Psychomotor Agitation Following Treatment with Hydroxychloroquine

Abstract

We describe the case of an elderly woman with elderly-onset rheumatoid arthritis, where the use of 4 mg/kg/day of hydroxychloroquine (HCQ) was followed by the onset of psychomotor agitation with marked physical and verbal violence towards her partner, including throwing objects at her partner. No disturbance in sleep and no anxiety, nervousness, or irritability had emerged before the onset of her psychomotor agitation. The disappearance of agitation following targeted pharmacologic intervention and HCQ interruption, its re-onset after reintroduction of the drug, and the high score (9) of Naranjo’s algorithm are surely linked to the existence of a causal relationship between HCQ and psychomotor agitation. HCQ may produce undesirable effects on the central nervous system, mainly irritability, nervousness, emotional changes, and nightmares. To the best of our knowledge, there are only a few case reports of psychosis due to HCQ. No favoring condition such as pharmacokinetic interactions or a personal and family psychiatric history was present in our patient. The neuropsychiatric manifestations we observed could be considered a bizarre-type adverse drug reaction linked to an individual’s hypersensitivity.

Hydroxychloroquine increased psychiatric-like behaviors and disrupted the expression of related genes in the mouse brain

“…Our results did not reveal a significant effect of HCQ treatment on working memory, but total exploration time was decreased after HCQ administration, which also suggests that the drugs increased anxiety. Previous human studies have reported that HCQ can induce anxiety-and depression symptoms (10,11), but no reports have shown that it impairs cognitive function. However, there have been only a few reports in humans, and there is a close relationship between cognitive impairment and psychiatric disorders (24).…”

“…There have been reports of serious adverse effects related to HCQ, including retinopathy, QT interval prolongation, hypoglycemia, cardiomyopathy, neuropsychiatric effects and so on (7,8), and QT interval prolongation is the most closely monitored adverse effect in patients with SARS-COV-2. Less attention has been paid to the effects of HCQ on mental health, although multiple studies have reported severe psychiatric symptoms, including agitation, hallucinations, anxiety, depression, and suicidal ideation, in patients treated with HCQ or chloroquine (9)(10)(11)(12). However, whether these neuropsychiatric symptoms are caused by HCQ alone or by the interaction between HCQ and the disease is not well studied, possibly due to the limited number of reported cases.…”

Severe acute respiratory syndrome coronavirus 2 may be an underappreciated pathogen of the central nervous system

“…For example, chloroquine and hydroxychloroquine, which were commonly used earlier in the pandemic, could potentially increase the likelihood of neurological disorders, especially in the elderly [114]. The use of hydroxychloroquine has been associated with neuropsychiatric manifestations including irritability, nervousness and psychosis, possibly by its ability to cross the BBB [115]. Corticosteroids, another common group of medications used to treat severe cases of COVID-19, have also been associated with psychiatric symptoms, especially when administered at high doses [116].…”

Sweet’s Syndrome Following Therapy with Hydroxychloroquine in a Patient Affected with Elderly-Onset Primary Sjogren’s Syndrome

“…There are numerous side effects during HCQ therapy, some of which are favored according to predisposing or precipitant factors. Among these, cytochrome P450 3A4 inhibitors (such as indinavir, nelfinavir, ritonavir, clarithromycin, erythromycin, fluconazole, itraconazole, ketoconazole, amiodarone, cimetidine, diltiazem, and verapamil) may increase the half-life of HCQ, favoring its toxicity [31].…”