Risk Of Tardive Dyskinesia Research Articles

The effect of atypical versus typical antipsychotics on tardive dyskinesia

Objective The aim was testing whether atypical antipsychotics (versus typicals) were associated with less risk of tardive dyskinesia (TD) in 516 severely mentally ill patients.

Tardive Dyskinesia in Geriatric Patients

Tardive (late-onset) dyskinesia (abnormal involuntary movement) is a debilitating and potentially irreversible hyperkinetic abnormal involuntary movement disorder caused by sustained exposure to antipsychotic medication. Tardive dyskinesia can affect any body region and possible associated features include unintelligible speech, respiratory distress and falls, as well as guilt, anger and depression. The diagnosis of tardive dyskinesia is one of exclusion, requiring complete physical and neurological examination and laboratory testing. Tardive dyskinesia rates with conventional antipsychotics vary from 2.9–29%. In older patients the incidence is much higher and increases with duration of exposure. Tardive dyskinesia risk appears to be substantially reduced with the atypical antipsychotics. Patient factors associated with tardive dyskinesia risk include increased age, psychiatric diagnosis, female sex, diabetes, organic brain damage, development of other neurological side effects (e.g., extrapyramidal), and the presence of negative symptoms of schizophrenia. The management of tardive dyskinesia includes discontinuing anticholinergic therapy and switching to an atypical antipsychotic; switching to clozapine; initiating suppressive therapy; and/or adding of one of the more experimental treatments.

Loxapine Treatment in an Autistic Child with Aggressive Behavior: Therapeutic Challenges

DESPITE EVIDENCE SUPPORTING the utility of atypical (second generation) antipsychotics in controlling aggressive behavior in autistic children (McCracken et al. 2002), these medications have been increasingly associated with a risk of adverse events such as obesity, diabetes, hyperlipidemia and metabolic syndrome (Allison et al., 1999; Arana, 2000; Lieberman III 2004; Nasrallah and Newcomer 2004; Newcomer 2004). Although the first generation (typical) antipsychotic haloperidol was found to be an efficacious treatment of aggression in autistic disorder (Anderson et al. 1984; Campbell et al. 1978; Campbell et al. 1982), the empirical data is less clear regarding the utility of the other typical dopamine antagonists in this patient population. While the benefits of typical antipsychotics should be balanced with the associated risk of tardive dyskinesia in autistic youths (Perry et al. 1985), the typical antipsychotics present another therapeutic option in children with autism who are either treatment-resistant or have other risk factors for metabolic syndrome, such as obesity. The following case illustrates the therapeutic challenges presented by an autistic patient whose treatment-resistant aggression and selfinjurious behavior was subsequently alleviated by a trial of loxapine. CHIEF COMPLAINT AND HISTORY OF THE PRESENT ILLNESS

A review of atypical antipsychotic drugs versus conventional medication in schizophrenia

Atypical antipsychotics are replacing conventional antipsychotics for the treatment of schizophrenia. They are considered to be at least as effective as conventional agents, with most producing fewer extrapyramidal symptoms. This review presents the evidence from published meta-analyses and describes differences in clinical effectiveness and tolerability between conventional and atypical antipsychotic agents. In addition, it discusses some of the more significant adverse effects including tardive dyskinesia, weight gain, diabetes and sudden death. Results from meta-analyses are conflicting, with some finding no significant advantages on measures of efficacy or tolerability for atypical antipsychotics over moderate daily doses of conventional drugs. Other results have shown that some atypical drugs have at least minor efficacy advantages over conventional comparators. Atypical antipsychotics exhibit a much reduced risk for tardive dyskinesia compared with conventional drugs. However, weight gain is more common with some atypical drugs (especially clozapine and olanzapine). Both conventional and atypical antipsychotics have been associated with diabetes, with most reports implicating both clozapine and olanzapine. Finally, atypical antipsychotics (unlike conventional drugs) have little or no effect on QT and are not associated with sudden death.

Tardive Dyskinesia Circa 2006

Tardive Dyskinesia Circa 2006

Evidence That Early Extrapyramidal Symptoms Predict Later Tardive Dyskinesia: A Prospective Analysis of 10,000 Patients in the European Schizophrenia Outpatient Health Outcomes (SOHO) Study

Objective: This study examined whether extrapyramidal symptoms predict incidence of tardive dyskinesia 1 year later. Method: Simple, global measures were used to rate extrapyramidal symptoms and tardive dyskinesia in a prospective, observational health outcomes study. Baseline and 3-, 6-, and 12-month data on 9,298 patients were analyzed by using a Cox proportional-hazard model. Onset of tardive dyskinesia was examined in two groups: 1) no tardive dyskinesia at baseline (broad risk set) and 2) no tardive dyskinesia at baseline and 3 months (narrow risk set). Results: Baseline extrapyramidal symptoms predicted later onset of tardive dyskinesia (broad risk set: hazard ratio=2.0, narrow risk set: hazard ratio=1.6). In analyses adjusted for age, gender, and medication exposure, this effect size was not reduced. About half of patients who developed tardive dyskinesia had earlier extrapyramidal symptoms. Conclusions: Although the association of tardive dyskinesia and extrapyramidal symptoms is significant, extrapyramidal symptoms do not robustly identify individuals at high risk for tardive dyskinesia. However, drug regimens and disease processes that increase extrapyramidal symptoms are likely to result in increased risk of tardive dyskinesia.

Evidence That Early Extrapyramidal Symptoms Predict Later Tardive Dyskinesia: A Prospective Analysis of 10,000 Patients in the European Schizophrenia Outpatient Health Outcomes (SOHO) Study

This study examined whether extrapyramidal symptoms predict incidence of tardive dyskinesia 1 year later. Simple, global measures were used to rate extrapyramidal symptoms and tardive dyskinesia in a prospective, observational health outcomes study. Baseline and 3-, 6-, and 12-month data on 9,298 patients were analyzed by using a Cox proportional-hazard model. Onset of tardive dyskinesia was examined in two groups: 1) no tardive dyskinesia at baseline (broad risk set) and 2) no tardive dyskinesia at baseline and 3 months (narrow risk set). Baseline extrapyramidal symptoms predicted later onset of tardive dyskinesia (broad risk set: hazard ratio=2.0, narrow risk set: hazard ratio=1.6). In analyses adjusted for age, gender, and medication exposure, this effect size was not reduced. About half of patients who developed tardive dyskinesia had earlier extrapyramidal symptoms. Although the association of tardive dyskinesia and extrapyramidal symptoms is significant, extrapyramidal symptoms do not robustly identify individuals at high risk for tardive dyskinesia. However, drug regimens and disease processes that increase extrapyramidal symptoms are likely to result in increased risk of tardive dyskinesia.

Epidemiology of tardive dyskinesia: Is risk declining with modern antipsychotics?

Second-generation antipsychotic drugs (APDs), including aripiprazole, clozapine, olanzapine, risperidone, quetiapine, and ziprasidone dominate outpatient and inpatient clinical practice, having largely displaced the older neuroleptics. Modern APDs have relatively low risk for acute extrapyramidal syndromes characteristic of older neuroleptics, particularly acute dystonia and Parkinsonism, with variable risks of akathisia and the rare neuroleptic malignant syndrome. Anticipated reduction in risk of tardive dyskinesia (TD) is less well documented. Nearly 50 years after initial reports on TD, it is appropriate to reexamine the epidemiology of this potentially severe late adverse effect of long-term APD treatment in light of current research and practice. We compared recent estimates of incidence and prevalence of TD identified with some modern APDs to the epidemiology of TD in the earlier neuroleptic era. Such comparisons are confounded by complex modern APD regimens, uncommon exposure limited to a single modern APD, effects of previous exposure to typical neuroleptics, and neurological assessments that are rarely prospective or systematic. Available evidence suggests that the risk of TD may be declining, but longitudinal studies of patients never treated with traditional neuroleptics and exposed to only a single modern APD are required to quantify TD risks with specific drugs. Long-term use of APDs should continue to be based on research-supported indications, with regular specific examination for emerging TD.

Patientenwissen über tardive Dyskinesien

Patients can provide appropriate and legally valid consent to treatment with antipsychotics only if they received adequate information on the risk of tardive dyskinesia (TD) and have the capacity to give informed consent. Eighty-seven patients in a psychiatric practice undergoing treatment with antipsychotics were interviewed for their level of information regarding TD and were subsequently provided with additional information on TD as needed. Three months after provision of this information, the interview was repeated. Though 82% of the patients had read the patient information leaflet and 44% had already received previous information, only 17% were found to be informed. The proportion of informed patients increased to 72% at the second interview. Among patients remaining uninformed despite previous information, a statistically significant higher proportion of elderly patients and patients with marked psychopathological impairments was found. Schizophrenic patients' knowledge on TD is low. With appropriate oral information being provided patients' knowledge can be considerably improved in the short run.

Tardive Dyskinesia in Schizophrenia is Associated with Prolactin-Related Sexual Disturbances

Tardive dyskinesia (TD) may occur in never-medicated patients with psychotic illness, indicating the existence of non-medication, possibly disease-related, causes. We tested the hypothesis that, independent of the antipsychotic-induced rise in prolactin, the incidence of TD would be associated with the incidence of prolactin-related sexual disturbances (PRSD), which would be suggestive of a common pathology involving multiple dopamine tracts. Simple, global measures of TD and PRSD (loss of libido, amenorrhea, gynaecomastia, impotence, and galactorrhea) were rated in a prospective, observational European Health Outcomes Study (SOHO). New onset of TD and new onset of PRSD at 3, 6, and 12 months was analyzed in a risk set of 4263 patients using a Cox proportional hazard model yielding adjusted hazard ratios (aHR). Incidence of TD was significantly and linearly comorbid with the incidence of PRSD in both men and women. Compared to those with no PRSD, the risk for TD was 2.0 (95% CI: 1.1, 3.7) with one PRSD, 2.4 (95% CI: 1.3, 4.5) with two PRSD, and 3.6 (95% CI: 1.1, 11.8) with three PRSD. Associations were stronger in those who only had received prolactin-sparing medications (aHR per unit PRSD increase=2.0, 95% CI: 1.2, 3.3) than in those who only had received prolactin-raising medications (aHR=1.3, 95% CI: 0.9, 1.9). In people with schizophrenia, TD and PRSD show comorbidities that are independent of antipsychotic-induced alterations in plasma prolactin. This may suggest a shared, pandopaminergic pathological mechanism associated with schizophrenia itself, rather than only a medication effect.

Pharmacogenetics for off-patent antipsychotics: reframing the risk for tardive dyskinesia and access to essential medicines

First-generation antipsychotics (FGAs) induce tardive dyskinesia, a debilitating involuntary hyperkinetic movement disorder, in 20 – 50% of individuals with a psychotic illness during chronic treatment. There is presently no curative treatment or definitive predictive test for tardive dyskinesia. The authors note that the three antipsychotic drugs enlisted in the most recent (14th) World Health Organization Model List of Essential Medicines – chlorpromazine, fluphenazine and haloperidol – belong to the FGA therapeutic class. In this regard, the need to choose between the competing objectives of ensuring global access to affordable and efficacious medicines, such as FGAs, and the formidable long-term risk for tardive dyskinesia, may create an ethical conundrum. Pharmacogenetics has thus far been conceptually framed as a tool to individualise therapy with new drugs under patent protection. However, the authors suggest that pharmacogenetics may also improve access to pharmacotherapy through the reintroduction of affordable second-line generic drugs or FGAs with suboptimal safety, as first-line therapy, in targeted subpopulations in whom they present a lower risk for tardive dyskinesia. To impact positively on global public health and distributive justice, a directory complementary to the essential medicines library – one that enlists the ‘essential biomarkers’ required for optimal pharmacotherapy – may benefit patients who do not have adequate access to new antipsychotic medications. This review discusses pharmacogenetic associations of tardive dyskinesia that are in part supported by meta-analyses and the oxidative stress-neuronal degeneration hypothesis.

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.

Implications of the CATIE Trial on Treatment: Extrapyramidal Symptoms

Development of extrapyramidal symptoms (EPS), particularly tardive dyskinesia (TD), has long been a troubling side effect for patients taking antipsychotics. Atypical antipsychotics have been hailed as an improvement over conventional antipsychotics, offering similar efficacy with more favorable EPS profiles. In the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, which compared the conventional antipsychotic perphenazine with atypical antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone in patients with schizophrenia, no significant differences in time to treatment discontinuation due to intolerability were observed between treatment groups. However, perphenazine was associated with a higher rate of patients experiencing EPS as well as a significantly higher rate of discontinuation due to EPS, despite the fact that patients with TD at baseline were excluded from the perphenazine group. Unfortunately, due to short treatment duration, the CATIE study did not have the assay sensitivity to detect differences in TD risk among any of the drugs. Thus, the atypical antipsychotics remain the first line of treatment for most patients, with specific drug selection based on benefit-risk profiles that best fit the individual patient's needs. Frequent monitoring, while noting a patient's subjective experience, remains the best strategy for choosing therapy to maximize symptom relief and minimize the impact of EPS and other side effects over the long- term. This article explores the reported results of the CATIE trial regarding EPS and emphasizes the differentiation of the atypicals from perphenazine on EPS and how these results should be incorporated into daily practice for the clinician.

The SOHO (Schizophrenia Outpatient Health Outcome) Study

The European SOHO (Schizophrenia Outpatient Health Outcome) study is an observational, naturalistic study of the outpatient treatment of schizophrenia. The patient recruitment and assessment began in September 2000 and finished in early 2005. A total of 10 972 adult patients from ten European countries who were initiating or changing antipsychotic medication for the treatment of schizophrenia within the normal course of care have been enrolled. The patients have been followed at regular intervals over the 3-year timeframe of the study. Evaluation includes clinical severity, measured with the Clinical Global Impression (CGI) scale; health-related quality of life; social functioning; and medication tolerability. The 6- and 12-month results have been published so far and have demonstrated that the patients in whom treatment was initiated with olanzapine or clozapine or who were started on more than one antipsychotic of any class at baseline tended to have somewhat greater improvement than patients treated with other atypical or typical antipsychotics, both in terms of symptoms measured with the CGI and quality of life. Numbers of social contacts increased with the treatment, but other aspects of social functioning did not show any significant change. Atypical antipsychotics as a class were associated with a lower frequency of extrapyramidal symptoms (EPS) and anticholinergic use than typical antipsychotics. The frequency of EPS was lowest in the clozapine-, quetiapine- and olanzapine-treated patients, at around 10%. The atypical antipsychotics also conferred a lower risk for tardive dyskinesia than the typical antipsychotics. Weight gain occurred in all treatment cohorts over the first 12 months of treatment and was statistically significantly greater in the patients who started treatment with olanzapine and clozapine. Prolactin- and sexually-related adverse events were frequent at baseline assessment: amenorrhoea was present in around one- third of women, impotence in around 40% of men, and loss of libido in 50% of both male and female patients. Patients treated with olanzapine, clozapine and quetiapine were significantly less likely to have sexual/endocrine-related dysfunctions after 6 months of treatment (the 12-month results of this parameter are yet to be published) than those in the other treatment cohorts (typical antipsychotics, risperidone and amisulpride). Concomitant medication use during the study has been high, ranging from 5% to 29% for anticholinergics, 8% to 23% for antidepressants, 22% to 37% for anxiolytics and 7% to 19% for mood stabilisers, depending on the type of antipsychotic prescribed. Fewer olanzapine-, quetiapine- and clozapine-treated patients used concomitant anticholinergics or anxiolytics/hypnotics. The current results from the SOHO study indicate that differences in effectiveness and tolerability do exist between the antipsychotics. Future results from the study will be published during the coming months and years, and will allow patterns of antipsychotic use in routine clinical practice (including how often and why changes are made) to be determined. This important information is likely to impact on the future use of antipsychotics and will assist clinicians in refining the use of these drugs and improving the outcome of patients to whom they are prescribed.

No Association Between a Functional NAD(P)H: Quinone Oxidoreductase Gene Polymorphism (Pro187Ser) and Tardive Dyskinesia

Several lines of evidence have indicated that free radicals may play a role in the pathophysiology of tardive dyskinesia (TD) (reviewed in Andreassen and Jorgensen, 2000). NAD(P)H: quinone oxidoreductase (NQO1) is an important enzyme in the human body that counteracts the oxidative stress-induced neuronal injury caused by the toxic free radicals such as dopamine-semiquinones. Taking the possible genetic predisposition to TD into account (Yassa and Ananth, 1981), the NQO1 gene is a good candidate gene that may confer increased susceptibility to TD. Based on this hypothesis, Pae et al. (2004) reported a significant association between the Pro187Ser polymorphism in the NQO1 gene and TD. In the present study, we attempted to replicate the findings of Pae et al. (2004) with the same polymorphism in 222 Japanese patients with schizophrenia. No significant difference was detected between patients with and without TD in the allelic distribution (chi2 = 0.070, d.f. = 1, p = 0.795) and in the genotypic distribution (chi2 = 0.910, d.f. = 2, p = 0.657). In addition, there was no significant difference in terms of total Abnormal Involuntary Movement Scale scores among the three genotype groups (p = 0.49). Our results suggest that the NQO1 gene polymorphism does not confer an increased risk of TD.

Multidose Risperidone Treatment Evaluated in a Rodent Model of Tardive Dyskinesia

Risperidone is a second-generation antipsychotic that lacks acute motor side effects at low doses (<6 mg/day), but above this level is associated with parkinsonism and akathesia. The literature suggests an association between acute motor side effects and tardive dyskinesia (TD); therefore, we hypothesized that low dose levels of risperidone will spare TD. As clinical studies of TD liability with fixed doses of risperidone are difficult to conduct, we tested low and high doses of risperidone in a rodent model of TD, vacuous chewing movements (VCMs) production. Low doses of risperidone (1.5 mg/kg/day) resulted in control levels of VCMs after 6 months of treatment, whereas high doses of risperidone (6 mg/kg/day) produced VCM in the same range as haloperidol. Plasma drug levels are reported. If this animal model predicts TD risk in humans, the TD liability with low-dose risperidone is at a placebo level, whereas higher doses show haloperidol-like TD risk, as predicted from the acute motor effects.

Polymorphic Variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and Dopamine D2 and D3 Receptors and Their Association With Tardive Dyskinesia in Severe Mental Illness

This study tested the association between tardive dyskinesia (TD) and polymorphic variations in (a) 2 cytochrome P450 (CYP) genes (CYP2D6 or CYP3A5), (b) 2 DRD2 variants (Ser311Cys and -141C Ins/del) and the Ser9Gly DRD3 variants, (c) 2 glutathione S-transferases (GSTT1 and GSTM1), and (d) variations in the PgP gene, MDR1. The study sample included 516 severely mentally ill patients from Central Kentucky facilities. Logistic regression models that included clinical variables associated with TD were developed. Gene variants were added to these clinical models. The total sample included 31% (162/516) with TD where 30% (49/162) of those had severe TD. Polymorphisms in DRD2, MDR1, and GSTT1 were never significant. Two gene variants appeared to be significant after adding them to the clinical regression models: (1) Ser9Gly DRD3 polymorphism was associated with severe TD (odds ratio for patients with 1 mutant allele when compared with individuals with 2 wild types was 2.5, 95% confidence interval 1.1-5.6, whereas the odds ratio for patients with 2 mutant alleles when compared with individuals with 1 mutant was 2.8, 95% confidence interval 1.0-7.4), and (2) GSTM1 absence was associated with TD (odds ratio 1.7, 95% confidence interval 1.2-2.4) particularly in white women. The CYP2D6 and CYP3A5 absence showed potential for significant associations in larger samples, particularly in white men. New studies need to replicate whether these or other genes could be used conjointly with clinical variables to identify subjects at risk for TD in clinical settings.

Clinical correlates of tardive dyskinesia in schizophrenia: Baseline data from the CATIE schizophrenia trial

Objective To examine the clinical characteristics of individuals with schizophrenia that develop tardive dyskinesia (TD) associated with antipsychotic treatment. Methods Baseline data on 1460 patients with schizophrenia were collected as part of the Clinical Antipsychotic Trials of Intervention Effectiveness schizophrenia study. Subjects who met Schooler–Kane criteria for probable TD were compared to those without TD. Multiple regression analyses were used to examine the relationship between TD and clinical variables. Results 212 subjects met the Schooler–Kane criteria for probable TD and 1098 had no history or current evidence of TD. Subjects with TD were older, had a longer duration of receiving antipsychotic medication, and were more likely to have been receiving a conventional antipsychotic and an anticholinergic agent. After controlling for important baseline covariates, diabetes mellitus (DM) and hypertension did not predict TD, whereas substance abuse significantly predicted TD. Differences in cognitive functioning were not significantly different after controlling for baseline covariates. The TD subjects also had higher ratings of psychopathology, EPSE, and akathisia. Conclusion Our results confirm the established relationships between the presence of TD and age, duration of treatment with antipsychotics, treatment with a conventional antipsychotic, treatment with anticholinergics, the presence of EPS and akathisia, and substance abuse. Subjects with TD had higher ratings of psychopathology as measured by the PANSS. We found no support for DM or hypertension increasing the risk of TD, or for TD being associated with cognitive impairment.

Effects of Antipsychotic Treatment on Tardive Dyskinesia

To compare the incidence and persistence of tardive dyskinesia between patients diagnosed with schizophrenia (ICD-10 and/or DSM-IV) who were treated with second-generation antipsychotics and first-generation antipsychotics in routine clinical practice. The European Schizophrenia Outpatient Health Outcomes (SOHO) study is a 3-year, prospective, observational study. Each country had a start date for patient enrollment before October 2000. All enrollment was completed by June 30, 2001. A simple, global measure of tardive dyskinesia was rated by participating clinicians. For the current analysis, data at baseline, 3 months, and 6 months were analyzed using a generalized estimating equation model. Second-generation antipsychotics conferred a lower risk for tardive dyskinesia at 6 months than first-generation antipsychotics (0.9% vs. 3.8%, odds ratio [OR] = 0.29, 95% confidence interval [CI] = 0.18 to 0.46). In addition, patients with tardive dyskinesia at baseline who were receiving second-generation antipsychotics were less likely than patients receiving first-generation antipsychotics to have tardive dyskinesia symptoms at 6 months (43.6% vs. 60.8%, OR = 0.50, 95% CI = 0.30 to 0.85). A sensitivity analysis suggested no bias related to pharmaceutical industry financial support. The results suggest that the relative advantage of second-generation antipsychotics in terms of lower rates of incidence and persistence of tardive dyskinesia, observed in technical randomized controlled trials, generalizes to routine clinical care.

Tardive Dyskinesia After Long-Term Veralipride Treatment

Back to table of contents Previous article Next article LetterFull AccessTardive Dyskinesia After Long-Term Veralipride TreatmentMichele Raja, M.D., and Antonella Azzoni, M.D., Michele RajaSearch for more papers by this author, M.D., and Antonella AzzoniSearch for more papers by this author, M.D., Rome, ItalyPublished Online:1 May 2005https://doi.org/10.1176/jnp.17.2.252-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: Veralipride (VRD) is a benzamide derivative that is effective in the treatment of menopausal syndrome. A double-blind study1 indicated a total elimination of the symptoms of menopause (hot flushes and excessive perspiration) in 63% to 80% of 50 patients treated with VRD.Despite its antidopaminergic action, VRD extrapyramidal side effects are reported as extremely uncommon.2 However, isolated case reports described parkinsonism induced by VRD, especially when dosing recommendations had not been respected.3 Four cases of tardive dyskinesia (TD) induced by VRD have already been described.4–7 Here, we describe a case of severe lingual TD following long-term treatment with VRD.Case ReportAn 81-year-old woman was admitted to a psychiatric intensive care unit of a general hospital for acute mania. She presented excitement, mood elevation, olfactory hallucinations, and persecutory delusion. In the past, she had never been treated with any psychotropic drug. However, she acknowledged past use of VRD to treat menopausal syndrome, for at least 7 years. She had never taken any other non psychotropic drug with antidopaminergic activity. On visit, a severe lingual TD was present (Abnormal Involuntary Movement Scale Score: 4). Although her movement disorder was severe and esthetically repulsive, the patient, who wore dentures, was unaware of it. She was treated with olanzapine (up to 15 mg/day) and valproate (up to 400 mg/day), with minimal improvement of her psychotic symptoms. The severity of the lingual TD remained stable.CommentTo our knowledge (MEDLINE, September 2003), this is the fifth case of TD observed after treatment of VRD. Since about 5% of old subjects present abnormal movements indistinguishable from typical TD, it is not possible to establish firmly a causal relationship between the treatment with VRD and the development of the movement disorder. Nevertheless, the risk of TD in subjects exposed to antidopaminergic drugs is at least four times greater than in subjects who had never been treated with antidopaminergic drugs. Furthermore, iatrogenic disorders resembling natural illnesses should have diagnostic priority.The introduction of novel antipsychotics led to a significant decrease of extrapyramidal symptoms in patients affected by psychotic disorders. However, the widespread use of non psychotropic antidopaminergic drugs (e.g., VRD, metoclopramide, domperidone,) in nonpsychiatric patients, mostly prescribed by physicians with poor experience in neurological side effects, remain a serious underrecognized risk of parkinsonism and tardive syndromes.In case of extrapyramidal signs arising in women not exposed to antipsychotic drugs, previous use of VRD should be investigated carefully. Likewise, extrapyramidal signs should be looked for in women treated with this drug.References1 David A, Don R, Tajchner G, Weissglas L: Veralipride: alternative antidopaminergic treatment for menopausal symptoms. Am J Obstet Gynecol 1988; 158:1107–1115Crossref, Medline, Google Scholar2 Brient-Clabaux J: Agreal: its acceptability: review of the literature. Rev Fr Gynecol Obstet 1985; 80:167–170Medline, Google Scholar3 Masmoudi K, Decocq G, Chetaille E, et al: Extrapyramidal disorders induced by veralipride (agreal): apropos of 5 cases. Therapie 1995; 50:451–454Medline, Google Scholar4 Laplane D, Dougados M, Macron JM: Dyskinesias due to veralipride. Nouv Presse Med 1982; 11:2015Medline, Google Scholar5 Destee A, Warot P: Dyskinesia due to veralipride. Presse Med 1983; 12:1018Medline, Google Scholar6 Gabellini AS, Pezzoli A, De Massis P, Sacquegna T: Veralipride-induced tardive dystonia in a patient with bipolar psychosis. It J Neurol Sci 1992; 13:621–623Crossref, Medline, Google Scholar7 Marta-Moreno E, Gracia-Naya M, Marzo-Sola ME: Respiratory dyskinesia induced by veralipride. Rev Neurol 1997; 25:245–247Medline, Google Scholar FiguresReferencesCited byDetailsCited byDrugs & Aging, Vol. 35, No. 11 Volume 17Issue 2 May 2005Pages 252-a-253 Metrics PDF download History Published online 1 May 2005 Published in print 1 May 2005