A Case of Rapid Clozapine Retitration in a Patient With COVID-19 Resulting in Acute Respiratory Demise
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Multiple drugsVarious toxicities, off-label use and lack of efficacy: case report A 68-year-old man developed acute mania, agitation and psychosis following clozapine withdrawal, and worsening of acute mania during off-label treatment with dexamethasone for COVID-19. Additionally, he developed sialorrhoea during treatment with clozapine for schizoaffective disorder, and exhibited lack of efficacy during treatment with olanzapine, valproate, clozapine and chlorpromazine for psychosis [not all routes, dosages, duration of treatments to reaction onsets and outcomes stated].The man, who had a history of schizoaffective disorder bipolar type, diabetes mellitus type 2, chronic obstructive pulmonary disease and chronic kidney disease, was admitted for acute cystitis and initiated on nitrofurantoin. At admission, clozapine was stopped from his regular medications. On day 2, he developed shortness of breath and was started on azithromycin and unspecified steroids for COPD exacerbation. Laboratory tests were positive for COVID-19, and the unspecified steroids were switched to offlabel dexamethasone. Supplemental oxygen was not required at that time. On day 4, he became acutely manic, which worsened secondary to dexamethasone use. In addition to acute mania, he developed agitation and psychosis following clozapine withdrawal. The psychiatry department was consulted for re-initiation of clozapine.On day 4, the man was restarted on clozapine 12.5 mg twice daily, which was increased by 50mg daily on day 6 until 100mg dose was achieved. However, he remained agitated and manic, and the dose titration was continued aggressively to 200mg on day 7, 300mg on day 8, and to his previous home dose of 400mg on day 9. Valproate 500mg twice daily was initiated on day 6. Olanzapine was trialed for agitation but was changed to chlorpromazine as needed on day 9 due to no effect. There was no improvement on olanzapine, valproate, clozapine and chlorpromazine for psychosis. On days 11-12, he continued to have agitation and suicidal thoughts. After checking his valproate levels on day 13, the dose was increased to 1 500mg daily. He had been receiving several comedications. Due to his worsening respiratory status, he required a nasal cannula. Remdesivir was not started due to inability to maintain IV access. At clozapine dose of 400mg, he developed sialorrhoea as a side-effect. His oxygen demands further progressed from 2L nasal cannula to 100% oxygen on nonrebreather. A speech language pathologist was consulted to assess for aspiration. Swallow evaluation showed wet cough with thin and nectar thick liquids, indicative of aspiration. Oxygenation dropped to mid 80s after a trial of honey thick liquids, indicative of silent aspiration. Repeat lab tests revealed increased inflammatory markers, ferritin, and CRP. After several days of the progressive respiratory failure, he was transitioned to comfort measures. Within 24h, he died due to acute respiratory failure.
Multiple drugsVarious toxicities, off-label use and lack of efficacy: case report A 68-year-old man developed acute mania, agitation and psychosis following clozapine withdrawal, and worsening of acute mania during off-label treatment with dexamethasone for COVID-19. Additionally, he developed sialorrhoea during treatment with clozapine for schizoaffective disorder, and exhibited lack of efficacy during treatment with olanzapine, valproate, clozapine and chlorpromazine for psychosis [not all routes, dosages, duration of treatments to reaction onsets and outcomes stated].The man, who had a history of schizoaffective disorder bipolar type, diabetes mellitus type 2, chronic obstructive pulmonary disease and chronic kidney disease, was admitted for acute cystitis and initiated on nitrofurantoin. At admission, clozapine was stopped from his regular medications. On day 2, he developed shortness of breath and was started on azithromycin and unspecified steroids for COPD exacerbation. Laboratory tests were positive for COVID-19, and the unspecified steroids were switched to offlabel dexamethasone. Supplemental oxygen was not required at that time. On day 4, he became acutely manic, which worsened secondary to dexamethasone use. In addition to acute mania, he developed agitation and psychosis following clozapine withdrawal. The psychiatry department was consulted for re-initiation of clozapine.On day 4, the man was restarted on clozapine 12.5 mg twice daily, which was increased by 50mg daily on day 6 until 100mg dose was achieved. However, he remained agitated and manic, and the dose titration was continued aggressively to 200mg on day 7, 300mg on day 8, and to his previous home dose of 400mg on day 9. Valproate 500mg twice daily was initiated on day 6. Olanzapine was trialed for agitation but was changed to chlorpromazine as needed on day 9 due to no effect. There was no improvement on olanzapine, valproate, clozapine and chlorpromazine for psychosis. On days 11-12, he continued to have agitation and suicidal thoughts. After checking his valproate levels on day 13, the dose was increased to 1 500mg daily. He had been receiving several comedications. Due to his worsening respiratory status, he required a nasal cannula. Remdesivir was not started due to inability to maintain IV access. At clozapine dose of 400mg, he developed sialorrhoea as a side-effect. His oxygen demands further progressed from 2L nasal cannula to 100% oxygen on nonrebreather. A speech language pathologist was consulted to assess for aspiration. Swallow evaluation showed wet cough with thin and nectar thick liquids, indicative of aspiration. Oxygenation dropped to mid 80s after a trial of honey thick liquids, indicative of silent aspiration. Repeat lab tests revealed increased inflammatory markers, ferritin, and CRP. After several days of the progressive respiratory failure, he was transitioned to comfort measures. Within 24h, he died due to acute respiratory failure.
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