Med Check

Seroquel was approved by the U.S. Food and Drug Administration (FDA) in October 20 for the “treatment of major depressive episodes associated with bipolar disorder. This is the agency's first approval of a drug to treat both the depressive and acute manic phases associated with the disorder.

The approval of Astrazeneca's formulation of quetiapine was based on results from two randomized, double-blind, placebo-controlled clinical trials involving 1,045 patients with bipolar I or bipolar II disorder. The eight-week trials examined efficacy and safety of both 300 mg a day and 600 mg a day of quetiapine compared with placebo. Efficacy was demonstrated with both doses; however, no additional benefit was seen at the higher dose; therefore, the recommended dose is 300 mg a day.

The most frequently observed adverse events associated with quetiapine were dry mouth, sedation, somnolence, dizziness, and constipation.

Quetiapine is also approved in the United States for treatment of schizophrenia and acute manic episodes associated with bipolar I disorder.

Aricept was approved by the FDA in October for “the treatment of dementia of the Alzheimer's type in patients with severe Alzheimer's disease.” The Eisai formulation of donepezil, co-marketed in the United States by Pfizer Inc., is already approved for the treatment of mild to moderate dementia of the Alzheimer's type.

The approval for the expanded indication was based on two randomized, double-blind, placebo-controlled trials involving more than 500 patients. One trial was completed in Sweden, the other in Japan. In these trials, patients taking donepezil showed significantly better performance than patients taking placebo on measures evaluating cognitive functions such as memory, language, orientation, and attention as well as overall level of function.

The most frequently observed adverse events noted with donepezil included nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and anorexia.

Risperdal was approved by the FDA October 6 for “the treatment of irritability associated with autistic disorder in children and adolescents (aged 5-16), including symptoms of aggression towards others, deliberate self-injury, tantrums, and quickly changing moods.” The approval is the first for any drug for the treatment of symptoms associated with an autistic spectrum disorder.

The approval of Janssen Pharmaceutica's formulation of risperidone is based on data from two eight-week, randomized, double-blind, placebo-controlled trials involving 156 patients aged 5 to 16 who met DSM-IV criteria for autistic disorder. Efficacy was determined using the Aberrant Behavior Checklist (ABC) and the Clinical Global Impression-Change scale, with the primary outcome being the change from baseline in the irritability subscale of the ABC. Patients taking risperidone showed statistically significant improvement compared with patients taking placebo.

The most frequently observed adverse events associated with risperidone in the trials were somnolence, increase in appetite, fatigue, upper respiratory infection, increase in saliva or dry mouth, extrapyramidal symptoms, and increase in weight.

Risperidone is also approved in the United States for treatment of acute manic or mixed episodes of bipolar I disorder and for treatment of schizophrenia.

The second-generation antipsychotics sold under the brand names Abilify, Geodon, Risperdal, Seroquel, and Zyprexa are the focus of an investigation by the California attorney General's Office. Subpoenas have been issued to the manufacturers of each drug requesting information regarding sales and marketing practices and side effects.

In filings with the Securities and Exchange Commission, the manufacturers disclosed the subpoenas to stockholders, noting that the investigation appears to surround “interactions between company representatives and state Medicaid officials regarding the state's formulary for Medicaid-reimbursed drugs.”

“Promotion of Paxil for use by children and adolescents while withholding negative information about the medication's safety and effectiveness” is the subject of a $63.8 million proposed settlement between Paxil maker GlaxoSmithKline and attorneys representing plaintiffs in a class-action lawsuit against the company.

As part of the settlement, GSK denies any wrongdoing alleged in the lawsuit's claims, including that the company artificially inflated the product's price and illegally promoted its use in youth without FDA approval. The suit also alleges the company hid clinical-trials data indicating an increased risk of suicidality in children and adolescents with major depression.

The settlement was unsealed October 27 by the Madison County, Ill., circuit court overseeing the class action; a hearing has been scheduled for March 9, 2007, to determine if the settlement is fair.

Ziprasidone may be associated with a significant improvement in cognition in patients with schizophrenia. A 12-week, open-label trial with 10 patients who met nonresponse criteria on their current antipsychotic medication were switched to ziprasidone. Comprehensive cognitive testing was done at baseline and 12 weeks.

Significant improvement was seen on three measures of episodic memory along with a trend toward improvement on tests involving processing speed and executive function.

The data, researchers said, “suggest that ziprasidone has cognitive benefits unrelated to an influence on other disease parameters.”

The study was funded by Pfizer Inc. Schizophr Res 2006: 87;181-184

Memantine may be associated with improvements in cognitive function and behavioral symptoms in children with pervasive developmental disorders (PDDs).

An eight-week, open-label trial with 14 children aged 3-12 looked at the effects of memantine on measures of expressive and receptive language, nonverbal IQ, and nonverbal memory. Their parents completed the Aberrant Behavior Checklist (ABC).

Significant improvement was seen in memory, but no significant changes were seen from baseline to week 8 on measures of expressive or receptive language or nonverbal IQ. Significant improvements were seen on the hyperactivity, lethargy, and irritability subscales of the ABC.

The data, researchers said, “suggests that memantine may be useful in the treatment of memory functioning and some behavioral symptoms in PDDs. The investigators did not see the same degree of change as endorsed by caretakers.”

The study was funded by the Autism Project of Illinois and grants from the National Institutes of Health.

J Child Adol Psychopharmacol 2006; 16:517-524

Both olanzapine and risperidone are associated with significant improvements in mania in patients with bipolar I disorder; however, significant differences are evident between the drugs' benefits and adverse effects.

A three-week, randomized, double-blind, parallel multicenter study involving 329 hospital inpatients with bipolar I, manic or mixed episode, compared olanzapine (n=165) with risperidone (n=164). Mean doses for olanzapine and risperidone were 14.7 mg a day and 3.9 mg a day, respectively.

No differences were found between the two drugs in remission or response rates. No significant differences were seen between treatments in scores on the Young Mania Rating Scale, Montgomery-Asberg Depression Rating Scale, Psychological General Well-Being Inventory, or Short Form Health Survey. However, patients taking olanzapine experienced significantly more improvement in scores on the 21-item Hamilton Depression Rating Scale and the Clinical Global Impressions-Bipolar Version severity of illness scale.

Significantly more patients taking olanzapine (78.7 percent) than risperidone (67 percent) completed the study. Olanzapine-treated patients experienced greater elevations in liver-function enzymes and increases in weight (2.5 kg over three weeks versus 1.6 kg for those taking risperidone), while patients taking risperidone were more likely to experience significant elevations in serum prolactin and experience sexual dysfunction.

The data, researchers said, “suggests similar efficacy for the two agents in the treatment of manic symptoms. The suggestion of a differential effect for olanzapine on depressive symptoms must be interpreted cautiously.”

J Clin Psychiatry 2006: 67:1747-1753

A new educational program by Pfizer inc. aims to help patients with bipolar disorder or schizophrenia reduce their potential treatment-related risks for heart disease.

The new program, “Simple Measures for Improving Wellness in Mental Health,” uses educational materials and community seminars to provide patients, families, and clinicians with information for simple steps such as improving food choices; increasing daily exercise; reducing smoking; keeping track of risk factors such as weight gain, cholesterol, and blood-sugar levels; improving patient-physician communication about risk factors; and understanding differences between treatment options.

Several chapters of the National Alliance on Mental Illness have partnered with Pfizer to conduct Simple Measures seminars, with more planned. The seminars provide patients, clinicians, and caregivers the opportunity to discuss with other patients and with medical and wellness experts what measures may work for them.

Program information and materials are posted at<www.simplemeasures.com>.

Aripiprazole: Abilify (Bristol-Myers Squibb)

Donepezil: Aricept (Eisai/Pfizer)

Memantine: Namenda (Forest)

Olanzapine: Zyprexa (Lilly)

Paroxetine: Paxil (GSK)

Quetiapine: Seroquel (AstraZeneca)

Risperidone: Risperdal (Janssen)

Ziprasidone: Geodon (Pfizer) ▪