An original pharmacoepidemiologic - pharmacodynamic method: application to antipsychotic-induced movement disorders (original) (raw)
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BMC Psychiatry
Background: Antidepressants-induced movement disorders are rare and imperfectly known adverse drug reactions. The risk may differ between different antidepressants and antidepressants' classes. The objective of this study was to assess the putative association of each antidepressant and antidepressants' classes with movement disorders. Methods: Using VigiBase®, the WHO Pharmacovigilance database, disproportionality of movement disorders' reporting was assessed among adverse drug reactions related to any antidepressant, from January 1967 to February 2017, through a case/non-case design. The association between nine subtypes of movement disorders (akathisia, bruxism, dystonia, myoclonus, parkinsonism, restless legs syndrome, tardive dyskinesia, tics, tremor) and antidepressants was estimated through the calculation first of crude Reporting Odds Ratio (ROR), then adjusted ROR on four potential confounding factors: age, sex, drugs described as able to induce movement disorders, and drugs used to treat movement disorders. Results: Out of the 14,270,446 reports included in VigiBase®, 1,027,405 (7.2%) contained at least one antidepressant, among whom 29,253 (2.8%) reported movement disorders. The female/male sex ratio was 2.15 and the mean age 50.9 ± 18.0 years. We found a significant increased ROR for antidepressants in general for all subtypes of movement disorders, with the highest association with bruxism (ROR 10.37, 95% CI 9.62-11.17) and the lowest with tics (ROR 1.49, 95% CI 1.38-1.60). When comparing each of the classes of antidepressants with the others, a significant association was observed for all subtypes of movement disorders except restless legs syndrome with serotonin reuptake inhibitors (SRIs) only. Among antidepressants, mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan and fluvoxamine were associated with the highest level to movement disorders and citalopram, paroxetine, duloxetine and mirtazapine were the most frequently associated with movement disorders. An association was also found with eight other antidepressants.
Movement Disorders After Exposure to Antipsychotic Drugs in Patients With Depressive Disorders
Clinical neuropharmacology
The aims of the study were to explore the frequency of movement disorders (MDs) in depressive patients exposed to antipsychotic drugs (APDs) and to compare it with nonexposed depressive patients and APDs-treated schizophrenic patients. Four hundred fifty-two depressive patients not exposed to APDs (group A), 156 depressives exposed to APDs (group B), and 75 patients with schizophrenia on APDs (group C) were recruited. Presence of MDs was explored by the Simpson-Angus and UKU scales (Registration: NCT02409823). Movement disorders were observed in 5%, 9%, and 13% of patients in groups A to C, respectively (P < 0.001, χ for linear trend). A logistic multivariate analysis revealed that male sex (odds ratio = 2.26, 95% confidence interval = 1.13-4.49, P < 0.01), exposure to first-generation (vs second-generation) APDs (odds ratio = 5.71, 95% confidence interval = 2.08-15.66, P < 0.01), and exposure to lithium (odds ratio = 3.99, 95% confidence interval = 1.74-9.14, P < 0.01) ...
Interrelations between psychiatric symptoms and drug-induced movement disorder
Journal of psychiatry & neuroscience : JPN, 2006
After 30 years of clinical research into drug-induced movement disorder (DIMD), we are still facing unresolved issues regarding the interrelations between psychiatric symptoms and DIMD. Recently, I proposed a new classification of DIMD that includes abnormal movements previously labelled extrapyramidal symptoms. DIMD caused by psychotropic drugs is still confused with psychiatric symptoms treated by the same drugs. The results from 2 international multicentre trials, the InterSePT and the Ris-Consta Studies, conducted in the era of both typical and atypical antipsychotic agents, which included over 3,000 patients with schizophrenia and schizoaffective disorder worldwide, still showed a high, but decreasing, incidence of pretreatment DIMD, which varied from 57.5% (1998-1999) to 47.4% (1999-2000), and a decreasing incidence of tardive dyskinesia, which varied from 12% (1998-1999) to 10.2% (1999-2000), reflecting the greater use of atypical antipsychotic drugs. Furthermore, in both stu...
Journal of Clinical Psychopharmacology, 2019
Purpose/Background: Dopamine receptor blocking agents (DRBAs), also known as antipsychotics, are medications widely used to treat a growing number of mental health diagnoses. However, their utility is limited by the potential to cause serious adverse movement reactions. Akathisia, dystonia, parkinsonism, and tardive dyskinesia (collectively known as extrapyramidal symptoms or EPSs) are associated with reduced social and occupational functioning, negative patient attitudes toward treatment, and nonadherence to pharmacotherapy. Neuroleptic malignant syndrome is a life-threatening reaction that can result from DRBA use and cause musculoskeletal dysfunction. The aim of this study is to profile patients who have developed DRBA-related movement adverse effects and identify risk factors significantly associated with each subtype of EPSs or other movement disorders (OMDs) such as neuroleptic malignant syndrome. Methods/Procedures: A report of all potential DRBA-related EPSs or OMDs occurrences within a large community hospital network was generated using International Classification of Diseases, Ninth Revision (ICD-9) and 10th Revision (ICD-10) billing codes. Each patient encounter was manually reviewed to confirm that a documented case of DRBA-related EPSs or OMDs had indeed occurred and subsequently determine the likely causative agent(s). Findings/Results: The resultant cohort of 148 patients experiencing unique DRBA-related EPS or OMD events was analyzed. The average patient was female, middle-aged, and overweight. The most common DRBAs precipitating EPSs or OMDs were haloperidol and quetiapine. In the population studied, age was significantly associated with the subtype of EPSs experienced such that those patients with akathisia and dystonia tended to be younger, whereas those with tardive dyskinesia tended to be older. Body mass index (BMI) category was also negatively correlated with the incidence of dystonia. In addition, it was observed that exposure to specific DRBAs, classes, and routes of administration significantly affected the risk of developing different subtypes of EPSs or OMDs in the study population. Implications/Conclusions: To our knowledge, this is the first study to describe an association between age and BMI with the risk of akathisia and dystonia, respectively, in patients taking DRBAs. Other trends observed with age and BMI in patients developing DRBA-related EPSs support previously reported findings. Expanding the knowledge base of individual characteristics associated with the risk of developing different subtypes of EPSs or OMDs can help providers and patients anticipate and attempt to mitigate these reactions, and may ultimately improve adherence to DRBA therapy.
Comparison of adverse drug reactions with typical and atypical antipsychotic drugs
2013
Organized studies on incidence of ADRs have been very few and are confined to very few centres. The prescribing of psychotropic medicines is rapidly increasing in psychiatry patients. Although treatment with antipsychotics is relatively effective, a large fraction of the patients may not respond, responding patients may develop treatment resistance eventually and severe adverse drug reactions (e.g. extra-pyramidal symptoms, sexual dysfunction, sedation, and diabetes mellitus) may occur. In attempt to control the use of psychotropic medicine the regulatory authorities have issued various warnings about risks associated with use of these psychotropic drugs. Little evidence has been reported about the ADRs of these medicines in practice. The objective was to understand, document, categories, and report ADRs for feature safety and well-being of the patients.
PloS one, 2013
Antipsychotics (APs) have been associated with risk of torsade de Pointes (TdP). This has important public health implications. Therefore, (a) we exploited the public FDA Adverse Event Reporting System (FAERS) to characterize their torsadogenic profile; (b) we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. FAERS data (2004-2010) were analyzed based on the following criteria: (1) ≥ 4 cases of TdP/QT abnormalities; (2) Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers); (3) ≥ 4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD); (4) Significant ROR for VA/SCD; (5) Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfill...
Adverse Drug Reactions of Atypical Antipsychotics: A Review
Background: Adverse Drug Reactions (ADRs) as responses to drugs that are dangerous, unwanted, and occurring at doses typically used for prophylaxis, diagnosis, or modification of physiological function in humans. ADRs are a very important health problem to pay attention to. Currently, information on ADRs of atypical antipsychotics is lacking. Therefore, this literature study aims to summarize the adverse drug reactions (ADR) that occur due to the use of atypical antipsychotics and to examine their causality, severity, prevention, and predictability. Methods: The method used in the writing of this article is a literature study using computerized databases such as Science Direct, Pubmed, Semantic Scholar, and Google Scholar. The keywords used were "Adverse drug reactions" OR "ADRs" and "Atypical antipsychotics" OR "Second-generation antipsychotics". Results: The most common adverse drug reactions are weight gain, constipation, insomnia, dry mouth, tremor, sedation, hypersalivation, somnolence, extrapyramidal signs and symptoms (EPS), and headache. Assessment of causality by using the Naranjo's scale and the WHO assessment scale the results were "probable" followed by "possible" and "certain". Assessment of the severity by using the Hartwig and Siegel scale the results were "mild" followed by "moderate" and "severe". Prevention assessment of ADRs for atypical antipsychotics by using the Modified Schumock and Thornton scale the results were "probably preventable", followed by "not preventable" and "definitely preventable". The majority of ADRs from these atypical antipsychotics are predictable. Conclusion: The majority of ADRs of these atypical antipsychotics are predictable. However, to ensure patient safety, a large enough prospective study should be considered to clarify this issue.
Drug Safety, 2013
Background Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FA-ERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QTinterval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1?2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1?2; (b) significant ROR in group 1?2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1?2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk.