Objective: To perform a systematic review on the psychiatric adverse effects of chloroquine (CQ) and hydroxychloroquine (HCQ); to summarize what is known about psychiatric adverse effects of these drugs; to compare clinical trials, populational studies, and case report studies; and to increase awareness of the potential psychiatric adverse effects of these drugs.
Data sources: A literature search of PubMed, Scopus, and Web of Science was performed to identify manuscripts published between December 1962 and June 2022. Search terms included CQ, HCQ, psychiatry, psychosis, depression, anxiety, bipolar disorder, delirium, and psychotic disorders.
Study selection and data extraction: Relevant studies included reports of adverse effects after CQ or HCQ ingestion.
Data synthesis: The current literature presents evidence for a risk of short-term psychiatric adverse effects induced by either CQ or HCQ. However, the populational-level studies presented some limitations regarding the voluntary response in survey data, self-report adverse effects, and placebo group reporting similar symptoms to the case group. Thus, populational-level studies addressing the discussed limitations and the nature and extent of possible psychiatric adverse effects are needed.
Relevance to patient care and clinical practice: Most of the patients who developed such adverse effects did not report a family history of psychiatric disease. The frequency of psychiatric adverse effects depends on the patient's biological sex, age, and body mass index, but not on the drug dosage.
Conclusions: Based on clinical trials and case reports, the current literature presents evidence for a risk of short-term psychiatric adverse effects induced by either drug.
Keywords: adverse drug reaction; chloroquine; drug safety; hydroxychloroquine; psychiatry.