A Systematic Review of Atypical Antipsychotics in Chronic Pain Management: Olanzapine Demonstrates Potential in Central Sensitization, Fibromyalgia, and Headache/Migraine

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Many psychopharmacologic agents are used as primary or adjuncts in pain management. Atypical antipsychotics (AAs) have also been used as adjuncts in pain management regimens in a variety of manners; however, their efficacy in this capacity is unclear.


A systematic review of all studies examining AA use for pain was conducted. Three literature databases were utilized to search for word combinations of “pain” and a variety of commonly prescribed AAs ie, (olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone, clozapine, paliperidone, iloperidone, lurasidone). Articles chosen for review included retrospective analyses, randomized control trials, and case series/reports. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram illustrates the study selection process.


Olanzapine, quetiapine, risperidone, aripiprazole, and ziprasidone are the only AAs with published studies in pain management. Among these, olanzapine and quetiapine have the most studies (11 and 6, respectively). Olanzapine shows preliminary and consistent efficacy in fibromyalgia and headache/migraine, although only 1 study was a randomized controlled trial with level I evidence of efficacy. Other AAs eg, (quetiapine) fail to demonstrate efficacy in pain syndromes and/or lack robust study designs.


Few studies have been conducted to evaluate the analgesic effects of AAs. The collective findings of multiple studies evaluating olanzapine in pain syndromes suggest a high, yet preliminary level of evidence of efficacy, warranting prospective studies in various pain syndrome contexts. Pharmacological mechanisms of AA action are elaborated, and the findings of this review are discussed. Risk and benefits of using AAs in chronic pain are described, and investigational implications and future directions are explored.

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