key: cord-0911827-242yq90p authors: Emmanuel, Stip; Ostlundh, Linda title: Psychiatric adverse events with hydrochloroquine during COVID-19 Pandemic date: 2020-06-20 journal: Asian J Psychiatr DOI: 10.1016/j.ajp.2020.102203 sha: ffbf299250930f7e39dc86d29f575fb261da14c2 doc_id: 911827 cord_uid: 242yq90p • Hydrochloroquine, well known in rheumatology, dermatology and tropical medicine is now considered in the treatment and prophylaxy for the SARS-CoVid19. • Mental and neurological manifestations should be assessed following the use of hydrochloroquine particularly following prophylactic use. • For acute malaria studies, hydroxychloroquine was associated with high prevalence of mental neurological manifestations amongst anti-malaria drugs. • Recommendations of using hydrochloroquine in COVID are variable and sometimes contradictory depending on agencies and countries. Psychiatric adverse events with hydrochloroquine during COVID-19 Pandemic. Emmanuel Stip *stipe@uaeu.ac.ae, Linda Ostlundh *Corresponding author: emmanuel stip, Affiliation: CMHS, United Arab Emirates University, Department of psychiatry and behavioural sciences, Al Ain, UAE +9171 505315058 Highlights  Hydrochloroquine, well known in rheumatology, dermatology and tropical medicine is now considered in the treatment and prophylaxy for the SARS-CoVid19 .  Mental and neurological manifestations should be assessed following the use of hydrochloroquine particularly following prophylactic use.  For acute malaria studies, hydroxychloroquine was associated with high prevalence  of mental neurological manifestations amongst anti-malaria drugs.  Recommendations of using hydrochloroquine in COVID are variable and sometimes contradictory depending on agencies and countries. The directives and evidence concerning drugs for the treatment and prophylaxis of Covid-19 are rapidly evolving. COVID-19 is now pandemic and recent publications in the Asian Journal of Psychiatry have fruitfully synthesized the impact of the pandemic on mental health (Mukhtar 2020 , Rajkumar 2020 , Tandon 2020 , Zhao 2020 . In such a context and given the worldwide experience, it is notable that the mental health of frontline health care providers is affected (Mohindra 2020). With this pandemic, some people receive hydrochloroquine (HCO) either as a treatment or as a prophylaxis (Abena 2020 , Colson 2020 , Cortegiani 2020 , ICMR 2020 , Liu 2020 , Rathi 2020 . Precautions have to be taken because of the psychiatric vulnerability in some individual and the side effects of this drug (Juurlink 2020 , Stip 2020 , Touret 2020 . For instance, the FDA has authorized clinicians to prescribe chloroquine and hydroxychloroquine for patients admitted to hospital with covid-19, and in parallel there were warnings from scientific advisers that no randomized controlled trial has been completed to date to support the drugs' safety and efficacy in this COVID-19 population (Lenzer 2020 , Owens 2020 insomnia and psychomotor agitation. The blood count, electrolytes, kidney, hepatic function, glycemia were normal, the thick smear microscopy was negative, no biological inflammatory syndrome, urine drug screen negative, as well as the CT scan, EEG and ECG. The chloroquine level was 0.5 mg / L. Chloroquine was stopped. Evolution was good after an 8-day stay in the psychiatric ward. She received olanzapine 7.5 mg 5 days and the episode was attributed to a psychiatric adverse event (PAE). Before going to India, the patient wants to be reassured and get evidence-based information. Chloroquine is used to prevent and treat malaria. The addition of a hydroxide derivative to Hydrochloroquine has also attracted attention as a possible treatment or prophylaxy for the COVID-19 (Mitja 2020). In recent years, biological and clinical work has shown that beyond its anti-inflammatory and immunomodulatory action, hydroxychloroquine can improve the risk vascular by acting directly on the lipid profile and has antithrombotic property (Frimpong 2018) . It shows also an in vitro antiviral activity against a range of RNA viruses. Its mechanism of action is likely acting via the golgi vesicle, lysosome pH increase. Psychiatric side effects could be related to the cholinergic imbalance and to the down regulation of P-glycoprotein. To answer the patient, a literature review was performed using PubMed and Scopus to identify relevant all-language articles published through April 2020. Search terms included various psychiatric symptoms or side effects (depression, anxiety, psychosis) and hydrochloride. Search terms for relevant publication types (case reports, case series, RCTs, systematic reviews and meta-analysis) were also included (See Table 1 ). We found 113 relevant case reports, 12 systematic reviews/meta-analysis and 18 RCTs. Additional relevant articles were identified from the army registry from different countries (France, Korea, Uganda, Italy, UK USA) (Migliani 2014 ,Korwal 2005 , Duparc 2020 , Touze 2001 , 2007 ,Yeom 2005 . Active clinical trials were Chloroquine and hydroxychloroquine for the prevention or treatment of Novel Coronavirus Disease (COVID-19) in Africa: caution for inappropriate off-label use in healthcare settings Antimalarial drugs and the prevalence of mental and neurological manifestations: A systematic review and metaanalysis Chloroquine for the 2019 novel coronavirus Neurological and psychiatric safety of tafenoquine in Plasmodium vivax relapse prevention: a review Safety and effectiveness of antimalarial therapy in sickle cell disease: a systematic review and network meta-analysis Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection Neuropsychiatric adverse events of chloroquine: A real-world pharmacovigilance study using the FAERS database Malaria control strategies in French armed forces Use of antiviral drugs to reduce COVID-19 transmission An Outbreak of Malaria in US Army Rangers Returning From Afghanistan Covid-19: US gives emergency approval to hydroxychloroquine despite lack of evidence Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro Issues relevant to mental health promotion in frontline health care providers managing quarantined/isolated COVID19 patients Psychosis following chloroquine ingestion: a 10-year comparative study from a malaria-hyperendemic district of India Exacerbations of bipolar disorder triggered by chloroquine in systemic lupus erythematosus-a case report Chloroquine psychosis Chloroquine psychosis masquerading as PCP: a case report Transient global amnesia following ingestion of chloroquine Psychosis likely induced by hydropxychloroquine in a patient with chronic Q fever: a case report and clinically relevant review of pharmacology Antimalarial psychosis revisited Toxic psychosis due to chloroquine Psychiatric symptoms induced by hydroxychloroquine Behavorial toxicity and equivocal suicide associated with chloroquine and its derivatives Hydroxychloroquine-induced acute psychosis in a systemic lupus erythematosus female Suicide by skull stab wounds: a case of drug-induced psychosis Chloroquine-associated psychosis mimicking very late-onset schizophrenia: case report Manic episode Lovestone S. Chloroquine-induced mania Psychose aiguë après prise de chloroquine Prolonged neuropsychiatric effects following management of chloroquine intoxication with psychotropic polypharmacy Chloroquine psychosis: a chemical psychosis? Toxic psychosis during chloroquine treatment Two cases of chloroquine psychosis Psychotic symptoms in volunteers serving overseas Insomnia Lupus Reis J. Insomnia induced by chloroquine in the treatment of lupus erythematosus disseminatus Psychiatric complications with chloroquine and quinacrine Chloroquine-induced recurrent psychosis Toxic psychosis due to quinacrine and chloroquine Serious psychiatric symptoms after chloroquine treatment following experimental malaria infection Chloroquine seizures Psychosis with paranoid delusions after a therapeutic dose of mefloquine: a case report Toxic psychosis : a complication of antimalarial therapy