Psychiatric side effects induced by chloroquine and hydroxychloroquine: a systematic review of case reports and population studies

Chloroquine and hydroxychloroquine are commonly used drugs in the treatment of malaria as well as chronic diseases, such as rheumatoid arthritis, and systemic lupus erythematosus. Although various reports on possible psychiatric side effects of these drugs exist, the nature and extent of these effects remain poorly understood. Moreover, the relevance of these drugs in the treatment of early stages of COVID-19 necessitates a careful estimation of their side effects. Here, we provide a systematic review of the psychiatric side effects associated with chloroquine and hydroxychloroquine. We used PubMed, Scopus, and Web of Science platforms to identify relevant literature published between 1962 and 2020. Search terms included chloroquine, hydroxychloroquine, psychiatry, psychosis, depression, anxiety, bipolar disorder, delirium, and psychotic disorders. Only case reports and clinical trials were included. All studies included records of psychiatric side effects induced by either chloroquine or hydroxychloroquine or both. Both retrospective and prospective, randomized as well as non-randomized population studies were included. Overall, the psychiatric side effects are dose- and sex-independent. The most common psychiatric side effects reported are increased speech output/ excessive talking, increased psychomotor activity, irritable mood, auditory hallucinations, delusion of grandiosity, and suicide attempts, likely due to brain intoxicationbe of chloroquine or hydroxychloroquine. The symptoms can develop in a few hours to 11 weeks after drug intake and are normally reversed within a week after the drug withdrawal. We conclude that CQ and HCQ have the potential to induce psychiatric side effects. This study calls for further investigation of psychiatric symptoms induced by these drugs in the short and long term.