Table 1.

Detailed description of identified cases from case reports and case series reporting toxicity of psychotropic drugs in context of a SARS-CoV-2 infection.

Authors	Sex, age (years)	Treatment suspected to have induced toxicity or side-effect and its daily dose	Dosage	Additional treatments	First symptoms at presentation	Psychiatric and medical disease	Vital signs at admission, and blood tests	Diagnosis	Management and outcome
1-Suwanwongse et al.2020 [18] Case 1	F, 67	Lithium 1200 mg/day	2.28 mEq/L	Quetiapine 800 mg/day Insulin, empagliflozin, metformin, sitagliptin, atorvastatin, irbesartan, and aspirin	Alteration of consciousness. Behavior changes. Confusion.	Schizoaffective disorder. Diabetes mellitus, hypertension, and hyperlipidemia	- RR: 18 breaths/min; T: 36.6 °C; HR: 100 bpm; BP: 145/82 mmHg; SpO2: 93%. - Lung exam revealed mild crepitation. A bilateral infiltration at X-ray was visible. - WBC: 7.78 × 10 3/mm3 (lymphocytes 9.4%) - Creatinine: 1.35 mg/dl - ECG was normal. - CT of the head was unremarkable.	- SARS-CoV-2 pneumonia (positive nasopharyngeal swab) -Acute kidney injury, and lithium toxicity	The patient benefit from hydroxychloroquine treatment as per hospital protocol; however, her hospital course was complicated with acute hypoxic respiratory failure and she eventually died on day 4 of her hospitalization.
2-Suwanwongse et al.2020 Case 2	M, 18	Lithium 900 mg/day	2.60 mEq/L	Clozapine 100 mg/day Levothyroxine	Alteration of consciousness. Fever, nasal congestion, and cough for 7 days.	Bipolar disorder, autistic spectrum disorder, attention deficit hyperactivity disorder. Hypothyroidism, and mild persistent asthma.	- RR: 18 breaths/min; T: 101.3 °F; HR: 120 bpm; BP: 120/60 mmHg; SpO2: 98%. - Lung exam was normal. - WBC: 11.79 × 103/mm3 (lymphocytes 17%) - ECG showed sinus tachycardia with an HR of 107 bpm. - CXR was normal.	- SARS-CoV-2 infection (positive nasopharyngeal swab) -Acute kidney injury, and lithium toxicity	Intravenous normal saline was administered for the treatment of lithium intoxication and acute kidney injury. The patient did not receive hemodialysis. The patient received symptomatic treatment for the COVID-19 infection. His conditions were resolving, and he was discharged home without any complications on hospital day 11. Lithium was discontinued.
3- Llesuy & Sidelnik, 2020 [19]	F, 50	Clozapine 300 mg/day	n.a.	Quetiapine 100 mg/day	At admission, the patient was febrile and in respiratory distress.	Schizophrenia Diabetes, obesity, and active cigarette use	- T: 38.3 °C; SpO2: 93% under oxygen - C-reactive protein: 330.4 mg/L - Lymphopenia: 900/μL - Hemoglobin A1c of 8% - CXR found bilateral opacities.	- Acute respiratory distress syndrome on a COVID-19 pneumonia -Implication of clozapine is unclear	Patient was intubated for hypoxic respiratory failure and admitted to the intensive care unit. On hospital day 6, she had evidence of pulmonary embolus, was started on tissue plasminogen activator with no improvement, and died. Both clozapine and quetiapine were held during the hospitalization.
4 -Cranshaw & Harikumar, 2020 [16]	M, 38	Clozapine 325 mg/day	Clozapine 730 ng/mL Norclozapine 310 ng/mL	Absence	Cough, headache, and reduced oxygen saturation. Followed the next day with drowsiness, markedly increased hypersalivation and myoclonus.	Organic psychosis	- SpO2 94% on room air	- SARS-CoV-2 infection (positive nasopharyngeal swab) - Possible precipitation of clozapine toxicity by SARS-CoV-2 infection	Clozapine was discontinued during one day due to COVID-19 induced lymphopenia (0.76 × 109/l), and the following day to a transient mild neutropenia (1.26 × 109/l). The patient made an uncomplicated recovery from COVID-19 however experienced a relapse in psychotic symptoms as result of temporary clozapine cessation.
5- Doston et al. 2020 [39] Case 1	M, 76	Clozapine 300 mg/day	1360 ng/mL	Absence	The patient was admitted to the hospital with COVID-19 and catatonia one month after missing his last ECT treatment.	Bipolar-type schizoaffective disorder complicated by recurrent catatonia	- Neutropenia with a nadir absolute neutrophil count of 1.100	-SARS-CoV-2 infection with catatonia -Implication of clozapine is unclear	The interpretation of the neutropenia is difficult, as the patient received an experimental COVID-19 medication (tocilizumab) that is associated with neutropenia. His absolute neutrophil count gradually rebounded to the 4000 s, and his catatonia resolved with lorazepam and a reduction of clozapine to 200 mg QHS.
6- Doston et al. 2020 Case 2	F, 63	Clozapine 400 mg/day (this treatment was started many years ago)	1060 ng/mL.	Citalopram 20 mg/day Olanzapine 20 mg/day	At admission, the patient initially presented with nausea and confusion. She was found to have COVID-19, hyponatremia, and an ileus.	Bipolar-type schizoaffective disorder	- Hyponatremia: 110 mmol/L - Absolute neutrophil count of 14.970	- SARS-CoV-2 infection with an paralytic ileus - Possible precipitation of clozapine side effect by SARS-CoV-2 infection	Due to the presence of an ileus, clozapine was held for 1 week without adverse consequences, and the drug was gradually reintroduced.
7- Doston et al. 2020 Case 3	F, 53	Clozapine 250 mg/day (this treatment was started many years ago)	Dosage before infection: 458 ng/mL. Dosage at admission: 2154 ng/mL	Fluphenazine 15 mg/day	The patient initially presented with delirium, fever, and vomiting.	Schizophrenia	- Absolute neutrophil count of 2200	- SARS-CoV-2 infection with delirium - Possible precipitation of a clozapine intoxication by SARS-CoV-2 infection	Clozapine dose was decreased to 50 mg with a temporary increase of fluphenazine to 10 mg twice daily. She tolerated a gradual return to her home dose with normalization in her mental status.
8-Sokolov et al. 2020 [40]	F, 57	Clozapine 100 mg in the morning and 175 mg at night (this treatment was started many years ago)	n.a.	Metformin and insulin	The patient presented with shortness of breath and fever. She was transferred to intensive care for intubation and ventilation. She was found to have COVID-19 and a community-acquired pneumonia.	Schizoaffective disorder Depression Chronic obstructive pulmonary disease Pulmonary embolism Type 2 diabetes	During admission: - SpO2 91% on 40% oxygen; RR:22/min - Type 1 respiratory failure At day ten post-extubation: - MRI brain scan was normal - EEG: Frequent (2.5–4 Hz), florid bilateral, non-synchronous epileptiform discharges were seen over both hemispheres.	- SARS-CoV-2 pneumonia (positive nasopharyngeal swab) - Acute kidney injury - Nonconvulsive status epilepticus following the reintroduction of clozapine	After a month of ventilation, the patient was extubated. Clozapine was slowly reintroduced. However, the patient was unable to speak or obey commands and opened her eyes only to pain. Some new onset intermittent right-sided facial jerks were noted. She was diagnosed with non-convulsive status epilepticus on EEG. She was commenced on levetiracetam, and clozapine was abruptly reduced from 275 to 125 mg/day with good effect.
9- Butler et al. 2020 Patient G [41]	F, 57	Clozapine 150 mg in the morning and 200 at night.	n.a.	Aripiprazole 10 mg/day, Lithium carbonate MR 400 mg, Sertraline 200 mg	The patient was admitted to acute inpatient medical care with hypoxia, hemodynamic instability. On day 2 she was transferred to intensive care and was intubated for mechanical ventilation.	Treatment resistant schizophrenia	- SpO2 94% on 10 L oxygen Supplementation - C-reactive protein: 122 mg/L - WBC: 14.2 × 109/L - Neutrophils: 10.3 × 109/L	- SARS-CoV-2 pneumonia (positive nasopharyngeal swab) - Type I respiratory failure - Nonconvulsive status epilepticus following the reintroduction of clozapine	Uptitration of clozapine was started on day 19, and she was extubated on day 32. Clozapine was started at 12.5 mg/day, increasing in steps of 12.5 mg daily, then increasing by 25 mg daily for the following 2 weeks until a dose of 450 mg was reached. Her lithium continued to be paused because of poor renal function. On day 44 she was noted to be ‘twitching’ and a subsequent electroencephalogram confirmed non-convulsive status epilepticus. Clozapine was reduced to 25 mg with good effect.
10- Soh et al. 2020 [14] Case 2	M, 44	Risperidone n.a.	n.a.	Favipiravir, 1600 mg/day Tazobactam/ piperacillin and azithromycin	On day 5, risperidone was started for delirium. On day 7 the patient body temperature increased to 40.8 °C. CK level elevated, tachycardia, tachypnea, altered consciousness, and diaphoresis appeared.	No previous psychiatric history	- T: 40 °C - CK level elevated - Tachycardia - Tachypnea	-Acute respiratory distress syndrome on a SARS-CoV-2 pneumonia with an acute delirium following intensive care - Neuroleptic malignant syndrome possibly precipitated by the SARS-CoV-2 infection	Neuroleptic malignant syndrome diagnosis was confirmed, and both, favipiravir and risperidone were discontinued on day 8. On the day 8, CK levels decreased, and body temperature normalized on day 9. Later on, the patient's condition stabilized.
11- Serrano et al. 2020 [15] Case 2	M, 78	Risperidone 2 mg/day in combination with lopinavir/ritonavir n.a.	n.a.	Lopinavir/ritonavir, 400/100 mg and hydroxychloroquine 200 mg, twice daily. Two doses of interferon beta-1b on days 3 and 4 Single administration of tocilizumab on day-9 Risperidone, 2 mg/day (started during hospitalization) Morphine 3 mg/day	By day-10 the patient developed acute delirium that required 1 mg of risperidone twice daily for the next 48 h and a single administration of 3 mg of morphine for dyspnea control. Subsequently, the patient's level of consciousness worsened, and he developed tachycardia, diaphoresis, and hyperthermia that was unresponsive to antipyretics.	No previous psychiatric history. Hypertension, diabetic chronic kidney disease, and prior colorectal cancer	- CK level 802 U/L - C-reactive protein: 1.06 mg/dL	- SARS-CoV-2 infection (positive nasopharyngeal swab) -Acute delirium possibly induced by the association of antivirals drugs -Serotoninergic syndrome possibly precipitated by the several combinations of drug, or the SRAS-CoV-2 infection	Due to serotoninergic syndrome suspicion, lopinavir/ritonavir and risperidone were immediately discontinued, instead adding fluid therapy, active cooling, and 0.25 mg of clonazepam every 6 h. The symptoms rapidly improved and resolved within the next several days.
12- Kajani et al. 2020 [42]	M, (35 to 58)	Haloperidol long-lasting injection n.a.	n.a.	Cefepime, linezolid, ampicillin, acyclovir, and hydroxychloroquine	The patient was admitted for an altered mental status. On admission, he was febrile, tachycardic, and tachypneic. On exam, the patient had a rigid posture and could not respond to painful stimuli.	Schizophrenia Hepatitis C	- RR: 18 breaths/min; T: 36.6 °C; HR: 122 bpm; BP: 109/71; SpO2: 93%. - Mild leukocytosis (12.3 K/mm3) with a neutrophilic predominance (87.2%) and lymphopenia (5.1%). Cerebral spinal fluid (CSF) analysis revealed 0 WBC, 0 RBC and normal protein. - C-reactive protein: 5.8 mg/dl - EEG showed slow background and occasional right hemispheric discharge associated with some left-hand tremor - CXR revealed bilateral peripheral infiltrates	- SARS-CoV-2 infection (positive PCR test) - Acute kidney failure - Neuroleptic malignant syndrome possibly precipitated by the SARS-CoV-2 infection	The patient was admitted to the ICU for ventilator management and treatment of his altered mental status with associated rhabdomyolysis and acute kidney failure. Maximum accumulated dose of dantrolene of 10 mg/kg IV was administered over a two-day period followed by bromocriptine 5 mg loading dose then 2.5 mg three times daily. He was initiated on hemodialysis for acute renal failure. Hydroxychloroquine treatment was continued for a planned duration of five days. His CK began to downtrend on hospital day 4, and rigidity also improved at around the same time. He remained intubated and sedated, with no improvement in mentation.
13- Serrano et al. 2020 Case 1	M, 66	Duloxetine in combination with lithium and lopinavir/ ritonavir n.a.	n.a.	Lithium (800 mg/day) and duloxetine (120 mg/day) Haloperidol 2 mg/day Lopinavir/ritonavir, 400/100 mg and hydroxychloroquine 200 mg, twice daily	By day-3, the patient developed delirium, and 1 mg of haloperidol twice daily was added. For the next 4 days, his level of consciousness progressively declined, in association with high blood pressure, tachycardia, diaphoresis, and urinary retention.	Bipolar disorder Cervical spinal stenosis	- CK level: 767 U/L - Creatinine level: 1.47 mg/dL	- SARS-CoV-2 bilateral pneumonia (positive nasopharyngeal swab) -Acute delirium possibly induced by the association of antivirals drugs -Serotoninergic syndrome possibly precipitated by the several combinations of drug, or the SRAS-CoV-2 infection	Due to serotoninergic syndrome suspicion, duloxetine, lithium, haloperidol, and lopinavir/ritonavir were discontinued. Cyproheptadine at 8 mg every 6 h was started. Over the next 10 days, the myoclonus disappeared and his neurological status improved steadily.

Abbreviations: beats per minute (bpm); blood pressure (BP); breaths per minute (breaths/min); cells per cubic millimeter (/mm3); chest X-Ray (CXR); computed tomography (CT); creatine kinase (CK); degrees Celsius (°C); electrocardiogram (ECG); electroencephalogram (EEG); heart rate (HR); not available (n.a.); oxygen saturation percentage on room air (SpO2); RR: respiratory rate (RR); temperature (T); white blood cells (WBC).