Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms.
Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms.
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DOI：
10.1097/jcp.0000000000000345
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发表时间：
2015-08
影响因子：
2.9
通讯作者：
Buchanan RW
中科院分区：
文献类型：
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作者：
Kelly DL;Sullivan KM;McEvoy JP;McMahon RP;Wehring HJ;Gold JM;Liu F;Warfel D;Vyas G;Richardson CM;Fischer BA;Keller WR;Koola MM;Feldman SM;Russ JC;Keefe RS;Osing J;Hubzin L;August S;Walker TM;Buchanan RW
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. 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). Brief Psychiatric Rating Scale (BPRS) psychosis factor (p=0.098, effect size ES=0.39) and BPRS total score (p=0.075, effect size 0.55) were not significant. A ≥30% change in total BPRS symptoms was observed in 7/28 (25%) among minocycline and 1/23 (4%) among placebo participants, respectively (p=0.044). Global cognitive function (MATRICS Consensus Cognitive Battery, MCCB) 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 SANS 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 to placebo. Minocycline’s effect on the MCCB 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.
