Relationship between clozapine dose and severity of obsessive-compulsive symptoms

Kim, David D.; Barr, Alasdair M.; Stewart, S. Evelyn; White, Ralph de Vere; Honer, William G.; Procyshyn, Ric M.

doi:10.1016/j.mehy.2021.110506

Cited by 3 publications

(3 citation statements)

References 53 publications

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“…This is challenged, however, in the literature, with some suggesting that these findings are confounded by the higher antipsychotic doses typically required by those with psychosis of greater severity. 8 …”

Section: Schizophrenia and Ocs/ocdmentioning

confidence: 99%

The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study

Fernandez-Egea,

Chen,

Sangüesa

et al. 2024

Br J Psychiatry

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BackgroundA significant proportion of people with clozapine-treated schizophrenia develop ‘checking’ compulsions, a phenomenon yet to be understood.AimsTo use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive–compulsive symptoms (OCS).MethodUsing the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking. Classic bivariate correlation tests were used to assess clozapine load and checking compulsions. The influence of specific genetic variants was tested in a subsample.ResultsA total of 196 clozapine-treated individuals and 459 face-to-face assessments were included. We found significant OCS to be common (37.9%), with checking being the most prevalent symptom. In mediation models, psychosis severity mediated checking behaviour indirectly by inducing obsessions (r = 0.07, 95% CI 0.04–0.09; P < 0.001). No direct effect of psychosis on checking was identified (r = −0.28, 95% CI −0.09 to 0.03; P = 0.340). After psychosis remission (n = 65), checking compulsions correlated with both clozapine plasma levels (r = 0.35; P = 0.004) and dose (r = 0.38; P = 0.002). None of the glutamatergic and serotonergic genetic variants were found to moderate the effect of psychosis on obsession and compulsion (SLC6A4, SLC1A1 and HTR2C) survived the multiple comparisons correction.ConclusionsWe elucidated different phases of the complex interplay of psychosis and compulsions, which may inform clinicians’ therapeutic decisions.

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Section: Schizophrenia and Ocs/ocdmentioning

confidence: 99%

The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study

Fernandez-Egea,

Chen,

Sangüesa

et al. 2024

Br J Psychiatry

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“…Clozapine dose, which ranges from 75 to 900 mg daily, was not the main focus as it is an inaccurate measure of clozapine load. This is because Clozapine metabolism is in uenced by a variety of factors, including concordance, gender, cytochrome polymorphisms, concurrent medication, and smoking habit [17]. Blood levels, therefore, represent a more precise measure.…”

Section: The Role Of Clozapine On the Persistence Of Excessive Checking After Psychosis Remissionmentioning

confidence: 99%

“…OCS is also associated with higher clozapine dose and length of treatment [15], suggesting a dose-dependent relationship, although there exists con icting results disagreement in the literature [16]. However, no previous work has found associations between clozapine plasma levels and OCS [15], despite plasma level being considered a more accurate measure of clozapine effect [17].…”

Section: Introductionmentioning

confidence: 99%

Phenomenology and genetic moderators of excessive checking after antipsychotic treatment

Fernandez-Egea

Chen

Sanguesa

et al. 2021

Preprint

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A significant proportion of antipsychotic-treated schizophrenia patients develop de novo checking compulsions, a phenomenon that is yet to be understood. Informed by models of habit formation developed in the cognitive neurosciences, we hypothesised that excessive checking could be understood as the by-product of psychosis, promoted by clozapine’s strong anti-serotoninergic action. Using the anonymised electronic records of a cohort of 204 clozapine-treated patients, including longitudinal assessments of obsessive-compulsive symptoms (OCS) and psychosis (n=724 face-to-face assessments), we performed longitudinal multi-level mediation and multi-level moderation analyses to explore OCS’ associations with psychosis and with patient genotype respectively. We found OCS to be common in clozapine-treated patients (54%), with checking being the most prevalent symptom. Mediation models showed psychosis severity to indirectly effect checking behaviour by inducing obsessions [0.08 (IC 0.05, 0.12); p<0.001). No direct effect of psychosis on checking was identified [-0.06 (IC -0.13, 0.02); p=0.145]. After psychosis remission, checking compulsion directly correlated with both clozapine plasma levels (r=0.33; p=0.005) and dose (r=0.30; p=0.010). The transition from psychosis to obsession and compulsion was moderated by glutamatergic genetic variants (GRIN2B). We also identified novel associations with the serotoninergic pathway (SLC6A4, HTR2A and HTR2C). Understanding the different phases of the complex transition from psychosis to compulsion may inform clinicians' therapeutic decisions.

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Obsessive-compulsive symptoms moderates the effects of cognitive functioning on quality of life in clozapine-treated schizophrenia

Agostoni

Bechi

Buonocore

et al. 2022

Psychiatry Research Communications

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Relationship between clozapine dose and severity of obsessive-compulsive symptoms

Cited by 3 publications

References 53 publications

The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study

The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study

Phenomenology and genetic moderators of excessive checking after antipsychotic treatment

Obsessive-compulsive symptoms moderates the effects of cognitive functioning on quality of life in clozapine-treated schizophrenia

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