Outcomes of Neuroleptic Malignant Syndrome With Depot Versus Oral Antipsychotics: A Systematic Review and Pooled, Patient-Level Analysis of 662 Case Reports

Objective: This systematic review and pooled, patient-level analysis of neuroleptic malignant syndrome (NMS) case reports and series compared NMS characteristics and outcomes during long-acting injectable antipsychotic (LAI) versus oral antipsychotic (OAP) treatment. Data Sources: Two authors independently searched MEDLINE, Embase, Cochrane, CINAHL, and PsycINFO databases for articles in English from database inception until October 9, 2018. Study Selection: Case reports with author-defined NMS during ongoing antipsychotic treatment or within 1 injection interval of LAIs in adults aged 18-65 years. Data Extraction: Demographic, clinical, treatment and outcome data were independently extracted following PRISMA guidelines. NMS severity was rated using the Francis-Yacoub scale. Characteristics and outcomes of NMS were compared when occurring during LAI versus OAP treatment, adjusting for significant between- group differences. Results: Of 662 reported cases (median age = 36 years, male = 61.2%), 122 (18.4%) involved LAIs (second-generation antipsychotic [SGA] LAIs [SGA-LAIs] = 10, 1.5%), whereas 540 (81.6%) involved OAPs (SGA-OAPs = 159, 24.0%). The 2 groups did not differ in age, illness duration, comorbidities, or presence or severity of NMS symptoms (median Francis-Yacoub score: LAIs = 26 vs OAPs = 23, P = .8276). Antipsychotic formulation was not significantly associated with longer duration of hospitalization (LAIs = 5.0 weeks vs OAPs = 3.8 weeks, P = .8322), post-NMS sequelae (LAIs = 8.8% vs OAPs = 7.0%, P = .7489), or death (LAIs = 10.7% vs OAPs = 6.7%, P = .0861). When different, post hoc confounder-adjusted models were used, duration of NMS (but not hospitalization for NMS) was longer with LAIs than with OAPs (median = 2.6 vs 1.8 weeks, P = .0339), driven by FGAs rather than SGAs. Conclusions: These data, plus the fact that only 10 published NMS cases exist with SGA-LAIs, should mitigate safety concerns regarding LAIs, but results should be interpreted cautiously since they are based on case reports.

Automated summary

This study compared the characteristics and outcomes of neuroleptic malignant syndrome (NMS) during long-acting injectable antipsychotic (LAI) and oral antipsychotic (OAP) treatment. There were no significant differences between the two treatments in terms of patient characteristics or severity of NMS symptoms, but the duration of NMS was longer with LAIs. Overall, LAIs and OAPs showed similar performance in managing NMS and its consequences.