Takala, Christopher R.

Background Bupropion is associated with a dose-dependent increased risk of seizures. Use of concomitant bupropion and electroconvulsive therapy (ECT) remains controversial because of an increased risk of prolonged seizures. This is the first systematic evaluation of the effect of bupropion on ECT. Methods A case group (n = 119), patients treated with concomitant ECT and bupropion, was compared with an age and gender frequency–matched control group (n = 261), treated with only ECT. Electroconvulsive therapy treatment data including seizure length, number of treatments, and concurrent medications were extracted. Longitudinal mixed models examined ECT versus ECT + bupropion group differences over the course of treatments measured by seizure duration (electroencephalogram [EEG] and motor). Multivariable models examined the total number of treatments and first and last seizure duration. All models considered group differences with ECT treatment measures adjusted for age, gender, benzodiazepine treatment, lead placement, and setting. Results Electroconvulsive therapy treatment with bupropion led to shorter motor seizure duration (0.047) and EEG seizure duration (P = 0.001). The number of ECT treatments (7.3 vs 7.0 treatments; P = 0.23), respectively, or the probability of a prolonged seizure (P = 0.15) was not significantly different. Benzodiazepine use was significantly more common in control subjects (P = 0.01). Limitations This is a retrospective analysis limited in part by unavailable variables (seizure threshold, nature of EEG and motor seizure monitoring, type of ECT device, dosing and formulation of bupropion, and duration of the current depressive illness). Conclusions This study revealed a significantly shorter duration in seizure length with ECT + concomitant bupropion, but not in the number of required treatments in those treated compared with ECT without bupropion. There remains a critical need to reevaluate the efficacy of concomitant use of psychotropic medications + ECT.

Objective: To describe 3 cases of clozapine toxicity associated with infectious and/or inflammatory processes. Case Summaries: Three patients stable on clozapine therapy prior to a medical hospital admission developed clozapine toxicity. It was suspected that an acute infectious and/or inflammatory process in each patient was related to abrupt mental status changes, onset of sialorrhea, myoclonus, and/or need for ventilatory support. Investigations of altered mental status did not reveal alternative causes and presentations were not consistent with neuroleptic malignant syndrome, other acute neurologic complications, or psychiatric decompensation. All patients improved after clozapine dose reductions allowing for transfer from intensive care units. Using the Naranjo ADR Probability Scale for each case, a probable relation between clozapine toxicity and the infectious and/or inflammatory process was determined. Discussion: Clozapine toxicity may manifest with multiple symptoms, including sedation, sialorrhea, and hypotension. In addition to overdose and drug interactions; infection and/or inflammation may precipitate clozapine toxicity. This may be related to cytokine-mediated inhibition of cytochrome P450 1A2. The likelihood of toxicity via this mechanism has not been well characterized, thus careful monitoring is required for medically ill patients receiving clozapine. Clozapine is extensively bound to the acute phase reactant, α-1 acid glycoprotein, which may unpredictably protect against clinical toxicity. C-reactive protein has also been investigated to relate clozapine toxicity to infection and/or inflammation. Conclusion: Clozapine toxicity developed in 3 patients admitted to a medical setting suspected to be related to infection and/or inflammation. Clinicians should be aware of this potential adverse drug event with clozapine.