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Schizophrenia Research Oct 2022Individuals with schizophrenia spectrum disorders (SSD) are at heightened risk of experiencing self-stigma, and some cultures are more stigmatizing towards SSD than... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Individuals with schizophrenia spectrum disorders (SSD) are at heightened risk of experiencing self-stigma, and some cultures are more stigmatizing towards SSD than others. The first purpose of this review is to provide an estimate of the relationship between self-stigma and clinical and psychosocial outcomes. The second purpose is to examine how these relationships vary across cultures.
METHOD
Studies reporting correlations between self-stigma and outcome variable(s) were identified through electronic database searches from June 1, 2021, to January 2, 2022. Mean effect sizes were calculated using Fisher's r-to-Z-transformation.
RESULTS
Sixty-three articles (N = 8925, 22 countries) were included in the systematic review and fifty-three articles (N = 7756) were included in the meta-analysis. For the most studied clinical correlates, self-stigma had a moderate, positive correlation with depressive symptoms (r = 0.49, p < .001), a moderate, negative correlation with functioning (r = -0.39, p < .001), and a positive, small correlation with severity of psychotic symptoms (r = 0.29, p < .001), negative symptoms (r = 0.18, p < .001) and positive symptoms (r = 0.13, p = .01). For the most studied psychosocial correlates, self-stigma had a strong, negative correlation with quality of life (r = -0.52, p < .001) and self-esteem (r = -0.55, p < .001). The correlates of self-stigma were similar across cultures.
DISCUSSION
Self-stigma shows strong to small correlations with clinical and psychosocial variables similarly across cultures. More research is needed to examine underlying mechanisms to develop effective interventions.
Topics: Humans; Schizophrenia; Quality of Life; Social Stigma; Self Concept; Psychotic Disorders
PubMed: 35963056
DOI: 10.1016/j.schres.2022.08.001 -
PLoS Medicine Apr 2022Severe mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and CVD-related mortality. To date, no systematic review has investigated changes in population level CVD-related mortality over calendar time. It is unclear if this relationship has changed over time in higher-income countries with changing treatments.
METHODS AND FINDINGS
To address this gap, a systematic review was conducted, to assess the association between SMI and CVD including temporal change. Seven databases were searched (last: November 30, 2021) for cohort or case-control studies lasting ≥1 year, comparing frequency of CVD mortality or incidence in high-income countries between people with versus without SMI. No language restrictions were applied. Random effects meta-analyses were conducted to compute pooled hazard ratios (HRs) and rate ratios, pooled standardised mortality ratios (SMRs), pooled odds ratios (ORs), and pooled risk ratios (RRs) of CVD in those with versus without SMI. Temporal trends were explored by decade. Subgroup analyses by age, sex, setting, world region, and study quality (Newcastle-Ottawa scale (NOS) score) were conducted. The narrative synthesis included 108 studies, and the quantitative synthesis 59 mortality studies (with (≥1,841,356 cases and 29,321,409 controls) and 28 incidence studies (≥401,909 cases and 14,372,146 controls). The risk of CVD-related mortality for people with SMI was higher than controls across most comparisons, except for total CVD-related mortality for BD and cerebrovascular accident (CVA) for mixed SMI. Estimated risks were larger for schizophrenia than BD. Pooled results ranged from SMR = 1.55 (95% confidence interval (CI): 1.33 to 1.81, p < 0.001), for CVA in people with BD to HR/rate ratio = 2.40 (95% CI: 2.25 to 2.55, p < 0.001) for CVA in schizophrenia. For schizophrenia and BD, SMRs and pooled HRs/rate ratios for CHD and CVD mortality were larger in studies with outcomes occurring during the 1990s and 2000s than earlier decades (1980s: SMR = 1.14, 95% CI: 0.57 to 2.30, p = 0.71; 2000s: SMR = 2.59, 95% CI: 1.93 to 3.47, p < 0.001 for schizophrenia and CHD) and in studies including people with younger age. The incidence of CVA, CVD events, and heart failure in SMI was higher than controls. Estimated risks for schizophrenia ranged from HR/rate ratio 1.25 (95% CI: 1.04 to 1.51, p = 0.016) for total CVD events to rate ratio 3.82 (95% CI: 3.1 to 4.71, p < 0.001) for heart failure. Incidence of CHD was higher in BD versus controls. However, for schizophrenia, CHD was elevated in higher-quality studies only. The HR/rate ratios for CVA and CHD were larger in studies with outcomes occurring after the 1990s. Study limitations include the high risk of bias of some studies as they drew a comparison cohort from general population rates and the fact that it was difficult to exclude studies that had overlapping populations, although attempts were made to minimise this.
CONCLUSIONS
In this study, we found that SMI was associated with an approximate doubling in the rate ratio of CVD-related mortality, particularly since the 1990s, and in younger groups. SMI was also associated with increased incidence of CVA and CHD relative to control participants since the 1990s. More research is needed to clarify the association between SMI and CHD and ways to mitigate this risk.
Topics: Cardiovascular Diseases; Heart Failure; Humans; Mental Disorders; Psychotic Disorders; Schizophrenia
PubMed: 35439243
DOI: 10.1371/journal.pmed.1003960 -
Neuropsychiatric Disease and Treatment 2017Antipsychotics are recommended as first-line therapy for acute mania and maintenance treatment of bipolar disorder; however, published literature suggests their... (Review)
Review
INTRODUCTION
Antipsychotics are recommended as first-line therapy for acute mania and maintenance treatment of bipolar disorder; however, published literature suggests their real-world use remains limited. Understanding attitudes toward these medications may help identify barriers and inform personalized therapy. This literature review evaluated patient and clinician attitudes toward the use of antipsychotics for treating bipolar disorder.
MATERIALS AND METHODS
A systematic search of the Cochrane Library, Ovid MEDLINE, Embase, and BIOSIS Previews identified English language articles published between January 1, 2000, and June 15, 2016, that reported attitudinal data from patients, health care professionals, or caregivers; treatment decision-making; or patient characteristics that predicted antipsychotic use for bipolar disorder. Results were analyzed descriptively.
RESULTS
Of the 209 references identified, 11 met the inclusion criteria and were evaluated. These articles provided attitudinal information from 1,418 patients with bipolar disorder and 1,282 treating clinicians. Patients' attitudes toward antipsychotics were generally positive. Longer duration of clinical stability was associated with positive attitudes. Implementation of psychoeducational and adherence enhancement strategies could improve patient attitudes. Limited data suggest clinicians' perceptions of antipsychotic efficacy and tolerability may have the greatest impact on their prescribing patterns. Because the current real-world evidence base is inadequate, clinician attitudes may reflect a relative lack of experience using antipsychotics in patients with bipolar disorder.
CONCLUSION
Although data are very limited, perceived tolerability and efficacy concerns shape both patient and clinician attitudes toward use of antipsychotic drugs in bipolar disorder. Additional studies are warranted.
PubMed: 28919760
DOI: 10.2147/NDT.S139557 -
PloS One 2017The vascular risk attributable to HIV infection is rising. The heterogeneity of the samples studied is an obstacle to understanding whether HIV is a vascular risk across... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
The vascular risk attributable to HIV infection is rising. The heterogeneity of the samples studied is an obstacle to understanding whether HIV is a vascular risk across geographic regions.
OBJECTIVE
To test the hypothesis that HIV infection is a vascular risk factor, and that the risk conferred by HIV varies by geographical region.
DATA SOURCES
A systematic search of publications was carried out in seven electronic databases: PubMed, The Cochrane Library, EMBASE, Web of Science, LILACS, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform from inception to July 2015.
STUDY SELECTION
We included longitudinal studies of HIV+ individuals and their risk of vascular outcomes of ≥ 50 HIV+ cases and excluded studies on biomarkers of vascular disease as well as clinical trials.
DATA EXTRACTION AND SYNTHESIS
Data was extracted by one of the authors and independently confirmed by the other two authors. We used incidence rate (IR), incidence risk ratio (IRR) and hazard ratio (HR) with their 95% confidence intervals as measures of risk.
MAIN OUTCOME
All-death, myocardial infarction (MI), coronary heart disease (CHD), any stroke, ischemic stroke (IS) or intracranial hemorrhage (ICH).
RESULTS
We screened 11,482 references for eligibility, and selected 117 for analysis. Forty-four cohorts represented 334,417 HIV+ individuals, 49% from the United States. Compared with their European counterparts, HIV+ individuals in the United States had higher IR of death (IRR 1.78, 1.69-1.88), MI (IRR 1.61, 1.29-2.01), CHD (IRR 2.27, 1.92-2.68), any stroke (IRR 1.94, 1.59-2.38), IS (IRR 1.56, 1.23-1.98), and ICH (IRR 4.03, 2.72-6.14). Compared with HIV- controls and independent of geographical region, HIV was a risk for death (HR 4.77, 4.55-5.00), MI (HR 1.60, 1.49-1.72), any CHD (HR 1.20, 1.15-1.25), any stroke (HR 1.82, 1.53-2.16), IS (HR 1.27, 1.15-1.39) and ICH (HR 2.20, 1.61-3.02). Use of antiretroviral therapy was a consistent risk for cardiac outcomes, while immunosuppression and unsuppressed viral load were consistent risks for cerebral outcomes.
CONCLUSIONS
HIV should be considered a vascular risk, with varying magnitudes across geographical and anatomical regions. We think that strategies to reduce the HIV-related vascular burden are urgent, and should incorporate the disparities noted here.
Topics: Case-Control Studies; Cerebrovascular Disorders; Cohort Studies; Coronary Disease; Demography; Female; Geography; HIV Infections; HIV Seropositivity; Humans; Incidence; Male; Myocardial Infarction; Risk Factors; Treatment Outcome; Vascular Diseases
PubMed: 28493892
DOI: 10.1371/journal.pone.0176686 -
Revista Brasileira de Psiquiatria (Sao... 2023To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis.
RESULTS
The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%.
CONCLUSION
Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention.
Topics: Humans; Antipsychotic Agents; Clozapine; Prevalence; Schizophrenia; Drug Resistance
PubMed: 37718484
DOI: 10.47626/1516-4446-2023-3126 -
Pharmacology & Therapeutics Aug 2022Almost fifty years after its first introduction into clinical care, clozapine remains the only evidence-based pharmacological option for treatment-resistant... (Review)
Review
Clozapine's multiple cellular mechanisms: What do we know after more than fifty years? A systematic review and critical assessment of translational mechanisms relevant for innovative strategies in treatment-resistant schizophrenia.
Almost fifty years after its first introduction into clinical care, clozapine remains the only evidence-based pharmacological option for treatment-resistant schizophrenia (TRS), which affects approximately 30% of patients with schizophrenia. Despite the long-time experience with clozapine, the specific mechanism of action (MOA) responsible for its superior efficacy among antipsychotics is still elusive, both at the receptor and intracellular signaling level. This systematic review is aimed at critically assessing the role and specific relevance of clozapine's multimodal actions, dissecting those mechanisms that under a translational perspective could shed light on molecular targets worth to be considered for further innovative antipsychotic development. In vivo and in vitro preclinical findings, supported by innovative techniques and methods, together with pharmacogenomic and in vivo functional studies, point to multiple and possibly overlapping MOAs. To better explore this crucial issue, the specific affinity for 5-HTR, D1R, α, and muscarinic receptors, the relatively low occupancy at dopamine D2R, the interaction with receptor dimers, as well as the potential confounder effects resulting in biased ligand action, and lastly, the role of the moiety responsible for lipophilic and alkaline features of clozapine are highlighted. Finally, the role of transcription and protein changes at the synaptic level, and the possibility that clozapine can directly impact synaptic architecture are addressed. Although clozapine's exact MOAs that contribute to its unique efficacy and some of its severe adverse effects have not been fully understood, relevant information can be gleaned from recent mechanistic understandings that may help design much needed additional therapeutic strategies for TRS.
Topics: Antipsychotic Agents; Clozapine; Humans; Receptors, Dopamine D2; Schizophrenia; Schizophrenia, Treatment-Resistant
PubMed: 35764175
DOI: 10.1016/j.pharmthera.2022.108236 -
The Lancet. Psychiatry Aug 2022Although antipsychotic maintenance treatment is widely recommended to prevent relapse in chronic psychoses, evidence-based guidelines do not provide clear indications on... (Meta-Analysis)
Meta-Analysis
Continuing, reducing, switching, or stopping antipsychotics in individuals with schizophrenia-spectrum disorders who are clinically stable: a systematic review and network meta-analysis.
BACKGROUND
Although antipsychotic maintenance treatment is widely recommended to prevent relapse in chronic psychoses, evidence-based guidelines do not provide clear indications on different maintenance treatment strategies, including continuing the antipsychotic at standard doses, reducing the dose, switching to another antipsychotic, or even stopping the antipsychotic. We aimed to compare the effectiveness of these maintenance treatment strategies, hypothesising the superiority of all strategies over stopping, and of continuing at standard doses over both switching and reducing the dose.
METHODS
We did a systematic review and network meta-analysis of randomized controlled trials (RCTs) that investigated antipsychotics for relapse prevention in adults with schizophrenia-spectrum disorders who were clinically stable, and which compared four treatment strategies: continuing the current antipsychotic at standard doses recommended for acute treatment; reducing the current antipsychotic dose; switching to a different antipsychotic; and stopping the antipsychotic and replacing it with placebo. We excluded RCTs with fewer than 25 individuals, a prerandomisation washout period greater than 4 weeks, a follow-up shorter than 6 weeks, and those recruiting treatment-resistant individuals. We searched MEDLINE, EMBASE, PsycINFO, CINAHL, CENTRAL, and online trial registers for published and unpublished RCTs from inception to Sept 1, 2021, combining terms describing all available antipsychotics, and terms describing continuation, maintenance, or long-term treatment for schizophrenia-spectrum disorders. Relative risks (RRs) and standardised mean differences were pooled using random-effects pairwise and network meta-analyses. We assessed risk of bias of each RCT with the Cochrane Risk-of-Bias 2 tool, and confidence of pooled estimates with CINeMA. The primary outcome was relapse prevention. The study protocol was registered in advance in the Open Science Forum registry.
FINDINGS
Of 3936 records identified, 119 records, reporting on 101 RCTs, were eligible, 98 of which (including 13 988 individuals) provided data that could be meta-analysed for at least one outcome. The mean proportion of female participants per study was 38% (range 0-100; median 39%, IQR 29-50), whereas for male participants it was 62% (range 0-100; median 61%, IQR 50-71), and the overall mean age was 38·8 years (range 23·2-63·9; median 39·3, IQR 35·0-43·9). Of the 98 RCTs meta-analysed, 89·8% were done in high-income and upper-middle-income countries. The ethnic group White or so-called Caucasian was the most represented (mean 56% participants per study), although this information was relatively scarce. All continuation strategies were significantly more effective in preventing relapse than stopping antipsychotic treatment, with a large risk reduction for continuing at standard doses (RR 0·37, 95% CI 0·32-0·43; number-needed-to-treat [NNT] 3·17, 95% CI 2·94-3·51) and antipsychotic switching (RR 0·44, 0·37-0·53; NNT 3·57, 3·17-4·25), and moderate risk reduction for dose reduction (RR 0·68, 0·51-0·90; NNT 6·25, 4·08-20·00). Continuing and switching antipsychotics did not differ significantly (RR 0·84, 0·69-1·02; with lower values favouring continuing), whereas reducing antipsychotic dose was outperformed by both continuing (RR 0·55, 0·42-0·71; NNT 4·44, 3·45-6·90) and switching (RR 0·65, 0·47-0·89; NNT 5·17, 3·77-18·18). Results were supported by moderate confidence of evidence and confirmed by secondary analyses and by several sensitivity and subgroup analyses, including removing studies with abrupt antipsychotic discontinuation or fast tapering (≤4 weeks). No tolerability differences emerged between treatment strategies. According to the Cochrane Risk-of-Bias tool, version 2, 16·8% of included RCTs had an overall high risk of bias for the primary outcome. We found moderate heterogeneity (τ=0·13; I=61%) and no overall incoherence for the primary analysis. Results were supported by moderate confidence of evidence and confirmed by secondary analyses.
INTERPRETATION
Contrary to our original hypothesis, we found that continuing antipsychotic treatment at standard doses or switching to a different antipsychotic are similarly effective treatment strategies, whereas reducing antipsychotic doses below standard doses is associated with higher risk of relapse than the other two maintenance treatment strategies and should therefore be limited to selected cases. Despite limitations, including moderate heterogeneity and moderate certainty of evidence, these results are of pragmatic relevance for clinicians, and should support the update of evidence-based guidelines.
FUNDING
None.
Topics: Adult; Antipsychotic Agents; Female; Humans; Male; Middle Aged; Network Meta-Analysis; Recurrence; Schizophrenia; Treatment Outcome; Young Adult
PubMed: 35753323
DOI: 10.1016/S2215-0366(22)00158-4 -
JAMA Psychiatry Oct 2019Recent meta-analyses of randomized clinical trials (RCTs) comparing clozapine with nonclozapine second-generation antipsychotics (NC-SGAs) in schizophrenia have... (Comparative Study)
Comparative Study Meta-Analysis
Association With Hospitalization and All-Cause Discontinuation Among Patients With Schizophrenia on Clozapine vs Other Oral Second-Generation Antipsychotics: A Systematic Review and Meta-analysis of Cohort Studies.
IMPORTANCE
Recent meta-analyses of randomized clinical trials (RCTs) comparing clozapine with nonclozapine second-generation antipsychotics (NC-SGAs) in schizophrenia have challenged clozapine's superiority in treatment-resistant patients. However, patients in RCTs are not necessarily generalizable to those in clinical practice.
OBJECTIVE
To conduct a systematic review and meta-analysis to compare various outcomes of clozapine vs oral NC-SGAs in cohort studies.
DATA SOURCES
Systematic literature search in PubMed, PsycINFO, and CINAHL without language restriction from database inception until December 17, 2018.
STUDY SELECTION
Nonrandomized cohort studies reporting effectiveness and/or safety outcomes comparing clozapine with NC-SGAs in schizophrenia or schizoaffective disorder.
DATA EXTRACTION AND SYNTHESIS
Independent investigators assessed studies and extracted data. Using a random-effects model, the study calculated risk ratio (RR) unadjusted for covariates and follow-up duration, number needed to treat/number needed to harm (NNT/NNH) for dichotomous data, and standardized mean difference (SMD) or mean difference (MD) for continuous data.
MAIN OUTCOMES AND MEASURES
Coprimary outcomes were hospitalization and all-cause discontinuation. Secondary outcomes included all effectiveness and safety outcomes reported in at least 3 analyzable studies.
RESULTS
Of 8446 hits, 68 articles from 63 individual cohort studies (n = 109 341) (60.3% male; mean [SD] age of 38.8 [6.5] years, illness duration of 11.0 [5.1] years, and study duration of 19.1 [23.3] months) were meta-analyzed. Compared with NC-SGAs, despite greater illness severity (17 studies [n = 38 766]; Hedges g, 0.222; 95% CI, 0.013-0.430; P = .04), clozapine was significantly associated with lower hospitalization risk (19 studies [n = 49 453]; RR, 0.817; 95% CI, 0.725-0.920; P = .001; NNT, 18; 95% CI, 12-40) and all-cause discontinuation (16 studies [n = 56 368]; RR, 0.732; 95% CI, 0.639-0.838; P < .001; NNT, 8; 95% CI, 6-12). Associations were statistically significant for comparisons with quetiapine fumarate and aripiprazole regarding hospitalization and all NC-SGAs, except aripiprazole, for all-cause discontinuation. Clozapine was also significantly associated with better outcomes regarding overall symptoms (SMD, -0.302; 95% CI, -0.572 to -0.032; P = .03) and Clinical Global Impressions scale severity (SMD, -1.182; 95% CI, -2.243 to -0.122; P = .03). Clozapine was significantly associated with increases in body weight (MD, 1.70; 95% CI, 0.31-3.08 kg; P = .02), body mass index (MD, 0.96; 95% CI, 0.24-1.68; P = .009), and type 2 diabetes (RR, 1.777; 95% CI, 1.229-2.570; P = .002; NNH, 27; 95% CI, 13-90).
CONCLUSIONS AND RELEVANCE
In cohort studies, despite more severely ill patients being treated with clozapine, use of clozapine was associated with better key efficacy outcomes and higher cardiometabolic-related risk outcomes vs NC-SGAs.
Topics: Adult; Antipsychotic Agents; Clozapine; Cohort Studies; Drug-Related Side Effects and Adverse Reactions; Female; Hospitalization; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Schizophrenia
PubMed: 31365048
DOI: 10.1001/jamapsychiatry.2019.1702 -
Schizophrenia (Heidelberg, Germany) Feb 2022Clinical practice guidelines (CPGs) translate evidence into recommendations to improve patient care and outcomes. To provide an overview of schizophrenia CPGs, we...
Clinical practice guidelines (CPGs) translate evidence into recommendations to improve patient care and outcomes. To provide an overview of schizophrenia CPGs, we conducted a systematic literature review of English-language CPGs and synthesized current recommendations for the acute and maintenance management with antipsychotics. Searches for schizophrenia CPGs were conducted in MEDLINE/Embase from 1/1/2004-12/19/2019 and in guideline websites until 06/01/2020. Of 19 CPGs, 17 (89.5%) commented on first-episode schizophrenia (FES), with all recommending antipsychotic monotherapy, but without agreement on preferred antipsychotic. Of 18 CPGs commenting on maintenance therapy, 10 (55.6%) made no recommendations on the appropriate maximum duration of maintenance therapy, noting instead individualization of care. Eighteen (94.7%) CPGs commented on long-acting injectable antipsychotics (LAIs), mainly in cases of nonadherence (77.8%), maintenance care (72.2%), or patient preference (66.7%), with 5 (27.8%) CPGs recommending LAIs for FES. For treatment-resistant schizophrenia, 15/15 CPGs recommended clozapine. Only 7/19 (38.8%) CPGs included a treatment algorithm.
PubMed: 35210430
DOI: 10.1038/s41537-021-00192-x -
Schizophrenia Research Jun 2024The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents.
BACKGROUND
The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents.
METHODS
Cases of clozapine-associated pericarditis and pancreatitis in children were studied using searches in: 1) PubMed (June 16, 2023), and 2) the World Health Organization's pharmacovigilance database (June 1, 2022), VigiBase. VigiBase uses a logarithmic measure of disproportionality called the information component (IC).
RESULTS
The PubMed search yielded 3 clozapine-associated pericarditis cases, 1 pancreatitis case and 1 with both. VigiBase provided a significant clozapine-associated pericarditis IC = 3.6 with an IC = 2.9 (only 3 cases were expected while 22 were observed). VigiBase provided a significant clozapine-associated pancreatitis IC = 2.2 with an IC = 1.4 (only 3 cases were expected while 16 were observed). In VigiBase clozapine-associated pericarditis and pericardial effusion in youth looked similar and on a continuum with myocarditis, as myocarditis, pericarditis and pancreatitis appeared to occur mainly during clozapine titration. Combining PubMed and VigiBase we identified: 1) 29 cases of at least possible clozapine-associated pericarditis/pericardial effusion (6 probable and 23 possible) including 7 cases with and 22 without myocarditis, and 2) 17 cases of clozapine-associated pancreatitis (1 definite and 16 possible). Two of the pancreatitis cases occurred during overdoses. No fatal outcomes were found in any clozapine-associated pericarditis and pancreatitis cases.
CONCLUSIONS
Despite the lack of attention in the literature to clozapine-associated pericarditis and pancreatitis, results demonstrate that they can happen in youth, particularly during titration. Pericarditis and pancreatitis appear to be forms of clozapine-associated inflammation during dose titration.
Topics: Humans; Pancreatitis; Clozapine; Pericarditis; Pharmacovigilance; Adolescent; Child; Antipsychotic Agents; Databases, Factual; Male; Female; Pericardial Effusion
PubMed: 37981478
DOI: 10.1016/j.schres.2023.10.027