December 2007

High Doses of Venlafaxine
Higher doses of venlafaxine (Effexor and others) likely increase the chance of antidepressant response, but also increase the risk of side effects.

SSRIs and Bleeding Risk in Patients with Hepatitis C
The risk of selective serotonin reuptake inhibitors causing bleeding in patients with hepatitis C is modest.

Bupropion versus SSRIs for Anxiety in MDD
According to Papakostas and colleagues, bupropion (Wellbutrin and others) appears to work as well as selective serotonin reuptake inhibitors to treat anxiety in patients with major depressive disorder.

Torsades de Pointes with Haloperidol
Intravenous administration of haloperidol (Haldol and others), especially at high doses, can cause QT prolongation and torsades de pointes.

In Brief
Ziprasidone for borderline personality disorder: A negative trial; Adjunctive medications for weight loss in patients with schizophrenia or bipolar disorder

High-Dose Ziprasidone
Patients with treatment-resistant psychosis may benefit from higher-than-recommended doses of ziprasidone (Geodon).

Baby Steps
Our clinical knowledge in psychiatry has increased over the past year, but scientific understanding and intervention technology still leaves much to be desired.

Index, Volume 30, 2007

In Brief

December 2007

Olanzapine (Zyprexa) and aripiprazole (Abilify) have both been proven efficacious in the treatment of patients with borderline personality disorder in double-blind, placebo-controlled trials. An open-label trial and a naturalistic study suggested that another atypical antipsychotic, ziprasidone (Geodon), also might be efficacious in treating patients with this condition. Pascual and colleagues conducted a double-blind, placebo-controlled, randomized study of ziprasidone (mean daily dose, 84.1 mg/day) in 60 patients with borderline personality disorder (J Clin Psychiatry, in press). After 12 weeks, there were no significant differences between ziprasidone and placebo on the Clinical Global Impressions scale for use in borderline personality disorder patients (CGI-BPD) or between groups in depressive, anxiety, psychotic, or impulsive symptoms. The medication was well tolerated and there were no serious adverse events reported. However, there were high dropout rates in both groups: 56.7% in the ziprasidone group and 46.7% in the placebo group. The majority of ziprasidone-treated patients who dropped out did so in the first 2 weeks of the study, which the authors suggest might explain their negative results. They also note that they used lower doses than in previous trials and call for further research.

Patients with bipolar disorder or schizophrenia have high rates of overweight and obesity. As we noted last month, olanzapine (Zyprexa) and other antipsychotics can contribute to weight gain (BTP 2007;30:45-46). The same problem can occur with medications used to treat bipolar disorder. Two recent reports looked at using adjunctive medication to induce weight loss in patients with these disorders. P. W. Wang and coauthors added open-label zonisamide (Zonegran) to current medication regimens in 25 euthymic overweight bipolar patients (J Psychiatr Res, in press). Patients showed a slight weight loss of 0.25 kg/week over 26 weeks, but 72% of the patients dropped out of the study—44% for emergent mood symptoms, 20% for adverse physical events, and 8% due to patient choice. Levy and colleagues had more success adding topiramate (Topamax) to antipsychotic treatment in 10 overweight patients with schizophrenia (Can J Clin Pharmacol 2007;14:e234-e239). After 2 months, there was a mean decrease in body mass index (BMI). For patients who took topiramate for 6 months or longer, the difference in BMI was even greater. Both of these studies were small and further research will be needed to confirm the results, but topiramate looks to be a more promising weight-loss medication than zonisamide.

Heather S. Hopkins