Med Check

Sibutramine (Meridia), a weight-loss drug approved for obesity treatment, was tested for efficacy to treat binge-eating disorder in a randomized, placebo-controlled, double-blind study published in the January American Journal of Psychiatry. After taking either sibutramine or placebo for 24 weeks, 152 patients in each group, all diagnosed with binge-eating disorder, were evaluated for frequency of binges, weight change, and other clinical indicators. The sibutramine group had a statistically significant reduction in the mean frequency of weekly binges (2.7) compared with the placebo group (2.0). The mean weight loss from baseline was also greater in the sibutramine group (4.8 kg) compared with the placebo group (0.8 kg). Adverse events more frequently reported by patients in the sibutramine group included headache, dry mouth, constipation, insomnia, and dizziness.

The study was sponsored by Knoll Pharmaceuticals, now a part of Abbott Laboratories.

“Efficacy of Sibutramine for the Treatment of Binge Eating Disorder: A Randomized Multicenter Placebo-Controlled Double-Blind Study” is posted at<ajp.psychiatryonline.org/cgi/content/full/165/1/51>. 


Osmotic-release oral system (OROS) methylphenidate did not improve overall depression symptoms compared with placebo when added to antidepressant treatment in 145 adult patients who had failed at least one monotherapy and no more than three. The primary endpoint, the Montgomery-Asberg Depression Rating Scale scores at week 5, did not differ significantly between patients taking adjunct methylphenidate and placebo.

The study was funded by Janssen-Ortho, Inc., a subsidiary of Johnson and Johnson, which makes OROS methylphenidate. It was published in the December 2007 Journal of Clinical Psychiatry.

An abstract of “Osmotic-Release Oral System Methylphenidate Augmentation of Antidepressant Monotherapy in Major Depressive Disorder: Results of a Double-Blind, Randomized, Placebo-Controlled Trial” is posted at<www.psychiatrist.com/abstracts/abstracts.asp?abstract=200801/010810.htm>. 


Zolpidem extended release (Ambien) was shown to be more effective than placebo in a double-blind study published in the January issue of Sleep. Adults suffering from chronic primary insomnia were randomly assigned to zolpidem 12.5 mg (n=669) or placebo (n=349) at least three nights a week for six months. Statistically significant differences were observed between the zolpidem and placebo groups. More patients in the zolpidem group reported improved sleep outcomes, including total sleep time, wake time after sleep onset, quality of sleep, and number of awakenings, compared with the placebo group. The zolpidem group also reported statistically significant improvement in morning sleepiness and ability to concentrate. The most common adverse events associated with zolpidem were headache, anxiety, and somnolence, but rebound effect within the first three nights of discontinuation was not observed with the drug. The study was funded by Sanofi-Aventis.

An abstract of “Long-Term Efficacy and Safety of Zolpidem Extended Release 12.5 mg, Administered 3 to 7 Nights Per Week for 24 Weeks, in Patients With Chronic Primary Insomnia: A 6-Month, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study” is posted at<www.journalsleep.org/viewabstract.aspx?citationid=3450>. 


The findings of a study posted on AJP in Advance on February 1 adds to the evidence supporting the use of D-cycloserine as an adjunct to enhance the effectiveness of behavior therapy in the treatment of obsessive-compulsive disorder (OCD). Twenty-three patients with OCD were randomly assigned to receive either 100 mg D-cycloserine (n=10) or placebo (n=13) one hour before each behavior therapy session. Therapy sessions were held twice a week for five weeks, for a total of 10 sessions. Both the subjects and the researchers were blinded to treatment assignment.

The reduction of OCD symptoms, measured by the Yale-Brown Obsessive Compulsive Scale, was nominally greater in the D-cycloserine-augmented group and reached statistical significance at the mid-treatment point. However, at the end of the study or at one-month follow-up, the reduction in OCD symptoms was not statistically significant.

Compared with placebo, the D-cycloserine group also saw a significant reduction in depressive symptoms on the Beck Depression Inventory II scale at the end of the treatment. No adverse events were reported. The study was conducted at and funded by Massachusetts General Hospital.

“Augmentation of Behavior Therapy With D-Cycloserine for Obsessive Compulsive Disorder” is posted at<http://ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2007.07050776v1>. 


Researchers discovered a neurochemical mechanism that may confirm the benefits of docosahexaenoic acid (DHA), a type of omega-3 fatty acid found in fish oil, in preventing or delaying late-onset Alzheimer's disease. DHA significantly increased the expression of a particular receptor, LR11, in rat and human neurons in vitro and in live rats fed dietary fish oil. In earlier research, certain genetic variations that reduce the LR11 receptor expression were linked to increased beta-amyloid production in the brain and in turn to the development of late-onset Alzheimer's disease. The authors suggested that DHA may be useful for early intervention and prevention of the disease.

The study was supported by the National Center for Complementary and Alternative Medicine and the National Institute on Aging and published in the December 25, 2007, Journal of Neuroscience.

An abstract of “Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein With Reduced Expression in Sporadic Alzheimer's Disease (AD): Relevance to AD Prevention” is posted at<www.jneurosci.org/cgi/content/abstract/27/52/14299>. 


Merck and Co. entered an agreement with Addex Pharmaceuticals in January to develop an investigative drug as a potential treatment for schizophrenia and other indications. The molecule, known as ADX63363, has been shown to modulate the metabotropic glutamate receptor (mGluR) type 5 and is in preclinical development. If the drug development proves fruitful, Addex could receive up to $702 million, the company announced. Glutamate receptors have been the subject of intense neuropsychiatric research in recent years and are believed to be an important pathway in the pathology of several psychiatric disorders including schizophrenia.


In December 2007, Schering-Plough released summary results of a clinical trial of its investigational drug asenapine in 448 schizophrenia subjects. The efficacy was measured by the Positive and Negative Syndrome Scale (PANSS) after six weeks of randomized, double-blind treatment with asenapine 5 mg or 10 mg twice daily, haloperidol 4 mg twice daily, or placebo. The change from baseline in PANSS total score was -21.4, -19.4, and -20.0 for those who took asenapine 5 mg, 10 mg, and haloperidol, respectively, and all scores were statistically significant compared with those of the placebo group (-14.6), according to the company's press release. A new drug application (NDA) for asenapine was filed with the FDA in 2007 (Psychiatric News, January 4).


Wyeth Pharmaceuticals announced results of its phase 3 clinical trials of desvenlafaxine succinate (Pristiq) in the treatment of major depressive disorder. The two randomized, double-blind, placebo-controlled trials enrolled a total of more than 900 patients with depression and tested two dosages, 50 mg/day and 100 mg/day. Compared with placebo, the groups receiving desvenlafaxine 50 mg/day saw a statistically significant reduction in their 17-item Hamilton Depression Rating Scale (HAM-D17) scores after eight weeks of treatment in both trials. The 100 mg/day dose was associated with a statistically significant greater reduction than placebo in HAM-D17 scores in one but not the other trial.

Desvenlafaxine is an active metabolite of venlafaxine (Effexor); both molecules are in the class of serotonin and norepinephrine reuptake inhibitors. The company has filed an NDA for desvenlafaxine succinate with the FDA and expects the agency's decision in the first quarter of this year, according to the press release.


The antitrust regulators of the European Commission (EC) raided several pharmaceutical companies in Europe in January to investigate allegations of illegal practices by conspiring to suppress competition from generic drugs.

Pfizer, AstraZeneca, GlaxoSmithKline, and Sanofi-Aventis all acknowledged that they are being investigated. The companies were suspected of colluding with each other to delay the generic drugs from entering the market and to prolong the patent exclusivity of brand-name drugs.

As more profitable, brand-name drugs have lost patent protection in recent years, large pharmaceutical companies have been using patent lawsuits to delay the marketing of generic products. The EC announced that it was conducting broad investigations into suspected illegal tactics used by drug companies, according to a report by Reuters.

The EC raid recalls a similar event in the U.S. in July 2006, when agents of the Federal Bureau of Investigation raided Bristol-Myers Squibb headquarters in New York as part of a criminal investigation into similar allegations. The company, along with Sanofi, was accused of trying to pay off a generic company to delay the launch of a generic version of their best-selling drug Plavix.


The FDA's Division of Drug Marketing, Advertising, and Communications (DDMAC) issued a warning letter in late 2007 against Wyeth regarding an advertisement of venlafaxine extended-release tablets (Effexor XR) printed in a professional journal. DDMAC considered the advertisement misleading as it used an open-label study to support “unsubstantiated superiority claims” and “minimizes the risks associated with the use of Effexor XR,” the letter states.

The warning letter is posted at<www.fda.gov/cder/warn/2007/Effexor_XR-wl.pdf>. 


The FDA has given tentative approval to a new formulation of valproic acid delayed-release capsules (Stavzor), owned by Noven Pharmaceuticals, according to the company. The capsules, which come in strengths of 125 mg, 250 mg, and 500 mg, are not equivalent to other valproic acid products on the market such as divalproex sodium (Depakote ER). Valproic acid is approved for treating epilepsy, bipolar disorder, and migraine.


Neurocrine Biosciences announced in December 2007 that it received an approvable letter from the FDA for its drug indiplon for the treatment of insomnia. However, the agency's letter requested further safety and efficacy data from additional clinical and nonclinical trials. According to the company's Web site, indiplon is a non-narcotic, non-benzodiazepine agent that specifically binds to the γ-aminobutyric acid (GABA)-A receptor.


AstraZeneca announced in January that it has submitted a supplemental NDA for quetiapine extended-release tablets (Seroquel XR) for the treatment of manic and depressive episodes in bipolar disorder. The immediate-release formulation has already been approved for the treatment of depressive and manic episodes of bipolar disorder in addition to schizophrenia. Once-daily quetiapine extended-release tablets currently carry only the indication for schizophrenia.


The ADHD drug lisdexamfetamine dimesylate (Vyvanse) has received FDA approval for new strengths of 20 mg, 40 mg, and 60 mg, according to manufacturer Shire. Currently the drug is available in 30 mg, 50 mg, and 70 mg capsules for once-daily administration. The new dosages will be available in the second quarter. ▪