Emerging treatments for bipolar disorder: Safety and adverse effect profiles

OBJECTIVE: To provide an overview of the safety and tolerability of newer agents used to treat bipolar disorder (BPD) and provide clinicians with management strategies for drug-related toxicity and adverse effects. DATA SOURCES: MEDLINE was searched through July 2005 for BPD treatment, adverse effects, tolerability, safety, emerging agents, atypical antipsychotics, new antiepileptic drugs (AEDs), risperidone, quetiapine, clozapine, ziprasidone, aripiprazole, lamotrigine, topiramate, gabapentin, oxcarbazepine, and olanzapine. STUDY SELECTION AND DATA EXTRACTION: Results from randomized controlled trials, open-label studies, and reviews are described. DATA SYNTHESIS: Emerging agents recently approved for BPD include atypical antipsychotics and new AEDs. Safety and tolerability are as important as efficacy because poor adherence in BPD worsens outcome; metabolic and other comorbidities pose specific challenges; and manic patients often require combination therapy, which increases adverse effects. Most atypical antipsychotics cause fewer extrapyramidal symptoms than conventional antipsychotics, but may cause more weight gain and metabolic complications. The newer AEDs generally cause less weight gain than the older agents, and some even promote weight loss. Several newer AEDs used in BPD also offer the advantages of fewer drug interactions and less need for therapeutic drug monitoring compared with older AEDs. CONCLUSIONS: Pending the results of ongoing controlled studies, several emerging agents may be useful additions to the therapeutic arsenal for BPD.