A randomized,double‐blind,placebo‐controlled study of maintenance treatment with adjunctive risperidone long‐acting therapy in patients with bipolar I disorder who relapse frequently

Objective: No large controlled trials have evaluated adjunctive maintenance treatment with long‐acting injectable antipsychotics in patients with bipolar disorder. This study assessed whether adjunctive maintenance treatment with risperidone long‐acting therapy (RLAT), added to treatment‐as‐usual (TAU) medications for bipolar disorder, delays relapse in patients with bipolar disorder type I. Methods: This study included patients with bipolar disorder type I with ≥ four mood episodes in the 12 months prior to study entry. Following a 16‐week, open‐label stabilization phase with RLAT plus TAU, remitted patients entered a 52‐week, double‐blind, placebo‐controlled, relapse‐prevention phase. Randomized patients continued treatment with adjunctive RLAT (25–50 mg every two weeks) plus TAU (n = 65) or switched to adjunctive placebo injection plus TAU (n = 59). The primary outcome measure was time to relapse to any mood episode. Results: Of 240 enrolled patients, 124 entered double‐blind treatment. Time to relapse was longer in patients receiving adjunctive RLAT (p = 0.010). Relapse rates were 23.1% (n = 15) with adjunctive RLAT versus 45.8% (n = 27) with adjunctive placebo; relative relapse risk was 2.3‐fold higher with adjunctive placebo (p = 0.011). Completion rates were: adjunctive RLAT, 60.0% (n = 39) and adjunctive placebo, 42.4% (n = 25; p = 0.050). Adverse event (AE)‐related discontinuations were 4.6% (n = 3) and 1.7% (n = 1), respectively. Common AEs (adjunctive RLAT versus adjunctive placebo) were: tremor (24.6% versus 10.2%), insomnia (20.0% versus 18.6%), muscle rigidity (12.3% versus 5.1%), weight increased (6.2% versus 1.7%), and hypokinesia (7.7% versus 0.0%). Conclusions: Adjunctive RLAT significantly delayed time to relapse in patients with bipolar disorder type I who relapse frequently. Safety and tolerability of RLAT were generally consistent with that previously observed.