Clozapine is a widely used atypical antipsychotic with a unique effectiveness in treatment-resistant schizophrenia. An important adverse effect is seizures, which have been observed at all stages of clozapine treatment. Valproate has traditionally been considered the drug of choice for the prophylaxis of clozapine seizures, however it may not be the most suitable choice for all patients. There is disagreement as to the best point to prescribe valproate or a suitable antiepileptic: as seizure prophylaxis at a certain clozapine dose or level, or only as remedial treatment. In this review, we examine the relevant literature with an aim to evaluate the following relationships: clozapine dose and electroencephalogram (EEG) abnormalities, plasma levels and EEG abnormalities, dose and occurrence of seizures and plasma levels and occurrence of seizures. Weighted linear regression models were fitted to investigate these relationships. There was a strong relationship between clozapine dose and plasma level and occurrence of clozapine-induced EEG abnormalities. However, a statistically significant relationship between dose and occurrence of seizures was not found. A relationship between clozapine plasma level and occurrence of seizures was not established because of the scarcity of useful data although our review found three case reports which suggested that there is a very substantial risk of seizures with clozapine plasma levels exceeding 1300 μg/l. Seizures are more common during the initiation phase of clozapine treatment, suggesting a slow titration to target plasma levels is desirable. An antiepileptic drug should be considered when the clozapine plasma level exceeds 500 μg/l, if the EEG shows clear epileptiform discharges, if seizures, myoclonic jerks or speech difficulties occur and when there is concurrent use of epileptogenic medication. The antiepileptics of choice for the treatment and prophylaxis of clozapine-induced seizures are valproate (particularly where there is mood disturbance) and lamotrigine (where there is resistance to clozapine).

A large number of drugs commonly used in older people are likely to be associated with cognitive impairment. Copyright © 2016 John Wiley & Sons, Ltd.

As yet, no agents have been approved for the treatment of COVID-19, although several experimental drugs are being used off licence. These may have serious adverse effects and potential drug interactions with psychotropic agents. We reviewed the common agents being used across the world for the treatment of COVID-19 and investigated their drug interaction potential with psychotropic agents using several drug interaction databases and resources. A preliminary search identified the following drugs as being used to treat COVID-19 symptoms: atazanavir (ATV), azithromycin (AZI), chloroquine (CLQ)/hydroxychloroquine (HCLQ), dipyridamole, famotidine (FAM), favipiravir, lopinavir/ritonavir (LPV/r), nitazoxanide, remdesivir, ribavirin and tocilizumab. Many serious adverse effects and potential drug interactions with psychotropic agents were identified. The most problematic agents were found to be ATV, AZI, CLQ, HCLQ, FAM and LPV/r in terms of both pharmacokinetic as well as serious pharmacodynamic drug interactions, including QTc prolongation and neutropenia. Significant caution should be exercised if using any of the medications being trialled for the treatment of COVID-19 until robust clinical trial data are available. An even higher threshold of vigilance should be maintained for patients with pre-existing conditions and older adults due to added toxicity and drug interactions, especially with psychotropic agents.

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