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Patient claims analyzed for BD-related inpatient admissions after ≥10% dose reductions of antipsychotic medication. Outcomes for case and control cohorts were assessed using Kaplan–Meier analysis and compared using a log-rank test. The number of patients at risk is represented for each time point. Case and control cohorts for ≥10%, N = 23,992 each. CI: confidence interval; BD: bipolar disorder
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Abstract Background The relative benefits and risks of long-term maintenance treatment with antipsychotics have not been well studied in patients with bipolar disorder and major depressive disorder. For example, while antipsychotic dose reduction has been recommended in the management of serious side effects associated with antipsychotics, there is...
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Long-acting injectable (LAI) antipsychotics are often used for the long-term management also of bipolar disorder (BD). Nonetheless, evidence on their effect on pragmatic outcomes such as hospitalization risk in BD is inconsistent. We carried out
a mirror-image study comparing rates and number of days of hospitalization, one year before and after th...
Citations
... A 2021 meta-analysis by Kishi et al., found benefit in continuing antipsychotic and mood stabilizer combination treatment up to 12 months [86]. Discontinuation and dose reduction of antipsychotics has been linked to a small but significant increase in subsequent hospitalization [87]. ...
Purposeof Review
Old age bipolar disorder (OABD), increasingly common as the population ages, presents unique diagnostic and treatment challenges. This selective review focuses on issues especially relevant to outpatient management.
Recent Findings
People with OABD may have similar frequency and severity of mood episodes compared to younger adults. Depression predominates, and mixed symptoms in both depressive and manic episodes are common. Comorbidity and excess mortality are high, with a particular bidirectional association with cerebrovascular disease. Lithium may outperform valproic acid and second-generation antipsychotics in efficacy. Tolerability and long-term safety can be improved with relatively lower target drug therapeutic levels.
Summary
Outpatient clinicians treating OABD should take an active role in the recognition and management of medical comorbidities. A careful history and examination might reveal subtle signs of bipolar disorder or mixed features and change treatment. A primary target for treatment is to reduce polypharmacy when appropriate. Further trials are needed to make specific and clear recommendations in OABD.
... Developmental disorders and mood disorders, primarily bipolar disorder, also may confer risk. [60][61][62] But more women and older patients with depression who receive intermittent treatment with antipsychotics during episodic relapses may confound the association with mood disorders. 6,46,47,62,63 TD is associated with medical co-morbidities as well. ...
Tardive dyskinesia (TD) is a heterogeneous, hyperkinetic movement disorder induced by dopamine-receptor blocking agents that presents a unique challenge in the treatment of psychosis. Although acceptance of TD as a serious consequence of antipsychotic treatment was resisted initially, subsequent research by many investigators in psychopharmacology contributed to a rich store of knowledge on many aspects of the disorder. While basic neuroscience investigations continue to deepen our understanding of underlying motor circuitry, past trials of potential treatments of TD focusing on a range of theoretical targets were often inconclusive. Development of newer antipsychotics promised to reduce the risk of TD compared to older drugs, but their improved tolerability unexpectedly enabled an expanding market that paradoxically both increased the absolute number of patients at risk and diminished attention to TD which was relegated to legacy status. Fortunately, development and approval of novel vesicular monoamine transporter inhibitors offered evidence-based symptomatic treatment of TD for the first time and rekindled interest in the disorder. Despite recent progress, many questions remain for future research including the mechanisms underlying TD, genetic predisposition, phenomenological diversity, whether new cases are reversible, how to implement best practices to prevent and treat TD, and whether the development of novel antipsychotics free of the risk of TD is attainable. We owe our patients the aspirational goal of striving for zero prevalence of persistent symptoms of TD in anyone treated for psychosis.
... 13 Depressive symptom severity was grouped into 3 ordinal severity categories derived by converting total scores from either the Hamilton Depression Rating Scale (HAM-D), 14 15 or the Center for Epidemiologic Studies Depression Scale (CES-D). 16 Categories were calculated based on clinical cutoffs as follows: no depression (HAM-D: 0-7, MADRS: 0-6, CES-D: 0-15); mild-moderate depression (HAM-D: 8-23, MADRS: 7-34, CES-D: [16][17][18][19][20][21][22][23][24][25][26][27]; and severe depression (HAM-D • 24, MADRS • 35, CES-D • 16). ...
... 23 A recent 6-year retrospective cohort study from 6 U.S. states analyzed the impact of APS dose reduction in patients with BD and major depressive disorder and evaluated survival analyses with matched controls receiving a stable dosage. 24 Results showed that patients who had APS reductions showed small but statistically significant increases in all-cause and mental health-related hospitalizations. There is clearly a need for additional long-term studies regarding the necessity and safety of maintenance APS in OABD. 25 Our findings also demonstrate that OABD prescribed APS are younger than those not prescribed APS. ...
Objectives:
Antipsychotic drugs (APS) are widely used to treat patients with bipolar disorder (BD), but there is limited information in older-age bipolar disorder (OABD). This analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated characteristics of OABD patients prescribed APS vs. those not prescribed APS.
Experimental design:
The observational analysis used baseline, cross-sectional data from 16 international studies for adults aged ≥ 50 years with BD comprising 1,007 individuals with mean age 63.2 years (SD = 9.0), 57.4% women, and mean age of onset 31.6 years (SD = 15.0). The dependent variable was current APS treatment status. The independent variables included demographic and clinical variables, and a random effect for study, that were included in generalized mixed models.
Principal observations:
46.6% of individuals (n = 469) were using APS. The multivariate model results suggest that those treated with APS were younger (p = 0.01), less likely to be employed (p < 0.001), had more psychiatric hospitalizations (p = 0.009) and were less likely to be on lithium (p < 0.001). Of individuals on APS, only 6.6% of those (n = 27) were on first-generation antipsychotics (FGAs) and experienced a greater burden of psychiatric hospitalizations (p = 0.012).
Conclusions:
APS are widely prescribed in OABD, observed in nearly half of this sample with great variation across sites. Individuals with OABD on APS have more severe illness, more frequent hospitalizations and are more often unemployed vs. those not on APS. Future studies need to examine longitudinal outcomes in OABD prescribed APS to characterize underlying causal relationships.
... 10,11 In a study assessing the risk of TD in Afro-Caribbean patients with severe mental illness, the number of prior neuroleptic interruptions longer than 3 months increased the occurrence of TD; when the number of prior discontinuations were dichotomized (≤2 vs >2) that odds ratio increased to 3.29 (CI 1.27-8.49). 12 Further, changes in antipsychotic treatment due to adverse effects, such as TD, have been linked to an increase in mood-related hospital admissions and exacerbation of BD. 13,14 Recognizing the negative impact of antipsychotic-induced movement disorders, this study aimed to assess clinical risk factors for TD in a large cohort of patients with BD. In addition, we examined antipsychotic use patterns among patients with TD. have been previously published. ...
Purpose:
Recognizing the negative impact that antipsychotic-induced movement disorders have on the quality of life and treatment outcomes in bipolar disorder (BD), this study aimed to assess clinical correlates and antipsychotic use patterns of tardive dyskinesia (TD+) in BD.
Materials and methods:
Participants with and without TD were included. Clinical variables were compared using t-test and χ2 test. Antipsychotic use patterns in TD+, including number of trials, mean doses, and estimated cumulative exposure, were assessed in a case-only analysis.
Results:
The prevalence rate of TD was 5.1%. In comparison to the TD- group (n = 1074), TD+ participants (n = 58) were older, more likely to be female and have type I bipolar illness. There were 60.3% of the TD+ group that continued using antipsychotics at study entry and had a mean cumulative exposure to antipsychotics of 18.2 ± 15.6 years. Average dose, in haloperidol equivalents, was 5.9 ± 3.5 mg and 77.7% of the trials were second-generation antipsychotics.
Conclusions:
This study confirms previously identified TD risk factors, such as age, sex, and bipolar subtype in a large BD cohort. Limitations included a cross-sectional design and the lack of tardive illness severity assessment. As atypical antipsychotics continue to be primary mood stabilization treatment, attempting to harmonize large data sets to identify additional biomarkers of tardive risk will optimize individualized care for patients with BD.
... Switching to a drug with a lower affinity to D2 receptors, such as clozapine, is recommended in case pursuing neuroleptic treatment is mandatory (140). Antipsychotic reduction or switching are likely to have a positive clinical effect on reduction or reversibility of tardive dyskinesia, although not always statistically confirmed by some studies (141)(142)(143)(144). Neither prophylaxis with anticholinergics nor symptomatic treatment with GABA agonists are recommended due to lack of evidence supporting their use (143,145,146). ...
Hyperkinetic movement disorders are characterized by the presence of abnormal involuntary movements, comprising most notably dystonia, chorea, myoclonus, and tremor. Possible causes are numerous, including autoimmune disorders, infections of the central nervous system, metabolic disturbances, genetic diseases, drug-related causes and functional disorders, making the diagnostic process difficult for clinicians. Some diagnoses may be delayed without serious consequences, but diagnosis delays may prove detrimental in treatable disorders, ranging from functional disabilities, as in dopa-responsive dystonia, to death, as in Whipple's disease. In this review, we focus on treatable disorders that may present with prominent hyperkinetic movement disorders.
... Τhe prevalence of clinically relevant depressive symptoms in seniors is higher than 15%, while the prevalence of major depression exceeds 5% [1,2]. Antipsychotics augment antidepressants in 12-32% of older adults with depression [3][4][5][6], albeit in most cases in an off-label manner [7]. Antipsychotics contribute not only to treating psychotic symptoms in severe depression with psychotic features [8], but also to depressive symptom improvement, since they enhance monoaminergic neurotransmission [9]. ...
Background
Parkinsonian symptoms are common adverse effects of antipsychotics. Older adults are particularly vulnerable to drug-induced parkinsonism. Nonetheless, parkinsonian symptoms in seniors treated with antipsychotics cannot be straightforwardly attributed to antipsychotic medication. A comprehensive diagnostic workup is necessary in many cases in order to shed light on the cause of such symptoms in this patient population.
Case series
Eight cases of hospitalized depressed older adults with parkinsonian symptoms, who were treated for at least one year with antipsychotics, are reported. Based on neurological consultation, structural brain imaging and Ioflupane (I-123) dopamine transporter (DAT) single photon emission computerized tomography (SPECT), Parkinson’s disease was diagnosed in one case, idiopathic tremor in another, vascular parkinsonism in another one, while in another individual parkinsonian symptoms persisted at 12-month post-discharge follow-up even though his/her symptoms were classified as drug-induced on discharge. In four patients, parkinsonian symptoms were definitely drug-induced and no movement disturbances were reported at follow-up.
Conclusions
Differences in the cause and outcome of parkinsonian symptoms in seniors treated with antipsychotics merit systematic and in-depth study considering the therapeutic and prognostic implications of an accurate detection of the cause of such symptoms. Familiarizing clinical psychiatrists with these differences could pave the way towards approaching seniors with severe, atypical and/or persistent parkinsonian symptoms in a more individualized diagnostic and therapeutic manner, and towards more cautious prescribing of antipsychotics in this age group.
Purpose/background:
Tardive dyskinesia (TD) is a hyperkinetic movement disorder caused by exposure to dopamine-receptor blockers. Data on TD burden in Israel are scarce. This analysis assesses the clinical and economic burden of TD in Israeli patients.
Methods/procedures:
This retrospective analysis used a national health plan database (Maccabi Healthcare Services), representing 25% of the Israeli population. The study included adults alive at index date with an International Classification of Diseases, Ninth Revision, Clinical Modification TD diagnosis before 2018 and more than or equal to 1-year enrollment before diagnosis. Tardive dyskinesia patients were matched to non-TD patients (1:3) by underlying psychiatric condition, birth year, and sex. Treatment patterns and 2018 annual health care resource utilization and costs were assessed.
Findings/results:
Of 454 TD patients alive between 2013 and 2018, 333 alive on January 1, 2018, were matched to 999 non-TD patients. At baseline, TD patients had lower socioeconomic status and higher proportion of chronic kidney disease and antipsychotic medication use; all analyses were adjusted accordingly. Tardive dyskinesia patients had significantly more visits to general physicians, neurologists, psychiatrists, physiotherapists, and emergency departments versus non-TD patients (all P < 0.05). Tardive dyskinesia patients also had significantly longer hospital stays than non-TD patients (P = 0.003). Total healthcare and medication costs per patient were significantly higher in the TD versus non-TD population (US 7145, P = 0.018).
Implications/conclusions:
Israeli TD patients have higher clinical and economic burden than non-TD patients. Understanding real-world health care resource utilization and costs allows clinicians and decision makers to quantify TD burden and prioritize resources for TD patients' treatment.
Background
Antipsychotic medications are used to treat schizophrenia and may be associated with adverse effects, including tardive dyskinesia (TD), following prolonged use or upon changes in dosing regimen.Objective
This retrospective analysis evaluated the burden of antipsychotic dose reduction in Medicare patients with schizophrenia.Methods
This matched cohort study used Medicare claims data (2006–2017) analyzed for patients with schizophrenia and two or more claims for antipsychotics, with one or more antipsychotic monotherapy period ≥ 90 days. Cohorts were defined for patients with antipsychotic dose reductions ≥ 10% and stable doses. A separate analysis was conducted using patients with dose reductions ≥ 30%. Outcomes included all-cause emergency room (ER) visits, all-cause inpatient visits, schizophrenia relapse, other psychiatric relapse, and TD diagnosis. Covariates included age, disease duration, comorbidities, and medication use.ResultsThe analysis included 276,030 patients with ≥ 10% dose reductions and 211,575 patients with ≥ 30% dose reductions. Patient characteristics were balanced between cohorts. Patients with ≥ 10% or ≥ 30% dose reductions had a shorter time to ER visit, inpatient visit, schizophrenia relapse, other psychiatric relapse, and TD diagnosis versus those receiving stable doses (all p < 0.001). Significance was maintained when unmatched baseline characteristics were adjusted.Conclusions
Patients with antipsychotic dose reductions may be at risk for increased ER visits, increased hospitalizations, and significant unfavorable mental health-related clinical outcomes, suggesting that dose reduction may increase overall health care burden in some patients with schizophrenia. This work highlights the need for alternative strategies in the management of patients with TD.
Tardive dyskinesia (TD) is a syndrome of abnormal involuntary movements that follows treatment with dopamine D2-receptor antagonists. Recent approval of vesicular monoamine transporter-2 (VMAT2) inhibitors offers hope for reducing the impact of TD. Although these drugs represent a significant advance in patient care and a practical step forward in providing relief for patients with TD, understanding of the pharmacology of TD that could inform future research to prevent and reverse TD remains incomplete. This review surveys evidence for the effectiveness of VMAT2 inhibitors and other agents in the context of theories of pathogenesis of TD. In patients for whom VMAT2 inhibitors are ineffective or intolerable, as well as for extending therapeutic options and insights regarding underlying mechanisms, a review of clinical trial results examined as experimental tests of etiologic hypotheses is worthwhile. There are still compelling reasons for further investigations of the pharmacology of TD, which could generate alternative preventive and potentially curative treatments. Finally, benefits from novel drugs are best realized within an overall treatment strategy addressing the condition and needs of individual patients.
