Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms

作者：Kelly Deanna L^*; Sullivan Kelli M; McEvoy Joseph P; McMahon Robert P; Wehring Heidi J; Gold James M; Liu Fang; Warfel Dale; Vyas Gopal; Richardson Charles M; Fischer Bernard A; Keller William R; Koola Maju Mathew; Feldman Stephanie M; Russ Jessica C; Keefe Richard S E; Osing Jennifer; Hubzin Leeka; August Sharon; Walker Trina M; Buchanan Robert W

来源：Journal of Clinical Psychopharmacology, 2015, 35(4): 374-381.

DOI：10.1097/JCP.0000000000000345

Objective
Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia, yet many patients only partially respond. Accumulating preclinical and clinical data suggest benefits with minocycline. We tested adjunct minocycline to clozapine in a 10-week, double-blind, placebo-controlled trial. Primary outcomes tested were positive, and cognitive symptoms, while avolition, anxiety/depression, and negative symptoms were secondary outcomes.
Methods
Schizophrenia and schizoaffective participants (n = 52) with persistent positive symptoms were randomized to receive adjunct minocycline (100 mg oral capsule twice daily; n = 29) or placebo (n = 23).
Results
Brief Psychiatric Rating Scale (BPRS) psychosis factor (P = 0.098; effect size [ES], 0.39) and BPRS total score (P = 0.075; ES, 0.55) were not significant. A change in total BPRS symptoms of more than or equal to 30% was observed in 7 (25%) of 28 among minocycline and 1 (4%) of 23 among placebo participants, respectively (P = 0.044). Global cognitive MATRICS Consensus Cognitive Battery) did not differ, although there was a significant variation in size of treatment effects among cognitive domains (P = 0.03), with significant improvement in working memory favoring minocycline (P = 0.023; ES, 0.41). The Scale for the Assessment of Negative Symptoms total score did not differ, but significant improvement in avolition with minocycline was noted (P = 0.012; ES, 0.34). Significant improvement in the BPRS anxiety/depression factor was observed with minocycline (P = 0.028; ES, 0.49). Minocycline was well tolerated with significantly fewer headaches and constipation compared with placebo.
Conclusions
Minocycline's effect on the MATRICS Consensus Cognitive Battery composite score and positive symptoms were not statistically significant. Significant improvements with minocycline were seen in working memory, avolition, and anxiety/depressive symptoms in a chronic population with persistent symptoms. Larger studies are needed to validate these findings.

• 出版日期2015-8