Superior chronic tolerability of adjunctive modafinil compared to pramipexole in treatment-resistant bipolar disorder

Background: Suboptimal outcomes are common in bipolar disorder (BD) pharmacotherapy, and may be mitigated with novel adjunctive agents such as modafinil (a low-affinity dopamine transport inhibitor) and pramipexole (a dopamine D2/D3 receptor agonist). While uncontrolled long-term effectiveness data have been reported for these treatments, reports specifically assessing their comparative acute versus chronic tolerability in BD are lacking. Such information, particularly in relation to discontinuation causes, has substantial relevance, providing initial indications to clinicians which treatment may be better tolerated, and to researchers which agent ought to be assessed in longer-term controlled trials. Methods: BD outpatients assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Affective Disorders Evaluation, and followed with the STEP-BD Clinical Monitoring Form, were naturalistically prescribed adjunctive modafinil or pramipexole, and somatic/psychiatric intolerability discontinuation rates were compared. Results: Among 63 BD outpatients (mean±SD age 43.5±14.3 years, 60.3% female, 42.9% type I, 44.4% type II, 12.7% type not otherwise specified), taking 3.5±1.5 (median 3) concurrent prescription psychotropics, adjunctive modafinil (n=24) for 626.9±863.9 (286) days versus pramipexole (n=39) for 473.7±613.4 (214; p=0.51) days yielded a 26.0% lower somatic/psychiatric intolerability discontinuation rate (12.5% vs. 38.5%; p