Ketamine and Bipolar Disorder

This article was written by Anne Harding for Reuters Health. I found it  interesting because I’ve been using ketamine 10 mg once or twice per day as needed in a nasal spray form for both pain and mood regulation. My psychiatrist and his partner are writing an article about the effectiveness of ketamine with their patients and I’m looking forward to reading their article.

Ketamine lifts mood quickly in bipolar disorder

“An infusion of the anesthetic ketamine can lift mood within minutes in patients suffering from severe bipolar depression, according to a small study out this month in the Archives of General Psychiatry.

The 18 patients in the study had tried an average of seven different drugs for treating their bipolar illness, and were still severely depressed; 55 percent had failed electroconvulsive therapy (ECT), or shock treatment. But within 40 minutes of receiving a ketamine injection, their depressive symptoms improved; the effect persisted for at least three days.

Right now, medications available for treating either major depression or bipolar illness can take weeks, or even months, to work, notes Dr. Carlos A. Zarate Jr. of the National Institutes of Health in Bethesda, Maryland, one of the researchers on the study.

And as a person waits for their medications to kick in, he added, they will continue to have difficulty working and coping with social and family life; they may even be having thoughts of suicide. “We want to alleviate the suffering and get them back to their life,” he said.

Zarate and his colleagues had previously demonstrated that ketamine shots helped some patients with treatment-resistant unipolar depression, meaning they did not cycle through manic episodes. In the new study, they gave patients with bipolar illness ketamine or a placebo on two test days two weeks apart.

All of the patients were on lithium or valproate – two drugs commonly used for bipolar illness – but had not responded to treatment. Nearly all were unemployed, Zarate and his team note, and two-thirds were on psychiatric disability.

Compared to placebo, patients showed significant improvement in mood within 40 minutes of receiving the ketamine infusion, using a common depression rating scale. Symptom improvement peaked two days after the injection, but remained significantly greater than for placebo for three days.

Seventy-one percent of the patients responded to ketamine, meaning they had at least a 50 percent improvement in their depressive symptoms. Six percent responded to placebo.

Side effects included anxiety, “feeling woozy or loopy,” headache, and dissociative symptoms, meaning a temporary sense of disconnection from reality, although there were no serious adverse events. By developing more specifically targeted drugs, Zarate noted, it may be possible to treat patients effectively while avoiding these symptoms.

Ketamine appears to work by “resetting” the way nerve cells process glutamate, a brain chemical key for learning, memory, and other functions, according to Zarate. The problem in bipolar illness and depression, he explains, doesn’t appear to be that a person has too much or too little glutamate; instead, it’s likely that the way their neurons release and take up the chemical is out of whack.

First introduced in 1962, ketamine is used legally in both human and veterinary medicine as an anesthetic. It’s also a drug of abuse, at much higher doses than those used in Zarate’s research; while patients in the current study received about 50 milligrams during a 40-minute period, a dose too low to induce anesthesia, recreational users of ketamine, known as “Special K,” may take hundreds of milligrams per week.

In 1999, US regulators classified ketamine as a Schedule III controlled substance, meaning it has the potential for abuse but is also useful medically.

Ketamine could improve treatment of bipolar illness and depression in a variety of ways, Zarate said; for example, as a means to jump-start standard drug treatment, or as an anesthetic before ECT. “It’s opened the floodgate of many different directions of research, and all of them are quite encouraging,” said Zarate, who along with a co-author has filed for a patent on the use of ketamine in depression. Those rights would be assigned to his employer, the National Institutes of Health.

Efforts are already underway in Europe to develop guidelines for how ketamine should be used and prescribed to treat bipolar illness and depression, the researcher said.

In the US, research is continuing on the drug, he added, and some physicians are likely trying the drug in their patients with bipolar illness or depression who aren’t helped by standard treatments. But, according to Zarate, more research is needed on how to use the drug in the safest and most effective way.

SOURCE: link.reuters.com/wek23n Archives of General Psychiatry, August 2010.”

Research Video on Bipolar Disorder Drugs

Good video about research on bipolar disorder treatment drugs and their effect on biochemistry.

Interpersonal and Social Rhythm Therapy

In several clinical trials, Interpersonal and Social Rhythm Therapy (IPSRT) in conjunction with taking prescribed medications has been shown to significantly increase the time between episodes of both mania and depression for individuals with bipolar I disorder (Frank et al., 2005).  IPSRT can be used both as an acute treatment for individuals currently in the midst of a depressive or manic episode or as a preventative treatment for individuals currently between episodes and seeking to remain symptom free for as long as possible. 

IPSRT was developed by Ellen Frank Ph.D. from the University of Pittsburgh. IPSRT is based on the observation that disruptions of circadian rhythms and sleep deprivation can stimulate or aggravate bipolar disorder symptoms. It combines behavioral psychology techniques like self-monitoring and self-management, with interpersonal principles, to help people with bipolar disorder maintain systematic routines for sleeping, eating, and other daily activities. 

It is important to stabilize circadian and social rhythms because they are often out of sync in people with bipolar disorder. Therapists who practice IPSRT will work with their clients to help them observe and then regulate sleep-wake cycles, daily routines, and social relationships. Limiting disruptions to these social and bodily “rhythms” can help minimize bipolar episodes in many people.

In an initial therapy session, the client may discuss the times she goes to sleep and wakes, time of day she has meals, what times she typically has her interactions with other people, and whether those interactions are positive, negative, stress producing, stimulating, boring, or emotionally upsetting. I keep a daily journal. I record moods, food, important interactions, exercise, etc. I didn’t realize that I was doing IPSRT.

Monitoring social rhythms can help you identify the  habits and patterns that may be aggravating the disorder. Sleep disruptions are often one of the primary triggers for manic episodes. Highly stimulating events or stressful social interactions during the day can also worsen both mania and depression. I found that I spontaneously eliminated certain people and activities from my life as I began to recover from my 2009 manic episode. Eliminating those stimuli allowed my body and mind to start calming down so that I could return to my pre-manic state. I observed that if a triggering stimuli appeared, I could actually feel the manic energy well up in me, and then I’d have difficulty sleeping for several nights afterwards. Eliminating the stimuli that is contributing to or triggering an episode is essential for recovery.

Treating Bipolar Disorder: A Clinician’s Guide to Interpersonal and Social Rhythm Therapy. Ellen Frank. New York: Guilford Press (www.guilford.com). 2005.

Did AstraZeneca Suppress Seroquel Drug Test Data?

 BBC article excerpts

Seroquel brings in almost 10% of AstraZeneca’s revenues. The marketing team being sued over the drug’s alleged side effects tried to suppress key data, an ex-employee has claimed. Seroquel’s former UK medical adviser told the BBC he was pressured to approve promotional material which said weight gain was not an issue.

Thousands of patients are suing AstraZeneca in US courts, claiming the anti-psychotic drug Seroquel caused weight gain and diabetes. The patients allege Seroquel, its second biggest selling drug worth $4.5bn a year, was marketed without adequate warning about possible side effects such as massive weight gain and the development of diabetes. However, this is denied by the company.

Dr John Blenkinsopp, the company’s former UK medical manager, claimed he was pressurised by the company’s marketing arm to approve claims about the drug which he felt did not reflect the medical evidence.

“The clinical studies at the time of the launch of Seroquel showed patients developed significant weight gain, significant both statistically and clinically,” he told the BBC’s File on 4. “They [the marketing team] came at me with a number of potential claims all of which were trying to intimate that Seroquel was not associated with weight gain – the data pointed in the opposite direction,” added Dr Blenkinsopp who was speaking publicly for the first time since he left the company in 2000.

To read the entire article click on: AstraZeneca ‘suppressed’ drug test data