Long-acting injectable antipsychotics for the maintenance treatment of bipolar disorder

Depot antipsychotics have been used as a strategy to reduce non-adherence to medications in schizophrenia and bipolar disorder (BD). This article reviews the literature on the efficacy and safety of first- and second-generation depot antipsychotics (FGDA and SGDA, respectively) for the maintenance treatment of BD. Although FGDA have been studied in BD, they have not been approved for use in this disease. Among the SGDA, only depot risperidone has been studied and approved for the maintenance treatment of BD. We found eight studies on FGDA (three on flupenthixol, two on depot haloperidol, one on fluphenazine and flupenthixol, two on a mix of diverse antipsychotics) and ten studies on SGDA (all on depot risperidone). Differences in efficacy and safety were found between the two classes of depot antipsychotics. Although FGDA may be effective in reducing manic relapses, they possibly increase the risk of worsening depression. Depot risperidone is effective as a maintenance treatment in BD with effect noted predominantly for preventing mania. However, no worsening in depression was observed. Depot risperidone also is better tolerated than FGDA, mainly in relation to extrapyramidal symptoms. Studies with the new depot antipsychotics, olanzapine pamoate and paliperidone palmitate, are needed in BD patients. Further, there is currently little information on the metabolic changes (apart from bodyweight gain) that may occur with the use of depot risperidone in patients with bipolar disorder, and this issue needs further investigation.