It has been suggested that the antipsychotic clozapine may modulate brain glutamate, and that this effect could contribute to its efficacy in treatment-resistant schizophrenia (TRS). The aim of this study was to examine the effects of clozapine on brain glutamate in TRS longitudinally. This study examined individuals with TRS before and 12 weeks after switching from a non-clozapine antipsychotic to treatment with clozapine as part of their normal clinical care. Proton magnetic resonance spectroscopy (1H-MRS) measured concentrations, corrected for voxel tissue content, of glutamate (Glucorr), and glutamate plus glutamine (Glxcorr) in the anterior cingulate cortex (ACC) and right caudate nucleus. Symptoms were monitored using the Positive and Negative Syndrome Scale (PANSS). Of 37 recruited patients (27 men, 39.30 years old, 84% clozapine naïve), 25 completed 1H-MRS at both timepoints. 12 weeks of clozapine was associated with a longitudinal reduction in Glucorr in the caudate (n = 23, F = 7.61 P = .01) but not in the ACC (n = 24, F = 0.02, P = .59). Percentage reduction in caudate Glucorr was positively correlated with percentage improvement in symptoms (total PANSS score, n = 23, r = .42, P = .04). These findings indicate that reductions in glutamate in the caudate nucleus may contribute to symptomatic improvement during the first months of clozapine treatment.
The wider use of clozapine is limited by the risk of agranulocytosis and the associated requirement for monitoring of neutrophil counts. We searched local electronic patient records for cases of agranulocytosis occurring during clozapine treatment during the period 2007–2020. We found 23 episodes recorded as agranulocytosis in clozapine patients. Of these, nine met pre-defined criteria and were considered episodes of life-threatening agranulocytosis (LTA). These episodes of clozapine-induced LTA exhibited a distinct pattern of continuous and rapid neutrophil count decline to zero or near zero. Mean time for neutrophils to fall from ANC > 2 to ANC <0.5 × 109/L was 8.4 days (range 2–15 days). Each event was also characterised by a prolonged nadir and delayed recovery (range 4–16 days). Non-LTA episodes were, in contrast, brief and benign. We conclude that an important proportion of cases of agranulocytosis identified in people prescribed clozapine are not life-threatening and may not even be clozapine-related. Monitoring schemes should aim to identify true clozapine-induced LTA as opposed to threshold-defined nominal agranulocytosis. Genetics studies might benefit from examining associations with clozapine-induced LTA rather than with recorded cases of agranulocytosis or neutropenia.
Background: Patients in mental health services’ seclusion require regular physical health assessments to identify, prevent and manage clinical deterioration. Sometimes it may be unsafe or counter-therapeutic for clinical staff to enter the seclusion room, making it challenging to meet local seclusion standards for physical assessments. Alternatives to standard clinical assessment models are required in such circumstances to assure high quality and safe care.Aim: The primary aim was to improve the quality of physical health monitoring by making accurate vital sign measurements more frequently available. Secondary aims were to explore the clinical experience of integrating a technological innovation with routine clinical care.Method: A non-contact monitoring device was installed in the mental health seclusion room and was used in addition to existing clinical care. Over six months, adherence to local clinical guidelines was compared against a time-period prior to installation. Feedback was sought from staff and patients throughquestionnaires and focus groups. A quality improvement framework was used to continually improve the process using plan, do, study, act (PDSA) cycles.Results: The non-contact monitoring device enabled a 12.3-fold increase overall in the monitoring of physical health observations when compared to a real-world baseline rate of checks. Enhancement to standard clinical care varied accordingto patient movement levels. Patients, carers and staff expressed positive views towards the integration of the technological intervention.Conclusion: The non-contact monitoring device improved the quality and safety of care by increasing availability of physical health monitoring. It was positively received by patients, carers and staff.
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