Abstract
Background
Clozapine is a very effective therapeutic option for schizophrenic disorders that have been refractory to most other therapies. This extremely positive aspect clashes easily with ...an adverse effect of the drug that is deemed to be a very dangerous one: agranulocytosis. We asked whether the mandatory strict hematological follow-up prescribed in the black box warning of clozapine's label is proportioned to the actual incidence of agranulocytosis, considering that is the main reason that such a drug is often used only late in the treatment course.
Methods
We carried out a systematic review of reports examining clozapine administration and agranulocytosis incidence. We specifically selected those where mild and moderate neutropenia was not used as a trigger to stop administration of clozapine, to better estimate the sheer incidence of agranulocytosis when clozapine was continued even with mild hematological effect, where detected. We used PubMed, MEDLINE, EMBASE, Cochrane, and ScienceDirect databases to identify clinical studies conducted between January 1975 and April 2023.
Results
We included 14 studies, mostly retrospective ones, that examined the incidence of hematological adverse effects in patients using clozapine. A total of 2354 subjects were included. The mean age of the subjects was 33.5 years. The mean duration of observation of subjects who took clozapine was 800 days, with a mean daily dose of 319.5 mg per day. Of the 2354 subjects examined, we found that 11 of them experienced agranulocytosis (0.47%).
Conclusions
These results suggest the evidence of a lower incidence of agranulocytosis than previously estimated and are in line with more recent meta-analyses. We may therefore think that clinical practice may demand a revision of the approach that both psychiatrists and supervising organizations often take when talking about clozapine.
This study aimed to conduct a systematic review and meta-analysis on cognitive performances of patients with treatment-resistant schizophrenia (TRS) after clozapine treatment and to examine the ...potential effect of follow-up duration and clozapine dosage.
Five electronic databases were searched and studies were included if treatment-resistant schizophrenia patients were treated with clozapine and with baseline and follow-up cognitive functions assessments. Cognitive measures were categorised into six domains based on DSM-5-TR. Random-effect model analysis was used to pool the effect estimates. Moderator effects of clozapine dosage, follow up duration, duration of illness, age, years of education and change in positive symptoms severity were examined with meta-regression.
Nineteen articles were included with 50 cognitive measures reported. Systematic review found inconsistent results. Twelve cognitive measures were included for meta-analysis and found overall improvement of cognitive performances after clozapine treatment SMD = 0.11 95 % CI 0.02, 0.20 (p = 0.021). Patients with younger age, more years of education and improvements in positive symptoms are more likely to improve in cognitive performances. Subgroup analysis found significant improvement in studies with follow-up periods of 6-months or longer but not for studies with shorter follow-up periods.
Clozapine may improve some domains of cognitive function, particularly over a longer period. However, the overall inconsistent results suggest that more studies with larger sample size and standard cognitive function assessments would be needed to enhance our understanding of the impact of clozapine on the cognitive functions in the TRS patients.
Resistance to pharmacological treatment poses a notable challenge for psychiatry. Such cases are usually treated with brain stimulation techniques, including repetitive transcranial magnetic ...stimulation (rTMS) and electroconvulsive therapy (ECT). Empirical evidence links treatment resistance to insufficient brain plasticity and chronic inflammation. Therefore, this study encompasses analysis of neurotrophic and inflammatory factors in psychiatric patients undergoing rTMS and ECT in order to refine the selection of patients and predict clinical outcomes. This study enrolled 25 drug‐resistant depressive patients undergoing rTMS and 31 drug‐resistant schizophrenia patients undergoing ECT. Clinical efficacy of brain stimulation therapies was gauged using MADRS and HAM‐D scales in the depression group and PANSS scale in the schizophrenia group. Blood‐derived BDNF, VEGF, and TNFα were analysed during the treatment course. For reference, 19 healthy control subjects were also enrolled. After statistical analysis, no significant differences were detected in BDNF, VEGF, and TNFα concentrations among healthy, depressive, and schizophrenic subject groups before the treatment. However, depressive patient treatment with rTMS has increased BDNF concentration, while schizophrenic patient treatment with ECT has lowered the concentration of TNFα. Our findings suggest that a lower initial TNFα concentration could be a marker for treatment success in depressed patients undergoing rTMS, whereas in schizophrenic patient group treated with ECT, a higher concentration of VEGF correlates to milder symptoms post‐treatment, especially in the negative scale.
Our study showed BDNF increase following rTMS course for depression patients and TNFα reduction after ECT for schizophrenia patients. However, from prognostic perspective, lower TNFα concentration predicted better depressive therapy response, while higher VEGF concentration correlated with milder schizophrenia symptoms after ECT course.
How and when to use clozapine Rubio, J. M.; Kane, J. M.
Acta psychiatrica Scandinavica,
March 2020, 2020-03-00, 20200301, Letnik:
141, Številka:
3
Journal Article
Recenzirano
Objective
Clozapine is the only approved strategy for treatment‐resistant schizophrenia, although it is highly underutilized. We aim to generate practical and actionable evidence‐based ...recommendations for the use of this drug considering prescription barriers.
Method
Narrative review.
Results
A consistent body of evidence supports the efficacy of clozapine reducing morbidity and mortality in schizophrenia. The main obstacles to its use are the lack of experience by prescribers and perceived treatment burden. Systematic screening of eligibility, utilization of available resources for consultation, developing a professional network with other stakeholders, as well as optimizing how clozapine is presented to patients is discussed. Furthermore, specific evidence‐based recommendations for initiation, maintenance, and safety monitoring with clozapine are provided.
Conclusion
Clozapine prescription is one of the areas in psychiatry with the greatest mismatch between efficacy and utilization in clinical practice. Although multiple barriers to the use of clozapine exist, some of these may be overcome by updates of routine clinical practice.
Objective
Increasing users' knowledge about the expected benefits and risks of clozapine may contribute to the initiation and maintenance of clozapine in persons with treatment‐resistant ...schizophrenia (TRS). The objective was to identify the educational needs of clozapine users and the interventions aimed at addressing these needs.
Method
We systematically searched multiple electronic databases for articles: (i) exploring educational needs of clozapine users and of their relatives; and (ii) reporting educational interventions aimed at addressing these needs. Data were synthesized narratively.
Results
A total of 30 articles published from 1990 to 2019 in 8 countries fulfilled our inclusion criteria. As most studies on educational needs (n = 18) were carried out in persons already taking clozapine, educational needs of TRS patients who were candidates for clozapine treatment are not well documented. Users’ level of knowledge about clozapine was often poor, especially about adverse effects or interactions with other substances, with a poor retention of information delivered at treatment initiation. Among 12 studies reporting educational interventions in clozapine users, five provided quantitative outcomes. Their findings suggest that structured educational programmes may contribute to promote clozapine initiation and to improve users' knowledge about this drug.
Conclusion
The literature is sparse on structured educational interventions about clozapine, and only one randomized controlled trial was identified. A promising strategy emerging from this review may be staging educational interventions according to the evolving needs of persons with TRS before clozapine use, at initiation and during maintenance treatment.
Clozapine is recognized as the gold standard medication for treatment-resistant schizophrenia. Despite the general recommendation of administering in a divided dosing regimen, clozapine is often ...prescribed once daily at night in clinical practice. This study aims to compare patient characteristics, psychiatric symptoms, side effects, and plasma concentration of clozapine between once-daily dosing and divided dosing regimens.
This cross-sectional study included 159 participants with treatment-resistant schizophrenia or schizoaffective disorder. Participant's demographic information, anthropometric data, and medical history were collected. Their psychiatric symptoms, cognition, functioning, and side effects were evaluated.
Once-daily dosing regimen was associated with younger age and competitive employment. Lower clinical symptom severity, better functioning and cognitive performance were observed in the once-daily dosing group. Lower daily dose of clozapine, trough plasma concentrations of clozapine and norclozapine were also significantly associated with once-daily dosing regimen.
The study results support once-daily dosing of clozapine as a viable option to selected patients in clinical practice, as no association of severe symptoms or side effects were associated with once-daily dosing regimen. More studies are needed to examine the relationship between clinical outcomes and clozapine dosing regimen.
Recent operational criteria for treatment-resistant schizophrenia (TRS) recognized positive and negative symptoms. TRS patients may have heterogeneity in negative symptoms, but empirical data were ...lacking. We aimed to characterize TRS patients based on negative symptoms using cluster analysis, and to examine between-cluster differences in social functioning.
We administered the Clinical Assessment Interview of Negative symptoms (CAINS), Brief Negative Symptom Scale (BNSS), the Positive and Negative Syndrome Scale (PANSS) and the Social and Occupational Functional Assessment (SOFAS to 126 TRS outpatients. All patients also completed the Temporal Experience of Pleasure Scale (TEPS), the Emotion Expressivity Scale (EES), and the Social Functional Scale (SFS). A two-stage hierarchical cluster analysis was performed with the CAINS, TEPS and EES as clustering variables. We validated the clusters using ANOVAs to compare group differences in the BNSS, PANSS, SOFAS and SFS.
Clustering indices supported a 3-cluster solution. Clusters 1 (n = 46) and 3 (n = 16) exhibited higher CAINS scores than Cluster 2 (n = 64), and were negative-symptom TRS subtypes. Cluster 1 reported lower TEPS than Cluster 3; but Cluster 3 reported lower EES than Cluster 1. Upon validation, Clusters 1 and 3 exhibited higher BNSS scores than Cluster 2, but only Cluster 1 exhibited lower SOFAS and higher PANSS general symptoms than Cluster 2. Both Clusters 1 and 3 had higher self-report functioning than Cluster 2.
We provided evidence for heterogeneity of negative symptoms in TRS. Negative symptoms can characterize TRS patients and predict functional outcome.
•This empirical study characterized TRS patients using the CAINS, self-rated experiential pleasure and emotion expressivity.•Hierarchical cluster analysis categorized 126 TRS patients into three clusters.•The cluster with the highest CAINS-negative symptoms and lowest experiential pleasure exhibited poor social functioning.•Our findings encouraged operational criteria for TRS to incorporate BNSS and CAINS-measured negative symptoms.
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