Psychiatric medications and the risk of autoimmune and immune-mediated inflammatory diseases: A systematic review and meta-analysis of observational studies

Abstract

Background: Pharmacovigilance reports have suggested that certain commonly used medications may trigger autoimmune diseases (ADs) and immune-mediated inflammatory diseases (IMIDs). We systematically reviewed the literature to evaluate whether psychiatric medication use is associated with ADs and IMIDs.

Methods: The protocol was registered in PROSPERO (CRD42022296524) before the start of the study. We searched Medline Ovid and Scopus up to November 28th, 2021, for comparative studies, with any psychiatric medication as exposure and ADs and IMIDs as outcomes. Meta-analysis was performed using DerSimonian-Laird random-effects modeling. The PRISMA 2020 guidelines were followed in reporting. Study-level risk of bias was assessed using the Newcastle-Ottawa Scale, and the overall certainty of evidence using GRADE.

Results: There were 7,265 citations from which 31 studies were eligible, all from high-income countries, covering 15 distinct immune diseases. The evidence for the association between selective serotonin reuptake inhibitor (SSRI) use and higher risk of microscopic colitis (meta-OR 2.60, 95% CI 1.05-6.39, I2 97.5%, 6 studies) was of low certainty. A subgroup analysis by the histological type of microscopic colitis showed a statistically significant association only with lymphocytic colitis (meta-OR 2.88, 95% CI 2.60-3.18, I2 00.00%, three studies). In two case-control studies, SSRI use had no significant association with psoriasis (meta-OR 0.80, 95% CI 0.58-1.10, I2 82.4%). The risk of acute pancreatitis was slightly increased with exposure to SSRIs (meta-OR 1.13, 95% CI 1.01-1.26, I2 00.0%), as was the risk of bullous pemphigoid after exposure to antipsychotics (meta-OR 1.79, 95% CI 1.17-2.73, I2 0%).

Conclusions: We reviewed the literature on whether psychiatric medications associate with the risk of ADs and IMIDs and concluded that, despite several signals, the credibility of evidence remains low at best. Prospective cohort studies would be needed as the next step to confirm the suggestions of increased risk.

Fig 1. Flowchart of study selection.

Fig 2. Forest plots for available meta-analyses of the risk of immune-mediated inflammatory diseases by the use of selective serotonin reuptake inhibitors (SSRI) and antipsychotics.

Fig 3. Harvest plot of the associations between the use of psychiatric medication and risk of psoriasis.

¹ Tzeng et al. (2021) is a cohort study reporting relative risks (RRs). ² Brauchli et al. (2009) is a case-control study with odds ratios (ORs) of the association shown. The harvest plot shows the risk of psoriasis by the type of psychiatric medication. Only associations with at least 50 psoriasis patients with the drug of interest are shown. The height of the column indicates the size of the study, and the green color represents a study with a low risk of bias according to the Newcastle–Ottawa Scale.