title: Adverse effects associated with second-generation antipsychotic long-acting injection treatment: a comprehensive systematic review.
abstract: As second-generation antipsychotic long-acting injections (SGA-LAIs) are rapidly replacing depot first-generation antipsychotics as first-line agents in treating schizophrenia spectrum disorders, a systematic assessment of their adverse effects is timely. English-language, peer-reviewed articles reporting original data on the safety and tolerability of SGA-LAIs were identified electronically by searching the MEDLINE, EMBASE, PsycINFO, and DARE databases and the Cochrane Library (January 2001-April 2013). In addition to second-generation (atypical) antipsychotics and long-acting injection (depot) antipsychotics, a separate search was performed for each available drug: aripiprazole LAI, olanzapine pamoate, paliperidone palmitate, and risperidone LAI. Articles were excluded if they were review articles, post hoc analyses, analyses of subsets of patients enrolled in previous trials, single case reports, case series studies, small naturalistic studies (involving less than 50 patients), studies providing no safety data, and studies lasting less than 8 weeks. Of 181 articles identified from the search, 140 were excluded; thus, 41 articles met the inclusion criteria. Predictably, the reviewed information revealed that SGA-LAIs have safety profiles consistent with their oral parent formulations. However, they seem to also show unforeseen and worrisome safety signals. Indeed, the routine use of olanzapine-LAI in clinical practice could be limited not only by the well-known risk of postinjection syndrome, whose clinical management remains a matter of concern, but also by the risk of worsening of psychosis. The reviewed information seems to suggest that worsening of psychotic symptoms and depression could also be associated with both risperidone-LAI and paliperidone palmitate. The leading cause of death among patients enrolled in risperidone-LAI studies was suicide. Given the exponential growth in the clinical use of SGA-LAIs, further studies must be urgently performed in order to confirm or exclude the potential safety signals associated with such drugs.
authors.affiliation: Department of Mental Health, ASL Salerno, Mental Health Center no. 63, Cava de' Tirreni, Italy; Department of Neurosciences, Medical School "Federico II", University of Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gentile
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D006801:Humans; D007267:Injections; D011618:Psychotic Disorders / Q000453:epidemiology / Q000209:etiology*; D012306:Risk; D012559:Schizophrenia / Q000188:drug therapy*; D013405:Suicide / Q000706:statistics & numerical data; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations
keywords: aripiprazole long-acting injection; atypical antipsychotic long-acting injections; olanzapine pamoate; paliperidone palmitate; risperidone long-acting injection; safety; tolerability