Lower Risk Of Tardive Dyskinesia Research Articles

LAI antipsychotics associated with lower risk of TD than oral versions

A study that was based on a review of adverse drug event reports in Japan has concluded that long‐acting injectable (LAI) antipsychotics appear to be associated with lower risk of tardive dyskinesia (TD) than their oral counterparts. TD also was less common with use of second‐generation LAI antipsychotics compared with first‐generation drugs.

Tardive Dyskinesia and Long-Acting Injectable Antipsychotics: Analyses Based on a Spontaneous Reporting System Database in Japan.

Objective: This study compared the reporting frequency of tardive dyskinesia (TD) between long-acting injectable antipsychotics (LAI-APs) and the equivalent oral antipsychotics (O-APs), LAI first-generation antipsychotics (LAI-FGAs) and LAI second-generation antipsychotics (LAI-SGAs), and individual LAI-APs.Methods: The Japanese Adverse Drug Event Report was used in this study, and data were obtained from April 2004 to February 2021. Patients who received LAI-APs available in Japan (LAI haloperidol, LAI fluphenazine, LAI aripiprazole, LAI risperidone, and LAI paliperidone) or the equivalent O-APs were included in this study. We calculated the adjusted reporting odds ratios (aRORs) to compare the reporting frequency of TD.Results: A total of 8,425 patients were included in the study. TD was reported significantly less frequently with LAI paliperidone than with oral paliperidone (aROR [95% confidence interval (CI)] = 0.13 [0.05-0.36]). Other LAI-APs were associated with a numerically lower reporting frequency of TD than the equivalent oral SGAs. The reporting frequency of TD associated with LAI-SGAs was significantly lower than that of LAI-FGAs (aROR [95% CI] = 0.18 [0.08-0.43]). All LAI-SGAs were significantly associated with a lower reporting frequency of TD than that of LAI fluphenazine (aROR [95% CI]: LAI aripiprazole, 0.11 [0.04-0.35]; LAI risperidone, 0.09 [0.03-0.32]; LAI paliperidone, 0.02 [0.005-0.09]). and LAI haloperidol, 8.58 [1.85-39.72]). LAI fluphenazine was significantly associated with a higher reporting frequency of TD than LAI haloperidol (aROR [95% CI] = 8.58 [1.85-39.72]). The reporting frequency of TD associated with LAI paliperidone was significantly lower than that with LAI aripiprazole (aROR [95% CI] = 0.18 [0.05-0.73]).Conclusions: Compared to O-APs, LAI-APs, particularly LAI-SGAs, may be associated with a lower risk of TD.

Tardive dyskinesia in patients treated with atypical antipsychotics: case series and brief review of etiologic and treatment considerations

Tardive dyskinesia (TD) is a disfiguring side-effect of antipsychotic medications that is potentially irreversible in affected patients. Newer atypical antipsychotics are felt by many to have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications. We report five cases of patients taking atypical antipsychotics who developed TD, review the risk of TD, its potential etiologic mechanisms, and treatment options available. The goal of this paper is to alert the reader to continue to be diligent in obtaining informed consent and monitoring for the onset of TD in patients taking atypical antipsychotics.

Off-label use of atypical antipsychotic agents for treatment of insomnia

Despite limited supporting evidence, off-label uses of atypical or second generation antipsychotics (particularly olanzapine, quetiapine, and risperidone) are not uncommon. The off-label use of these agents for the treatment of insomnia is the focus of this review. While atypical antipsychotics are associated with a lower risk of tardive dyskinesia, extrapyramidal side effects, and more favorable effects on cognitive deficits and negative symptomatology in schizophrenic patients compared to typical or first generation antipsychotic agents, they are not without risks. Metabolic adverse effects are particularly problematic with atypical antipsychotics, even at doses lower than those used to treat FDA-approved indications. The receptor affinity profiles of most atypical antipsychotic agents promote sedation. The level of H1-histamine receptor blockade is believed to be most associated with somnolence and sedation. Several studies evaluating the safety and efficacy of the atypical antipsychotics quetiapine, olanzapine, and risperidone for the treatment of insomnia were identified and are summarized in this article.

Risperidone-Induced Enuresis Nocturna

Atypical antipsychotics are recognized as an important step in the treatment of psychotic disorders. An atypical antipsychotic drug, risperidone, is a D2 and 5-HT2 receptor blocker which is commonly used due to its lower risk of tardive dyskinesia and extrapyramidal symptoms (1,2). Increased appetite, weight gain and sedation are among the most common side effects of it, whereas, the incidence of risperidone-induced enuresis is under 1% (3,4). Despite being a quite rare side effect, nocturnal enuresis reduces compliance to medication (2,5). Not only the patient but also all family members may be negatively affected by enuresis nocturna (6). Enuresis caused by risperidone with the use of mood stabilizers or serotonin reuptake inhibitors (SSRIs) in children is discussed in the literature as case reports (4,7). Here, we aimed to present a psychotic patient with nocturnal enuresis during his treatment with risperidone.

The CATIE and CUtLASS Studies in Schizophrenia

Numerous double-blind studies have compared second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs), with most finding better efficacy and tolerability for SGAs. However, these 'efficacy trials' were generally short term and included only highly selected patients. Mostly because of weight gain and other metabolic effects of the SGAs, as well as their high acquisition price, the debate on the (cost) effectiveness of the SGAs led to two pragmatic clinical trials with no sponsorship by industry. Both trials had broad inclusion criteria and long follow-up, and tried to mimic clinical routine: CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) and CUtLASS (Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study). 1493 patients participated in CATIE, an 18-month, double-blind trial comparing the SGAs olanzapine, quetiapine, risperidone and ziprasidone with the FGA perphenazine. If efficacy or tolerability was insufficient, patients were re-randomized to a medication other than the one they previously received. Improvement of psychopathology and of quality of life was only moderate. Overall, 74% of patients discontinued study medication before 18 months, and the median time to discontinuation was 4.6 months. Aside from olanzapine (time to discontinuation 9.2 months), the other SGAs did not differ from each other or from perphenazine. Except for adverse effects as a reason for discontinuation, differences between the SGAs and the FGA were minimal. In CUtLASS, a 12-month open-label trial, 277 patients were randomized to receive an FGA or a SGA. Again, efficacy was rather similar between the two groups, with only limited improvement of psychopathology and quality of life. The authors of both trials concluded that SGAs do not markedly differ from FGAs regarding compliance, quality of life and effectiveness. The methodological problems of both trials have been discussed extensively. Patients had psychotic symptoms that were moderate in severity and were at least partially treatment resistant. The marginal improvement observed indicated that this population might not be appropriate to detect differences between FGAs and SGAs. Specific issues of CATIE include the exclusion of patients with tardive dyskinesia in the perphenazine arm and the high discontinuation rate. In CUtLASS, the concept of including 13 different FGAs and four SGAs in the respective classes was problematic. It is of interest that the most widely prescribed drug was sulpiride--of the FGAs, this is probably the 'most atypical' drug. Aside from the finding that the advantages of the SGAs are not as strong as early trials and marketing suggested or promised, the trials do not provide much helpful information regarding everyday practice. For tardive dyskinesia, no conclusions at all can be drawn. Similarly, methodological problems inhibited the detection of the other major advantage of the SGAs, i.e. the improved subjective well-being/quality of life while receiving these agents. It is well known that patients' and doctors' perspectives differ markedly, and the Quality of Life Scale (QLS), an expert-rated scale used in both trials, might not be sensitive enough to detect the subjective advantages reported by the majority of patients in other trials. CATIE and CUtLASS suggest that SGAs do not live up to all the previous expectations. However, even if most of these advantages are debatable, the lower risk of tardive dyskinesia and the better subjective effects should be strong enough reasons to favour these drugs. There is no single antipsychotic that is best for every schizophrenia patient, as individual responses differ markedly. For successfully individualized treatment, a multitude of antipsychotic options are needed.

What CATIE Found: Results From the Schizophrenia Trial

What CATIE Found: Results From the Schizophrenia Trial

Comparative Assessment of the Incidence and Severity of Tardive Dyskinesia in Patients Receiving Aripiprazole or Haloperidol for the Treatment of Schizophrenia

To comparatively assess the incidence of tardive dyskinesia in patients with schizophrenia receiving either aripiprazole or haloperidol. Data from 2 controlled, long-term trials of subjects meeting DSM-IV criteria for schizophrenia treated with aripiprazole (N = 861, 20-30 mg/day) or haloperidol (N = 433, 5-10 mg/day) were analyzed. The primary outcome measure was the rate of new-onset tardive dyskinesia. The analysis was limited to patients without baseline tardive dyskinesia. There were no significant differences between treatment groups in demographic or disease characteristics. The Abnormal Involuntary Movement Scale (AIMS) and Research Diagnostic Criteria for tardive dyskinesia were used to define the comparative incidence rates of long-term treatment-emergent tardive dyskinesia. A significantly lower percentage of aripiprazole-treated patients developed new-onset tardive dyskinesia compared with haloperidol-treated patients (p < .0001). The annualized rate of treatment-emergent tardive dyskinesia was significantly lower in aripiprazole-treated versus haloperidol-treated patients. In patients without a baseline diagnosis of tardive dyskinesia, aripiprazole significantly improved AIMS scores compared with haloperidol (p <or= .0001). These findings support the potential for a significantly lower risk of tardive dyskinesia with aripiprazole than with haloperidol among patients requiring maintenance antipsychotic treatment.

Focus on Lower Risk of Tardive Dyskinesia with Atypical Antipsychotics

Tardive dyskinesia (TD) is one of the most serious iatrogenic neurological complications of the first-generation antipsychotics. Identifying the risk factors for TD is important to minimize the risk of this potentially irreversible movement disorder in susceptible populations. A Medline search was conducted for the literature on risk factors for TD with the first-generation antipsychotics, as well as the emerging literature of the lower risk of TD with the second-generation antipsychotics. Several demographic, phenomenological, comorbidities and treatment variables have been reported to be associated with higher risk of TD. On the other hand, significantly lower rates of TD have been reported with the second-generation atypical antipsychotics, even in high risk groups such as the elderly. The use of the second-generation antipsychotics as first-line treatment of psychosis appears to have lowered the overall prevalence of acute movement disorders as well as TD, and have led them to become the standard of care in part because of their safer extrapyramidal profiles.

What's atypical about atypical antipsychotic drugs?

Atypical antipsychotic drugs, by definition, differ from typical antipsychotic agents in producing significantly fewer extrapyramidal symptoms and having a lower risk of tardive dyskinesia in vulnerable clinical populations at doses that produce comparable control of psychosis. The atypical drugs differ from the typicals in their mechanism of action, but not all share the same mechanism. Many, but not all, atypicals have been found to improve cognitive function, which could be their most important advantage with regard to efficacy. Clozapine, the prototype of these agents, has been found to improve delusions and hallucinations in patients who fail to respond to other antipsychotic drugs, and to reduce the risk of suicide. These agents have been found to increase cortical dopamine and acetylcholine release, as well as have a variety of effects on the glutamatergic system not shared by the typical agents. Effects on neuronal survival and plasticity, together with decreased neurotoxicity, might also contribute to their clinical advantage over typical neuroleptic drugs.

Safety and tolerability of atypical antipsychotics in patients with bipolar disorder: prevalence, monitoring and management.

Atypical antipsychotics are associated with fewer movement disorders and a lower risk of tardive dyskinesia than conventional antipsychotics, but are not without side-effects. Metabolic side-effects associated with some of the atypical antipsychotics are a concern for both clinicians and patients. Adverse events related to central nervous system effects, weight gain, and alterations in glucose, lipid, and prolactin levels in patients with depression, bipolar, and anxiety disorders have been reported. Balancing the significant benefits of treatment with these agents against the potential risks of metabolic disturbances and other adverse effects is crucial. Emerging data are making it possible to determine the risk-benefit analysis for specific atypical antipsychotics in individual patients and allow for targeted selection of treatment. A new concept of effectiveness is emerging that attempts to balance adverse effects of treatment with patient quality of life. Patients treated with atypical antipsychotics should have their weight, waist circumference, glucose, and lipids monitored on a regular basis. Monitoring of prolactin levels is not suggested; however, a baseline measurement before initiating treatment can be useful, with subsequent assessment only if a patient demonstrates symptoms. Prevention of weight gain is important. Diet and exercise should be considered for prevention and management, with the use of pharmacologic strategies approached with caution in patients with mood disorders. If a patient is at high risk of developing diabetes, certain pharmacologic agents have been shown to delay the onset of overt diabetes. Once diabetes or dyslipidemia are diagnosed, management should proceed in accordance with approved guidelines for these conditions.

Atypical antipsychotics are associated with a lower risk of tardive dyskinesia (TD) than conventional antipsychotics,

Atypical antipsychotics are associated with a lower risk of tardive dyskinesia (TD) than conventional antipsychotics,

Atypical antipsychotics are associated with a lower risk of tardive dyskinesia (TD) than conventional antipsychotics,

Atypical antipsychotics are associated with a lower risk of tardive dyskinesia (TD) than conventional antipsychotics,

Safety and tolerability: How do second-generation atypical antipsychotics compare?

Previously, clinicians could only utilize antipsychotic drugs that almost invariably caused extrapyramidal side effects (EPS) at the dose at which they were clinically effective. By definition, second-generation atypical antipsychotic agents are significantly better than conventional agents with regard to EPS; that is, they are clinically effective at doses at which they are less likely to cause EPS. This advantage translates into several important clinical benefits, including better negative symptom efficacy, lesser dysphoria, less impaired cognition, and a lower risk of tardive dyskinesia; in fact, this “EPS advantage” is the principal basis of the clinical advantages provided by this class of atypical antipsychotics. Pharmacologically, “atypical” antipsychotics differ in their side-effect profiles. Six second-generation antipsychotics are currently available in the United States: clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole. There are meaningful differences between these agents with regard to weight gain, sedation, anticholinergic side effects, cardiovascular issues, endocrine side effects, and hepatic and sexual issues; these are considered and their clinical implications discussed.

Assessment of drug-related movement disorders in schizophrenia

Conventional antipsychotic drugs remain one of the mainstays of treatment of schizophrenia and related psychotic disorders. The therapeutic efficacy of these drugs is well established, both for treatment of acute symptoms and in relapse prevention. Unfortunately, they are associated with a broad range of side-effects, the most prominent of which is the development of a variety of movement disorders (see Box 1). Compared with the conventional antipsychotic agents, the newer, atypical antipsychotics have a lower liability for the acute extrapyramidal side-effects (EPS) and, for a few of the new drugs, there is some evidence of a lower risk of tardive dyskinesia (Barnes &amp; McPhillips, 1999). Nevertheless, even with these newer agents, movement disorders are seen in a significant proportion of patients.

Anticholinergic Side Effects in Perspective.

Some of our readers may read the cover and table of contents for this issue of The Primary Care Companion to The Journal of Clinical Psychiatry and sense that they have received a journal of pharmacology by mistake. Further examination of the contents will be reassuring, but I felt it necessary to justify to our readers the presence of a seemingly esoteric study of anticholinergic side effects of 2 atypical antipsychotics—risperidone and olanzapine. This is, after all, a journal dedicated to primary care neuropsychiatric illness. The article by Kennedy et al. is clinical in nature, comparing anticholinergic adverse events experienced by schizophrenic patients taking 2 different medications for which in vitro and in vivo data and experience are at odds. The comparison and the clinical rationale supporting the investigation are sound. Clinicians use perceived side effect profiles as part of the selection process in treatment protocols. Studies of this kind help establish links between bench work studies and clinical trials. Information on expected anticholinergic effects may inform a decision about appropriateness for certain patient groups, such as the elderly. When such investigations might help our readership offer more exacting care to their patients, we are happy to review and publish the results. Another factor in the decision to publish this article on atypical antipsychotics is the topic of atypical antipsychotics themselves. These “novel neuroleptics,” introduced by clozapine in the 1980s, have surpassed older agents except possibly in the use of depot forms of haloperidol or fluphenazine when adherence is problematic. Clozapine is now considered the gold standard neuroleptic where efficacy is concerned. Problems of clozapine-associated agranulocytosis may have limited the use of clozapine to and within the specialty of psychiatry, however. Significantly, the newer atypical antipsychotics risperidone, olanzapine, and quetiapine do not have agranulocytosis as a major concern. Atypical antipsychotics offer several additional advantages over older neuroleptics. They are associated with a lower incidence of the extrapyramidal syndrome—in most patients obviating the need to add additional anticholinergic or dopaminergic medications to treat this side effect common to older agents. They are also associated with a lower risk of tardive dyskinesia—the dreaded and treatment-refractory complication of neuroleptic therapy. Prolactinemia as an adverse effect of dopamine receptor blockade may be reduced by some agents, limiting galactorrhea and irregular menstruation. Finally, and perhaps most significantly, the atypical antipsychotics offer potential efficacy in a broad range of nonschizophrenic illness. Olanzapine is now indicated for the treatment of mania. Other investigations suggest efficacy for atypicals as adjuvants to or augmentations of antidepressants in the treatment of refractory depressed and anxious states, including dysthymia and obsessive-compulsive disorder. Atypical antipsychotics are the next wave of psychotropic medications. Their introduction and appeal parallel those of the SSRIs in the treatment of depressive and anxious states. Just as SSRIs heralded a new opportunity for primary care physicians to treat depression and anxiety more effectively in nonpsychiatric settings, atypical antipsychotics hand those in primary care a new generation of safe and effective agents to offer our patients. Most of us treat, exclusively or collaboratively, some patients with thought disorders or other psychoses, but there is an ever-enlarging therapeutic circle for atypical antipsychotics that already circumscribes a significant portion of our practice. I suggest that we get up to speed on the indications, efficacy, clinical rationale, and differential prescription of these agents as soon as possible. A primer on this very topic will be offered in the Companion very soon.

Conventional vs. Newer Antipsychotics in Elderly Patients

Elderly patients with schizophrenia and dementia patients with agitation are frequently candidates for antipsychotic treatment. Conventional neuroleptics have relatively little effect on negative symptoms and may cause considerable side effects, especially in elderly patients. The authors have found a 29% cumulative annual incidence of tardive dyskinesia (TD) in middle-aged and elderly outpatients treated with relatively low doses of conventional neuroleptics Newer antipsychotics are less likely to cause extrapyramidal symptoms and may be associated with a lower risk of TD. They are generally effective for both positive and negative symptoms and may also improve some aspects of cognition, but these drugs have their own side effects. Dosing requirements for elderly patients tend to be much lower than those for younger adults.

Tardive dyskinesia in psychosis: are women really more at risk? UK700 Group.

It is commonly held that women are more at risk of developing tardive dyskinesia (TD). However, recent evidence suggests that this may only be the case in samples of older patients, men being more at risk in the younger age groups. Abnormal movements were measured with the Abnormal Involuntary Movement Scale (AIMS) in a sample of 706 chronic psychotic patients aged not older than 65 years (median age 36 years). Female gender was associated with a lower risk of TD (OR, 0.5; 95% CI, 0.3-0.7). The effect of gender was independent of other risk factors such as older age, severity of negative symptoms and exposure to antipsychotic medication in the previous 2 years. There was no evidence that the effect of these risk factors differed between the sexes. In samples of relatively young patients with chronic psychotic illness, who typically represent the majority of patients in community programmes for the severely mentally ill, men are more at risk of TD than women.

Conventional vs. Newer Antipsychotics in Elderly Patients

Elderly patients with schizophrenia and dementia patients with agitation are frequently candidates for antipsychotic treatment. Conventional neuroleptics have relatively little effect on negative symptoms and may cause considerable side effects, especially in elderly patients. The authors have found a 29% cumulative annual incidence of tardive dyskinesia (TD) in middle-aged and elderly outpatients treated with relatively low doses of conventional neuroleptics. Newer antipsychotics are less likely to cause extrapyramidal symptoms and may be associated with a lower risk of TD. They are generally effective for both positive and negative symptoms and may also improve some aspects of cognition, but these drugs have their own side effects. Dosing requirements for elderly patients tend to be much lower than those for younger adults. Elderly patients with schizophrenia and dementia patients with agitation are frequently candidates for antipsychotic treatment. Conventional neuroleptics have relatively little effect on negative symptoms and may cause considerable side effects, especially in elderly patients. The authors have found a 29% cumulative annual incidence of tardive dyskinesia (TD) in middle-aged and elderly outpatients treated with relatively low doses of conventional neuroleptics. Newer antipsychotics are less likely to cause extrapyramidal symptoms and may be associated with a lower risk of TD. They are generally effective for both positive and negative symptoms and may also improve some aspects of cognition, but these drugs have their own side effects. Dosing requirements for elderly patients tend to be much lower than those for younger adults.

Lower risk of tardive dyskinesia with olanzapine

Lower risk of tardive dyskinesia with olanzapine