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

Abstract

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.

Systematic Review of Psychiatric Adverse Effects Induced by Chloroquine and Hydroxychloroquine: Case Reports and Population Studies

“…A total of 22 psychiatric adverse effects were mentioned, which the most common were auditory hallucinations, increased psychomotor activity, irritable mood, suicide ideation, and visual hallucinations (Supplemental Table S1). One study 79 reported a suicide attempt. Psychiatric adverse effects for 3 case reports reemerged, respectively, in 2 weeks, 72 3 weeks, 65 3 months, 68 and 5 years 8 after HCQ was reintroduced.…”

Concurrent infection of human brain with multiple species of Lyme disease spirochetes

“…It remains an open question whether long-term antimicrobial treatment may have contributed to the progression of neurological symptoms in reported patient. Two of the drugs he used are suspected to have neurological or neuropsychiatric side effects, namely minocycline (64)(65) and hydroxychloroquine (66)(67)(68). Either long-term or repeated antibiotic therapy of PTLDS also carries a number of other risks, including development of significant, even life-threatening disorders such as necrotising enterocolitis or systemic candidiasis (69)(70).…”

A Prospective Multicenter Longitudinal Analysis of Suicidal Ideation among Long-COVID-19 Patients

“…This discrepancy might be explained by the absence of a direct and acute impact of SARS-CoV2 infection on vulnerable neurobiological circuits underlying SI/SB development. However, while a direct and acute impact may be absent, it is essential to consider that indirect effects, such as chronic residual low-grade inflammation, the use of certain medications like chloroquine, and the gradual development of psychiatric symptoms, including depression and anxiety [15,[38][39][40][41][42][43], may still play a significant role in predicting a possible rise in SI/SB risk during the post-acute phase of SARS-CoV-2 infection.…”