Risk of depression, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis: a multinational network cohort study

Lane, Jennifer C E; Weaver, James; Kostka, Kristin; Duarte‐Salles, Talita; Abrahão, Maria Tereza Fernandes; Alghoul, Heba; Alser, Osaid; Alshammari, Thamir M; Areia, Carlos; Biedermann, P; Banda, Juan M.; Burn, Edward; Casajust, Paula; Fišter, Kristina; Hardin, Jill; Hester, Laura; Hripcsak, George; Kaas‐Hansen, Benjamin Skov; Khosla, Sajan; Kolovos, Spyros; Lynch, Kristine E.; Makadia, Rupa; Mehta, Paras; Moralès, Daniel; Morgan-Stewart, H; Mosseveld, Mees; Newby, Danielle; Nyberg, Fredrik; Ostropolets, Anna; Park, Rae Woong; Prats‐Uribe, Albert; Rao, Gowtham; Reich, Christian; Sena, Anthony G.; Shoaibi, Azza; Spotnitz, Matthew; Subbian, Vignesh; Suchard, Marc A.; Vizcaya, David; Wen, Haini; Wilde, Marcel de; Xie, Junqing; You, Seng Chan; Zhang, Lin; Lovestone, Simon; Ryan, Patrick B.; Prieto‐Alhambra, Daniel

doi:10.1093/rheumatology/keaa771

Cited by 41 publications

(16 citation statements)

References 42 publications

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“…This risk was particularly signalized among patients in co-treatment with metformin or elderly (possibly due to diminished neuronal reserve and presence of mixed neurodegenerative and vascular brain injuries) [ 23 , 26 , 30 ]. However, these findings have not been corroborated in other studies [ 24 , 25 , 28 ]. Of interest to its neuropsychiatric AEs, CQ/HCQ exhibits neurotropism as CQ level in the CNS was shown to be 10–30 times higher than its serum concentration after dosing [ 31 ].…”

Section: Discussioncontrasting

confidence: 74%

“…CQ/HCQ have been associated with several neuropsychiatric AEs in rheumatic diseases, infectious diseases, and COVID-19 [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. These AEs can range from relatively mild psychiatric symptoms, such as irritability, nervousness, and insomnia, to intermediate and severe clinical conditions including adjustment disorder, anxiety also with pervasive features, “personality change”, major depression, psychosis, confusion, psycho-motor agitation, delirium, and neurocognitive disorders [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ] ( Table 1 ). Notably, some evidence of increased risk of SI/SB has been described [ 21 , 22 , 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…Since CQ and HCQ exhibit similar physiochemical properties, many pharmacokinetic features of HCQ are often inferred from CQ studies [ 1 ].. Given the neurotropic impact of CQ/HCQ, all studies recommend informing patients and their relatives about this possible increase in suicide risk without discouraging the necessary use of CQ/HCQ for the underlying pathological conditions [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

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Chloroquine/Hydroxychloroquine Use and Suicide Risk: Hypotheses for Confluent Etiopathogenetic Mechanisms?

Costanza

Placenti

Amerio

et al. 2021

Behavioral Sciences

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Chloroquine (CQ) and hydroxychloroquine (HCQ) are classical anti-malarial and anti-inflammatory treatments, which were used as first-line therapy at the beginning of the 2019 coronavirus disease (COVID-19) pandemic. Besides the emerging data on their lack of efficacy against COVID-19 infection, such treatments have been associated with some severe health concerns, including those of neuropsychiatric nature, such as a possible increase in suicide risk. Here we report a case of a patient with no history of psychiatric illnesses, who abruptly developed depression with melancholic features, severe suicidal ideation (SI), and attempted suicide (SA) shortly after receiving HCQ for his COVID-19 infection. The case was followed by a mini-review of the heterogeneous scientific literature on the hypothetical association between neuropsychiatric symptoms, with a focus on SI and suicidal behavior (SB, including SA and death by suicide), when CQ and HCQ are used in COVID-19, rheumatologic diseases, and malaria settings. Considering the anti-inflammatory properties of CQ and HCQ and the implications for neuroinflammation in suicide pathogenesis, the possible increase in suicide risk caused by these medications appears paradoxical and suggests that other underlying pathological trajectories might account for this eventuality. In this regard, some of these latter mechanistic postulates were proposed. Certainly the role and contribution of psycho-social factors that a COVID-19 patient had to face can neither be minimized nor excluded in the attempt to understand his suffering until the development of SI/SB. However, while this case report represents a rare scenario in clinical practice and no consensus exists in the literature on this topic, a psychiatric screening for suicide risk in patients using of CQ and HCQ could be carefully considered.

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Chloroquine/Hydroxychloroquine Use and Suicide Risk: Hypotheses for Confluent Etiopathogenetic Mechanisms?

Costanza

Placenti

Amerio

et al. 2021

Behavioral Sciences

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“…One example is the association of hydroxychloroquine with psychiatric conditions such as suicidal and self-injurious behaviors and hallucinations with hydroxychloroquine. This association has indeed been detected, in COVID-19 patients in the WHO spontaneous reporting system ( Garcia et al, 2020 ), although there is also contrary evidence pointing to the psychiatric safety of hydroxychloroquine in rheumatoid arthritis ( Lane et al, 2020 ).…”

Section: Discussionmentioning

confidence: 96%

Development of a Network-Based Signal Detection Tool: The COVID-19 Adversome in the FDA Adverse Event Reporting System

et al. 2021

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Introduction: The analysis of pharmacovigilance databases is crucial for the safety profiling of new and repurposed drugs, especially in the COVID-19 era. Traditional pharmacovigilance analyses–based on disproportionality approaches–cannot usually account for the complexity of spontaneous reports often with multiple concomitant drugs and events. We propose a network-based approach on co-reported events to help assessing disproportionalities and to effectively and timely identify disease-, comorbidity- and drug-related syndromes, especially in a rapidly changing low-resources environment such as that of COVID-19.Materials and Methods: Reports on medications administered for COVID-19 were extracted from the FDA Adverse Event Reporting System quarterly data (January–September 2020) and queried for disproportionalities (Reporting Odds Ratio corrected for multiple comparisons). A network (the Adversome) was estimated considering events as nodes and conditional co-reporting as links. Communities of significantly co-reported events were identified. All data and scripts employed are available in a public repository.Results: Among the 7,082 COVID-19 reports extracted, the seven most frequently suspected drugs (remdesivir, hydroxychloroquine, azithromycin, tocilizumab, lopinavir/ritonavir, sarilumab, and ethanol) have shown disproportionalities with 54 events. Of interest, myasthenia gravis with hydroxychloroquine, and cerebrovascular vein thrombosis with azithromycin. Automatic clustering identified 13 communities, including a methanol-related neurotoxicity associated with alcohol-based hand-sanitizers and a long QT/hepatotoxicity cluster associated with azithromycin, hydroxychloroquine and lopinavir-ritonavir interactions.Conclusion: Findings from the Adversome detect plausible new signals and iatrogenic syndromes. Our network approach complements traditional pharmacovigilance analyses, and may represent a more effective signal detection technique to guide clinical recommendations by regulators and specific follow-up confirmatory studies.

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“…In China, the Delta variant accounts for most of the new cases since the year of 2021. Previous research has implicated that the COVID-19 pandemic is likely to cause abnormality of emotion, cognition, behavior and quality of life, especially in population with chronic diseases such as systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease (IBD), in whom psychological distress and somatic diseases could influence mutually ( 14 – 16 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of the SARS-CoV-2 Delta Variant on the Psychological States and Health-Related Quality of Life in Patients With Crohn’s Disease

Sun

et al. 2022

Front. Med.

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BackgroundSince the outbreak of the coronavirus disease 2019 (COVID-19) pandemic first reported in Wuhan, China, several research on the psychological impact of the pandemic on patients with Crohn’s disease (CD) have been conducted. However, with the progression of the global pandemic and the emergence of the SARS-CoV-2 B.1.617.2 (Delta) variant, follow-up studies need to be performed to monitor the alterations of psychological status and health-related quality of life (HRQoL) among CD patients.AimsWe aimed to evaluate the impact of the SARS-CoV-2 Delta variant on the mental health and life quality among the CD population and tried to explore potent risk factors.MethodsThis observational study included 153 CD patients who responded to our pre-designed self-reported questionnaire. Demographic, clinical, and psychological information were collected and analyzed.ResultsQuite a number of CD patients were confronted with different levels of anxiety and depression, with incidence of 28.10 and 31.37% for anxiety and depression, respectively. Compared with non-pandemic circumstances, the life quality of CD patients due to the present situation was more often compromised. Isolation [odds ratio (OR): 4.71, P = 0.007] was verified as a risk factor for anxiety while use of telemedicine could help relieve anxiety (OR: 0.22, P < 0.001). Worsening of symptoms (OR: 4.92, P = 0.006), isolation (OR: 5.75, P = 0.005), and drug withdrawn (OR: 2.66, P = 0.026) were identified to be independent factors for developing depression. Likewise, use of telemedicine (OR: 0.13, P < 0.001) was negatively related to depression. Considering life quality, vaccination (OR: 3.07, P = 0.021) together with no medication (OR: 7.73, P = 0.010) was relevant to better life quality while worsening of symptoms (OR: 0.09, P = 0.034) were an independent risk factor for impaired life quality.ConclusionMany CD patients suffered from symptoms of anxiety and depression and impaired life quality during the COVID-19 pandemic. Those in isolation or with worsening of symptoms and drug withdrawn were more prone to experience psychological stress. Individualized management such as drug delivery and telemedicine should be promoted to maintain control of mental health and life quality during the pandemic.

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Risk of depression, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis: a multinational network cohort study

Cited by 41 publications

References 42 publications

Chloroquine/Hydroxychloroquine Use and Suicide Risk: Hypotheses for Confluent Etiopathogenetic Mechanisms?

Chloroquine/Hydroxychloroquine Use and Suicide Risk: Hypotheses for Confluent Etiopathogenetic Mechanisms?

Development of a Network-Based Signal Detection Tool: The COVID-19 Adversome in the FDA Adverse Event Reporting System

Impact of the SARS-CoV-2 Delta Variant on the Psychological States and Health-Related Quality of Life in Patients With Crohn’s Disease

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