Clozapine, a second-generation antipsychotic (SGA), is known for its superior efficacy in the treatment of refractory schizophrenia. Clozapine's hallmark side effects are well-known, including, but not limited to, drug-induced seizures associated with daily goal doses greater than 600mg and rapid dose escalation, which can also contribute to significant risk of orthostatic hypotension, bradycardia, and syncope. However, less well-known is the potential withdrawal that can occur from its rapid discontinuation. Here, we describe a case of seizure-like activity that occurred 72 hours after an abrupt high-dose clozapine discontinuation in a patient with schizoaffective disorder, bipolar type. Seizures, although known to be a high-serum-concentration-dependent side effect of clozapine, could not be excluded as a possible withdrawal syndrome in this patient.
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J Psychopharmacol
December 2024
Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton, UK.
Background: Schizophrenia is considered to have a lifetime prevalence of around 1%. Up to 30% of patients diagnosed with schizophrenia are subsequently categorised as treatment resistant. Current guidelines advise against the use of antipsychotic polypharmacy (APP) or high-dose antipsychotic therapy (HDAT) in the treatment of schizophrenia; however, these treatment approaches continue to be used in up to 25% of cases.
View Article and Find Full Text PDFPsychopharmacology (Berl)
August 2024
Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Rationale: Clozapine, the standard treatment for treatment-resistant schizophrenia (TRS), is generally recommended in a multiple-daily dosing regimen. However, it is commonly administered once daily in clinical practice. Few studies have compared the longitudinal clinical outcomes of these two dosing regimens.
View Article and Find Full Text PDFNeurobiol Dis
October 2024
Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Brain Connectome and Behaviour, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China. Electronic address:
The gut microbiota produces metabolites that enrich the host metabolome and play a part in host physiology, including brain functions. Yet the biological mediators of this gut-brain signal transduction remain largely unknown. In this study, the possible role of the gut microbiota metabolite indole, originating from tryptophan, was investigated.
View Article and Find Full Text PDFJAMA Psychiatry
October 2024
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Importance: Antipsychotic drugs (particularly clozapine) have been associated with pneumonia in observational studies. Despite studies of the associations between antipsychotic use and incident pneumonia, it remains unclear to what degree antipsychotic use is associated with increased risk of pneumonia, whether dose-response associations exist, and what agents are specifically associated with incident pneumonia.
Objective: To estimate pneumonia risk associated with specific antipsychotics and examine whether polytherapy, dosing, and receptor binding properties are associated with pneumonia in patients with schizophrenia.
Psychiatry Res
September 2024
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; Center for Psychiatric Research, Stockholm City Council, Stockholm, Sweden.
The risk of fatal choking for people with schizophrenia and associations with antipsychotic medication are largely unknown. Therefore, we calculated the choking-related standardized mortality ratio for schizophrenia relative to the general population (SMR). We also computed adjusted hazard ratios (aHR) of choking-related mortality for antipsychotics in a nationwide cohort of patients with schizophrenia (N = 59,916).
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