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Clinical Breast Cancer Dec 2023Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a... (Meta-Analysis)
Meta-Analysis Review
Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a systematic review to evaluate the efficacy and safety of T-DXd in treating breast cancer, based on clinical trials. A systematic search of the literature was conducted to identify clinical trials investigating the efficacy and safety of T-DXd in breast cancer. Clinical trials of any phase were included. Outcome measures were any adverse events and survival. Meta-analysis was conducted where possible. Pooled prevalence for each adverse event of any grade and grade 3 or greater were estimated. Progression-free survival (PFS), overall survival (OS) and objective response rates (ORRs) were also reported to evaluate the efficacy of T-DXd in breast cancer. A total of 1593 patients from 6 clinical trials were included. Common adverse events of any grade were nausea, anemia, neutropenia, vomiting, fatigue, constipation and diarrhea, occurring in greater than 30% of cases. In terms of adverse events of grade 3 or more, only anemia and neutropenia occurred at a relatively high rate. Median PFS ranged from 11.1 to 22.1 months. There was evidence of a benefit of T-DXd compared to controls in terms of both PFS (OR: 0.38; 95% CI: 0.32, 0.45) and OS (OR: 0.61; 95% CI: 0.48, 0.78). ORRs ranged from 37% to 79.9%. The present systematic review shows evidence that T-DXd is a safe and effective agent in the treatment of breast cancer based on currently available data. The most common adverse events affected the blood, lymphatic and gastrointestinal systems. Interstitial lung disease (ILD) is a notable and potentially serious adverse event.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Camptothecin; Neutropenia; Anemia; Receptor, ErbB-2
PubMed: 37775347
DOI: 10.1016/j.clbc.2023.09.005 -
Endocrine Practice : Official Journal... Feb 2020The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating... (Meta-Analysis)
Meta-Analysis
The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism. Qualitative analysis was performed for studies identified in a literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control, randomized controlled, and retrospective cohort. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared. Odds of liver function injury were higher in the PTU group than in the MMI/CMZ group (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.16 to 4.96; = .02). Odds of elevated transaminase were much higher in the PTU group than in the MMI/CMZ group (OR, 3.96; 95% CI, 2.49 to 6.28; <.00001). No significant between-group differences were found in odds of elevated bilirubin, agranulocytosis, rash, or urticaria; incidence of other adverse events; or in children. Odds of birth defects during the first trimester of pregnancy were higher in the MMI/CMZ group than in the PTU group (OR, 1.29; 95% CI, 1.09 to 1.53; = .003). The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy. = alanine aminotransferase; = antithyroid drug; = confidence interval; = carbimazole; = Graves disease; = methimazole; = methylthiouracil; = Newcastle-Ottawa Scale; = odds ratio; = propylthiouracil; = radioactive iodine.
Topics: Aged; Antithyroid Agents; Child; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Propylthiouracil; Retrospective Studies; Thyroid Neoplasms
PubMed: 31652102
DOI: 10.4158/EP-2019-0221 -
Cancer Jan 2023Antibody-drug conjugates (ADCs) have complex molecular structures and have been tested in numerous clinical trials. Therefore, understanding the mechanisms of their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antibody-drug conjugates (ADCs) have complex molecular structures and have been tested in numerous clinical trials. Therefore, understanding the mechanisms of their toxicity when applied in medical practice is of high importance.
METHODS
In a systematic review and meta-analysis of data gathered from different scientific databases (PubMed, Embase, Cochrane, and Web of Science) between January 1, 2000, and June 7, 2022, the authors applied a random-effects model with logit transformation and evaluated the heterogeneity between studies using I statistics. The primary outcome was the incidence and 95% confidence interval (CI) for all-grade and grade ≥3 treatment-related adverse events and differences between different drugs, molecular structures, and cancer types.
RESULTS
In total, 2511 records were identified that included 169 clinical trials involving 22,492 patients. The overall incidence of treatment-related adverse events was 91.2% (95% CI, 90.7%-91.7%; I = 95.9%) for all-grade adverse events and 46.1% (95% CI, 45.2%-47.0%; I = 96.3%) for grade ≥3 adverse events. The most common all-grade adverse events were lymphopenia (53.0%; 95% CI, 48.7%-57.3%), nausea (44.1%; 95% CI, 43.2%-44.9%), neutropenia (43.7%; 95% CI, 42.6%-44.9%), blurred vision (40.5%; 95% CI, 37.4%-43.6%), and peripheral neuropathy (39.6%; 95% CI, 38.2%-41.1%); and the most common grade ≥3 adverse events were neutropenia (31.2%; 95% CI, 30.2%-32.3%), hypoesthesia (23.3%; 95% CI, 10.6%-35.9%), thrombocytopenia (22.6%; 95% CI, 21.3%-23.9%), febrile neutropenia (21.2%; 95% CI, 19.3%-23.1%), and lymphopenia (21.0%; 95% CI, 18.2%-23.7%).
CONCLUSIONS
Different ADCs appear to affect various treatment-related adverse events and provide comprehensive data on treatment-related adverse events for ADCs. The current results provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.
LAY SUMMARY
Unique anticancer drugs called antibody-drug conjugates (ADCs) have made significant progress in oncology in recent years because of their great success, and they are rapidly being used in the clinic as well as in hundreds of ongoing trials exploring their further use. The occurrence of serious side effects (adverse events) related to the receipt of ADCs was studied using data from 169 clinical trials involving 22,492 patients to determine the treatment-related causes of higher toxicity and adverse events in patients who receive ADCs, because these data are crucial for informing physicians how to safely treat patients using ADCs. The results indicate that different ADCs appear to affect various adverse events related to their use, providing comprehensive data on these ADCs that provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.
Topics: Humans; Immunoconjugates; Antineoplastic Agents; Neoplasms; Neutropenia; Lymphopenia
PubMed: 36408673
DOI: 10.1002/cncr.34507 -
Clinical Lymphoma, Myeloma & Leukemia Apr 2021Acute lymphoblastic leukemia (ALL) typically responds better when treated with multiagent chemotherapy in the pediatric and young adolescent populations. Treatment of... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-analysis of CD19-Specific CAR-T Cell Therapy in Relapsed/Refractory Acute Lymphoblastic Leukemia in the Pediatric and Young Adult Population: Safety and Efficacy Outcomes.
Acute lymphoblastic leukemia (ALL) typically responds better when treated with multiagent chemotherapy in the pediatric and young adolescent populations. Treatment of relapsed/refractory (RR) ALL remains a challenge. Even after stem-cell transplantation and intensive chemotherapy, the prognosis of RR-ALL remains grave. The advent of chimeric antigen receptors has demonstrated promising results in RR-ALL. Chimeric antigen receptor-modified T cells (CAR-T) and engineered T cells are used to target cancer cells. In 2017, the US Food and Drug Administration approved CD19-specific CAR-T (tisagenlecleucel) therapy for RR-B-cell ALL in patients under 25 years old. In this systematic review, we discuss the efficacy and safety of CD19-specific CAR-T therapy in RR-B-cell ALL in the pediatric and young adult population. We searched the PubMed, Embase, Web of Science, Cochrane Library, and clinical trials databases. A total of 448 patients received a CD19-specific CAR-T product, and 446 patients had evaluable data. The age range was 0 to 30 years. The incidence rate of complete remission was 82%. The cumulative incidence of relapse after CD19-specific CAR-T therapy is 36%. Similarly, the incidence rate of grade 3 or higher adverse events of neutropenia, thrombocytopenia, neurotoxicity, infections, and cytokine release syndrome were 38%, 23%, 18%, 29%, and 19%, respectively. Our subgroup analysis shows the incidence rate of minimal residual negative complete remission was 69% with the CD28z costimulatory domain, 81% with the 4-1BB domain, and 77% with fourth-generation CD19-specific CAR-T therapy.
Topics: Adolescent; Antigens, CD19; Child; Cytokine Release Syndrome; Drug Resistance, Neoplasm; Humans; Immunotherapy, Adoptive; Neoplasm Recurrence, Local; Neurotoxicity Syndromes; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Progression-Free Survival; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Remission Induction; Thrombocytopenia; Young Adult
PubMed: 33573914
DOI: 10.1016/j.clml.2020.12.010 -
BMJ Supportive & Palliative Care Dec 2019Multiple studies have questioned the benefit of neutropenic diets in decreasing infections in patients with cancer, but recent surveys showed that such diets are still... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Multiple studies have questioned the benefit of neutropenic diets in decreasing infections in patients with cancer, but recent surveys showed that such diets are still prescribed. In this study, we sought to evaluate the effectiveness of neutropenic diet in decreasing infection and mortality in neutropenic patients with cancer with neutropenia. This review is an update of a previously published systematic review.
MATERIALS AND METHODS
We searched different databases to identify comparative studies that investigated the effect of neutropenic diet compared with regular diet in neutropenic adults and children with cancer. We conducted random-effects meta-analyses using the Der-Simonian and Laird method to pool treatment effects from included studies. Outcomes of interest were mortality, bacteremia/fungemia, major infections, quality of life, and the composite outcome for neutropenic fever and/or infection.
RESULTS
We included six studies (five randomised) with 1116 patients, with 772 (69.1%) having underwent haematopoietic cell transplant. There was no statistically significant difference between neutropenic diet and regular diet in the rates of major infections (relative risk [RR] 1.16; 95% CI 0.94 to 1.42) or bacteremia/fungemia (RR 0.96; 95% CI 0.60 to 1.53). In haematopoietic cell transplant patients, neutropenic diet was associated with a slightly higher risk of infections (RR 1.25; 95% CI 1.02 to 1.54). No difference in mortality was seen between neutropenic diet and regular diet (RR 1.08, 95% CI 0.78 to 1.50).
CONCLUSION
There is currently no evidence to support the use of neutropenic diet or other food restrictions in neutropenic patients with cancer. Patients and clinicians should continue to follow the safe food-handling guidelines as recommended by the U.S. Food and Drug Administration.
Topics: Adult; Bacterial Infections; Child; Diet; Humans; Neoplasms; Neutropenia
PubMed: 30948447
DOI: 10.1136/bmjspcare-2018-001742 -
Hematology (Amsterdam, Netherlands) Dec 2023The meta-analysis sought to evaluate the efficacy and safety of a combination of venetoclax (Ven) and azacitidine (AZA) in the treatment of acute myeloid leukemia (AML)... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of venetoclax and azacytidine combination treatment in patients with acute myeloid leukemia and myelodysplastic syndrome: systematic review and meta-analysis.
OBJECTIVES
The meta-analysis sought to evaluate the efficacy and safety of a combination of venetoclax (Ven) and azacitidine (AZA) in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
METHODS
We searched PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, and Web of Science for eligible studies from inception to June 2022. We used the Cochrane Risk of Bias 2.0 (RoB 2.0) and Methodological Index for Non-Randomized Studies (MINORS) to evaluate the quality of the included literature. The inverse variance method was used to calculate the pooled proportion and 95% confidence interval (CI).
RESULTS
The meta-analysis included nineteen studies with a total of 1615 patients. The pooled overall CR/CRi (complete response (CR)/complete response with incomplete blood count recovery (CRi)) rate for AML and MDS was 57.9% (95% CI 49.5-65.9%, I = 83%). Subgroup analyses showed that the rate of pooled CR/CRi was 67.5% (95% CI 61.1-73.3%, I = 54%) for the new-diagnosed (ND) AML group, 30% (95% CI 20-44.1%, I = 66%) for relapsed/refractory (R/R) AML, and 67.6% (95% CI 52.6-79.8%, I = 65%) for MDS, respectively. One randomized controlled trial (RCT) showed that CR/CRi was 64.7% in ND-AML patients. A total of 9 studies reported adverse events, with neutropenia being the most common of grade 3-4 adverse events, with a rate of 53.7% (95% CI 61.1-73.3%, I = 54%).
CONCLUSION
The present meta-analysis demonstrated that the Ven + AZA regimen is efficacious for the treatment of AML and MDS, with it being more effective for ND-AML than R/R AML. The most common adverse effects of this regimen are grade 3-4 neutropenia and neutropenia with fever.
Topics: Humans; Azacitidine; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Antineoplastic Combined Chemotherapy Protocols; Neutropenia
PubMed: 37036307
DOI: 10.1080/16078454.2023.2198098 -
The Cochrane Database of Systematic... Sep 2023Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with shorter survival and a higher likelihood of the cancer returning. In early... (Review)
Review
BACKGROUND
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with shorter survival and a higher likelihood of the cancer returning. In early TNBC, platinum-based chemotherapy has been shown to improve pathological complete response (pCR); however, its effect on long-term survival outcomes has not been fully elucidated and recommendations to include platinum chemotherapy are not consistent in international guidelines.
OBJECTIVES
To evaluate the benefits and harms of platinum-based chemotherapy as adjuvant and neoadjuvant treatment in people with early triple-negative breast cancer.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 4 April 2022.
SELECTION CRITERIA
We included randomised controlled trials examining neoadjuvant or adjuvant platinum chemotherapy for early TNBC.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were disease-free survival (DFS) and overall survival (OS). Our secondary outcomes were pCR, treatment adherence, grade III or IV toxicity related to chemotherapy, and quality of life. Prespecified subgroups included BRCA mutation status, homologous recombination deficiency (HRD) status, frequency of chemotherapy, type of platinum agent used, and the presence or absence of anthracycline chemotherapy. We assessed risk of bias using Cochrane's RoB 1 tool and certainty of evidence using the GRADE approach.
MAIN RESULTS
From 3972 records, we included 20 published studies involving 21 treatment comparisons, and 25 ongoing studies. For most domains, risk of bias was low across studies. There were 16 neoadjuvant chemotherapy studies (one of which combined neoadjuvant and adjuvant therapy) and four adjuvant chemotherapy trials. Most studies used carboplatin (17 studies) followed by cisplatin (two), and lobaplatin (one). Eight studies had an anthracycline-free intervention arm, five of which had a carboplatin-taxane intervention compared to an anthracycline-taxane control. All studies reporting DFS and OS used carboplatin. Inclusion of platinum chemotherapy improved DFS in neoadjuvant and adjuvant settings (neoadjuvant: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.53 to 0.75; 7 studies, 8 treatment comparisons, 1966 participants; high-certainty evidence; adjuvant: HR 0.69, 95% CI 0.54 to 0.88; 4 studies, 1256 participants; high-certainty evidence). Platinum chemotherapy in the regimen improved OS (neoadjuvant: HR 0.69, 95% CI 0.55 to 0.86; 7 studies, 8 treatment comparisons, 1973 participants; high-certainty evidence; adjuvant: 0.70, 95% CI 0.50 to 0.96; 4 studies, 1256 participants; high-certainty evidence). Median follow-up for survival outcomes ranged from 36 to 97.6 months. Our analysis confirmed platinum chemotherapy increased pCR rates (risk ratio (RR) 1.44, 95% CI 1.31 to 1.59; 15 studies, 16 treatment comparisons, 3083 participants; high-certainty evidence). Subgroup analyses showed no evidence of differences in DFS according to BRCA mutation status, HRD status, lymph node status, or whether the intervention arm contained anthracycline chemotherapy or not. Platinum chemotherapy was associated with reduced dose intensity, with participants more likely to require chemotherapy delays (RR 2.23, 95% CI 1.70 to 2.94; 4 studies, 5 treatment comparisons, 1053 participants; moderate-certainty evidence), dose reductions (RR 1.77, 95% CI 1.56 to 2.02; 7 studies, 8 treatment comparisons, 2055 participants; moderate-certainty evidence) and early cessation of treatment (RR 1.20, 95% CI 1.04 to 1.38; 16 studies, 17 treatment comparisons, 4178 participants; moderate-certainty evidence). Increased haematological toxicity occurred in the platinum group who were more likely to experience grade III/IV neutropenia (RR 1.53, 95% CI 1.43 to 1.63; 19 studies, 20 treatment comparisons, 4849 participants; moderate-certainty evidence), anaemia (RR 8.20, 95% CI 5.66 to 11.89; 18 studies, 19 treatment comparisons, 4757 participants; moderate-certainty evidence) and thrombocytopenia (RR 7.59, 95% CI 5.10 to 11.29; 18 studies, 19 treatment comparisons, 4731 participants; moderate-certainty evidence). There was no evidence of a difference between chemotherapy groups in febrile neutropenia (RR 1.16, 95% CI 0.89 to 1.49; 11 studies, 3771 participants; moderate-certainty evidence). Renal impairment was very rare (0.4%, 2 events in 463 participants; note 3 studies reported 0 events in both arms; 4 studies; high-certainty evidence). Treatment-related death was very rare (0.2%, 7 events in 3176 participants and similar across treatment groups; RR 0.58, 95% 0.14 to 2.33; 10 studies, 11 treatment comparisons; note 8 studies reported treatment-related deaths but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 3 studies rather than 11; 3176 participants; high-certainty evidence). Five studies collected quality of life data but did not report them.
AUTHORS' CONCLUSIONS
Platinum-based chemotherapy using carboplatin in the adjuvant or neoadjuvant setting improves long-term outcomes of DFS and OS in early TNBC, with no evidence of differences by subgroup. This was at the cost of more frequent chemotherapy delays and dose reductions, and greater haematological toxicity, though serious adverse events including neuropathy, febrile neutropenia or treatment-related death were not increased. These findings support the use of platinum-based chemotherapy for people with early TNBC. The optimal dose and regimen are not defined by this analysis, but there is a suggestion that similar relative benefits result from the addition of carboplatin to either anthracycline-free regimens or those containing anthracycline agents.
Topics: Humans; Triple Negative Breast Neoplasms; Platinum; Carboplatin; Quality of Life; Adjuvants, Immunologic; Anthracyclines; Febrile Neutropenia
PubMed: 37681577
DOI: 10.1002/14651858.CD014805.pub2 -
Journal of Clinical PsychopharmacologyClozapine is a very effective therapeutic option for schizophrenic disorders that have been refractory to most other therapies. This extremely positive aspect clashes...
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.
Topics: Humans; Adult; Clozapine; Antipsychotic Agents; Retrospective Studies; Agranulocytosis; Neutropenia; Schizophrenia
PubMed: 37930206
DOI: 10.1097/JCP.0000000000001765 -
Acta Psychiatrica Scandinavica May 2022Clozapine is substantially underutilized in most countries and clinician factors including lack of knowledge and concerns about adverse drug effects (ADEs) contribute... (Review)
Review
OBJECTIVE
Clozapine is substantially underutilized in most countries and clinician factors including lack of knowledge and concerns about adverse drug effects (ADEs) contribute strongly to treatment reluctance. The aim of this systematic review was to provide clinicians with a comprehensive information source regarding clozapine ADEs.
METHODS
PubMed and Embase databases were searched for English language reviews concerned with clozapine ADEs; publications identified by the automated search were manually searched for additional relevant citations. Following exclusion of redundant and irrelevant reports, pertinent information was summarized in evidence tables corresponding to each of six major ADE domains; two authors reviewed all citations for each ADE domain and summarized their content by consensus in the corresponding evidence table. This study was conducted in accordance with PRISMA principles.
RESULTS
Primary and secondary searches identified a total of 305 unique reports, of which 152 were included in the qualitative synthesis. Most clozapine ADEs emerge within 3 months, and almost all appear within 6 months, after initiation. Notable exceptions are weight gain, diabetic ketoacidosis (DKA), severe clozapine-induced gastrointestinal hypomotility (CIGH), clozapine-induced cardiomyopathy (CICM), seizures, and clozapine-induced neutropenia (CIN). Most clozapine ADEs subside gradually or respond to dose reduction; those that prompt discontinuation generally do not preclude rechallenge. Rechallenge is generally inadvisable for clozapine-induced myocarditis (CIM), CICM, and clozapine-induced agranulocytosis (CIA). Clozapine plasma levels >600-1000 μg/L appear more likely to cause certain ADEs (e.g., seizures) and, although there is no clear toxicity threshold, risk/benefit ratios are generally unfavorable above 1000 μg/L.
CONCLUSION
Clozapine ADEs rarely require discontinuation.
Topics: Antipsychotic Agents; Cardiomyopathies; Clozapine; Drug-Related Side Effects and Adverse Reactions; Humans; Myocarditis; Neutropenia; Seizures
PubMed: 35178700
DOI: 10.1111/acps.13406 -
Journal of Child and Adolescent... Feb 2022Schizophrenia at a young age deserves investigation because of the greater severity and burden of illness on individuals and health care than its adult onset. For this... (Meta-Analysis)
Meta-Analysis Review
Schizophrenia at a young age deserves investigation because of the greater severity and burden of illness on individuals and health care than its adult onset. For this study, we included both childhood-onset schizophrenia and early-onset schizophrenia. We used the common term "childhood and adolescent-onset schizophrenia (CAOS)" for either type. This systematic review provides an overview of the clinical use, efficacy, and safety of clozapine treatment in managing CAOS. We conducted a systematic literature search in PubMed, Embase, and PsycINFO databases. We searched for randomized controlled trials (RCTs), open-label studies (OLSs), review articles, meta-analytic and observational studies. Our literature search resulted in 1242 search results. After the title, abstract, and full article review, 18 studies qualified (double-blind RCTs = 4; OLS = 4; observational studies = 7; case reports = 3). Clozapine use in CAOS was generally well tolerated and not associated with any fatalities. Clozapine use in the short term (6 weeks) and long term (2-9 years) was superior in efficacy than other antipsychotics in CAOS management. Improvement in overall symptoms was maintained during long-term follow-up over the years in OLSs. Clozapine appeared to have a favorable clinical response and shorter hospital stays. Sedation and hypersalivation were commonly reported (90%), constipation was next in frequency (13%-50%). Neutropenia was seen in 6%-15% of cases and agranulocytosis (<0.1%). Although weight gain was common (up to 64%), followed by metabolic changes (8%-22%), treatment-onset diabetes was less frequent (<6%). Akathisia, tachycardia, and blood pressure changes were less commonly seen. Limited studies indicate that clozapine is a safe and efficacious option for CAOS management. We need large-scale and well-designed long-term RCTs for the use of clozapine in the management of CAOS.
Topics: Adolescent; Adult; Antipsychotic Agents; Clozapine; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Weight Gain
PubMed: 35099269
DOI: 10.1089/cap.2021.0092