Ketamine May Relieve Depression By Restoring Brain Cell Connections

The NPR (10/5, Hamilton) “Shots” blog reports that “scientists say they have figured out how an experimental drug called ketamine is able to relieve major depression in hours instead of weeks.” Ketamine is an FDA-approved anesthetic. It’s also a popular club drug that can produce out-of-body experiences and hallucinations. Not exactly what you’d want from a depression drug.  “It’s exciting,” says Ron Duman, a a psychiatarist and neurobiologist at Yale University. “The hope is that this new information about ketamine is really going to provide a whole array of new targets that can be developed that ultimately provide a much better way of treating depression.”  In stressed mice, a dose of ketamine was able to “rapidly increase  connections and also to rapidly reverse the deficits that are caused by stress,” Duman says.   Research is intended to produce drugs that will work like ketamine, but without the hallucinations.  Several of these alternative drugs are already being tried in people.

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Vilazodone Submitted to FDA for Approval.

The Boston Business Journal (3/23, Donnelly, http://tinyurl.com/vilazodone)  reported that “Clinical Data Inc. has filed an application with the U.S. Food and Drug Administration seeking approval for its drug target for the treatment of major depressive disorder.  Vilazodone is an anti-depressant that has two different mechanisms — it is both a selective-serotonin re-uptake inhibitor (SSRI) along the lines of other common depression treatments such as Prozac and Zoloft, while it also includes a so-called 5-HT1A receptor partial agonist, which is the mechanism in several other anti-depressant treatments on the market including buspirone.  The most common adverse reactions included diarrhea, nausea and insomnia.”

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Antidepressant Combinations May Double the Likelihood of Remission.

According to a study done by Blier et al published in the American Journal of Psychiatry (http://tinyurl.com/mirtazapine-combo) “the use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication”. Various classes of antidepressant medications generally induce remission of major depressive disorder in only about one-third of patients. In a previous study using  mirtazapine or paroxetine alone or in combination from treatment initiation, the rate of patients who remitted within a 6-week period was twice that of patients using either drug alone. In the current study “remission rates (defined as a HAM-D score of 7 or less) were 25% for fluoxetine, 52% for mirtazapine plus fluoxetine, 58% for mirtazapine plus venlafaxine, and 46% for mirtazapine plus bupropion”.  “The study results, which add to a growing body of evidence, suggest that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication”.

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Antidepressants May Work Immediately to Elevate Mood and Alleviate Depression

BBC News (10/26, Roberts) reports that, according to research (http://tinyurl.com/antidepressants-work-fast) published in the American Journal of Psychiatry, “antidepressants get to work immediately to lift mood,” even though “patients may not notice the effects until months into the therapy.” Researchers from the UK’s Oxford University “closely studied the reactions of 33 depressed patients and 31 healthy controls given either an antidepressant or a” placebo, finding that “depressed patients who took the active” medicine “showed positive improvements in three specific measures within three hours of taking them.” In an accompanying editorial psychiatrist Michael Thase, MD, characterized the study’s findings as “potentially ‘paradigm-changing,'” but called for further research.

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Researchers use brain wave measuring device to predict patient response to antidepressant.

MIT’s Technology Review (9/22, Kremen) reported that, according to a study published this month in the journal Psychiatry Research, researchers at the University of California-Los Angeles found that “brain waves measured using a simple device just one week into treatment can indicate whether a depressed patient should continue taking a medication or be switched to another.” For the study, the team “used a customized version of a quantitative electroencephalography (QEEG) system to study the brainwave patterns of 375 people suffering from major depression” in order “to predict which patients would respond to escitalopram.” The investigators used “an algorithm that considers various QEEG characteristics, called the antidepressant treatment response (ATR) index,” and “found that they could accurately predict whether the patient would respond to the escitalopram 74 percent of the time.”

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Groups issue guidelines for treatment of depression during pregnancy.

Following a Wall Street Journal article, the Los Angeles Times (9/18, Healy) reports that the American Psychiatric Association and the American College of Obstetricians and Gynecologists “have issued the first guidelines for the treatment of depression during pregnancy.” The groups say that “for women with serious, recurring depression or suicidal inclinations, the dangers of under-treatment may well outweigh the risks that antidepressants may pose to a developing fetus. At the same time, the guidelines stress that for many pregnant women suffering from depression, ‘talk therapy’ alone may be the best option, and should be routinely offered.”

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Imaging tests, electrophysiologic studies may help predict antidepressant efficacy.

The Los Angeles Times (9/16) “Booster Shots” blog reported that in a study appearing in the journal Psychiatry Research, researchers tested “noninvasive ways — such as imaging tests and electrophysiologic studies– to assess how the brain responds to” antidepressants. In “375 depressed people,” researchers “measured brain wave patterns before — and after — a week of Lexapro [escitalopram] use” to find “changes in brain activity that come well before a depressed person’s mood actually improves.” They “were able to predict medication effectiveness with 74 percent accuracy.”

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FDA considers adding antidepressant warning to tamoxifen label.

Bloomberg News (6/3, Rapaport) reports, “US regulators may warn patients taking tamoxifen, a breast cancer medicine…not to use certain types of antidepressants because they block the tumor-fighting drug’s effectiveness.” According to Karen Riley, a spokeswoman for the FDA, the agency is considering “‘adding new information to the tamoxifen label’ to advise women taking the cancer drug against using some antidepressants.” The move follows new evidence, presented a study May 30 at the meeting of the American Society of Clinical Oncology, that “tumors were more than twice as likely to return after two years in women taking the antidepressants while on the cancer drug, compared with those taking tamoxifen alone.” The drug works with “a liver enzyme called CYP2D6 to morph into an active tumor fighter,” but “many antidepressants use the same enzyme, sapping supplies.” Riley added that “the FDA may add details on CYP2D6 to the tamoxifen label.”

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Clinical Data says vilazodone reduced depression symptoms in trial.

The AP (6/3) reports that Clinical Data, Inc. said Tuesday “its depression drug vilazodone succeeded in a late stage clinical trial.” The company “said vilazodone significantly reduced the symptoms of major depression when compared to a sugar pill,” and “also reported positive trial results for vilazodone in September 2007.” Based on the “two studies, it plans to file for approval with Food and Drug Administration by the end of the year.” 
Dow Jones Newswires (6/3, Benoit) points out that the study showed “that the effects on sexual function from vilazodone were comparable to those on the placebo, which Clinical Data said is important given the tendency for antidepressants to inhibit sexual function.” In addition, “the study also showed high rates of some side-effects, including diarrhea and nausea.” It also “didn’t succeed in finding a biomarker — an important discovery analysts say may have given vilazodone an advantage in the overcrowded antidepressant market.” 
The medicine also was seen to reduce “depression on two rating scales among those who took it compared with a placebo, upholding earlier results,” Bloomberg News (6/3, Ziegler) adds. The Boston Business Journal (6/2) and the Boston Globe (6/3, Reidy) also covered the story.

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Researchers evaluate SSRIs against older antidepressants, each other.

Medscape (5/14, Anderson) reported that, according to a meta-analysis published Apr. 15 in the Cochrane Database of Systematic Reviews, “sertraline, one of the oldest selective serotonin-reuptake inhibitors (SSRIs), is superior to a number of other antidepressants in terms of efficacy and tolerability.” For the study, researchers from Italy’s University of Verona “searched several medical databases, including MEDLINE and EMBASE,” and “included 59 randomized controlled trials allocating a total of 10,000 patients with major depression to sertraline or another antidepressant agent.” The investigators found that “sertraline proved more effective than fluoxetine and more acceptable or tolerable than amitriptyline, imipramine, paroxetine…and mirtazapine.” Notably, the team “uncovered some differences favoring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion).” In a “second literature review, researchers searched medical databases for randomized controlled trials comparing escitalopram against any other antidepressant,” and found that “escitalopram was significantly more effective than citalopram…in achieving acute response and remission.”

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