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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 -
Therapeutic Drug Monitoring Apr 2024Therapeutic drug monitoring of clozapine in children and adolescents has received insufficient attention. Calculation of concentration-to-dose (C/D) ratios from trough...
A Systematic Review of Clozapine Concentration-Dose Ratio from Therapeutic Drug Monitoring Studies in Children and Adolescents Treated with Clozapine for Mental Disorders.
BACKGROUND
Therapeutic drug monitoring of clozapine in children and adolescents has received insufficient attention. Calculation of concentration-to-dose (C/D) ratios from trough steady-state concentrations estimate drug clearance.
METHODS
A systematic electronic literature search was conducted in 3 article databases from inception until January 10, 2023, and articles reporting clozapine concentrations in children and adolescents were retrieved. The pharmacokinetic quality of the studies was assessed, and clozapine C/D ratios were calculated using the sample mean clozapine dose and concentration.
RESULTS
Of the 37 articles of potential interest, only 7 reported clozapine trough and steady-state concentrations. After excluding case reports and a study confounded by fluvoxamine, 4 studies on psychosis from Europe and the United States were included. The clozapine C/D ratios were similar to published adult values and ranged from 0.82 to 1.24 with a weighted mean of 1.08 ng/mL per mg/d. The weighted means were 334 mg/d for the dose and 380 ng/mL for the concentration. The stratified analysis of the weighted mean clozapine C/D ratios from 2 studies showed lower values in 52 male (1.05 ng/mL per mg/d) than in 46 female (1.46 ng/mL per mg/d) children and adolescents, with values similar to those reported for European adult nonsmokers. Two female adolescents had high clozapine C/D ratios (2.54 ng/mL per mg/d), an Asian American patient with borderline obesity and a patient with intellectual disability with low dosage (mean = 102 mg/d) and concentration (mean = 55 ng/mL).
CONCLUSIONS
Reports on clozapine therapeutic drug monitoring in children and adolescents are limited in number and quality. Future studies should focus on basic pharmacokinetic issues, such as stratification by sex, smoking, and relevant comedications with inductive or inhibitory properties.
Topics: Adult; Child; Male; Humans; Female; Adolescent; Clozapine; Antipsychotic Agents; Drug Monitoring; Mental Disorders; Psychotic Disorders
PubMed: 38018845
DOI: 10.1097/FTD.0000000000001154 -
Psychiatry Research Mar 2024It has been previously reported that among patients with schizophrenia that long-acting injectable (LAI) antipsychotic formulations can delay time to relapse longer when...
A comparison of recurrence rates after discontinuation of second-generation antipsychotic long-acting injectable versus corresponding oral antipsychotic in the maintenance treatment of bipolar disorder: A systematic review.
It has been previously reported that among patients with schizophrenia that long-acting injectable (LAI) antipsychotic formulations can delay time to relapse longer when compared to their oral equivalents when patients discontinue therapy. Unanswered is whether this same pattern would be observed for patients with bipolar disorder receiving maintenance treatment. A systematic review was undertaken to identify relevant studies of LAI antipsychotics in maintenance treatment of bipolar disorder, employing a placebo-controlled randomized withdrawal design, and where equivalent studies using the corresponding oral formulation were also available. We found five studies [one aripiprazole monohydrate once monthly (AOM) study, one oral aripiprazole (OARI) study, two 2 weeks risperidone-LAI (RIS-LAI) studies, and one oral paliperidone (OPAL) study]. Numerically lower recurrence rates at 2, 4, 6, 8, 12, 16, 20, and 26 weeks were observed when AOM was discontinued when compared with discontinuation from OARI. Numerically lower recurrence rates at 2, 4, 6, 8, and 16 weeks were observed when RIS-LAI was discontinued when compared with discontinuation from OPAL. These results can be interpreted as a substantial delay in time to recurrence with a LAI antipsychotics formulation compared to the oral equivalent when medication is discontinued in patients with mania who had been stabilized on LAI antipsychotics or corresponding oral antipsychotics.
Topics: Humans; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Delayed-Action Preparations; Paliperidone Palmitate; Schizophrenia; Recurrence
PubMed: 38301289
DOI: 10.1016/j.psychres.2024.115761 -
Schizophrenia Research Jun 2024Antipsychotic polypharmacy (APP) is frequent but evidence-based guidelines on reducing APP to antipsychotic monotherapy (APM) are sparse. We aimed to systematically...
BACKGROUND
Antipsychotic polypharmacy (APP) is frequent but evidence-based guidelines on reducing APP to antipsychotic monotherapy (APM) are sparse. We aimed to systematically review clinical interventions randomizing patients to reducing APP to APM versus continuing APP.
METHODS
Systematic literature review searching Medline and Embase (latest search January 10, 2024) for randomized clinical trials (RCTs) studying interventions comparing individuals randomized to reduction of APP to APM with individuals continuing on APP. Two independent reviewers performed the literature screening, data extraction, and risk of bias assessment (RoB2). We performed random effects meta-analyses on the main outcome all-cause discontinuation/"acceptability" of the treatment strategy and secondary outcomes change in psychopathology, functional level, and side effects.
RESULTS
The search identified 4672 hits, whereof 8 trials (N = 1204, 6 patient-level RCTs and 2 cluster-RCTs) were included, primarily in patients with schizophrenia. All trials were associated with high risk of bias. Compared to APP continuation, reduction to APM was associated with no significant change in all-cause discontinuation (studies = 6, n = 455, RR = 1.48, 95%CI = 0.74-2.95, I = 78 %) or inefficacy-related discontinuation (studies = 5, n = 351, RR = 1.60, 95%CI = 0.46-5.55, I = 70 %). Patients randomized to APM showed a trend towards greater reduction in psychopathology (studies = 5, n = 244, SMD = -0.24, 95%CI = -0.49, 0.02, I = 0 %) but no difference in functional level nor side effects. The cluster-RCTs found that interventions at the departmental level can result in lower rates of APP.
CONCLUSION
Although switching patients from APP to APM can be a viable approach, too few RCTs exist on this important topic. Clinicians need to evaluate potential benefits and risks of APP and APM on an individual basis.
PROSPERO REGISTRATION
CRD42022329955.
PubMed: 38908279
DOI: 10.1016/j.schres.2024.06.001 -
The Mental Health Clinician Aug 2023
PubMed: 37860589
DOI: 10.9740/mhc.2023.08.196