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The article presents a study which highlighted the long-term effects of orlistat, a lipase inhibitor, in adult clozapine- or olanzapine-treated patients with "Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition" (DSM-IV)-diagnosed schizophrenia. The study showed that continued treatment with orlistat has no additional advantages as compared to short treatment. It also revealed that orlistat appeared to modestly decrease lipid levels.

Objective: Undesirable metabolic effects of modern antipsychotics, especially clozapine and olanzapine, merit development of new weight-control strategies, including pharmacologic ones. We investigated the feasibility of treatment with orlistat, a weight-control drug with no central effects, for overweight/obesity in clozapine- or olanzapine-treated male and female patients., Method: Add-on orlistat was prescribed for 16 weeks in a randomized, double-blind, placebo-controlled clinical trial to patients who were receiving stable clozapine or olanzapine medication and were aged 18 to 65 years, with no compliance with nonpharmacologic programs or hypocaloric diet required. The primary efficacy variable was body weight change. The study was conducted from 2004 through 2005., Results: Of 71 randomly assigned subjects, 63 were eligible for modified intent-to-treat analysis. While no statistically significant effect was observed in the whole population, male (but not female) patients benefited from treatment with orlistat (-2.36 kg vs. 0.62 kg on placebo, p = .011). There were 5 responders (16.1%) (those with >or= 5% weight loss) that received orlistat versus 2 responders (6.3%) that received placebo (number needed to treat = 11), but the difference was not statistically significant., Conclusions: Without a hypocaloric diet, the effect of orlistat in overweight/obese clozapine-or olanzapine-treated patients is modest and may only be seen in men. More studies should define the optimal length of treatment and feasibility of combination of orlistat with behavioral programs in this population.

Objective: We tested the hypothesis that topiramate is more effective than placebo in reducing symptoms in patients with treatment-resistant schizophrenia when combined with ongoing antipsychotic medication., Method: Twenty-six hospitalized treatment-resistant patients with chronic DSM-IV-diagnosed schizophrenia participated in a randomized, double-blind, placebo-controlled trial in which 300 mg/day of topiramate was gradually added to their ongoing treatment (clozapine, olanzapine, risperidone, or quetiapine) over two 12-week crossover treatment periods. Data were collected from April 2003 to November 2003., Results: In intention-to-treat analysis, topiramate was more effective than placebo in reducing Positive and Negative Syndrome Scale general psychopathologic symptoms (effect size = 0.7, p = .021), whereas no significant improvement was observed in positive or negative symptoms., Conclusion: Glutamate antagonist topiramate may be an effective adjuvant treatment in reducing general psychopathologic symptoms in patients with schizophrenia resistant to treatment with second-generation antipsychotics.