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New Drug Combo Shows Promise for Treatment of Depression and Addiction
The combination of naltrexone and ketamine can help treat both symptoms of addiction and depression, a preliminary study by Yale University researchers suggests.
Substance abuse and depression are common in many patients, and efforts to treat both conditions simultaneously have had limited success. One recent study suggested that the antidepressant effects of ketamine might blunted by administration of naltrexone, used to limit cravings of those addicted to opioid drugs and alcohol.
A preliminary study of five patients suffering from both depression and substance abuse disorders suggest that isn’t the case. The study was published Jan. 9 in the journal JAMA Psychiatry.
The results “raise the possibility that for people who have depression complicated by substance abuse disorders, the combination of ketamine and naltrexone may be a strategy to explore in the effort to optimally treat both conditions,” said senior author John Krystal, Yale’s Robert L. McNeil Jr. Professor of Translational Research; professor of psychiatry, neuroscience, and psychology; and chair of the Department of Psychiatry.
Krystal and lead author Gihyun Yoon, assistant professor of psychiatry, treated the five patients suffering from depression and alcohol use disorder with a long-lasting form of naltrexone and then administered ketamine. Four of the five responded to the first ketamine dose and all five found relief from depression after multiple doses.
The study also challenges the idea that ketamine might produce antidepressant effects by stimulating opiate receptors.
Krystal cautioned that larger studies are needed to confirm beneficial effects of the combination treatment.
Krystal and Yoon have provisional patents on the use of ketamine and naltrexone to treat comorbid depression and substance abuse.
The study was primarily funded by the U.S. Department of Veterans Affairs.
Publication: Gihyun Yoon, et al., “Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder,” JAMA Psychiatry, 2019; doi:10.1001/jamapsychiatry.2018.3990
At NOVA Health Recovery, we do use Ketamine and other combinations to treat Alcoholism and Opioid and Pain pill addiction using Ketamine Treatment. Dr. Sendi is Board Certified in Addiction Medicine. Call 703-844-0184 Today. Fairfax, Va 22304.
A one-off dose of the drug could help alcohol addicts reduce their intake by ‘erasing’ drink-related memories, say psychologists testing treatment. There is a growing body of research to support the idea that ketamine, a horse tranquiliser, can be used to disrupt harmful patterns of behaviour
Scientists believe that a radical treatment involving the tranquilliser ketamine could help overcome alcohol addiction by “erasing” drink-related memories.
Psychologists based at University College London are testing whether a one-off dose of the drug could help hazardous drinkers who are trying to reduce their alcohol intake. Alcohol addiction is notoriously difficult to treat, and there are few effective therapies available.
Using a recreational drug to treat addiction may sound counterintuitive, but the researchers say there is a growing body of research suggesting that ketamine can be used to disrupt harmful patterns of behaviour.
Ravi Das, one of the lead researchers, said: “There is evidence that it could be useful as a treatment for alcoholism.”
Crucially, ketamine can disrupt the formation of memories, and scientists believe that this property could be harnessed to over-write the memories that drive addiction and harmful patterns of behaviour.
“Memories that you form can be hijacked by drugs in some people,” said Das. “If you were an alcoholic you might have a strong memory of being in a certain place and wanting to drink. Those memories get continuously triggered by things in the environment that you can’t avoid.”Advertisement
For instance, seeing a glass of beer, hearing the clinking of glasses or even arriving home from work may trigger memories of the rewarding sensation of taking a drink – and might prompt a person to follow this urge.
“The main problem is the really high relapse rate after treatment,” said Das. “People can successfully quit using over the short term while they’re being monitored in the hospital … but when they return home they’re exposed to those environmental triggers again.”
There is increasing evidence, however, that memories are less stable than once assumed and may be open to manipulation.
Each time our brain accesses a memory, the neural connections that encode it are temporarily destabilised, meaning that our recollection can be slightly altered before it goes back into storage. This is one reason why, in everyday life, people can recall wildly different versions of the same events.
In the clinic, scientists believe this short period of instability, represents a window of opportunity. Ketamine blocks a brain receptor called NMDA, which is required for the formation of memories. So the logic is that giving someone the drug just as a memory has been destabilised could help weaken the memory, or even erase it.
A similar approach with a different drug was shown to eradicate people’s phobia of spiders. And research in rats that were made to be addicted to cocaine showed that the memories underpinning their addiction could be completely wiped out using a similar strategy (although this involved injecting a chemical into the brain).
In the UCL trial, the scientists will intentionally trigger alcohol-related memories by placing a glass of beer in front of the participants, who are all heavy drinkers. They will then disrupt the memory, by surprising the participant (the team is not disclosing the exact details as this could bias the results).
Participants will then be given either a ketamine infusion, with a concentration equivalent to a high recreational dose, or a placebo. The team will follow up the people for a year and monitor whether their drinking has changed and by how much.
In total the scientists are aiming to include 90 people in the trial and more than 50 have already taken part. It involves people who drink harmful quantities of alcohol, but excludes anyone who meets the clinical criteria for alcoholism. The participants were drinking at least 40 units a week for men (equivalent to four bottles of strong wine) and 28 units for women, and drinking on at least four days. The UK needs common sense about ketamine
Nikki, 31, who works as a consultant in London said she decided to take part in the study when she had some time off between jobs and realised she was drinking more than she wanted to. “It’s just in the culture, that’s what all my friends are like. Everyone drinks to excess,” she said.
She described the experience of being given the ketamine as “overwhelming and intense”, but not unpleasant. “My body felt like it was melting away,” she said. “It was quite psychedelic, I felt untethered from my body.”
In the week after the session, she said, she felt in an “incredibly positive mood” and that since taking part she has been more conscious about deciding whether to have a drink, although said this could also be linked to starting a new job and taking up meditation. “In the past, there were occasions where I would be drinking and I’d be on autopilot ‘Let’s get another drink’,” she said.
If the trial yields promising results, the team hope that the approach could form the basis for therapy sessions targeted at alcoholics and people who are drinking unhealthily. However, they acknowledge that there may be resistance to the use of a recreational drug to treat people with addiction.
“There’s just the general social attitude that everything that’s illegal is terrible. There will obviously be that kind of narrow-sighted pushback,” said Das. “But if it’s safe and effective enough it should be recommended.”
Andrew Misell, a spokesman for Alcohol Concern, said: “The researchers have quite rightly highlighted what a lot of people in recovery from alcohol problems know from experience, namely that cues or triggers like the smell of beer can cause a relapse even after long periods of abstinence. Any work looking at how people can overcome these pitfalls is going to be useful.”
However, he added, no drug-based therapy is risk-free “and that certainly includes ketamine”.
Professor Michael Saladin, of the Medical University of South Carolina, is looking at similar approaches to help people quit smoking. “There is a vast animal research literature that suggests memories can be manipulated following reactivation,” he said. “I am convinced that there is sufficient evidence to believe that memory reconsolidation can be harnessed for clinical purposes.”
January 2018 has come to an end and with it the month that people increasingly use to abstain from alcohol. It is still unknown whether Dry January has a lasting effect on drinking behaviours, and people with an alcohol dependency problem should always seek support from their GP before going through detox. Nonetheless, Dry January undoubtedly drives a critical conversation about alcohol use and provides an opportunity for us to reconsider our relationship with alcohol (one of the main goals of the charity Alcohol Concern, who support the challenge).
While overall alcohol consumption in the UK is falling, alcohol abuse still represents the fifth biggest risk factor for illness, death and disability across all ages. With current treatments often failing to prevent relapse in the long term, researchers are investigating the possibility of using ketamine combined with psychological therapy to help people stay dry, and not just for January. Despite its often cited use as a recreational drug and “horse-tranquilizer” ketamine is also the most widely used anaesthetic in humans. Administered appropriately in a controlled and safe medical environment, ketamine may also have benefits in the treatment of drug problems.
Evidence for this originally came from a research group in Russia in the 1980s. In this study, patients who had alcohol problems were given three weekly ketamine treatments in conjunction with psychological therapy. After one year, 66% of patients who underwent this treatment regime were abstinent, in comparison to 24% of patients who received treatment as usual, without any ketamine. This abstinence rate is much greater than those documented with any other relapse prevention method.
Inspired by the promising results seen in Russia, we are now conducting the KARE trial (Ketamine for reduction of Alcoholic Relapse) at the University of Exeter and University College London. In this trial participants who have made the decision to abstain are administered ketamine once a week for three weeks. Participants also receive seven sessions of cognitive behavioural therapy to aid their quit attempt and are followed up for six months. Unlike the earlier study, this trial is placebo controlled, thus participants have an equal chance of receiving either ketamine or a matched placebo as well as either cognitive behavioural therapy or alcohol education as a placebo for therapy. It is also double-blind, meaning neither the participant nor the researcher know whether the active treatment or a placebo treatment are administered. This controls for placebo effects and bias due to expectancies of the researcher – putting the original findings to the test with a more rigorous research design.
Why might ketamine help people stay sober? Recent studies have demonstrated that ketamine has rapid and powerful anti-depressant properties, while people with alcohol problems often also experience symptoms of depression. The direction of the relationship between alcohol problems and depression is not clear, but depressive symptoms are thought to be a common trigger for relapse. Treating people who have alcohol problems with ketamine, therefore, could help them to remain abstinent for longer by lifting their mood.
Furthermore, laboratory research has demonstrated that ketamine promotes the growth of new neurons and connections in the brain. These processes are essential to learning and memory, and are suggested to be impaired in both depression and problematic alcohol use. Thus ketamine might make people more receptive to new information and able to plan effectively for the future, which in turn may enhance the effect of psychological therapy.
We do not yet know how effective the ketamine treatment will be. However, well-designed research studies, such as the KARE trial, could be critical in helping people achieve their abstinence goals.
A super-strength drug which users have described as making them think they’re dead is being sold as ketamine in Britain, experts have warned. The drug, 2-FDCK, or 2-Fluorodeschloroketamine, is similar to ketamine, but much stronger – and the effects can last two to three times as long. On trip-report site Erowid, one user said, ‘My room looked like a cartoon. I thought I was dead and I was afraid about this, but then I understood this new way of existing wasn’t terrible.’ Be careful out there (Getty) The chemical was spotted by drug-testing organisation The Loop in a club in Durham – which found ‘multiple samples’. The drug is a ‘new psychoactive substance’ (NPS), a chemical derivative similar to those sold as legal highs – and often made abroad in illicit labs and bought online by dealers. First picture of man charged with stabbing dad to death on Surrey train Such substances can be much stronger, and more dangerous, than the drugs they are based on, experts warn. The Loop said that it found ‘2-FDCK (2-fluorodeschloroketamine) sold as ketamine. The new chemical is much stronger than ketamine (Getty) The organisation said, ‘Tested by The Loop in Durham, UK. ‘About 1.5x more potent than ketamine with 2-3x longer duration.’
As I have previously reported, off-label use of ketamine for treatment-resistant depression has resulted in numerous anecdotal reports regarding its unique mechanism of action and overwhelming success in symptom reduction among treatment-resistant and suicidal patients.
This is an important finding because approximately one-third of patients with major depressive disorder (MDD) do not respond to currently available antidepressants. As a result, The American Psychiatric Association (APA, 2016) had issued guidelines for psychiatrists who wish to use ketamine for this purpose. At the time, a slow intravenous infusion was the primary delivery system used to attain the reported results. There are of course numerous challenges and costs associated with this delivery system, including the use of a clinical facility with available advanced life support systems in place.
What Is Ketamine?
Ketamine was developed and FDA approved more than 50 years ago as a fast-acting anesthetic with an impressive safety profile. It is still used today in anesthesiology on both pediatric and adult patients and animals. Ketamine in higher doses also has unique dissociative properties, which explains its popularity as a club drug known as “Special K” in the U.S. It is currently a highly abused club drug in southern Asia today.
Intranasal Ketamine Clinical Trial
In this well-designed original research conducted by Daly and colleagues, a phase 2, double-blind, doubly randomized, placebo-controlled study was employed to assess the efficacy, safety and dose-response of intranasal esketamine hydrochloride (ketamine) in patients with treatment-resistant depression (TRD). The primary positive endpoint was a statistically significant change from baseline to day eight during each study period, measured by the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS).
This study consisted of four phases:
Double-blind treatment (days 1-15), composed of two 1-week periods
Optional open-label treatment (days 15-74)
Post-treatment follow-up at 8 weeks
The results are impressive. Change in MADRS total score in all three esketamine groups was superior to placebo (esketamine 28 mg: −4.2 (2.09), P = .02; 56 mg: −6.3 (2.07), P = .001; 84 mg: −9.0 (2.13), P < .001), with a significant ascending dose-response relationship (P < .001). Even more impressive is the continuous reduction of depressive symptoms despite reduced dosing frequency during the open-label phase.
Why Does This Matter?
First, the mortality rate for untreated and undertreated depression is between 15 and 20%. Moreover, depression and suicidality are increasing in the U.S., most notably among children and adolescents. Ketamine is thought to inhibit the N-Methyl-D-Aspartame (NMDA) system, which is unrelated to our 50-year-old catecholamine hypothesis, suggesting that the inhibition of NDMA is a viable, and perhaps primary, target for future intervention. In addition, there is growing anecdotal data suggesting that ketamine may also be a viable treatment for pain and perhaps even addictive disease.
Second, the results of this important study show that esketamine has a significant effect on symptom reduction among patients with TRD (Montgomery- Asberg Depression Rating Scale) after only one week of twice-weekly administration, which is substantially faster than the SSRIs or SSNRIs. It is also of interest that esketamine is well tolerated with few adverse effects, evidenced by the fact that a mere 5% of participants discontinued treatment during the double-blind phase. In addition, the use of an intranasal delivery system allows lower dosage compared to oral administration by avoiding first-pass hepatic metabolism.
Third, because of its low molecular weight (238 Daltons), esketamine is a good candidate for intranasal delivery because lower molecular weight improves nasal mucosa absorption. This route will get the dose to the brain rapidly, and for reasons that remain unclear, the therapeutic effect remains when using a twice-per-week dosing system.
All this is to say that compared to currently available oral antidepressant medications, which have a poor adherence rate, esketamine should vastly improve treatment adherence. Combined with few reported adverse effects, more people will get well. This is good day to be a neuroscientist.
Reference: Ella J. Daly, MD; Jaskaran B. Singh, MD; Maggie Fedgchin, PharmD; Kimberly Cooper, MS; Pilar Lim, PhD; Richard C. Shelton, MD; Michael E. Thase, MD; Andrew Winokur, MD, PhD; Luc Van Nueten, MD; Husseini Manji, MD, FRCPC; Wayne C. Drevets, MD Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression. A Randomized Clinical Trial. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.3739. Published online December 27, 2017.
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At NOVA Health recovery [703-844-0184 | Fairfax, Va 22306 ] we offer our patients cutting-edge treatment options for their depression, and one of our main stars is IV (intravenous) ketamine. But why does it have to be IV? “I don’t like needles, why can’t I just take this as a pill or as that nasal spray everyone is talking about?” you may be thinking. IV is the best route for your brain to receive ketamine because of something called bioavailability. In addition, it is also more effective, more precise, and safer for you.
What is bioavailability? It is the amount of medication that your body and brain is actually able to use, which is sometimes different than the amount of medication that your body receives. When you take any medication, parts of the active ingredients in them don’t go to your bloodstream; they get digested, altered into an unusable form, metabolized and excreted into your body. This is particularly prevalent in oral and intranasal medications. In fact, receiving a medication intravenously is the only way to have 100% bioavailability. Let’s take a look at the different bioavailability percentages based on what route you receive ketamine:
When we give ketamine intravenously, we know exactly where your entire dose is going: straight to your brain. The same cannot be said for other forms of ketamine. Intranasal ketamine has to bypass several layers of tissue before it can reach your brain, and too many things can happen that could cause you to lose some or most of your dose: sneezing, dripping, running down the back of your throat, etc. The same can be said for an oral pill and an intramuscular injection; these routes are just too unpredictable, and when it comes to treating your depression, we don’t want the results to be unpredictable.
When you receive IV ketamine in our office setting, it is given slowly over one hour. By doing this, we are able to monitor you closely, and if you experience any unpleasant side effects and want to stop the infusion, we are able to do that. By contrast, a dose of ketamine via intranasal spray would be done at home with no physician or nursing supervision, so side effects cannot be immediately addressed if they arise. The same is true for intramuscular or oral dosing – after you take the pill, or receive a shot of ketamine into your muscle, there is no way to stop the absorption of the medication into your bloodstream as the full dose is administered within seconds.
IV ketamine is by far the safest and most effective approach in using ketamine to treat depression. You are in a comfortable setting with healthcare providers with you the whole time, the potential for side effects is low, and you are certain that the dose you receive is the dose that is going to your brain, maximizing the benefits of this cutting-edge treatment.
However, we do offer the other routes of administration and take – home prescriptions for Ketamine therapies for those who are in our program. Contact us today at 703-844-0184 to get started on your treatment.
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.
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
BackgroundKetamine has been demonstrated to improve depressive symptoms.
AimsEvaluation of efficacy, safety and feasibility of repeated oral ketamine for out-patients with treatment-resistant depression (TRD).
MethodIn a randomised, double-blind, placebo-controlled, proof-of-concept trial, 41 participants received either 1 mg/kg oral ketamine or placebo thrice weekly for 21 days (ClinicalTrials.gov Identifier: NCT02037503). Evaluation was performed at baseline, 40 and 240 min post administration and on days 3, 7, 14 and 21. The main outcome measure was change in Montgomery–Åsberg Depression Rating Scale (MADRS).
ResultsTwenty-two participants were randomised to the ketamine group, and 19 to the control, with 82.5% (n = 33) completing the study. In the ketamine group, a decrease in depressive symptoms was evident at all time points, whereas in the control group a decrease was evident only 40 min post administration. The reduction in MADRS score on day 21 was 12.75 in the ketamine group versus 2.49 points with placebo (P < 0.001). Six participants in the ketamine group (27.3%) achieved remission compared with none of the controls (P < 0.05). The number needed to treat for remission was 3.7. Side-effects were mild and transient.
ConclusionsRepeated oral ketamine produced rapid and persistent amelioration of depressive symptoms in out-patients with TRD, and was well tolerated. These results suggest that add-on oral ketamine may hold significant promise in the care of patients suffering from TRD in the community.
Repeated oral ketamine produced rapid and persistent improvement of depressive symptoms in a small sample of outpatients with treatment-resistant depression who continued their usual treatment, according to a proof-of-concept study published in The British Journal of Psychiatry.
“Intravenous ketamine … has been demonstrated to act as a novel antidepressant, with an extended effect following repeated infusions while maintaining a good safety profile,” Yoav Domany, MD, from Tel Aviv Sourasky Medical Center and Sackler School of Medicine, and postdoctoral research fellow, department of psychiatry and behavioral neuroscience, University of Cincinnati, and colleagues wrote. “However, intravenous administration presents major obstacles to clinical applicability, especially in community setting.”
Though previous study has examined IV and intranasal ketamine for treatment-resistant depression, research on oral ketamine is lacking. Therefore, the investigators conducted a randomized, placebo-controlled, proof-of-concept trial to determine the efficacy, safety and feasibility of add-on repeated oral ketamine for outpatients with treatment-resistant depression.
The researchers randomly allocated 41 participants to receive either 1 mg/kg oral ketamine or placebo three times a week for 21 days. All participants were instructed to continue taking their usual prescribed care. Patients were assessed at baseline, 40 minutes and 240 minutes after administration and on days 3, 7, 14 and 21 to measure change in Montgomery–Åsberg Depression Rating Scale (MADRS) scores.
Of 22 participants who received treatment with ketamine and 19 who received placebo (control group), 33 patients completed the study. Among those receiving ketamine, Domany and colleagues observed a reduction in depressive symptoms between baseline and all other time points (P < .005), including day 21. In the control group, there was also a decrease in symptoms, but only at 40 minutes after initial administration (P < .05).
At the endpoint (day 21), the reduction in MADRS score was 12.75 among those receiving ketamine compared with 2.49 points among those receiving placebo (P < .001). The researchers reported that 27.3% of the ketamine group (n = 6) achieved remission as opposed to none in the control group (P < .05) at day 21.
Adverse effects were mild and transient, according to the safety analysis. Common adverse effects included increased systolic blood pressure, euphoria, dizziness and drowsiness after initial administration, all of which resolved within 1 hour. Follow-up safety evaluation at day 28 showed a maintained effect on MADRS scores in the ketamine group.
“Our results, although promising, cannot yet be applied to clinical practice without larger, randomized studies,” Domany and colleagues wrote. “Such studies are needed to address questions such as optimal dosing regimens, patient selection and treatment duration to properly assess the safety of long-term ketamine usage, the risk of misuse and the restricted means appropriate for at-home prescription.”
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.