Incidence Of Tardive Dyskinesia Research Articles

THE FIRST GENERATION AND SECOND-GENERATION ANTIPSYCHOTIC DRUGS AND THEIR PHARMACOLOGY IN TREATMENT OF SCHIZOPHRENIA

Schizophrenia is a complex and severe psychiatric disorder that affects millions of people worldwide. Antipsychotic drugs have been widely used for the treatment of schizophrenia for over 60 years. The first-generation antipsychotic drugs (FGAs) were introduced in the 1950s and revolutionized the treatment of schizophrenia. However, their use is associated with a number of adverse effects, including Extrapyramidal Symptoms (EPS) and Tardive Dyskinesia (TD). Second-generation antipsychotic drugs (SGAs), also known as atypical antipsychotics, were developed in the 1990s and have become the preferred treatment for schizophrenia due to their lower incidence of EPS and TD. They also have a broader range of therapeutic effects, such as improving negative symptoms and cognitive impairment associated with schizophrenia. This review article summarizes the pharmacology of both FGAs and SGAs, including their mechanism of action, pharmacokinetics, and adverse effects. The efficacy and safety of these drugs in the treatment of schizophrenia are also discussed. In addition, this review examines the controversy surrounding the use of SGAs and their potential metabolic side effects, such as weight gain, hyperlipidemia, and diabetes. Despite the availability of SGAs, FGAs still have a role in the treatment of schizophrenia, particularly for patients who are unresponsive to SGAs or experience intolerable side effects. Furthermore, research continues to identify new pharmacological targets and treatment strategies for schizophrenia. Understanding the pharmacology and clinical use of antipsychotic drugs is essential for optimizing the treatment of schizophrenia and improving patient outcomes.

Addendum: Drugs for depression.

In our article on Drugs for Depression, we should have included tardive dyskinesia (TD) in our list of adverse effects of second-generation antipsychotic (SGA) drugs. TD, which is more commonly associated with first-generation antipsychotics, can also occur in patients taking an SGA, especially with prolonged use. A meta-analysis found that the annualized incidence of TD was 2.6% in SGA users (M Carbon et al. World Psychiatry 2018; 17:330). Older adults are at increased risk.

Health Care Resource Utilization and Costs for Patients with Tardive Dyskinesia.

Tardive dyskinesia (TD) is an often-irreversible movement disorder affecting any part of the body. Patients experience debilitating symptoms that lower quality of life and increase mortality. Prolonged exposure to dopamine antagonists, which are frequently prescribed for psychiatric disorders as neuroleptic (antipsychotic) drugs, is a common cause of TD. The estimated prevalence of TD is 20%-50% among patients on antipsychotics, and the reported incidence of TD ranges from < 1% to 42%, depending on the antipsychotics studied. However, there are few real-world studies examining health care utilization and the economic burden of TD. To assess health care utilization and costs in a sample of patients with TD from the commercially insured and Medicare supplemental U.S. A retrospective analysis was conducted using Truven MarketScan Commercial and Medicare administrative claims data. Patients were included in the TD group if they had the first TD diagnosis (index date) between January 1, 2008, and September 30, 2014, with ≥ 1 inpatient or ≥ 2 outpatient nondiagnostic claims for TD (ICD-9-CM code 333.85). Patients without TD were randomly assigned an index date. Further inclusion criteria for all patients were ≥ 12 months of pre- and post-index medical and pharmacy continuous enrollment and no evidence of TD claims during the pre-index period. Patients with TD were directly matched to patients without TD within subgroups for schizophrenia, major depressive disorder, bipolar disorder, and other psychiatric disorders and propensity matched on other demographic and clinical factors. Descriptive statistics on the incidence of resource utilization and costs of health care were reported. Of 3,397 patients with TD, 834 met the selection criteria and were matched to 834 non-TD controls. Patients with TD generally had significantly greater utilization during the 12 months after TD diagnosis than in the 12 months before TD diagnosis. Their rates for health care utilization and costs were also substantially higher than for those without TD. During the post-TD-diagnosis time, inpatient admissions (55.5% vs. 26.1%; P < 0.001) and emergency room visits (61.5% vs. 50.6%; P < 0.001) occurred more for patients with TD than for patients without TD. Total health care costs were significantly greater for patients with TD than for those without TD ($54,656 vs. $28,777; P < 0.001). Patients diagnosed with TD demonstrate significantly higher health care utilization and costs compared with non-TD patients. This study was funded by Teva Pharmaceuticals (Petach Tikva, Israel). Truven Health Analytics, an IBM Watson Health Company, received payment from Teva Pharmaceuticals for the analysis in this study. Carroll is employed by Teva Pharmaceuticals and Irwin is employed by Truven Health Analytics, an IBM Watson Health Company.

Tardive dyskinesia risk with first- and second-generation antipsychotics in comparative randomized controlled trials: a meta-analysis.

Tardive dyskinesia (TD) risk with D2/serotonin receptor antagonists or D2 receptor partial agonists (second-generation antipsychotics, SGAs) is considered significantly lower than with D2 antagonists (first-generation antipsychotics, FGAs). As some reports questioned this notion, we meta-analyzed randomized controlled studies (RCTs) to estimate the risk ratio (RR) and annualized rate ratio (RaR) of TD comparing SGAs vs. FGAs and SGAs vs. SGAs. Additionally, we calculated raw and annualized pooled TD rates for each antipsychotic. Data from 57 head-to-head RCTs, including 32 FGA and 86 SGA arms, were meta-analyzed, yielding 32 FGA-SGA pairs and 35 SGA-SGA pairs. The annualized TD incidence across FGA arms was 6.5% (95% CI: 5.3-7.8%) vs. 2.6% (95% CI: 2.0-3.1%) across SGA arms. TD risk and annualized rates were lower with SGAs vs. FGAs (RR=0.47, 95% CI: 0.39-0.57, p<0.0001, k=28; RaR=0.35, 95% CI: 0.28-0.45, p<0.0001, number-needed-to-treat, NNT=20). Meta-regression showed no FGA dose effect on FGA-SGA comparisons (Z=-1.03, p=0.30). FGA-SGA TD RaRs differed by SGA comparator (Q=21.8, df=7, p=0.003), with a significant advantage of olanzapine and aripiprazole over other non-clozapine SGAs in exploratory pairwise comparisons. SGA-SGA comparisons confirmed the olanzapine advantage vs. non-clozapine SGAs (RaR=0.66, 95% CI: 0.49-0.88, p=0.006, k=17, NNT=100). This meta-analysis confirms a clinically meaningfully lower TD risk with SGAs vs. FGAs, which is not driven by high dose FGA comparators, and documents significant differences with respect to this risk between individual SGAs.

There has been very little progress in treating or preventing antipsychotic-induced tardive dyskinesia.

Commentary on : Bergman H, Walker DM, Nikolakopoulou A, et al . Systematic review of interventions for treating or preventing antipsychotic-induced tardive dyskinesia. Health Technol Assess 2017;21:1-218. Tardive dyskinesia (TD) is a relatively frequent side effect of long-term use of antipsychotics and there is conflicting evidence if the incidence of TD is lower with second-generation antipsychotics (excluding clozapine), compared with first-generation antipsychotics. Until now there is no evidence-based algorithm to prevent or to treat TD. This systematic review1 evaluated any intervention for treating or preventing deterioration of symptoms of antipsychotic-induced TD in adult patients. Included were all relevant studies, regardless of language, about adults who had used antipsychotic drugs for ≥3 months and in whom the antipsychotic doses had been stable for at least 1 month. The authors included 112 randomised trials and eight prospective cohort studies. Seventy-nine separate interventions were the focus of the trials, whereas prospective cohort studies focused on comparing different strategies for antipsychotics. These were grouped into three broad categories: 1. Reducing antipsychotic dose. 2. Switching antipsychotic drug. (3) Adjunctive treatments in …

Real-world data on paliperidone palmitate for the treatment of schizophrenia and other psychotic disorders: a systematic review of randomized and nonrandomized studies.

The aim of this study was to perform a systematic review of the effects of 1-month paliperidone palmitate (PP1M) for the treatment of schizophrenia and related psychotic disorders in terms of outcomes reported in real-world evidence studies. A systematic review of real-world randomized and nonrandomized studies with PP1M was performed and is reported according to PRISMA guidelines. Comparative effectiveness data with oral antipsychotics indicate that PP1M has a lower likelihood of relapse-related events, including rehospitalization, and these differences are clinically relevant. A randomized, double-blind study showed that PP1M has no advantage over haloperidol decanoate in the time to treatment failure. Although there was a marked variability across studies, PP1M was not superior to other antipsychotics in terms of study completion rates. Pharmacoeconomic data show that, during a follow-up period of 12 months, the mean total healthcare cost was not significantly different in patients treated with PP1M compared with those receiving oral antipsychotics. The mean maximum prolactin levels were significantly higher with PP1M than with haloperidol decanoate; however, neither drug differs in the frequency of prolactin-related adverse events. Results on prolactin-related adverse events were inconsistent in two randomized comparisons with oral antipsychotics and were not reported in a randomized comparison with aripiprazole. There were no significant differences between haloperidol decanoate and PP1M in the severity of abnormal involuntary movements and parkinsonism, or in the incidence of tardive dyskinesia; however, patients treated with haloperidol decanoate showed greater worsening of akathisia and required treatment for parkinsonism and akathisia significantly more frequently than patients who received PP1M. In conclusion, real-world data that originate from both pragmatic randomized clinical trials and observational studies indicate that PP1M is superior to oral antipsychotics in delaying the time to relapse or treatment failure. Furthermore, the pharmacoeconomic data reviewed for this article suggest that the advantages of PP1M compared with oral antipsychotics are not associated with an increased total cost for healthcare providers.

Systematic review of interventions for treating or preventing antipsychotic-induced tardive dyskinesia.

Antipsychotic medication can cause tardive dyskinesia (TD) - late-onset, involuntary, repetitive movements, often involving the face and tongue. TD occurs in > 20% of adults taking antipsychotic medication (first-generation antipsychotics for > 3 months), with this proportion increasing by 5% per year among those who continue to use these drugs. The incidence of TD among those taking newer antipsychotics is not different from the rate in people who have used older-generation drugs in moderate doses. Studies of TD have previously been found to be limited, with no treatment approach shown to be effective. To summarise the clinical effectiveness and safety of treatments for TD by updating past Cochrane reviews with new evidence and improved methods; to undertake public consultation to gauge the importance of the topic for people living with TD/the risk of TD; and to make available all data from relevant trials. All relevant randomised controlled trials (RCTs) and observational studies. Cochrane review methods, network meta-analysis (NMA). Systematic reviews, patient and public involvement consultation and NMA. Any setting, inpatient or outpatient. For systematic reviews, adults with TD who have been taking a stable antipsychotic drug dose for > 3 months. Any, with emphasis on those relevant to UK NHS practice. Any measure of TD, global assessments and adverse effects/events. We included 112 studies (nine Cochrane reviews). Overall, risk of bias showed little sign of improvement over two decades. Taking the outcome of 'TD symptoms improved to a clinically important extent', we identified two trials investigating reduction of antipsychotic dose [n = 17, risk ratio (RR) 0.42, 95% confidence interval (CI) 0.17 to 1.04; very low quality]. Switching was investigated twice in trials that could not be combined (switching to risperidone vs. antipsychotic withdrawal: one RCT, n = 42, RR 0.45, 95% CI 0.23 to 0.89; low quality; switching to quetiapine vs. haloperidol: one RCT, n = 45, RR 0.80, 95% CI 0.52 to 1.22; low quality). In addition to RCTs, six observational studies compared antipsychotic discontinuation with decreased or increased dosage, and there was no clear evidence that any of these strategies had a beneficial effect on TD symptoms (very low-quality evidence). We evaluated the addition to standard antipsychotic care of several treatments, but not anticholinergic treatments, for which we identified no trials. We found no clear effect of the addition of either benzodiazepines (two RCTs, n = 32, RR 1.12, 95% CI 0.6 to 2.09; very low quality) or vitamin E (six RCTs, n = 264, RR 0.95, 95% CI 0.89 to 1.01; low quality). Buspirone as an adjunctive treatment did have some effect in one small study (n = 42, RR 0.53, 95% CI 0.33 to 0.84; low quality), as did hypnosis and relaxation (one RCT, n = 15, RR 0.45, 95% CI 0.21 to 0.94; very low quality). We identified no studies focusing on TD in people with dementia. The NMA model found indirect estimates to be imprecise and failed to produce useful summaries on relative effects of interventions or interpretable results for decision-making. Consultation with people with/at risk of TD highlighted that management of TD remains a concern, and found that people are deeply disappointed at the length of time it has taken researchers to address the issue. Most studies remain small and poorly reported. Clinicians, policy-makers and people with/at risk of TD are little better informed than they were decades ago. Underpowered trials of limited quality repeatedly fail to provide answers. TD reviews have data from current trials extracted, tabulated and traceable to source. The NMA highlights one context in which support for this technique is ill advised. All relevant trials, even if not primarily addressing the issue of TD, should report appropriate binary outcomes on groups of people with this problem. Randomised trials of treatments for people with established TD are indicated. These should be large (> 800 participants), necessitating accrual through accurate local/national registers, including an intervention with acceptable treatments and recording outcomes used in clinical practice. This study is registered as PROSPERO CRD4201502045. The National Institute for Health Research Health Technology Assessment programme.

Forgotten but not gone: new developments in the understanding and treatment of tardive dyskinesia

The broad use of atypical antipsychotics was expected to dramatically reduce the prevalence and incidence of tardive dyskinesia (TD), but data show that TD remains an important challenge due the persistent nature of its symptoms and resistance to numerous treatment modalities, including antipsychotic discontinuation. Recent insights on genetic risk factors and new concepts surrounding pathophysiology have spurred interest in the possibility of targeted treatment for TD. As will be reviewed in this article, the number of evidence-based strategies for TD treatment is small: only clonazepam, amantadine, ginkgo biloba extract, and the vesicular monoamine transporter 2 (VMAT2) inhibitor tetrabenazine have compelling data. Using new insights into the metabolism of tetrabenazine and the properties of its active metabolites, 2 modifications of tetrabenazine have been synthesized to improve the kinetic profile, and are currently involved in double-blind placebo controlled studies aimed at U.S. Food and Drug Administration (FDA) regulatory approval. The possible availability of these new agents, deuterated tetrabenazine and valbenazine, significantly widens the range of treatment choices for patients with TD. For clinicians with patients at risk for TD due to dopamine antagonist exposure, experience has shown that the problem of TD will be an ongoing issue in modern psychiatry, and that an appreciation of new developments in the pathophysiology of, risk factors for, and treatment of TD is crucial to managing this condition.

P.3.a.014 - Gene polymorphism of dopaminergic, serotoninergic and glutamatergic receptors and tardive dyskinesia in schizophrenia

Introduction: For over six decades, antipsychotic drugs have remained the mainstay of schizophrenia treatment. Tardive dyskinesia (TD) is a potentially irreversible antipsychotic-induced. movement disorder with a prevalence of about 20-30% in psychiatric patients chronically exposed to antipsychotics. TD can be dissected into two distinct subsyndromes: orofaciolingual (TDof, involves movements of mouth and face) and limb-truncal dyskinesias (TDlt, involves purposeless choreiform movements of trunk and/or limbs) which probably have different genetic liability [1]. TD in schizophrenic patients is associated with poor outcome and TD patients may suffer from more physical or psychological problems. The genetic basis of pathogenesis of TD is thought to be primarily related to dopamine dysregulation. Genes of other neurotransmitter systems are less investigated [2,3]. Aim: Study the association between antipsychotic-induced TD and a set of 43 tag single nucleotide polymorphisms (SNPs) from dopaminergic, serotoninergic and glutamatergic receptors genes GRIN2A, GRIN2B, DRD3, DRD4, and HTR2C in schizophrenic patients in Russian population. Methods: 431 Russian patients with schizophrenia were investigated. TD was assessed cross-sectionally using the Abnormal Involuntary Movement Scale (AIMS). TD of and TDlt were assessed with AIMS items 1-4 and 5-7, respectively. The DNA extraction and genotyping of 43 polymorphisms of GRIN2A, GRIN2B, DRD3, DRD4, and HTR2C genes were conducted using Veracode Assay according to standard protocols. All calculations were performed in the R statistical environment with the SNPassoc package and basic R functions. Results and Discussion: Significant associations were found between five SNPs encoding three receptors: GRIN2B (rs220599, P = 0.04451), GRIN2A (rs11646587, P = 0.04652; rs7206256, P = 0.03570); rs1345423, P = 0.01043)), DRD3 (rs167770, P = 0.01751) and TDof. Also significant associations were found between six SNPs of two receptors GRIN2A (rs1345423, P = 0.02504; rs7190619, P = 0.04292; rs9788936, P = 0.04020; rs11644461, P = 0.03875), DRD3 (rs963468, P = 0.01533; rs167770, P = 0.012236) and TDlt. Moreover, significant associations were found in four specific SNPs encoding three receptors GRIN2B (rs2192970, P = 0.005411), GRIN2A (rs1345423, P = 0.015210) and DRD3 (rs324035, P = 0.03211; rs167770, P = 0.02197). Only rs1345423 in GRIN2A was significantly associated with overall TD in studied group of schizophrenic patients. No associations between polymorphism of receptors genes DRD4 and HTR2C were revealed. It is thought that TD is primarily related to DA dysregulation. Antipsychotic treatment with both serotoninergic HTR2A and HTR2C antagonists resulted in a lower annual incidence of TD [4]. This finding led to the hypothesis that HTR2A and HTR2C activate GABAergic interneurons [5], within the cerebral cortex, basal ganglia and mesencephalic areas, resulting in decreased dopaminergic activity. Hence, HTR2A and HTR2C antagonism increases dopamine release. Our results do not differ much from those found in relevant meta-analyses, which led us to propose that genetically determined variations of dopamine type 2 receptors and/or dopamine type 2 receptor signaling are unlikely to affect the sensitivity to TD. Conclusion: We suggest that mechanism other than HTR2- induced augmentation of dopamine release is responsible for explaining the lower incidence of TD after treatment with atypical antipsychotics.

Comparing the risk of tardive dyskinesia in older adults with first-generation and second-generation antipsychotics: a systematic review and meta-analysis.

The advent of second-generation antipsychotics (SGAs) in the 1990s brought optimism that neuroleptic-induced tardive dyskinesia (TD) may become relegated to history. Whether or not this is the case remains inconclusive, and this review aims to compare the risk of TD in older adults treated with first-generation antipsychotics (FGAs) versus SGAs. Relevant papers were sourced via a range of electronic databases, with a date range from 1957 to January 2015. Included studies used both a validated rating scale and research diagnostic criteria to report on the prevalence or incidence of TD in older adults exposed to antipsychotic medications. For FGAs, the prevalence estimate was 53% (95% confidence interval [CI] [39.0, 68.4]) for mild TD and 38% (95% CI [25.9, 50.3]) for probable TD. Incidence estimates for probable TD with FGAs were 23% (95% CI [15.3, 30.6]) at 1 year, 42% (95% CI [24.8, 58.4]) at 2 years and 57% (95% CI [45.3, 69.1]) at 3 years. For SGAs, the incidence estimates at 1 year were 7% (95% CI [4.4, 10.2]) for probable TD and 3% (95% CI [1.5, 4.2]) for persistent TD. The risk of probable TD is more than three times lower in older adults receiving SGAs in comparison with FGAs after 1 year of treatment (23% vs 7%). The risk of persistent TD at 1 year with SGAs is particularly low. Evidence is lacking in regard to the longer-term risk of TD with SGAs, although the rates associated with the prolonged use of FGAs are high. Caution is therefore still required, particularly with the protracted use of both FGAs and SGAs.

A quantitative measure of handwriting dysfluency for assessing tardive dyskinesia.

Tardive dyskinesia (TD) is a movement disorder commonly associated with chronic exposure to antidopaminergic medications, which may be in some cases disfiguring and socially disabling. The consensus from a growing body of research on the incidence and prevalence of TD in the modern era of antipsychotics indicates that this disorder has not disappeared continues to challenge the effective management of psychotic symptoms in patients with schizophrenia. A fundamental component in an effective strategy for managing TD is its reliable and accurate assessment. In the present study, we examined the clinical utility of a brief handwriting dysfluency measure for quantifying TD. Digitized samples of handwritten circles and loops were obtained from 62 psychosis patients with or without TD and from 50 healthy subjects. Two measures of dysfluent pen movements were extracted from each vertical pen stroke, including normalized jerk and the number of acceleration peaks. Tardive dyskinesia patients exhibited significantly higher dysfluency scores than non-TD patients and controls. Severity of handwriting movement dysfluency was correlated with Abnormal Involuntary Movement Scale severity ratings for some tasks. The procedure yielded high degrees of test-retest reliability. These results suggest that measures of handwriting movement dysfluency may be particularly useful for objectively evaluating the efficacy of pharmacotherapeutic strategies for treating TD.

Tardive dyskinesia (syndrome): Current concept and modern approaches to its management.

Tardive dyskinesia is a serious, disabling and potentially permanent, neurological hyperkinetic movement disorder that occurs after months or years of taking psychotropic drugs. The pathophysiology of tardive dyskinesia is complex, multifactorial and still not fully understood. A number of drugs were tried for the management of this motor disturbance, yet until now no effective and standard treatment has been found. It is very disappointing to realize that the introduction of antipsychotics from the second generation has not significantly decreased the prevalence and incidence of tardive dyskinesia. Therefore, the management of this motor disturbance remains an actual topic as well as a challenge for clinicians. This review summarizes recent relevant publications concerning the treatment of tardive dyskinesia.

Aripiprazole in the treatment of paliperidone-induced tardive dyskinesia

Tardive dyskinesia (TD) is a potentially serious and irreversible side effect of anti-psychotic medications. It is characterized by choreiform movements, or rhythmic abnormal involuntary movements of the face, mouth, tongue, trunk, and limbs. Although no reliable treatment for TD exists, atypical anti-psychotics are associated with a significantly lower incidence of TD than typical anti-psychotics. Recent reports suggest that atypical anti-psychotics may have a beneficial effect on TD remission. We present a case of severe oro-bucco-lingual TD, which was effectively managed with aripiprazole.

Incidence of tardive dyskinesia: a comparison of long-acting injectable and oral paliperidone clinical trial databases.

BackgroundTo assess the tardive dyskinesia (TD) rate in studies of once-monthly long-acting injectable (LAI) paliperidone palmitate (PP) and once-daily oral paliperidone extended release (Pali ER).MethodsCompleted schizophrenia and bipolar studies for PP and Pali ER (≥ 6 month duration with retrievable patient-level data) were included in this post hoc analysis. Schooler–Kane research criteria were applied using Abnormal Involuntary Movement Scale (AIMS) scores to categorise probable (qualifying AIMS scores persisting for ≥ 3 months) and persistent TD (score persisting ≥ 6 months). Spontaneously reported TD adverse events (AEs) were also summarised. Impact of exposure duration on dyskinesia (defined as AIMS total score ≥ 3) was assessed by summarising the monthly dyskinesia rate.ResultsIn the schizophrenia studies, TD rates for PP (four studies, N = 1689) vs. Pali ER (five studies, N = 2054), were: spontaneously reported AE, 0.18% (PP) vs. 0.10% (Pali ER); probable TD, 0.12% (PP) vs. 0.19% (Pali ER) and persistent TD, 0.12% (PP) vs. 0.05% (Pali ER). In the only bipolar study identified [Pali ER (N = 614)], TD rate was zero (spontaneously reported AE reporting, probable and persistent TD assessments). Dyskinesia rate was higher within the first month of treatment with both PP (13.1%) and Pali ER (11.7%) and steadily decreased over time (months 6–7: PP: 5.4%; Pali ER: 6.4%). Mean exposure: PP, 279.6 days; Pali ER, 187.2 days.ConclusionsRisk of TD with paliperidone was low (< 0.2%), regardless of the formulation (oral or LAI), in this clinical trial dataset. Longer cumulative exposure does not appear to increase the risk of dyskinesias.

Incidence of tardive dyskinesia in older adult patients treated with olanzapine or conventional antipsychotics.

The risk of persistent tardive dyskinesia (TD) was compared in patients with acute psychosis or agitation aged 55 years or older who were treated with olanzapine (OLZ) or conventional antipsychotic (CNV) drug therapy. Patients without TD were randomized to treatment with OLZ (2.5-20 mg/d; n = 150) or CNV (dosed per label; n = 143). Following a 6-week drug tapering/initiation period, patients without TD were treated with OLZ or CNV for up to 1 year. The a priori defined primary outcome end point was persistent TD defined as Abnormal Involuntary Movement Scale (AIMS) scores = 2 on at least 2 items or ≥3 on at least 1 item (items 1-7) lasting at least for 1 month (Criterion A). Post hoc analyses assessed persistent TD meeting the criterion of moderate severity defined as AIMS score ≥3 on at least 1 item persisting for 1 month (Criterion B) and probable TD defined as elevated AIMS scores (Criterion A or B) not persisting for 1 month. Treatment groups were compared using Kaplan-Meier curve with log-rank exact test. On average, patients were 78 years of age; the predominant diagnosis was dementia (76.7% in the OLZ group and 82.5% in the CNV group). Approximately, 40.6% of patients in the CNV group received haloperidol. No significant difference in time to developing persistent TD was observed during treatment with OLZ or CNV (cumulative incidence: OLZ, 2.5% [95% confidence interval [95% CI]: 0.5-7.0]; CNV, 5.5% [95% CI: 2.1-11.6], P = .193). The exposure-adjusted event rates per 100 person-years were not significantly different between treatment groups: OLZ (2.7) and CNV (6.3; ratio: 0.420; 95% CI: 0.068-1.969). Post hoc analyses revealed a significantly lower risk of at least moderately severe persistent TD persisting for 1 month (P = .012) and probable TD not persisting for 1 month (Criterion A, P = .030; Criterion B, P = .048) in OLZ-treated patients. For those patients without significant extrapyramidal symptoms at baseline, significantly more patients in the CNV treatment group developed treatment-emergent parkinsonism than for patients in the OLZ treatment group (CNV: 70%, 35 of 50 patients; OLZ 44%, 25 of 57 patients; P = .011). No significant difference between the groups was observed for treatment-emergent akathisia (CNV: 6%, 7 of 117 patients; OLZ: 10%, 13 of 130 patients; P = .351). The cumulative incidence of persistent TD was low and the risk of persistent TD did not differ significantly among predominantly older adult patients having dementia with acute psychosis or agitation treated with OLZ or CNV.

Tardive dyskinesia in patients with schizophrenia treated with olanzapine - results from a 20-month, prospective, open study under naturalistic conditions

The objective of the study was to assess the prevalence and incidence of tardive dyskinesia in patients treated with olanzapine during the follow-up period of 20 months. It was a prospective, observational, non-interventional study under naturalistic conditions, without a control group. The evaluation of the severity and presence of tardive dyskinesia was performed with the Abnormal Involuntary Movement Scale and research criteria by Schooler and Kane. The study included 573 patients (woman 43,3%) with the diagnosis of schizophrenia (ICD-10), the mean age of 41.8 (± 12) years. The mean dose of olanzapine was 15.9 (± 4.2) mg. The prevalence of tardive dyskinesia was 16.4%. The cumulative incidence assessed in the group of 479 patients was 6.47%. The annual incidence was 3.9%. An increased risk of tardive dyskinesia was observed in smokers - RR of 1.99 (CI 0.88-4.49), those taking higher doses of olanzapine 1.57 (CI 0.91-2.7) and in those who used polytherapy: 3.55 (CI 1.43-8.82). Only in the case of polytherapy a multidimensional analysis confirmed that this factor had a significant influence on the risk of tardive dyskinesia (p=0.006). The study demonstrated high (16,4%) prevalence of tardive dyskinesia, and the annual incidence (3,9%) comparable to the results of a meta-analysis by Corell et al. In the case of olanzapine in monotherapy the annual incidence was lower (1.96%) but the use of antipsychotics in polytherapy more than tripled the risk of tardive dyskinesia.

Tardive Dyskinesia Induced by a Switch From Haloperidol Depot to Paliperidone Palmitate

Tardive Dyskinesia Induced by a Switch From Haloperidol Depot to Paliperidone Palmitate

The Incidence of Tardive Dyskinesia in the Study of Pharmacotherapy for Psychotic Depression

Tardive dyskinesia (TD) is a debilitating adverse effect associated with antipsychotic treatment. Older age and the presence of mood disorder have been identified as risk factors for the development of TD. Thus, we assessed the incidence of TD in younger and older patients with major depressive disorder with psychotic features who participated in a 12-week clinical trial comparing olanzapine plus sertraline versus olanzapine plus placebo. All subjects (n = 259) were assessed with the Abnormal Involuntary Movement Scale at baseline and after 4, 8, and 12 weeks of treatment (or at termination). We used 7 different published criteria to estimate the prevalence of TD at baseline and the incidence over the duration of the trial. We compared the incidence of TD in subjects 60 years or older and those younger than 60 years. The overall prevalence and incidence of TD varied almost 10-fold, depending on the criteria (prevalence range, 1.2%-8.9%; incidence range, 0.0%-5.9%). Tardive dyskinesia was observed as a clinical adverse event in only 1 subject (0.4%). Whereas older subjects had a higher prevalence of TD at baseline, the incidence in younger and older subjects did not differ significantly. The incidence of TD was relatively low in both younger and older patients with major depressive disorder with psychotic features treated acutely with olanzapine. However, the estimate of the risk of TD varies widely, depending on the criteria used to define TD.

Antipsychotics in Adults With Schizophrenia: Comparative Effectiveness of First-Generation Versus Second-Generation Medications

Debate continues about the comparative benefits and harms of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) in treating schizophrenia. To compare the effects of FGAs with those of SGAs in the treatment of adults aged 18 to 64 years with schizophrenia and related psychosis on illness symptoms, diabetes mellitus, mortality,tardive dyskinesia, and a major metabolic syndrome. English-language studies from 10 electronic databases to March 2012, reference lists of relevant articles, and gray literature. Randomized trials for efficacy and cohort studies at least 2 years in duration for adverse events. Two independent reviewers extracted data from 114 studies involving 22 comparisons and graded the strength of evidence for primary outcomes as insufficient, low, moderate, or high using the Grading of Recommendations Assessment, Development and Evaluation approach. Few differences of clinical importance were found for core illness symptoms; lack of precision in effect estimates precluded firm conclusions for many comparisons. Moderate-strength evidence showed a clinically important benefit of haloperidol over olanzapine for improving positive symptoms, but the benefit was scale-dependent: It was seen when the Scale for the Assessment of Positive Symptoms was used but not when the Positive and Negative Syndrome Scale (PANSS) was used. Moderate-strength evidence showed a clinically important benefit of olanzapine over haloperidol in improving negative symptoms when the PANSS and the Scale for the Assessment of Negative Symptoms were used. Low-strength evidence showed no difference in mortality for chlorpromazine verus clozapine or haloperidol versus aripiprazole,increased incidence of the metabolic syndrome for olanzapine versus haloperidol (risk differences, 2% and 22%), and higher incidence of tardive dyskinesia for chlorpromazine versus clozapine (risk differences, 5% and 9%). Evidence was insufficient to draw conclusions for diabetes mellitus. All studies had high or unclear risk of bias. Length of study follow-up was often too brief to adequately measure adverse events. Medication comparisons, dosage, and outcome measurement were heterogenous for head-to-head comparisons. Selective patient populations limit generalizability. Clear benefits of FGAs versus SGAs for treating schizophrenia remain inconclusive because of variation in assessing outcomes and lack of clinically important differences for most comparisons. The strength of evidence on safety for major medical events is low or insufficient. Agency for Healthcare Research and Quality.

Improvement of Oral Dyskinesia After Switching From Aripiprazole to Paliperidone: A Case Report

Back to table of contents Previous article Next article LettersFull AccessImprovement of Oral Dyskinesia After Switching From Aripiprazole to Paliperidone: A Case ReportChien-Han Lai, M.D., M.Sc.Chien-Han LaiSearch for more papers by this author, M.D., M.Sc.Published Online:1 Jul 2011AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Paliperidone is associated with fewer extrapyramidal side effects (EPS) than typical antipsychotics. Here, we reported a case of schizophrenia with oral and tongue dyskinesia after aripiprazole treatment. The patient had improvement of dyskinesia after switching to paliperidone.Case Report“Miss B” had her first episode of schizophrenia 1 year ago. The symptoms included delusion of persecution toward her colleagues, delusion of reference toward her boss, auditory hallucinations, and visual hallucinations. Her psychotic symptoms improved after the first 3 months of therapy with aripiprazole 15 mg/day. However, she had irregular, involuntary, persistent, and repetitive movements of mouth and tongue after aripiprazole treatment for 1 month. These movements were very irregular, either in intensity or direction. The intensity of movements varied over time and ranged from mild to moderate. The direction of tongue movements was random, in any possible direction, either within the oral cavity or outside the mouth. Her oral dyskinesia was not relieved after the aripiprazole was tapered to 10 mg/day in the 6th month and 5 mg/day in the 9th month. After 3 months of 5 mg/day aripiprazole therapy, her oral dyskinesia had still not responded to biperidin 2 mg/day. Because of the possibility of aripiprazole-related oral dyskinesia, the antipsychotic was switched to paliperidone. The irregular movements improved, with gradual decline in intensity, frequency, and duration within 1 month. No significant cholinergic rebound symptoms or side effects were noted after the abrupt switch. Her psychotic symptoms still remained stable. The remission of dyskinesia remained after therapy of paliperidone for the next 3 months.DiscussionThis patient had improvement of dyskinesia after switching to paliperidone. The dose (3 mg/day) is relatively low for schizophrenia but equal to her previous aripiprazole dose of 5 mg/day. This patient had dramatic relief of dyskinesia side effects, which might be related to different binding patterns for neurotransmitter receptors of these two kinds of atypical antipsychotics. In a positron emission tomography study, 6–9 mg/day of paliperidone showed equal dopamine-binding at D2 receptors (around 70%–80%) over striatum and temporal cortex.1 This patient just received 3 mg/day of paliperidone and had complete remission of dyskinesia. Lower binding of D2 receptors over striatum at the dose of 3 mg/day might be the reason. Aripiprazole has a well-known low risk of EPS, with incidence comparable to placebo, and it could modulate dopamine release over prefrontal cortex through the action on serotonin 5-HT1A receptors.2 The dopamine release is not observed over sriatum areas, and, with D2 occupancy over 90%, still did not produce EPS.3 Its tardive dyskinesia incidence is also comparable to placebo group without significant risk. However, this patient had dyskinesia side effects even using aripiprazole at a lower dose. The relatively higher antagonism over 5-HT2A receptor of paliperidone than aripiprazole4 might provide another reason why this patient had remission of dyskinesia after the antipsychotic switch. 5-HT2A antagonism also suppressed the abnormal involuntary movements and dyskinesia of dopamine-depleted rats after receiving dopamine agonists.5 These findings might help explain clinical phenomenon in this patient.Dept. of Psychiatry, Buddhist Tzu-Chi General Hospital, Taipei Branch, Taipei, Taiwan;Institute of Brain Science, National Yang Ming University, Taipei City, Taiwan e-mail: [email protected]com.tw1. Arakawa R , Ito H , Takano A , et al.: Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. Psychopharmacology (Berl) 2008; 197:229–235Crossref, Medline, Google Scholar2. Bortolozzi A , Diaz-Mataix L , Toth M , et al.: In-vivo actions of aripiprazole on serotonergic and dopaminergic systems in rodent brain. Psychopharmacology (Berl) 2007; 191:745–758Crossref, Medline, Google Scholar3. Yokoi F , Grunder G , Biziere K , et al.: Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [11C]raclopride. Neuropsychopharmacology 2002; 27:248–259Crossref, Medline, Google Scholar4. Pae CU , Serretti A , Patkar AA , et al.: Aripiprazole in the treatment of depressive and anxiety disorders: a review of current evidence. CNS Drugs 2008; 22:367–388Crossref, Medline, Google Scholar5. Taylor JL , Bishop C , Ullrich T , et al.: Serotonin 2A receptor antagonist treatment reduces dopamine D1 receptor-mediated rotational behavior but not L-dopa-induced abnormal involuntary movements in the unilateral dopamine-depleted rat. Neuropharmacology 2006; 50:761–768Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 23Issue 3 Summer 2011Pages E18-E18 Metrics PDF download History Published online 1 July 2011 Published in print 1 July 2011