person has severe depression plus some form of psychosis, such as having disturbing false beliefs or a break with reality (delusions), or hearing or seeing upsetting things that others cannot hear or see (hallucinations).
Postpartum depression, which is much more serious than the “baby blues” that many women experience after giving birth, when hormonal and physical changes and the new responsibility of caring for a newborn can be overwhelming. It is estimated that 10 to 15 percent of women experience postpartum depression after giving birth.
Seasonal affective disorder (SAD), which is characterized by the onset of depression during the winter months, when there is less natural sunlight. The depression generally lifts during spring and summer. SAD may be effectively treated with light therapy, but nearly half of those with SAD do not get better with light therapy alone. Antidepressant medication and psychotherapy can reduce SAD symptoms, either alone or in combination with light therapy.
Bipolar depression, also called manic-depressive illness, is not as common as major depression or persistent depressive disorder. Bipolar disorder is characterized by cycling mood changes—from extreme highs (e.g., mania) to extreme lows (e.g., depression).
Most likely, depression is caused by a combination of genetic, biological, environmental, and psychological factors.
Depressive illnesses are disorders of the brain. Brain-imaging technologies, such as magnetic resonance imaging (MRI), have shown that the brains of people who have depression look different than those of people without depression. The parts of the brain involved in mood, thinking, sleep, appetite, and behavior appear different. But these images do not reveal why the depression has occurred. They also cannot be used to diagnose depression.
Some types of depression tend to run in families. However, depression can occur in people without family histories of depression too. Scientists are studying certain genes that may make some people more prone to depression. Some genetics research indicates that risk for depression results from the influence of several genes acting together with environmental or other factors. In addition, trauma, loss of a loved one, a difficult relationship, or any stressful situation may trigger a depressive episode. Other depressive episodes may occur with or without an obvious trigger.
Signs & Symptoms
“It was really hard to get out of bed in the morning. I just wanted to hide under the covers and not talk to anyone. I didn’t feel much like eating and I lost a lot of weight. Nothing seemed fun anymore. I was tired all the time, and I wasn’t sleeping well at night. But I knew I had to keep going because I’ve got kids and a job. It just felt so impossible, like nothing was going to change or get better.”
People with depressive illnesses do not all experience the same symptoms. The severity, frequency, and duration of symptoms vary depending on the individual and his or her particular illness.
Signs and symptoms include:
Persistent sad, anxious, or “empty” feelings
Feelings of hopelessness or pessimism
Feelings of guilt, worthlessness, or helplessness
Loss of interest in activities or hobbies once pleasurable, including sex
Fatigue and decreased energy
Difficulty concentrating, remembering details, and making decisions
Insomnia, early-morning wakefulness, or excessive sleeping
Overeating, or appetite loss
Thoughts of suicide, suicide attempts
Aches or pains, headaches, cramps, or digestive problems that do not ease even with treatment.
Who Is At Risk?
Major depressive disorder is one of the most common mental disorders in the United States. Each year about 6.7% of U.S adults experience major depressive disorder. Women are 70 % more likely than men to experience depression during their lifetime. Non-Hispanic blacks are 40% less likely than non-Hispanic whites to experience depression during their lifetime. The average age of onset is 32 years old. Additionally, 3.3% of 13 to 18 year olds have experienced a seriously debilitating depressive disorder.
“I started missing days from work, and a friend noticed that something wasn’t right. She talked to me about the time she had been really depressed and had gotten help from her doctor.”
Depression, even the most severe cases, can be effectively treated. The earlier that treatment can begin, the more effective it is.
The first step to getting appropriate treatment is to visit a doctor or mental health specialist. Certain medications, and some medical conditions such as viruses or a thyroid disorder, can cause the same symptoms as depression. A doctor can rule out these possibilities by doing a physical exam, interview, and lab tests. If the doctor can find no medical condition that may be causing the depression, the next step is a psychological evaluation.
The doctor may refer you to a mental health professional, who should discuss with you any family history of depression or other mental disorder, and get a complete history of your symptoms. You should discuss when your symptoms started, how long they have lasted, how severe they are, and whether they have occurred before and if so, how they were treated. The mental health professional may also ask if you are using alcohol or drugs, and if you are thinking about death or suicide.
Other illnesses may come on before depression, cause it, or be a consequence of it. But depression and other illnesses interact differently in different people. In any case, co-occurring illnesses need to be diagnosed and treated.
Anxiety disorders, such as post-traumatic stress disorder (PTSD), obsessive-compulsive disorder, panic disorder, social phobia, and generalized anxiety disorder, often accompany depression. PTSD can occur after a person experiences a terrifying event or ordeal, such as a violent assault, a natural disaster, an accident, terrorism or military combat. People experiencing PTSD are especially prone to having co-existing depression.
Alcohol and other substance abuse or dependence may also co-exist with depression. Research shows that mood disorders and substance abuse commonly occur together.
Depression also may occur with other serious medical illnesses such as heart disease, stroke, cancer, HIV/AIDS, diabetes, and Parkinson’s disease. People who have depression along with another medical illness tend to have more severe symptoms of both depression and the medical illness, more difficulty adapting to their medical condition, and more medical costs than those who do not have co-existing depression. Treating the depression can also help improve the outcome of treating the co-occurring illness.
Once diagnosed, a person with depression can be treated in several ways. The most common treatments are medication and psychotherapy.
Antidepressants primarily work on brain chemicals called neurotransmitters, especially serotonin and norepinephrine. Other antidepressants work on the neurotransmitter dopamine. Scientists have found that these particular chemicals are involved in regulating mood, but they are unsure of the exact ways that they work. The latest information on medications for treating depression is available on the U.S. Food and Drug Administration (FDA) website .
Popular newer antidepressants
Some of the newest and most popular antidepressants are called selective serotonin reuptake inhibitors (SSRIs). Fluoxetine (Prozac), sertraline (Zoloft), escitalopram (Lexapro), paroxetine (Paxil), and citalopram (Celexa) are some of the most commonly prescribed SSRIs for depression. Most are available in generic versions. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are similar to SSRIs and include venlafaxine (Effexor) and duloxetine (Cymbalta).
SSRIs and SNRIs tend to have fewer side effects than older antidepressants, but they sometimes produce headaches, nausea, jitters, or insomnia when people first start to take them. These symptoms tend to fade with time. Some people also experience sexual problems with SSRIs or SNRIs, which may be helped by adjusting the dosage or switching to another medication.
One popular antidepressant that works on dopamine is bupropion (Wellbutrin). Bupropion tends to have similar side effects as SSRIs and SNRIs, but it is less likely to cause sexual side effects. However, it can increase a person’s risk for seizures.
Tricyclics are older antidepressants. Tricyclics are powerful, but they are not used as much today because their potential side effects are more serious. They may affect the heart in people with heart conditions. They sometimes cause dizziness, especially in older adults. They also may cause drowsiness, dry mouth, and weight gain. These side effects can usually be corrected by changing the dosage or switching to another medication. However, tricyclics may be especially dangerous if taken in overdose. Tricyclics include imipramine and nortriptyline.
Monoamine oxidase inhibitors (MAOIs) are the oldest class of antidepressant medications. They can be especially effective in cases of “atypical” depression, such as when a person experiences increased appetite and the need for more sleep rather than decreased appetite and sleep. They also may help with anxious feelings or panic and other specific symptoms.
However, people who take MAOIs must avoid certain foods and beverages (including cheese and red wine) that contain a substance called tyramine. Certain medications, including some types of birth control pills, prescription pain relievers, cold and allergy medications, and herbal supplements, also should be avoided while taking an MAOI. These substances can interact with MAOIs to cause dangerous increases in blood pressure. The development of a new MAOI skin patch may help reduce these risks. If you are taking an MAOI, your doctor should give you a complete list of foods, medicines, and substances to avoid.
MAOIs can also react with SSRIs to produce a serious condition called “serotonin syndrome,” which can cause confusion, hallucinations, increased sweating, muscle stiffness, seizures, changes in blood pressure or heart rhythm, and other potentially life-threatening conditions. MAOIs should not be taken with SSRIs.
How should I take medication?
All antidepressants must be taken for at least 4 to 6 weeks before they have a full effect. You should continue to take the medication, even if you are feeling better, to prevent the depression from returning.
Medication should be stopped only under a doctor’s supervision. Some medications need to be gradually stopped to give the body time to adjust. Although antidepressants are not habit-forming or addictive, suddenly ending an antidepressant can cause withdrawal symptoms or lead to a relapse of the depression. Some individuals, such as those with chronic or recurrent depression, may need to stay on the medication indefinitely.
In addition, if one medication does not work, you should consider trying another. NIMH-funded research has shown that people who did not get well after taking a first medication increased their chances of beating the depression after they switched to a different medication or added another medication to their existing one.
Sometimes stimulants, anti-anxiety medications, or other medications are used together with an antidepressant, especially if a person has a co-existing illness. However, neither anti-anxiety medications nor stimulants are effective against depression when taken alone, and both should be taken only under a doctor’s close supervision.
Report any unusual side effects to a doctor immediately.
IV Ketamine Therapy
One of the most exciting new treatment options for depression is with a long known drug, ketamine. Ketamine has been used historically as an anesthetic. Recently, it has emerged as an effective treatment option for severe depression (citations below). The mechanism of action for ketamine’s antidepressant effects is not fully understood and hotly debated. However, studies of the neurobiology of depressed patients have revealed possible abnormalities that may have a causal link to depression such as increased inflammatory cytokines, decreased BDNF, and reduced hippocampal volume. Interestingly, there is much overlap in the neurobiology of depression and known consequences of ketamine treatment. Ketamine has been found to reduce neuroinflammation, increase BDNF production and hippocampal volume. Thus, it is highly likely that ketamine possesses a robust pharmacological profile that works collectively to correct abnormalities common to severe depression. Although only FDA-approved as an anesthetic, ketamine is used off-label by many physicians in cases of severe, treatment-resistant depression.
Depression is more common among women than among men. Biological, life cycle, hormonal, and psychosocial factors that women experience may be linked to women’s higher depression rate. Researchers have shown that hormones directly affect the brain chemistry that controls emotions and mood. For example, women are especially vulnerable to developing postpartum depression after giving birth, when hormonal and physical changes and the new responsibility of caring for a newborn can be overwhelming.
Some women may also have a severe form of premenstrual syndrome (PMS) called premenstrual dysphoric disorder (PMDD). PMDD is associated with the hormonal changes that typically occur around ovulation and before menstruation begins.
During the transition into menopause, some women experience an increased risk for depression. In addition, osteoporosis—bone thinning or loss—may be associated with depression. Scientists are exploring all of these potential connections and how the cyclical rise and fall of estrogen and other hormones may affect a woman’s brain chemistry.
Finally, many women face the additional stresses of work and home responsibilities, caring for children and aging parents, abuse, poverty, and relationship strains. It is still unclear, though, why some women faced with enormous challenges develop depression, while others with similar challenges do not.
How do men experience depression?
Men often experience depression differently than women. While women with depression are more likely to have feelings of sadness, worthlessness, and excessive guilt, men are more likely to be very tired, irritable, lose interest in once-pleasurable activities, and have difficulty sleeping.
Men may be more likely than women to turn to alcohol or drugs when they are depressed. They also may become frustrated, discouraged, irritable, angry, and sometimes abusive. Some men throw themselves into their work to avoid talking about their depression with family or friends, or behave recklessly. And although more women attempt suicide, many more men die by suicide in the United States.
How do older adults experience depression?
Depression is not a normal part of aging. Studies show that most seniors feel satisfied with their lives, despite having more illnesses or physical problems. However, when older adults do have depression, it may be overlooked because seniors may show different, less obvious symptoms. They may be less likely to experience or admit to feelings of sadness or grief.
Sometimes it can be difficult to distinguish grief from major depression. Grief after loss of a loved one is a normal reaction to the loss and generally does not require professional mental health treatment. However, grief that is complicated and lasts for a very long time following a loss may require treatment. Researchers continue to study the relationship between complicated grief and major depression.
Older adults also may have more medical conditions such as heart disease, stroke, or cancer, which may cause depressive symptoms. Or they may be taking medications with side effects that contribute to depression. Some older adults may experience what doctors call vascular depression, also called arteriosclerotic depression or subcortical ischemic depression. Vascular depression may result when blood vessels become less flexible and harden over time, becoming constricted. Such hardening of vessels prevents normal blood flow to the body’s organs, including the brain. Those with vascular depression may have, or be at risk for, co-existing heart disease or stroke.
Although many people assume that the highest rates of suicide are among young people, older white males age 85 and older actually have the highest suicide rate in the United States. Many have a depressive illness that their doctors are not aware of, even though many of these suicide victims visit their doctors within 1 month of their deaths.
Most older adults with depression improve when they receive treatment with an antidepressant, psychotherapy, or a combination of both. Research has shown that medication alone and combination treatment are both effective in reducing depression in older adults. Psychotherapy alone also can be effective in helping older adults stay free of depression, especially among those with minor depression. Psychotherapy is particularly useful for those who are unable or unwilling to take antidepressant medication.
How do children and teens experience depression?
Children who develop depression often continue to have episodes as they enter adulthood. Children who have depression also are more likely to have other more severe illnesses in adulthood.
A child with depression may pretend to be sick, refuse to go to school, cling to a parent, or worry that a parent may die. Older children may sulk, get into trouble at school, be negative and irritable, and feel misunderstood. Because these signs may be viewed as normal mood swings typical of children as they move through developmental stages, it may be difficult to accurately diagnose a young person with depression.
Before puberty, boys and girls are equally likely to develop depression. By age 15, however, girls are twice as likely as boys to have had a major depressive episode.
Depression during the teen years comes at a time of great personal change—when boys and girls are forming an identity apart from their parents, grappling with gender issues and emerging sexuality, and making independent decisions for the first time in their lives. Depression in adolescence frequently co-occurs with other disorders such as anxiety, eating disorders, or substance abuse. It can also lead to increased risk for suicide.
An NIMH-funded clinical trial of 439 adolescents with major depression found that a combination of medication and psychotherapy was the most effective treatment option. Other NIMH-funded researchers are developing and testing ways to prevent suicide in children and adolescents.
Childhood depression often persists, recurs, and continues into adulthood, especially if left untreated.
How can I help a loved one who is depressed?
If you know someone who is depressed, it affects you too. The most important thing you can do is help your friend or relative get a diagnosis and treatment. You may need to make an appointment and go with him or her to see the doctor. Encourage your loved one to stay in treatment, or to seek different treatment if no improvement occurs after 6 to 8 weeks.
To help your friend or relative
Offer emotional support, understanding, patience, and encouragement.
Talk to him or her, and listen carefully.
Never dismiss feelings, but point out realities and offer hope.
Never ignore comments about suicide, and report them to your loved one’s therapist or doctor.
Invite your loved one out for walks, outings and other activities. Keep trying if he or she declines, but don’t push him or her to take on too much too soon.
Provide assistance in getting to the doctor’s appointments.
Remind your loved one that with time and treatment, the depression will lift.
How can I help myself if I am depressed?
If you have depression, you may feel exhausted, helpless, and hopeless. It may be extremely difficult to take any action to help yourself. But as you begin to recognize your depression and begin treatment, you will start to feel better.
To Help Yourself
Do not wait too long to get evaluated or treated. There is research showing the longer one waits, the greater the impairment can be down the road. Try to see a professional as soon as possible.
Try to be active and exercise. Go to a movie, a ballgame, or another event or activity that you once enjoyed.
Set realistic goals for yourself.
Break up large tasks into small ones, set some priorities and do what you can as you can.
Try to spend time with other people and confide in a trusted friend or relative. Try not to isolate yourself, and let others help you.
Expect your mood to improve gradually, not immediately. Do not expect to suddenly “snap out of” your depression. Often during treatment for depression, sleep and appetite will begin to improve before your depressed mood lifts.
Postpone important decisions, such as getting married or divorced or changing jobs, until you feel better. Discuss decisions with others who know you well and have a more objective view of your situation.
Remember that positive thinking will replace negative thoughts as your depression responds to treatment.
Researchers from the University of Minnesota and The Mayo Clinic found that ketamine caused an average decrease of 42% on the Children’s Depression Rating Scale(CDRS)—the most widely used rating scale in research trials for assessing the severity of depression and change in depressive symptoms among adolescents. The study recruited adolescents, 12-18 years of age, with treatment-resistant depression (TRD; failure to respond to two previous antidepressant trials). The teens were administered intravenous ketamine (0.5 mg/kg) by infusion six times over two weeks.
The study reported that the average decrease in CDRS-R was 42.5% (p = 0.0004). Five (38%) adolescents met criteria for clinical response (defined as >50% reduction in CDRS-R). Three responders showed sustained remission at 6-week follow-up; relapse occurred within 2 weeks for the other two responders. The ketamine infusions were generally well tolerated; dissociative symptoms and hemodynamic symptoms were transient. Interestingly, higher dose was a significant predictor of treatment response.
“Adolescence is a key time period for emergence of depression and represents an opportune and critical developmental window for intervention to prevent negative outcomes,” the authors wrote in the study.
“Unfortunately, about 40% of adolescents do not respond to their first intervention and only half of non-responders respond to the second treatment,” they said. “Because standard interventions require prolonged periods (e.g., weeks to months) to assess efficacy, serial treatment failures allow illness progression, which in turn worsens the outcome. Hence, novel treatment strategies to address treatment-resistant depression in adolescents are urgently needed.”
The authors concluded that their results demonstrate the potential role for ketamine in treating adolescents with TRD. Additionally, evidence suggested a dose–response relationship; future studies are needed to optimize dose
Yale study found no safety issues with long-term ketamine treatment
Researchers at Yale published a new study titled “Acute and Longer-Term Outcomes Using Ketamine as a Clinical Treatment at the Yale Psychiatric Hospital” in Clinical Psychiatry. In late 2014, Yale began providing ketamine as an off-label therapy on a case-by-case basis for patients who could not participate in research protocols. The authors observed 54 patients that received IV ketamine infusion for the treatment of severe and treatment-resistant mood disorders such as depression.
“Ketamine is being used as an off-label treatment for depression by an increasing number of providers, yet there is very little long-term data on patients who have received ketamine for more than just a few weeks,” Samuel T. Wilkinson, MD,from the department of psychiatry, Yale School of Medicine and Yale Psychiatric Hospital, told Healio Psychiatry.
The Yale researchers studied the acute and longer-term outcomes in this patient population. Importantly, a subset of patients (n=14) received ketamine on a long-term basis, ranging from 12 to 45 total treatments, over a course of 14 to 126 weeks. The researchers found no evidence of cognitive decline, increased proclivity to delusions, or emergence of symptoms consistent with cystitis in this subset of long-term ketamine patients. They also reported that the infusions were generally well-tolerated.
Although this study population was relatively small, limiting the conclusions that can be drawn, this is still an important first step in establishing the long-term safety of ketamine for the treatment of a myriad of diseases that it’s being used to treat
CNN featured a segment on the use of ketamine for treating suicidal ideation–a novel, off-label use for ketamine that is currently being explored in human clinical trials. The segment featured Dr. Sanjay Gupta sharing the story of Alan Ferguson. Mr. Ferguson discussed his experience with suicidal ideation, stating that he had planned his own suicide prior to a psychiatrist suggesting the off-label use of ketamine. Fortunately, ketamine worked for him as it has for many others, completely eliminating all thoughts of suicide and depression.
While ketamine is a long-known, FDA-approved anesthetic, new uses for this old drug have recently been discovered. The new indication that is probably the farthest along is for the treatment of depression. It’s even undergoing phase III clinical trials for the treatment of depression, which are expected to be completed next year. In depression, ketamine’s mechanism of action is still being explored. Scientists know that ketamine antagonizes the NMDA receptor, which causes a number of downstream cascades that may be relevant to it’s antidepressant effects. Ketamine also increases important neuronal growth factors that can create new synaptic connections.
While there are numerous anti-depressants that are already FDA-approved, they don’t always work and–even when they do–it takes weeks to see the effect. This is what’s special about ketamine. The anti-depressant effects of ketamine are instantaneous. In the case of Alan Ferguson, his depression went from severe to mild after the first infusion, and was gone after the second. In cases of depression that involve suicidality, this rapid improvement can be the difference between life and death. Even though ketamine is not yet approved for the treatment of depression or suicidal ideation, there is an abundance of data showing that it works and it’s already being used off-label in the clinic.
Australian researchers completed the world’s first randomized control trial (RCT), assessing the efficacy and safety of ketamine as a treatment for depression in elderly patients.
In this double-blind, controlled, multiple-crossover study with a 6-month follow-up, 16 participants (≥60 years) with treatment-resistant depression who relapsed after remission or did not remit in the RCT were administered an open-label phase. Up to five subcutaneous doses of ketamine (0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg) were administered in separate sessions (≥1 week apart), with one active control (midazolam) randomly inserted. Twelve ketamine treatments were given in the open-label phase. Mood, hemodynamic, and psychotomimetic outcomes were assessed by blinded raters. Remitters in each phase were followed for 6 months.
The results, published in the latest American Journal of Geriatric Psychiatry, provide preliminary evidence that ketamine is effective as an antidepressant – when delivered in repeated intravenous doses.
“What we noticed was that ketamine worked incredibly quickly and incredibly effectively,” Professor Colleen Loo, who led the pilot program told ABC News. “By incredibly effective, we mean going rapidly from severely depressed to being completely well in one day.”
“Some people think, ‘oh maybe it was just a drug induced temporary high’ — and it wasn’t,” she said. “You had the woozy effects in the first hour or so, but the antidepressant effects kicked in later.”
None of the participants experienced problematic side effects, according to the research team who administered the drug through a small injection under the skin.
“Our results indicate a dose-titration method may be particularly useful for older patients, as the best dose was selected for each individual person to maximize ketamine’s benefits while minimizing its adverse side effects,” she said.
The authors noted that further study is needed, however, to understand the risks of ketamine use and possible side effects, such as its impact on liver function in the elderly.
PTSD Treatment – Ketamine is a novel treatment for several psychiatric disorders including: Major Depressive Disorder, Bipolar Depression, Postpartum Depression, Obsessive-Compulsive Disorder (OCD), and Posttraumatic Stress Disorder or PTSD. It was originally FDA approved for anesthesia but is now frequently used off-label due to its positive effects on the various disorders listed above. PTSD is an devastating disorder that has become more and more common but medical treatments overall are still lacking.
What is PTSD?
PTSD is a disorder that develops after a traumatic experience. Such trauma sometimes involves combat, car accidents, natural disasters or sexual assaults. Up to 80% of individuals in their life will experience at least one traumatic event but, fortunately, most people do not go on to develop PTSD. The lifetime prevalence of developing PTSD is about 10% and women are twice as likely as men to develop PTSD. Those who do go on to develop PTSD typically will have one or more of the following symptoms:
• traumatic nightmares
• flashbacks taking them back to the event
• distress after exposure to traumatic reminders or stimuli
• avoidance of certain thoughts and situations
• negative thoughts and mood including shame, despair and depression.
A constellation of these symptoms must persist for at least a month for a diagnosis of PTSD to be made.
Most PTSD Treatment are ineffective for some patients and their all generally slow acting—meaning that the patient must wait weeks to have a meaningful impact on the patient’s wellness. Ketamine has now been shown to be effective at managing PTSD in several clinical studies. Moreover, physicians are beginning to present case reports where ketamine has helped their patients. One of the largest benefits of using Ketamine off label for the treatment of depression is that it is generally very fast-acting. Patients typically report feeling better after the first infusion or two. Sometimes, they report feeling 100% better after 5 days of IV ketamine therapy.
Lauren Pestikas sits as she receives an infusion of the drug ketamine during a 45-minute session at an outpatient clinic in Chicago on July 25, 2018. Pestikas struggled with depression and anxiety and made several suicide attempts before starting ketamine treatments earlier in the year. (AP Photo/Teresa Crawford)
CHICAGO (AP) — It was launched decades ago as an anesthetic for animals and people, became a potent battlefield pain reliever in Vietnam and morphed into the trippy club drug Special K.
Now the chameleon drug ketamine is finding new life as an unapproved treatment for depression and suicidal behavior. Clinics have opened around the United States promising instant relief with their “unique” doses of ketamine in IVs, sprays or pills. And desperate patients are shelling out thousands of dollars for treatment often not covered by health insurance, with scant evidence on long-term benefits and risks.
Chicago preschool teacher Lauren Pestikas long struggled with depression and anxiety and made several suicide attempts before trying ketamine earlier this year.
The price tag so far is about $3,000, but “it’s worth every dime and penny,” said the 36-year-old.
Pestikas said she feels much better for a few weeks after each treatment, but the effects wear off and she scrambles to find a way to pay for another one.
For now, ketamine has not received approval from the U.S. Food and Drug Administration for treating depression, though doctors can use it for that purpose.
Some studies show ketamine can provide relief within hours for tough-to-treat depression and suicidal behavior and clinics promising unproven benefits have popped up nationwide. But more research is needed to know long-term benefits and risks. (Oct. 31)
Ketamine has been around since the 1960s and is widely used as an anesthesia drug during surgery because it doesn’t suppress breathing. Compared to opioids such as morphine, ketamine isn’t as addictive and doesn’t cause breathing problems. And some studies have shown that ketamine can ease symptoms within hours for the toughest cases.
Its potential effects on depression were discovered in animal experiments in the late 1980s and early 1990s showing that glutamate, a brain chemical messenger, might play a role in depression, and that drugs including ketamine that target the glutamate pathway might work as antidepressants.
Conventional antidepressants like Prozac target serotonin, a different chemical messenger, and typically take weeks to months to kick in — a lag that can cause severely depressed patients to sink deeper into despair.
A vial of ketamine, which is normally stored in a locked cabinet, on display in Chicago on July 25, 2018. AP Photo/Teresa Crawford)
Ketamine’s potential for almost immediate if temporary relief is what makes it so exciting, said Dr. Jennifer Vande Voort, a Mayo Clinic psychiatrist who has used ketamine to treat depression patients since February.
“We don’t have a lot of things that provide that kind of effect. What I worry about is that it gets so hyped up,” she said.
The strongest studies suggest it’s most useful and generally safe in providing short-term help for patients who have not benefited from antidepressants. That amounts to about one-third of the roughly 300 million people with depression worldwide.
“It truly has revolutionized the field,” changing scientists’ views on how depression affects the brain and showing that rapid relief is possible, said Yale University psychiatrist Dr. Gerard Sanacora, who has done research for or consulted with companies seeking to develop ketamine-based drugs.
But to become standard depression treatment, he said, much more needs to be known.
Last year, Sanacora co-authored an American Psychiatric Association task force review of ketamine treatment for mood disorders that noted the benefits but said “major gaps” remain in knowledge about long-term effectiveness and safety. Most studies have been small, done in research settings and not in the real world.
When delivered through an IV, ketamine can cause a rapid increase in heart rate and blood pressure that could be dangerous for some patients. Ketamine also can cause hallucinations that some patients find scary.
“There are some very real concerns,” Sanacora said. “We do know this drug can be abused, so we have to be very careful about how this is developed.”
Dr. Rahul Khare, an emergency medicine specialist in Chicago, first learned about ketamine’s other potential benefits a decade ago from a depressed and anxious patient he was preparing to sedate to fix a repeat dislocated shoulder.
“He said, ‘Doc, give me what I got last time. For about three weeks after I got it I felt so much better,’” Khare recalled.
Khare became intrigued and earlier this year began offering ketamine for severe depression at an outpatient clinic he opened a few years ago. He also joined the American Society for Ketamine Physicians, formed a year ago representing about 140 U.S. doctors, nurses, psychologists and others using ketamine for depression or other nonapproved uses.
Dr. Rahul Khare poses for a portrait at his outpatient Chicago clinic on July 25, 2018. (AP Photo/Teresa Crawford)
There are about 150 U.S. ketamine clinics, compared with about 20 three years ago, said society co-founder Dr. Megan Oxley.
Khare said the burgeoning field “is like a new frontier” where doctors gather at meetings and compare notes. He has treated about 50 patients with depression including Pestikas. They’re typically desperate for relief after failing to respond to other antidepressants. Some have lost jobs and relationships because of severe depression, and most find that ketamine allows them to function, Khare said.
Typical treatment at his clinic involves six 45-minute sessions over about two weeks, costing $550 each. Some insurers will pay about half of that, covering Khare’s office visit cost. Patients can receive “booster” treatments. They must sign a four-page consent form that says benefits may not be long-lasting, lists potential side effects, and in bold letters states that the treatment is not government-approved.
At a recent session, Pestikas’s seventh, she leaned back on a reclining white examining-room chair as a nurse hooked her up to a heart and blood pressure monitor. She grimaced as a needle was slipped into the top of her left palm. Khare reached up with a syringe to inject a small dose of ketamine into an IV bag hanging above the chair, then dimmed the lights, pulled the window curtains and asked if she had questions and was feeling OK.
“No questions, just grateful,” Pestikas replied, smiling.
Pestikas listened to music on her iPhone and watched psychedelic videos. She said it was like “a controlled acid trip” with pleasant hallucinations. The trip ends soon after the IV is removed, but Pestikas said she feels calm and relaxed the rest of the day, and that the mood boost can last weeks.
Studies suggest that a single IV dose of ketamine far smaller than used for sedation or partying can help many patients gain relief within about four hours and lasting nearly a week or so.
Exactly how ketamine works is unclear, but one idea is that by elevating glutamate levels, ketamine helps nerve cells re-establish connections that were disabled by depression, said ketamine expert Dr. Carlos Zarate, chief of experimental therapies at the National Institute of Mental Health.
A small Stanford University study published in August suggested that ketamine may help relieve depression by activating the brain’s opioid receptors.
Janssen Pharmaceuticals and Allergan are among drug companies developing ketamine-like drugs for depression. Janssen leads the effort with its nasal spray esketamine. The company filed a new drug application in September.
Meanwhile, dozens of studies are underway seeking to answer some of the unknowns about ketamine including whether repeat IV treatments work better for depression and if there’s a way to zero in on which patients are most likely to benefit.
Until there are answers, Zarate of the mental health institute said ketamine should be a last-resort treatment for depression after other methods have failed.
Geuris “Jerry” Rivas, a native of New York, was diagnosed with severe obsessive-compulsive disorder when he was 15. Obsessions with organizing and reorganizing the belongings in his bedroom — posters, comic books, videos — took over most of his life.
Forced by germ obsessions to compulsively wash and rewash his hands, he started wearing gloves all day to both protect him from the germs and stop him from washing his hands raw. Now, at 36, OCD symptoms continue to cost him jobs and relationships. He’s managed to turn his organizational skills into a profession — he’s a home organizer and house cleaner — but still he struggles daily with his obsessions.
“It’s caused me a great deal of suffering,” Rivas says. “I’ve tried many, many medications. I’ve wasted so much of my life.”
In 2012, running out of answers, Rivas took part in the first clinical trial to test ketamine as a treatment for OCD. While ketamine is approved by the U.S. Food and Drug Administration as an anesthetic, it is also an illicit party drug known as “Special K,” with hallucinogenic effects and the potential for abuse. Over the past 10 years, dozens of small studies of ketamine’s ability to treat a variety of mood and anxiety disorders have reported remarkable results — including the sudden alleviation of treatment-resistant depression, bipolar disorder and post-traumatic stress disorder. And these effects lasted days, sometimes weeks, after the hallucinogenic effects of the drug wore off.
With a single infusion of the drug, Rivas experienced for two weeks what it was like to live without the compulsions and obsessions that had for years controlled his life.
“I felt like, for the first time, I was able to function like a regular person,” he says.
Pros and cons
Ketamine has brought hope to a psychiatric field desperate to find new treatments for severe OCD, a chronic condition marked by debilitating obsessions and repetitive behaviors. Current treatments, which include antidepressants such as Prozac, can take months to have any effect on the disease, if they work at all.
“Severe OCD takes such a toll on patients,” says Carolyn Rodriguez, MD, PhD, who as a researcher at Columbia University ran the OCD trial. Now an assistant professor of psychiatry and behavioral sciences at Stanford, she has continued to explore the pros and cons of using ketamine to treat OCD. “The constant, intrusive thoughts that something is contaminated, the checking and rechecking, the repetitive behaviors. It interferes with your life, your jobs, your relationships.”
Ketamine was developed in the 1960s and has been used for decades as an anesthetic during surgery. It remains a mystery just how the drug works in the brain, and there are safety concerns. There is evidence from people who take the drug routinely — in much higher doses — that chronic, high-frequency ketamine use may be associated with increased risk of bladder inflammation and cognitive impairment, Rodriguez says. And if taken regularly, it can lead to dependence.
But researchers like Rodriguez are intrigued about the drug’s potential to help them identify a whole new line of medicines for fast-acting treatment of mental health disorders.
“What most excites me about ketamine is that it works in a different way than traditional antidepressants,” Rodriguez says. “Using ketamine, we hope to understand the neurobiology that could lead to safe, fast-acting treatments. I feel that is part of my mission as a physician and researcher.”
‘Right out of a movie’
Rodriguez’s interest in ketamine as a treatment for OCD was sparked about a decade ago when she was starting out as a research scientist at Columbia. A small, placebo-controlled study published in 2006 by a mentor of hers, Carlos Zarate, MD, now chief of the section on neurobiology and treatment of mood disorders at the National Institute of Mental Health, had shown that ketamine induced dramatic improvement in treatment-resistant depression within two hours of infusion. It was a landmark study, drawing attention among the psychiatric community and launching a new field of research into the use of ketamine to treat various mood and anxiety disorders.
“What most excites me about ketamine is that it works in a different way than traditional antidepressants.”
Rodriguez, intent on searching for better, faster treatments for her patients like Rivas with OCD, took note. There was an emerging theory that ketamine affects the levels of the neurotransmitter glutamate in the brain and increasing evidence that glutamate plays a role in OCD symptoms, she says. Perhaps ketamine could help regulate OCD symptoms as well as depression.
In 2013, Rodriguez and colleagues published their results from that first clinical trial of ketamine in OCD patients. The trial randomized 15 patients with OCD to ketamine or placebo.
In those patients who were given ketamine, the effect was immediate. Patients reported dramatic decreases in their obsessive-compulsive symptoms midway through the 40-minute infusion, according to the study. The diminished symptoms lasted throughout the following week in half of the patients. Most striking were comments by the patients quoted in the study: “I tried to have OCD thoughts, but I couldn’t,” said one. Another said, “I feel as if the weight of OCD has been lifted.” A third said, “I don’t have any intrusive thoughts. … This is amazing, unbelievable. This is right out of a movie.” And while nearly all initially had dissociative effects like feelings of unreality, distortions of time or hallucinations, they were gone within two hours after the start of the infusion.
“Carolyn’s study was quite exciting,” Zarate says, adding that there were a number of similar, small but rigorous studies following his 2006 study that found fast-acting results using ketamine to treat bipolar disorder and post-traumatic stress disorder.
“We had no reason to believe that ketamine could wipe out any symptoms of these disorders within hours or days,” he says.
So how does it work?
Virtually all of the antidepressants used in the past 60 years work the same way: by raising levels of serotonin or one or two other neurotransmitters. Ketamine, however, doesn’t affect serotonin levels. Exactly what it does remains unclear.
“There’s a recognition that people like me and others are using the drug to treat patients now. There’s an incredible need for something.”
Since coming to Stanford in 2015, Rodriguez has been funded by the National Institute of Mental Health for a large clinical trial of ketamine’s effects on OCD. This five-year trial aims to follow 90 OCD patients for as long as six months after they’ve been given a dose of ketamine or an alternative drug. Rodriguez and her research team want to observe how ketamine changes participants’ brains, as well as test for side effects.
Ultimately, Rodriguez says, she hopes the study will lead to the discovery of other fast-acting drugs that work in the brain like ketamine but without its addictive potential.
Recent research in the field indicates that the glutamate hypothesis that triggered her pilot study might be further refined.
“Ketamine is a complicated drug that works on many different receptor sites,” she says. “Researchers have fixated on the NMDA receptor, one of the glutamate-type receptors, but it might not be the only receptor bringing benefit.”
In May 2016, researchers from NIMH and the University of Maryland — Zarate among them — published a study conducted in mice showing that a chemical byproduct, or metabolite, created as the body breaks down ketamine might hold the secret to its rapid antidepressant actions. This metabolite, hydroxynorketamine, reversed depressionlike symptoms in mice without triggering any of the anesthetic, dissociative or addictive side effects associated with ketamine, Zarate says.
“Ideally, we’d like to test hydroxynorketamine and possibly other drugs that act on glutamate pathways without ketamine-like side effects as possible alternatives to ketamine in OCD,” Rodriguez says.
Beyond the clubs
Meanwhile, dozens of commercial ketamine clinics have popped up across the country, making treatments available to patients who are searching for help to stop their suffering now. Medical insurance companies usually cover ketamine’s FDA-approved use as an anesthetic but won’t cover its use for other purposes, such as mental health disorders. So patients who have run out of treatment options are paying hundreds of dollars a dose for repeated ketamine infusions.
“The fact that these clinics exist is due to the desperation of patients,” says Rodriguez.
She and other researchers are calling for guidelines to protect patients and more research to learn how to use the drug safely.
“I think it’s a game changer, and it’s here to stay,” says David Feifel, MD, PhD, professor emeritus of psychiatry at UC-San Diego, who studies the effect of ketamine on clinical depression. Feifel began prescribing the drug for patients with treatment-resistant depression in 2010.
“I’ve found it to be very safe,” Feifel says, adding that the American Psychiatric Association this year issued safety guidelines on how to use ketamine clinically for treatment of depression.
“There’s a recognition that people like me and others are using the drug to treat patients now,” he says. “There’s an incredible need for something.”
The drug hasn’t worked for everyone he’s treated, Feifel says, but for many it’s been “life-changing.”
Rodriguez says she understands what motivates the clinicians to prescribe the drug now to patients in dire straits — those who are suicidal or who have tried every possible medication and therapeutic option and continue to suffer each day.
“I see it as a way to treat people whose OCD is very, very severe,” she says. “People who can’t come out of the house, who are suicidal, who have no other options.
“I just don’t like the idea of people being in pain,” Rodriguez adds. “I want to see science translated into treatments now.”
Meanwhile, researchers are learning more about the drug. Janssen Pharmaceutical is testing the efficacy of a version of ketamine, known as esketamine, as a therapy for treatment-resistant depression and for major depressive disorder with imminent risk for suicide. The FDA has fast-tracked both investigations. At Stanford, Alan Schatzberg, MD, a professor of psychiatry and behavioral sciences, along with other faculty including Rodriguez, is studying the mechanism of action for ketamine in treating depression.
Rodriguez is also interested in using ketamine to kick-start a type of cognitive behavioral therapy called exposure and response prevention, an evidence-based psychological treatment designed to help patients overcome OCD. The therapy involves teaching patients with OCD to face anxieties by refraining from ritualizing behaviors, then progressing to more challenging anxieties as they experience success.
Relaxation and other techniques also help patients tolerate their anxiety — for example, postponing the compulsion to wash their hands for at least 30 minutes, then extending that time period.
“My goal isn’t to have people taking ketamine for long periods of time,” Rodriguez says. But perhaps a short-term course of ketamine could provide its own kind of exposure and response prevention by allowing patients to experience that it is possible not to be controlled by their OCD, she says.
Rivas well remembers that infusion of ketamine he received during Rodriguez’s first clinical trial to test the drug. The rush made him feel “like Superman.”
“I felt like my body was bigger, that I was more muscular, that I could tackle anything,” he says. But that feeling only lasted the duration of the 40-minute infusion. His OCD symptoms disappeared immediately and were still gone for two weeks after.
“I was amazed that something like that would work and work so fast,” he says. His OCD symptoms today are still intrusive, but he manages to keep them under control by taking antidepressants and seeing a therapist. Still, each day when he comes home from work, he has to put gloves on before he enters his apartment building, and as soon as he enters his apartment, he must wash his hands.
“It’s a ritual now,” he says. “There has never been a time that I haven’t done that, except those two weeks after the ketamine.”
When he heard that certain private ketamine clinics are now offering the drug as treatment for OCD, he said he understands why patients take the risks and pay the high prices. As more research has become available, he’s begun considering it himself.
“I’ve been suffering through my OCD for so long, I’ve gotten to the point where I’d try anything,” he says.
USING KETAMINE TO TREAT SEVERE MENTAL ILLNESSA conversation with Stanford psychiatrist Carolyn Rodriguez, MD, PhD, about how she got interested in the use of ketamine to treat obsessive-compulsive disorder and how she is determined to find out why, in studies, the drug has provided relief from symptoms.
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