Supplementary material. S4. Evaluating the methodological quality of case reports and case series with the Naranjo scale
Cases
1. Are there previous conclusive reports on this reaction?
2. Did the adverse event appear after the suspected drug was administered?
3.Did the adverse reaction improve when the drug was discontinued or a specific antagonist was administered?
4. Did the adverse event reappear when the drug was re‐
administered?a
5. Are there alternative causes (other than the drug) that could on their own have caused the reaction?a
6. Did the reaction reappear when a placebo was given?
7. Was the drug detected in blood (or other fluids) in concentrations known to be toxic?
8. Was the reaction more severe when the dose was increased or less severe when the dose was
decreased?
9. Did the patient have a similar reaction to the same or similar drugs in any previous exposure?
10. Was the
adverse event confirmed by any objective evidence?
Overall rating
1-Suwanwongse et al.2020 [1]
Case 1
Yes Yes Yes Do not know Yes Do not know Yes Yes No Yes Probable
2-Suwanwongse et al.2020 Case 2
Yes Yes Yes Do not know Yes Do not know Yes Yes No Yes Probable
3- Llesuy &
Sidelnik, 2020[2] Yes Yes Do not know Do not know Yes Do not know Do not know Do not know No Yes Possible
4 -Cranshaw &
Harikumar, 2020 [3]
Yes Yes Yes No Yes Do not know No Do not know No Yes Possible
5- Doston et al.
2020 [4]
Case 1 Yes Yes Yes No Yes Do not know Yes Yes No Yes Possible
6- Doston et al.
2020 Case 2
Yes Yes Yes No Do not know Do not know Yes Yes No Yes Possible
7- Doston et al.
2020 Case 3
Yes Yes Yes No Yes Do not know Yes Yes No Yes Possible
8-Sokolov et al.
2020 [5] Yes Yes Yes No Yes Do not know Yes Yes No Yes Probable
9- Butler et al.
2020[6]
Patient G
Yes Yes Yes No Yes Do not know Yes Yes No Yes Probable
10- Soh et al.
2020 [7]
Case 2
Yes Yes Yes Do not know No Do not know Do not know Yes No Yes Possible
11- Serrano et al.
2020 [8]
Case 2 Yes Yes Yes Do not know No Do not know Do not know Yes No Yes Possible
12- Kajani et al.
2020 [9] Yes Yes Yes Do not know Yes Do not know Do not know Do not know No Yes Possible
13- Serrano et al.
2020 Case 1
Yes Yes Yes Do not know No Do not know Do not know Do not know No Yes Possible
a Item 4 must be interpreted with caution, as the patient were affected with a SARS-COV-2 infection only once.
The ADR Probability Scale consists of 10 questions that are answered as either Yes, No, or “Do not know”. Different point values (-1, 0, +1 or +2) are assigned to each answer. The actual ADR Probability Scale form and instructions on how it is completed are provided below. Total scores range from -4 to +13.
Naranjo Algorithm - ADR Probability Scale Interpretation of Scores:
Total Score ≥9- Definite. The reaction (1) followed a reasonable temporal sequence after a drug or in which a toxic drug level had been established in body fluids or tissues, (2) followed a recognized response to the suspected drug, and (3) was confirmed by improvement on withdrawing the drug and reappeared on reexposure.
Total Score 5 to 8- Probable. The reaction (1) followed a reasonable temporal sequence after a drug, (2) followed a recognized response to the suspected drug, (3) was confirmed by withdrawal but not by exposure to the drug, and (4) could not be reasonably explained by the known characteristics of the patient’s clinical state.
Total Score 1 to 4- Possible. The reaction (1) followed a temporal sequence after a drug, (2) possibly followed a recognized pattern to the suspected drug, and (3) could be explained by characteristics of the patient’s disease.
Total Score ≤0- Doubtful. The reaction was likely related to factors other than a drug.
References
[1] Suwanwongse K and Shabarek N. Lithium Toxicity in Two Coronavirus Disease 2019 (COVID-19) Patients. Cureus 2020;12:e8384-e8384.
[2] Llesuy JR and Sidelnik SA. Death From COVID-19 in a Patient Receiving Clozapine: Factors Involved and Prevention Strategies to Consider. Prim Care Companion CNS Disord. 2020.
[3] Cranshaw T and Harikumar T. COVID-19 Infection May Cause Clozapine Intoxication: Case Report and Discussion. Schizophrenia Bulletin 2020;46:751-751.
[4] Dotson S, Hartvigsen N, Wesner T, Carbary TJ, Fricchione G and Freudenreich O. Clozapine Toxicity in the Setting of COVID-19. Psychosomatics 2020;61:577-578.
[5] Sokolov E, Hadavi S, Mantoan Ritter L and Brunnhuber F. Non-convulsive status epilepticus: COVID-19 or clozapine induced? BMJ Case Reports 2020;13:e239015.
[6] Butler M, Bano F, Calcia M, McMullen I, Sin Fai Lam CC, Smith LJ, et al. Clozapine prescribing in COVID-19 positive medical inpatients: a case series. Ther Adv Psychopharmacol 2020;10:2045125320959560-2045125320959560.
[7] Soh M, Hifumi T, Isokawa S, Shimizu M, Otani N and Ishimatsu S. Neuroleptic malignant syndrome in patients with COVID-19. The American Journal of Emergency Medicine 2020.
[8] Mas Serrano M, Pérez-Sánchez JR, Portela Sánchez S, De La Casa-Fages B, Mato Jimeno V, Pérez Tamayo I, et al. Serotonin syndrome in two COVID-19 patients treated with lopinavir/ritonavir. J Neurol Sci 2020;415:116944-116944.
[9] Kajani R, Apramian A, Vega A, Ubhayakar N, Xu P and Liu A. Neuroleptic malignant syndrome in a COVID-19 patient. Brain Behav Immun 2020;88:28-29.
