key: cord-0989170-s3hqv6zh
authors: García, C.A. Carrajo; Sánchez, E.B. Alonso; Huerta, D. Hernández; Gómez-Arnau, J.
title: Covid-19 treatment-induced neuropsychiatric adverse effects
date: 2020-06-10
journal: Gen Hosp Psychiatry
DOI: 10.1016/j.genhosppsych.2020.06.001
sha: 9a53c157bb825b3ef45e56e05a6fbf3795521305
doc_id: 989170
cord_uid: s3hqv6zh

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J o u r n a l P r e -p r o o f the blood-brain barrier they are inherently neurotoxic, showing perioral (25%) and peripheral (7%) paresthesias, as well as changes in taste (12%) since the first month of treatment [4] . The lopinavir-ritonavir combination has been associated with bilateral sensorineural hearing loss after 4 weeks of treatment, and with the appearance of depressive symptoms. Darunavir, however, has not shown increased neurotoxicity [4] .

Corticosteroids modulate hyper inflammation and inhibit inmune responses that are vital for the host defense against the virus. However, side-effects are common, appearing in up to 90% of patients with more than 60 days of treatment, according to the dose range and route of administration. Memory deficits and cognitive impairment have been described, probably in relation to the high number of corticosteroid receptors in the hippocampus. Short course high-dose corticosteroid treatment, as occurs in COVID-19, may cause delirium and changes in mood (with a frequency of up to 52% of patients treated with more than 20 mg a day of prednisone during 3 months) [5] , being mania and hypomania more frequently observed than depression.

Azithromycin is an antibiotic that has been proven to be active in vitro against Zika and Ebola viruses by interfering with their protein synthesis. The distinctive feature of azithromycin is its high and sustained concentration in brain tissue, presumably due to its amphipathic properties and high volume of distribution. Neurological adverse events reported in premarketing clinical trials were mild, occurring in less than 1% of patients.

Serious adverse neuropsychiatric effects such as delirium have been rarely reported in adults [6] .

Despite there is no clear evidence of its efficacy it seems relevant to mention chloroquine and related agents, whose compassionate use is based on the role that they could have in stopping the cytokine storm which contributed to acute respiratory distress caused by SARS-CoV-2. These treatments are able to induce neuropsychiatric symptoms from mild (mood lability, nervousness) to severe degree (psychosis, suicidal tendencies) and the high dose administration is a predictor of complications [7] .

Tocilizumab is a humanized monoclonal antibody approved for the treatment of rheumatoid arthritis (RA). It plays a significant role in IL-6 blockade, which could contribute to reduce the inflammatory cascade in COVID-19. Inhibition of IL-6 may also be responsible for improvements in depression, fatigue and pain, common extraarticular features of RA [8] . Improvements in cognition have also been demonstrated in psychotic disorders such as schizophrenia, although no changes in psychopathology have been described [9] .

Treatments with interferon, remdesivir and nitazoxanide are also being repurposed. In particular, remdesivir, a nucleotide analogue prodrug, is considered a promising antiviral agent in the treatment of critically ill patients, as it causes a blockade in viral RNA polymerases reducing the viral load and alleviating pathological damage to lung tissue. Although there is no evidence of neuropsychiatric side-effects, a close monitoring is necessary in order to minimize risks [10] .

J o u r n a l P r e -p r o o f increasing spread of COVID-19, it is important that psychiatrists stay up-to-date on treatments and remain aware of the occurrence of neuropsychiatric side effects, even not previously described.

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