TY - JOUR
T1 - Risk of depression, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis
T2 - A multinational network cohort study
AU - Lane, Jennifer C.E.
AU - Weaver, James
AU - Kostka, Kristin
AU - Duarte-Salles, Talita
AU - Abrahao, Maria Tereza F.
AU - Alghoul, Heba
AU - Alser, Osaid
AU - Alshammari, Thamir M.
AU - Areia, Carlos
AU - Biedermann, Patricia
AU - Banda, Juan M.
AU - Burn, Edward
AU - Casajust, Paula
AU - Fister, Kristina
AU - Hardin, Jill
AU - Hester, Laura
AU - Hripcsak, George
AU - Kaas-Hansen, Benjamin Skov
AU - Khosla, Sajan
AU - Kolovos, Spyros
AU - Lynch, Kristine E.
AU - Makadia, Rupa
AU - Mehta, Paras P.
AU - Morales, Daniel R.
AU - Morgan-Stewart, Henry
AU - Mosseveld, Mees
AU - Newby, Danielle
AU - Nyberg, Fredrik
AU - Ostropolets, Anna
AU - Woong Park, Rae
AU - Prats-Uribe, Albert
AU - Rao, Gowtham A.
AU - Reich, Christian
AU - Rijnbeek, Peter
AU - Sena, Anthony G.
AU - Shoaibi, Azza
AU - Spotnitz, Matthew
AU - Subbian, Vignesh
AU - Suchard, Marc A.
AU - Vizcaya, David
AU - Wen, Haini
AU - Wilde, Marcel De
AU - Xie, Junqing
AU - You, Seng Chan
AU - Zhang, Lin
AU - Lovestone, Simon
AU - Ryan, Patrick
AU - Prieto-Alhambra, Daniel
N1 - Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Objectives: Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA. Methods: We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%. Results: A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, 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/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, 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/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis. Conclusion: HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation. Trial registration: Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.
AB - Objectives: Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA. Methods: We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%. Results: A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, 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/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, 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/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis. Conclusion: HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation. Trial registration: Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.
UR - http://www.scopus.com/inward/record.url?scp=85105017507&partnerID=8YFLogxK
U2 - 10.1093/rheumatology/keaa771
DO - 10.1093/rheumatology/keaa771
M3 - Article
C2 - 33367863
AN - SCOPUS:85105017507
SN - 1462-0324
VL - 60
SP - 3222
EP - 3234
JO - Rheumatology (United Kingdom)
JF - Rheumatology (United Kingdom)
IS - 7
ER -