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Selected adverse effects of antipsychotic medications for schizophrenia[1,2]

Selected adverse effects of antipsychotic medications for schizophrenia[1,2]
  Weight gain Glucose abnormalities Hyperlipidemia Akathisia Parkinsonism Dystonia Tardive dyskinesia Prolactin elevation Sedation Anticholinergic Orthostatic hypotension QTc prolongation
Second-generation agents
Aripiprazole + + + ++ + + + + + + + *
Asenapine ++ ++ ++ ++ + ++ ++ ++ ++ + ++ +
Brexpiprazole + + ++ ++ + + + + ++ + + *
Cariprazine ++ + + ++ + + + + ++ ++ + *
ClozapineΔ +++ +++ +++ + + + + + +++ +++ +++ ++
Iloperidone ++ ++ + + + + + ++ ++ + +++ +
Lumateperone + + + + + + + + + + + *
Lurasidone + ++ ++ ++ ++ ++ ++ + ++ + + *
Olanzapine +++ +++ +++ ++ ++ + + ++ +++ ++ ++ ++
Paliperidone ++ + ++ ++ ++ ++ ++ +++ + + ++ +
Pimavanserin – + + + + + + + + + ++ +
Quetiapine ++ ++ +++ + + + + + +++ ++ ++ ++
Risperidone ++ ++ + ++ ++ ++ ++ +++ ++ + ++ ++
Ziprasidone + + + ++ + + + ++ ++ + ++ +++
First-generation agents
Chlorpromazine ++ ++ + ++ ++ ++ +++ + +++ +++ +++ +++
Fluphenazine ++ + + +++ +++ +++ +++ +++ + + + +
Haloperidol ++ + + +++ +++ +++ +++ +++ + + + Oral: ++
IV: +++
Loxapine + + + ++ ++ ++ ++ ++ ++ ++ ++ *
Molindone + + + ++ ++ ++ ++ ++ ++ + + *
Perphenazine ++ + + ++ ++ ++ ++ ++ ++ ++ ++ *
Pimozide + + + +++ +++ ++ +++ +++ + + + ++◊
Thioridazine§ ++ + + + + + + ++ +++ +++ +++ ++
Thiothixene + + + +++ +++ +++ +++ +++ + + + *
Trifluoperazine ++ + + ++ ++ ++ ++ ++ + ++ + *
Adverse effect rankings, with the exception of the QTc classifications, are consistent with American Psychiatric Association practice guidelines for the treatment of schizophrenia.[1] The QTc classifications are determined by Lexicomp according to US Food & Drug Administration guidance.[2,3] Other sources may use different classification systems resulting in some agents being classified differently.
IV: intravenous.
* Clinically significant QTc prolongation was not detected in preliminary studies or reported in the manufacturer's labeling.
¶ Based upon limited experience.
Δ Clozapine also causes granulocytopenia or agranulocytosis in approximately 1% of patients requiring regular blood cell count monitoring. Clozapine has been associated with excess risk of myocarditis and venous thromboembolic events including fatal pulmonary embolism. These issues are addressed in the UpToDate topic review of guidelines for prescribing clozapine section on adverse effects.
◊ Although the available evidence concerning the average QTc prolonging effect of pimozide is consistent with a classification of moderate significance (ie, ++), label warnings have characterized the QTc effect and cardiovascular risks as severe and sudden deaths in patients on pimozide have been reported.
§ Thioridazine is also associated with dose-dependent retinitis pigmentosa. Refer to UpToDate text.
References:
  1. Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. American Psychiatric Association 2020. Available at: https://www.psychiatry.org/psychiatrists/practice/clinical-practice-guidelines (Accessed on March 24, 2020).
  2. Lexicomp Online. Copyright © 1978-2023 Lexicomp, Inc. All Rights Reserved.
  3. Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythic Potential for Non-Antiarrhythmic Drugs – Questions and Answers; Guidance for Industry US Food and Drug Administration, June 2017 (revision 2). Available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073161.pdf.
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