Clozapine-related EEG changes and seizures: dose and plasma-level relationships

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)

An exploratory investigation into the nursing management of aggression in acute psychiatric settings

The management of aggression in inpatient psychiatric facilities is a major concern for nurses. Despite the prevalence of research on aggression within psychiatric settings, very few studies have tracked the clinical management of identified patients in a systematic manner. The overall aim of this study was to explore the clinical management of patients identified as potentially aggressive in psychiatric inpatient settings. A multimethod approach was used to collect the data. This included surveys, focus groups, and a file audit of patients identified from a random sample of completed aggression incident forms. The findings indicated that 88% of nurses who participated in the survey were assaulted and indicated the need for risk assessment; team management and review; and the importance of the first 5 days of admission as crucial for assessment and review. The development of support structures, formal preceptoring and supervisory arrangements and postincident supports were suggested as part of an overall strategy to support nurses working in acute inpatient settings