Subscribe to Biological Therapies in Psychiatry -  Choose your plan >
IN THIS ISSUE:
April 2010

Depression during Pregnancy
New guidelines aid clinicians in treating pregnant women with depression.

SSRIs versus an SNRI
A new study failed to find enhanced benefit from duloxetine (Cymbalta) compared with generic selective serotonin reuptake inhibitors in patients with depression.

Zopiclone and Morning-After Impairment
In a small trial of older adults, driving ability and cognitive performance were impaired the morning after subjects took a dose of zopiclone at bedtime.

In Brief
Antipsychotic Polypharmacy Does Not Increase Mortality Risk in Schizophrenia; Tarenflurbil Fails to Slow Cognitive Decline in Alzheimer’s Disease

Second-Generation Antipsychotics Cause Weight Gain and Adverse Metabolic Effects in Young Patients
Second-generation antipsychotics can be life-saving for youth with serious psychiatric illnesses, but they carry the risk for weight gain and possible long-term cardiovascular and metabolic problems.

In Brief

April 2010

As we discussed last December (BTP 2009;32:49-50), people with serious and chronic mental illness have a greater rate of mortality than the general population. A study by Tiihonen and others found that some antipsychotic medications increase excess mortality in patients with schizophrenia, whereas other antipsychotics decrease it. Baandrup and others investigated the effects of antipsychotic polypharmacy on the risk of death from natural causes in patients with schizophrenia (J Clin Psychiatry, in press). Using data from central Danish registers, they identified 27,633 patients, aged 18 to 53 years, who were diagnosed with schizophrenia or other mainly nonaffective psychoses between 1996 and 2005. From these cases, they found 193 cases of death from natural causes within a 2-year period and 1,937 age- and sex-matched controls. The number of concurrently used antipsychotic medications did not significantly increase the risk of natural death compared with antipsychotic monotherapy. The authors did find an association, however, between an increased risk of natural death and the concomitant use of antipsychotics and benzodiazepine derivatives with long elimination half-lives. They call for further research before conclusions are drawn regarding a causal role for benzodiazepines but point out the scarce evidence for any benefit of benzodiazepines in treating patients with schizophrenia.

The common etiology for Alzheimer's disease has been proposed to be excess accumulation of amyloid ß (Aß) peptides, as well as the accumulation of abnormally phosphorylated tau protein. Tarenflurbil alters γ-secretase activity to favor production of shorter, less neurotoxic forms of Aß peptides (Montine and Larson, JAMA 2009;302:2593-2594). Preclinical studies have shown that γ-secretase modulators can reduce amyloid levels and deposits in amyloid precursor protein transgenic mice. Green and coworkers recently evaluated tarenflurbil in patients with mild Alzheimer's disease in a randomized, double-blind trial at 133 sites in the United States (JAMA 2009;302:2557-2564). Subjects received tarenflurbil, 800 mg, or placebo twice daily for 18 months. Concomitant treatment with other medications was permitted. Of 1684 patients randomized, 1046 completed the trial. Forty percent of subjects from the tarenflurbil group and 33% from the placebo group dropped out. Tarenflurbil had no beneficial effect on the co-primary outcomes—difference versus placebo in change from baseline to month 18 in total score on the Alzheimer Disease Assessment Scale-Cognitive Subscale (80-point version) and the Alzheimer Disease Cooperative Studies-activities of daily living scale—using an intent-to-treat analysis. Subjects taking tarenflurbil had a small increase in frequency of dizziness, anemia, and infections. The authors note that their results remind us that interventions affecting amyloid have not yet been shown to alter the course of Alzheimer's disease.

Heather S. Hopkins