A 40-week double-blind aripiprazole versus lithium follow-up of a 12-week acute phase study (total 52 weeks) in bipolar I disorder.

Background: This study followed manic or mixed bipolar I subjects for an additional 40 weeks after initial randomization to 12 weeks of lithium versus aripiprazole monotherapy. This is the only long-term, double-blind study comparing lithium and aripiprazole.

Methods: Patients continued receiving either aripiprazole 15 or 30 mg/day, or lithium 900, 1200 or 1500 mg/day in a double-blind fashion for 40 weeks after completing a 12-week double-blind study (52 weeks total treatment). Efficacy endpoints included adjusted mean change from baseline to Week 52 in Young Mania Rating Scale (YMRS) total score and Montgomery-Åsberg Depression Rating Scale (MADRS) total scores (observed cases). Remission was defined as YMRS total score≤12. Safety and tolerability were also assessed.

Results: Of the 66 patients who entered the extension phase, only 20 patients (30.3%) completed the entire phase (aripiprazole n=7; lithium n=13). The significant improvement that occurred over the first 12 weeks was maintained over the 40 weeks of blinded continuation (from Week 12 through Week 52). The most common treatment-emergent adverse events in the extension phase for aripiprazole were akathisia, headache, somnolence, anxiety and nasopharyngitis (all 8%), and for lithium were insomnia (15.8%), headache (13.2%), diarrhea (13.2%) and vomiting (10.5%). Mean weight change was +2.71 kg for lithium and +5.66 kg for aripiprazole (p=0.46).

Limitations: This trial was not powered to statistically compare active treatments, and long-term completion rates were low in both groups.

Conclusions: Aripiprazole monotherapy appears to be equivalently useful to lithium for the extended treatment of mixed or manic bipolar disorder patients.