Hydroxychloroquine for RA does not increase risk for suicide, depression

Hydroxychloroquine as a treatment for rheumatoid arthritis does not appear to increase the risk for depression, suicide, suicidal ideation or psychosis, compared with sulfasalazine, according to data published in Rheumatology.

“Commonly used for autoimmune disorders (eg, systemic lupus erythematosus) and inflammatory arthritis, HCQ was released for emergency use for COVID-19 due to its postulated antiviral efficacy in cellular studies,” Jennifer C.E. Lane, MRCS, of the University of Oxford, in the United Kingdom, and colleagues wrote. “Results to date have been conflicting, with emerging data suggesting a lack of clinical efficacy against COVID-19.”

“Case report literature suggests that chloroquine, the compound from which HCQ was derived, is associated with neurological and psychiatric side effects when used as an antimalarial treatment or prophylaxis,” they added. “Similar potential side effects that have been described in the use of HCQ include neuropsychiatric side effects such as psychosis, depression and suicidal behavior. New reports of serious side effects associated with HCQ used in COVID-19 are concerning to the rheumatology community, leading to confusion and anxiety for patients who are taking HCQ for autoimmune conditions.”

To analyze the risk for depression, suicidal ideation or psychosis associated with hydroxychloroquine for RA, Lane and colleagues conducted a new-user cohort study, based on claims and electronic medical records from 10 data sources in the United States, the United Kingdom and Germany. Focusing on the period from September 2000 to present, the researchers compared adult patients with RA who initiated hydroxychloroquine to those who started sulfasalazine.

A total of 918,144 patients treated with hydroxychloroquine, and 290,383 who received sulfasalazine, all with 30-day and long-term follow-ups, were included in the study. Outcomes included depression, suicide, suicidal ideation and hospitalization for psychosis. The researchers used propensity score stratification and calibration, via negative control outcomes, to address confounding. In addition, they used Cox models to estimate database-specific calibrated hazard ratios, with estimates pooled where I²was less than 40%.

According to the researchers, there was no consistent risk for psychiatric events reported with 30-day hydroxychloroquine use, compared with sulfasalazine, with meta-analytic HRs of 0.96 (95%, CI 0.79-1.16) for depression, 0.94 (95% CI, 0.49-1.77) for suicide and suicidal ideation, and 1.03 (95% CI, 0.66-1.60) for psychosis. There was also no consistent long-term risk associated with hydroxychloroquine compared with sulfasalazine, with meta-analytic HRs of 0.94 (95% CI, 0.71-1.26) for depression, 0.77 (95% CI, 0.56-1.07) for suicide and suicidal ideation, and 0.99 (95% CI, 0.72-1.35) for psychosis.

“This large observational study shows that in routine health care treatment of RA, there is no association with the use of HCQ with acute psychosis, depression or suicide as compared with sulfasalazine,” Lane and colleagues wrote. “These results are seen both in the short-term and long-term risk analyses. While an excess of psychiatric events have been reported during the COVID pandemic in those prescribed HCQ, this risk does not appear to be associated with HCQ prescribed in RA compared with those prescribed sulfasalazine.”