Magnitude, Nature, and Risk Factors of Adverse Drug Reactions Associated with First Generation Antipsychotics in Outpatients with Schizophrenia: A Cross-Sectional Study

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Abstract

Background

ADRs to antipsychotics are amongst the major challenges in the treatment of patients with psychotic disorders. The extent of patient-reported ADRs assessed in many studies using standardized scales is found to be inconsistent. However, there is a paucity of such research in Eritrea. The aim of the study is therefore to determine the magnitude, nature, and the possible risk factors associated with ADRs of the first generation antipsychotics in outpatients with schizophrenia at Saint Mary Neuro-Psychiatric National Referral Hospital in Asmara, Eritrea, using the LUNSERS self-rating scale.

Methods

A cross-sectional, descriptive and analytical study design utilizing a quantitative approach was employed. Data were collected from patients’ self-administered questionnaires, interviews, and medical records. The collected variables were analyzed using SPSS 22.0 with descriptive statistics, correlation, t-tests, ANOVA, and multiple regression. Statistical significance was tested at P-value<0.05.

Results

In this study, 93.8% of the research participants experienced at least one ADR. LUNSERS total mean score of the relevant items was 28.01 (SD=18.46) with 24.7% of the study participants scoring medium-to-high. The prevalence of the categories of ADRs was psychic (91.3%), autonomic (78.1%), extra-pyramidal (76.9%), miscellaneous (66.5%), hormonal (58.3%), anti-cholinergic (44.2%), and allergic reactions (44.2%). At multivariate level, factors significantly and positively associated with total ADR score were smoking ( P=0.028) and being at secondary educational level ( P=0.015).

Conclusion

There was high prevalence of ADRs with moderate-to-high overall ADR scores in a significant number of patients. The most frequently reported ADRs were psychic, autonomic, extra-pyramidal, hormonal, and miscellaneous. Smoking and secondary level of education were found to be the main determinants of ADRs.

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Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis.

Stefan Leucht, Andrea Cipriani, Loukia Spineli … (2013)

The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on the randomised evidence. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs. We did a Bayesian-framework, multiple-treatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation. We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0·88, 0·73-1·03; amisulpride 0·66, 0·53-0·78; olanzapine 0·59, 0·53-0·65; risperidone 0·56, 0·50-0·63; paliperidone 0·50, 0·39-0·60; zotepine 0·49, 0·31-0·66; haloperidol 0·45, 0·39-0·51; quetiapine 0·44, 0·35-0·52; aripiprazole 0·43, 0·34-0·52; sertindole 0·39, 0·26-0·52; ziprasidone 0·39, 0·30-0·49; chlorpromazine 0·38, 0·23-0·54; asenapine 0·38, 0·25-0·51; lurasidone 0·33, 0·21-0·45; and iloperidone 0·33, 0·22-0·43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug (haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76 (haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from -0·09 for the best drug (haloperidol) to -0·74 for the worst drug (olanzapine), for prolactin increase 0·22 (aripiprazole) to -1·30 (paliperidone), and for QTc prolongation 0·10 (lurasidone) to -0·90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in meta-regressions and sensitivity analyses. Antipsychotics differed substantially in side-effects, and small but robust differences were seen in efficacy. Our findings challenge the straightforward classification of antipsychotics into first-generation and second-generation groupings. Rather, hierarchies in the different domains should help clinicians to adapt the choice of antipsychotic drug to the needs of individual patients. These findings should be considered by mental health policy makers and in the revision of clinical practice guidelines. None. Copyright © 2013 Elsevier Ltd. All rights reserved.

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Schizophrenia

René S Kahn, Iris Sommer, Sir Robin M Murray … (2015)

Schizophrenia is a chronic psychiatric disorder with a heterogeneous genetic and neurobiological background that influences early brain development, and is expressed as a combination of psychotic symptoms - such as hallucinations, delusions and disorganization - and motivational and cognitive dysfunctions. The mean lifetime prevalence of the disorder is just below 1%, but large regional differences in prevalence rates are evident owing to disparities in urbanicity and patterns of immigration. Although gross brain pathology is not a characteristic of schizophrenia, the disorder involves subtle pathological changes in specific neural cell populations and in cell-cell communication. Schizophrenia, as a cognitive and behavioural disorder, is ultimately about how the brain processes information. Indeed, neuroimaging studies have shown that information processing is functionally abnormal in patients with first-episode and chronic schizophrenia. Although pharmacological treatments for schizophrenia can relieve psychotic symptoms, such drugs generally do not lead to substantial improvements in social, cognitive and occupational functioning. Psychosocial interventions such as cognitive-behavioural therapy, cognitive remediation and supported education and employment have added treatment value, but are inconsistently applied. Given that schizophrenia starts many years before a diagnosis is typically made, the identification of individuals at risk and those in the early phases of the disorder, and the exploration of preventive approaches are crucial.

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Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis

Toby Pillinger, Robert McCutcheon, Luke Vano … (2020)

Summary Background Antipsychotic treatment is associated with metabolic disturbance. However, the degree to which metabolic alterations occur in treatment with different antipsychotics is unclear. Predictors of metabolic dysregulation are poorly understood and the association between metabolic change and change in psychopathology is uncertain. We aimed to compare and rank antipsychotics on the basis of their metabolic side-effects, identify physiological and demographic predictors of antipsychotic-induced metabolic dysregulation, and investigate the relationship between change in psychotic symptoms and change in metabolic parameters with antipsychotic treatment. Methods We searched MEDLINE, EMBASE, and PsycINFO from inception until June 30, 2019. We included blinded, randomised controlled trials comparing 18 antipsychotics and placebo in acute treatment of schizophrenia. We did frequentist random-effects network meta-analyses to investigate treatment-induced changes in body weight, BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, and glucose concentrations. We did meta-regressions to examine relationships between metabolic change and age, sex, ethnicity, baseline weight, and baseline metabolic parameter level. We examined the association between metabolic change and psychopathology change by estimating the correlation between symptom severity change and metabolic parameter change. Findings Of 6532 citations, we included 100 randomised controlled trials, including 25 952 patients. Median treatment duration was 6 weeks (IQR 6–8). Mean differences for weight gain compared with placebo ranged from −0·23 kg (95% CI −0·83 to 0·36) for haloperidol to 3·01 kg (1·78 to 4·24) for clozapine; for BMI from −0·25 kg/m2 (−0·68 to 0·17) for haloperidol to 1·07 kg/m2 (0·90 to 1·25) for olanzapine; for total-cholesterol from −0·09 mmol/L (−0·24 to 0·07) for cariprazine to 0·56 mmol/L (0·26–0·86) for clozapine; for LDL cholesterol from −0·13 mmol/L (−0.21 to −0·05) for cariprazine to 0·20 mmol/L (0·14 to 0·26) for olanzapine; for HDL cholesterol from 0·05 mmol/L (0·00 to 0·10) for brexpiprazole to −0·10 mmol/L (−0·33 to 0·14) for amisulpride; for triglycerides from −0·01 mmol/L (−0·10 to 0·08) for brexpiprazole to 0·98 mmol/L (0·48 to 1·49) for clozapine; for glucose from −0·29 mmol/L (−0·55 to −0·03) for lurasidone to 1·05 mmol/L (0·41 to 1·70) for clozapine. Greater increases in glucose were predicted by higher baseline weight (p=0·0015) and male sex (p=0·0082). Non-white ethnicity was associated with greater increases in total cholesterol (p=0·040) compared with white ethnicity. Improvements in symptom severity were associated with increases in weight (r=0·36, p=0·0021), BMI (r=0·84, p<0·0001), total-cholesterol (r=0·31, p=0·047), and LDL cholesterol (r=0·42, p=0·013), and decreases in HDL cholesterol (r=–0·35, p=0·035). Interpretation Marked differences exist between antipsychotics in terms of metabolic side-effects, with olanzapine and clozapine exhibiting the worst profiles and aripiprazole, brexpiprazole, cariprazine, lurasidone, and ziprasidone the most benign profiles. Increased baseline weight, male sex, and non-white ethnicity are predictors of susceptibility to antipsychotic-induced metabolic change, and improvements in psychopathology are associated with metabolic disturbance. Treatment guidelines should be updated to reflect our findings. However, the choice of antipsychotic should be made on an individual basis, considering the clinical circumstances and preferences of patients, carers, and clinicians. Funding UK Medical Research Council, Wellcome Trust, National Institute for Health Research Oxford Health Biomedical Research Centre.

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Author and article information

Journal

Journal ID (nlm-ta): Integr Pharm Res Pract

Journal ID (iso-abbrev): Integr Pharm Res Pract

Journal ID (publisher-id): iprp

Journal ID (pmc): iprp

Title: Integrated Pharmacy Research & Practice

Publisher: Dove

ISSN (Electronic): 2230-5254

Publication date (Electronic): 14 October 2020

Publication date Collection: 2020

Volume: 9

Pages: 205-217

Affiliations

[1 ]School of Pharmacy, Asmara College of Health Sciences , Asmara, Eritrea

[2 ]Department of Addictions and Mental Health, University of Alberta , Edmonton, Canada

[3 ]Eritrean Pharmacovigilance Centre, National Medicines and Food Administration , Asmara, Eritrea

[4 ]Biostatistics and Epidemiology Unit, Department of Statistics, College of Science, Eritrean Institute Technology , Asmara, Eritrea

[5 ]College of Pharmacy, Princess Nourah Bint Abdulrahman University , Riyadh, Saudi Arabia

Author notes

Correspondence: Merhawi Bahta School of Pharmacy, Asmara College of Health Sciences , Asmara, EritreaTel +291-7294279 Email meramcp19@gmail.com

Author information

Merhawi Bahta http://orcid.org/0000-0002-1690-7876

Mulugeta Russom http://orcid.org/0000-0003-1939-5842

Eyasu H Tesfamariam http://orcid.org/0000-0002-8462-0500

Azieb Ogbaghebriel http://orcid.org/0000-0002-4818-9741

Article

Publisher ID: 271814

DOI: 10.2147/IPRP.S271814

PMC ID: 7569056

PubMed ID: 33117667

SO-VID: 2e0b07d7-e566-44e7-9103-d2fe31f57d26

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 13 July 2020

Date accepted : 10 September 2020

Page count

Figures: 0, Tables: 20, References: 43, Pages: 13

Funding

Funded by: National Higher Education and Research Institute of Eritrea;

The study was funded by the National Higher Education and Research Institute of Eritrea.

Magnitude, Nature, and Risk Factors of Adverse Drug Reactions Associated with First Generation Antipsychotics in Outpatients with Schizophrenia: A Cross-Sectional Study

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Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis.

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Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis

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