A Review of the Pharmacological and Clinical Profile of Newer Atypical Antipsychotics as Treatments for Bipolar Disorder: Considerations for Use in Older Patients

Bipolar disorder prevalence rates vary in the older adult population (defined as age ≥ 65 years), ranging from 1% in community dwellers to as high as 8–10% in hospital inpatients. Although older agents, including lithium and valproic acid, offer significant antimanic efficacy, as supported by a recent randomized controlled trial (RCT), there is growing interest in using atypical antipsychotics to treat bipolar disorder in older adults. Newer atypical antipsychotics are of interest based on their tolerability and efficacy in the general adult bipolar population. The aim of this review was to systematically examine efficacy and tolerability of newer atypical antipsychotics for older adult bipolar disorder (OABD). We conducted a systematic search utilizing the MEDLINE, EMBASE, PsycINFO and Cochrane Library electronic databases, with the aim of identifying all RCTs comparing newer atypical antipsychotics approved by the US FDA since 2002 (including brexpiprazole, cariprazine, lurasidone, iloperidone, asenapine, paliperidone, and aripiprazole) with placebo or another comparator, in the treatment of any phase of bipolar disorder (including mania, depression or mixed episodes while used as an acute or maintenance treatment) in older adults (> 65 years). We found no RCT data on any of the examined agents. Hence, we changed our search criteria to include studies with a lower age cut-off (≥ 55 years), as well as the inclusion of post hoc studies. Two post hoc studies on lurasidone suggest its reasonable safety and efficacy profile in the acute and maintenance treatment of OABD; however, there are no pharmacoeconomic data on the use of lurasidone in the treatment of OABD. Research data from open-label studies on oral asenapine and aripiprazole as add-on therapy suggest that these two agents are adequately tolerated and improved symptoms of depression and mania in OABD; hence, there is an urgent need to conduct RCTs on these two agents. Lastly, we found no studies for the treatment of OABD with brexpiprazole, cariprazine, iloperidone, or paliperidone.