Systematic Review of Psychiatric Adverse Effects Induced by Chloroquine and Hydroxychloroquine: Case Reports and Population Studies

  1. Fernanda Talarico
  2. Sucheta Chakravarty
  3. Yang S. Liu
  4. Andrew J. Greenshaw
  5. Ives Cavalcante Passos
  6. Bo Cao

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Abstract

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.

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  1. Version published to 10.1177/10600280221113572
  2. ScreenIT

    SciScore for 10.1101/2020.10.05.20207423: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableRisk of bias across studies: The case-report and population studies differ on male/female rate, age (mean and range), medication dose, and the patient’s diagnosis (malaria, LSE, and RA).

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Information sources, search strategy, and study selection: Studies were identified by searching four electronic databases in the following order: PubMed, Scopus, Web of Science, and Embase.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    The following Medical Subject Heading (MeSH) term filters were applied: (“Chloroquine” OR “Hydroxychloroquine”
    MeSH
    suggested: (MeSH, RRID:SCR_004750)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Nonetheless, due to the limitations brought up regarding the voluntary response in survey data, self-reports side effects, and placebo group reporting similar symptoms than case group, populational level studies addressing these limitations is needed as well as more investigation to understand the psychiatric side effects nature and extent. Below we discuss the possible mechanisms for the occurrence of these symptoms with the intake of CQ/HCQ. Prevalence and risks of psychiatric side effects induced by CQ or HCQ: There are inconsistencies among studies on the prevalence of psychiatric side effects induced by CQ/HCQ. In 2015, Gonzalez-Nieto JA and Costa-Juan E calculated a prevalence of 0.09%, while Mascolo A and co-workers in 2018 reported 1% and 7% prevalence of neuropsychiatric disorders and psychiatric disorders, respectively. Although having a small sample size, other studies reported that 43% of patients treated with CQ for RA developed depression (Drew J.F., 1962; Mohan D. et al., 1981) and 29% of patients taking HCQ for RA developed mild to severe depression (Wilkey I.S., 1971). Some studies found a higher prevalence among women in menopausal age (Drew J.F., 1962), while in others the frequency was higher in children (Akhtar S. & Mukherjee S., 1993). Other two studies calculated the incidence rate (IR) (Table 6). Although studies suggested family history or presence of previous psychiatric disorders as the major predisposing factor (Collins G.B. & McAllister M.S., 2008...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.10.05.20207423v1 on medRxiv