Fiza Singh, MD Center of Recovery Education San Diego VA Medical Center Associate Clinical Professor Department of Psychiatry University of California San Diego San Diego, California
Andrew Allen, MD Attending Psychiatrist Aurora Behavioral Health-San Diego Achieve Medical Center San Diego, California
Disclosures The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Metformin is generally well tolerated. Common adverse effects include diarrhea, nausea, and abdominal pain, which are generally transient and can be ameliorated by using the extended-release formulation and lower starting doses.15 The frequency of medication discontinuation was minimal and similar in patients receiving metformin vs placebo.8,16 Despite these positive findings, most studies of metformin have had a follow-up of ≤24 weeks, and its long-term effects on antipsychotic-induced weight gain and metabolic parameters remain unknown.
When prescribing metformin for a patient with schizophrenia, consider a starting dose of 500 mg twice daily.
Topiramate
Topiramate is FDA-approved for treating generalized tonic-clonic and complex partial seizures17 and for migraine prophylaxis. More recently, it has been used off-label for weight loss in both psychiatric and non-psychiatric patients. Topiramate’s proposed mechanism for weight loss is by decreasing plasma leptin levels and increasing plasma adiponectin. A recent literature review of 8 RCTS that included 336 patients who received second-generation antipsychotics (SGAs) and adjunctive placebo or topiramate (100 to 300 mg/d) found that patients who received topiramate lost a statistically significant 2.83 kg vs placebo.18 Several case studies confirm similar findings, showing that patients with schizophrenia lost 2 to 5 kg when started on topiramate along with an SGA.19 Importantly, weight loss has been observed both in patients started on topiramate prophylactically along with an SGA, and those who had been receiving SGAs for an extended period of time before starting topiramate.
Tolerability has been a concern in patients receiving topiramate. Frequent complaints include cognitive dulling, sedation, and coldness or tingling of the extremities. In a meta-analysis of topiramate, metformin, and other medications used to induce weight loss in patients receiving SGAs, Zhuo et al20 found that topiramate was reported intolerable more frequently than other agents, although the difference was not statistically significant.
When prescribing topiramate for a patient with schizophrenia, consider a starting dose of 25 mg at bedtime.
