Improvement In Tardive Dyskinesia Research Articles

Long-Term Deutetrabenazine Treatment Is Associated With Continued Improvement in Tardive Dyskinesia in the Completed 3-Year Open-Label Extension Study

The 12-week ARM-TD and AIM-TD studies in tardive dyskinesia (TD) patients showed statistically significant improvements in TD symptoms with deutetrabenazine. The completed open-label extension (OLE) study (SD-809-C-20) evaluated long-term efficacy and safety of deutetrabenazine in TD. Patients who completed ARM-TD or AIM-TD enrolled in the OLE study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in Abnormal Involuntary Movement Scale (AIMS) score was assessed by local site raters. Treatment success was evaluated locally as patients being "much improved" or "very much improved" on Clinical Global Impression of Change (CGIC). 343 patients enrolled in the OLE study; 6 patients were excluded from analyses. At Week 54 (n=249; dose [mean±SE]: 38.7±0.66mg/day), mean change from baseline in AIMS score was -4.8±0.28; 66% of patients experienced treatment success. At Week 106 (n=194; dose: 39.3±0.75mg/day), mean change from baseline in AIMS score was -5.4±0.33; 65% of patients experienced treatment success. At Week 145 (n=160; dose: 39.4±0.83mg/day), mean change from baseline in AIMS score was -6.6±0.37; 73% of patients experienced treatment success. Treatment was generally well tolerated across 723 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) for akathisia/restlessness were 0.01, somnolence/sedation were 0.07, and symptoms which may represent parkinsonism or depression were 0.08 each. Patients who received long-term treatment with deutetrabenazine achieved sustained improvement in AIMS scores. Findings from this open-label trial with response-driven dosing suggest the possibility of increasing benefit over time. Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel.

Long-Term Treatment With Deutetrabenazine Is Associated With Continued Improvement in Tardive Dyskinesia (TD): Results From an Open-Label Extension Study (S4.009)

Long-Term Treatment With Deutetrabenazine Is Associated With Continued Improvement in Tardive Dyskinesia (TD): Results From an Open-Label Extension Study (S4.009)

45 Long-term Treatment with Deutetrabenazine Is Associated with Continued Improvement in Tardive Dyskinesia: Results from an Open-label Extension Study

AbstractStudy ObjectiveTo evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.BackgroundIn the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.MethodPatients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.Results343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.ConclusionsPatients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

Long-Term Treatment With Deutetrabenazine is Associated With Continued Improvement in Tardive Dyskinesia (TD): Results From an Open-Label Extension Study (P4.076)

Long-Term Treatment With Deutetrabenazine is Associated With Continued Improvement in Tardive Dyskinesia (TD): Results From an Open-Label Extension Study (P4.076)

Divalproex sodium leading to sustained significant improvement in tardive dyskinesia in a patient with bipolar disorder.

Byline: Raman. Pattanayak, Deepak. Charan Sir, Not many therapeutic options are available to treat tardive dyskinesia (TD). Usual algorithm involves a reduction of antipsychotic dosage, clozapine, or tetrabenazine. [sup][1] Apart from that, available literature is scant and inconclusive. [sup][2] We report a case where divalproex sodium at a relatively higher serum concentration lead to improvement in TD. A 35-year-old married male with no family history first visited the outpatient clinic in August 2014 with irritable behavior, racing thoughts, referential ideas for 1 week. He had been a known case of bipolar affective disorder [sup][3] (four episodes between 1994 and 2009) and cannabis dependence for 6 months in 2009 (as per subjective and objective corroboration). Between 2009 and 2013, he maintained largely euthymic and occupationally functional while on unknown medications. In December 2013, patient stopped all medications, maintained well for subsequent 8 months until current presentation. He was prescribed aripiprazole 5 mg/day by the treating doctor (pending a detailed assessment), with which remission was achieved. After being on low-dose aripiprazole for 2 months, patient started to experience involuntary movements involving lips, mouth, and jaw. As a result, patient reported feeling inhibited while attending to customers at workplace. Patient presented again in November 2014 for a detailed work-up. He was euthymic. However these movements were present consistently for a month. The movements were noticeable during the interview and an impression of TD was made. On Abnormal Involuntary Movement Scale (AIMS), [sup][4] these were rated as 3 for lips and perioral area (0-4) and 3 for jaw (0-4), three for awareness (0-4) with moderate distress. During that visit, tablet valproate 1000 mg/day was added as prophylaxis for bipolar disorder. Aripiprazole was continued with a plan to stop it later. The patient was compliant to both medications. During his next visit after 10 days, patient and informants reported a significant improvement (of more than 90%) in TD. It was now barely noticeable during the interview. The AIMS rating was 1 for lips/perioral movements (0-3) and 0 for jaws (0-3), and 1 for awareness (0-3) with no accompanying distress. [sup][5] Serum valproate level (12-h postdose) was 134 [micro]g/ml. Clinically, neurological examination was within normal limits. Considering that level was on somewhat higher side, an attempt was made to reduce divalproex sodium to 750 mg/day. However, TD re-surfaced almost at previous intensity, as observed after 2 weeks. Consequently, the dosage was increased to 1000 mg/day, which was well tolerated. During the next 4 months, he continued on both divalproex sodium and aripiprazole, with no TD, and periodic review every 2-4 weeks. Aripiprazole was discontinued in early April 2015. In the same visit, he was shifted to tablet valproate sodium 1000 mg/day (free of cost at hospital's pharmacy). The urinalysis (thin layer chromatography) was negative for cannabis. He was euthymic and free of movements during his recent visit in August 2015. …

Resolution of Tardive Dyskinesia with Clozapine: A Case Report

Tardive dyskinesia is an extrapyramidal side effect that can occur after a prolonged use of antipsychotic medication, it appears to be about 0.4% to 4% worldwide. Prior reports suggest that clozapine may be effective in the management of tardive dyskinesia. We present the case of a patient with tardive dyskinesia induced by antipsychotics. After treatment failure with other psychotropic medications, clozapine medication was initiated; we used the "evaluation of tardive dyskinesia" scale to assess severity of tardive dyskinesia. We noticed a significant improvement in tardive dyskinesia from the fifth week of treatment with clozapine at the dose of 250 mg per day with a decrease in the scale score for "evaluation of tardive dyskinesia" from 70 to 22. Clozapine appears to be efficacious in the management of tardive dykinesia. Larger, randomized, blinded, and controlled prospective studies are needed to confirm these findings and to determine optimal dosage.

Two Instances of Improvement in Tardive Dyskinesia After Administration of Aripiprazole in a Single Patient

To the Editor: Tardive dyskinesia (TD) is a serious involuntary movement syndrome characterized by purposeless, repetitive movements that involve several locations such as the bucco-linguo-masticatory region.1 It often develops as a result of taking antipsychotic drugs, and the prevalence rate reaches 20% with typical antipsychotics.2,3 The atypical antipsychotics have smaller risk, but a percentage of patients treated with them still develop TD. Some physicians, especially the neurologists, have tried different strategies for this serious syndrome. There is literature available that presents several cases of improvement after aripiprazole therapy.4,5 Here, we report a patient who had improvement in TD with aripiprazole use. Case report. Ms A, a 68-year-old woman who is prone to anxiety and obsession, was initially diagnosed with DSM-IV-TR major depressive disorder 15 years prior to this report. Due to persistent depression and anxiety symptoms, her previous doctor had prescribed low-dose sulpiride and flupentixol/melitracen as adjunctive therapy since 9 years ago (she had received antidepressant treatment with fluoxetine and venlafaxine in the past). She has fair compliance with drug treatment, but sometimes she adjusted the dosage herself. The oral-lingual TD developed in April 2007, at which time she went to another hospital, where the physician discontinued all typical antipsychotics and administrated aripiprazole for treatment of dyskinetic symptoms after admission. Oral aripiprazole 3.75 mg at bedtime was initiated in June 2007. The dyskinetic symptoms were well controlled with the strategy a few weeks later. After she was discharged, the outpatient department doctor continued her aripiprazole treatment for about a month and then shifted to previous medications, including sulpiride. The oral-lingual dyskinesia relapsed in February 2009, and the physician added risperidone to her regimen. The TD symptoms did not respond to risperidone, and Ms A started to visit our psychiatric section in September 2009. We arranged admission for her after evaluation in February 2010 due to persistent suicidal ideation and stopped the typical antipsychotic agent soon after admission. After a few days’ observation, we noted that Ms A had severe and refractory depression (DSM-IV-TR major depressive disorder, recurrent, severe with psychotic features) and TD symptoms. We chose to add aripiprazole (10 mg once per day) as adjuvant therapy for depression. Her Hamilton Depression Rating Scale6 score diminished from 17 to 7 after 3 weeks’ treatment. At the same time, we noted that her TD symptoms improved. Her score on the Abnormal Involuntary Movement Scale7 diminished from 25 to 6 after 4 weeks’ treatment. Aripiprazole is a unique atypical antipsychotic agent: its pharmacologic mechanism has a partial agonist effect on dopamine D2 and D3 and 5-HT1A receptors and an antagonistic effect on 5-HT2A receptors.8,9 It has alterative affinity to the dopamine receptor and may have the D2 receptor up-regulation effect.10 Some suggested that the property of partial dopamine D2 and D3 agonist of aripiprazole has a stabilization effect on dopamine receptors. This atypical antipsychotic agent has several possible mechanisms that can have a therapeutic effect on TD patients. There have been several clinical reports and some additional research,11–13 but there was no single principle or guideline for clinical use on treating TD patients. In this case, we used aripiprazole as adjunctive therapy to an antidepressant; it also helped to diminish TD symptoms. From her medical history at the previous hospital, we also noted that she had been treated before with aripiprazole. The combination of that outcome and the current one suggests that aripiprazole potentially has efficacy in patients with recurrent TD. However, more research is needed in this direction.

Anticholinergics in the era of atypical antipsychotics: short-term or long-term treatment?

Anticholinergic agents are usually prescribed to prevent or treat antipsychotic-induced extrapyramidal symptoms. Their long-term benefits are questionable and they carry diverse adverse effects, including cognitive impairment and worsening of tardive dyskinesia. This literature review explores the impact of anticholinergic medication discontinuation on movement disorders, cognition and psychopathology in patients receiving antipsychotics. Medline, Embase and PsycInfo were searched from 1950 to July 2011 using "cessation /withdrawal /discontinuation /stopping" with "anticholinergic*" or "antiparkinson*" and "neuroleptic*" or "antipsychotic*". Additional articles were obtained by searching the bibliographies of relevant references. Earlier studies of anticholinergic agent discontinuation in patients receiving first-generation antipsychotics reported relapse rates of extrapyramidal symptoms between 4% and 80%, reflecting the heterogeneity of the studies. Two recent studies of patients prescribed second-generation antipsychotics obtained relapse rates of 4% and 33%. Some studies suggest improvement in tardive dyskinesia with cessation of anticholinergics. Four studies examined the effects of anticholinergic agent discontinuation on cognition and all observed an improvement post-discontinuation. Changes in symptoms of schizophrenia with anticholinergic discontinuation are conflicting, with more recent studies suggesting an improvement. Given their questionable benefit with continued use, clinicians should consider a gradual withdrawal of anticholinergic agents in stable patients receiving antipsychotics.

Improvement of tardive dyskinesia and dystonia associated with aripiprazole following a switch to quetiapine: case report and review of the literature

Aripiprazole has a low risk of extrapyramidal symptoms. Switching to aripiprazole has been reported to improve tardive dyskinesia caused by other medications. The authors report a case and review previous reports of dystonia and dyskinesia associated with aripiprazole. We present a case of a 22-year-old man with schizophrenia who experienced dyskinesia and dystonia associated with aripiprazole. Switching from olanzapine to aripiprazole resulted in worsening dyskinesia and new onset of dystonia. The patient's dyskinesia and dystonia improved after switching from aripiprazole to quetiapine therapy. There were several previous case reports on dyskinesia and dystonia associated with aripiprazole medication. The risk factors for tardive dyskinesia include older age and female sex. However, our case was a male patient who was younger compared with the previous cases and so should have been less at risk for dyskinesia in comparison with the previous cases. The effects of aripiprazole can include tardive movement disorders. Dyskinesia, dystonia and psychotic symptoms were improved with relatively small dose of quetiapine in this case. Whether some second-generation antipsychotics are more effective than others in the treatment of tardive dyskinesia remains unclear.

Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia

Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist drugs, which have intense sedative properties and may exacerbate psychotic symptoms, have been used to treat TD. To determine the clinical effects of GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide, muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP) for people with schizophrenia or other chronic mental illnesses who also developed neuroleptic-induced tardive dyskinesia. We updated the previous Cochrane review by searching the Cochrane Schizophrenia Group Register (June 2010). We included reports if they were controlled trials dealing with people with neuroleptic-induced TD and schizophrenia or other chronic mental illness who had been randomly allocated to either non-benzodiazepine GABA agonist drugs with placebo or no intervention. Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RR) and their 95% confidence intervals (CI) with the number needed to treat (NNT). For continuous data we calculated mean differences (MD). We identified eight small poorly reported studies for inclusion. For the outcome of 'no clinically important improvement in tardive dyskinesia' GABA agonist drugs were not clearly better than placebo (n = 108, 3 RCTs, RR 0.83 CI 0.6 to 1.1). Deterioration in mental state was more likely to occur in people receiving GABA medication (n = 95, 4 RCTs, RR 2.47 CI 1.1 to 5.4), but this effect was influenced by the decision to assign a negative outcome to those who left early before the end of the study. A greater proportion of people allocated GABA medication may fail to complete the trial compared with those allocated placebo (20% versus 9%), but this difference was not statistically significant (n = 136, 5 RCTs, RR 1.99 CI 0.8 to 4.7). There is a suggestion of an increase in ataxia (loss of power of muscular coordination) for both baclofen and sodium valproate (n = 95, 2 RCTs, RR 3.26 CI 0.4 to 30.2), and in sedation (n = 113, 3 RCTs, RR 2.12 CI 0.8 to 5.4) compared with placebo, but this was not significant. Withdrawal of tetrahydroisoxazolopyridine (THIP) may cause seizures. Evidence of the effects of baclofen, progabide, sodium valproate, or THIP for people with antipsychotic-induced TD is inconclusive and unconvincing. Any possible benefits are likely to be outweighed by the adverse effects associated with their use.

Signs of striatal dopamine transporter density increase in association with improvement of tardive dyskinesia in a patient with schizophrenia, as demonstrated by a DAT scan

The imaging of the dopamine transporter could demonstrate the implication of dopaminergic pathway in the appearance of tardive dyskinesia. We report a case with psychotic and tardive dyskinesia symptoms. A DAT scan showed decreased dopamine transporter uptake in the area of brain's basal gaglia. A trial with quetiapine improved both psychotic and TD symptoms while a second DAT scan showed improvement status. We conclude that increased dopamine transporter uptake seemed to associate with the improvement of TD.

Reasons and Outcomes of Olanzapine Dose Adjustments in the Outpatient Treatment of Schizophrenia

Antipsychotic treatment dose adjustments may influence treatment outcomes in patients with schizophrenia. We analysed data from 4,247 outpatients with schizophrenia who started olanzapine monotherapy in the 3-year, prospective, observational SOHO study to determine factors associated with olanzapine dose adjustments and how these impact on treatment effectiveness and tolerability. Regression analyses showed an association between changes in the Clinical Global Impression (CGI) and olanzapine dose changes: patients with a lack of effectiveness were more likely to have their dose increased, whereas patients with good treatment response were more likely to have a dose decrease. Improvement in tardive dyskinesia was associated with dose increase or no change (p=0.034) and worsening of sexual problems was associated with dose decrease (p=0.001). Conversely, an increase in olanzapine dose was associated with subsequent clinical improvement (CGI), but dose adjustment had no significant effects on tolerability outcomes. These results indicate that psychiatrists tend to modify olanzapine dose according to treatment response. Dose increases seem to be associated with a better response to treatment and not with a worsening of side-effects.

Yi-gan san for the treatment of neuroleptic-induced tardive dyskinesia: An open-label study

Background Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS, yokukan-san in Japanese), a serotonin modulator, may be safe and useful in treating behavioral and psychological symptoms in dementia and borderline personality disorder patients. The authors examined the efficacy, tolerability, and safety of YGS in patients with tardive dyskinesia. Methods Twenty-two patients with schizophrenia who had neuroleptic-induced tardive dyskinesia were given 7.5 g/day of YGS for 12 weeks in an open-label study. Results Administration of YGS resulted in a statistically significant improvement in tardive dyskinesia and psychotic symptoms. Conclusions YGS may be an effective and safe therapy to control tardive dyskinesia and psychosis in patients with schizophrenia, that should be further tested in double-blind, placebo-controlled trials.

Improvement of tardive dyskinesia with aripiprazol use. Case report and review of 4 cases

Improvement of tardive dyskinesia with aripiprazol use. Case report and review of 4 cases

Aripiprazole-Induced Tardive Dystonia

Sir: Tardive dystonia is a persistent syndrome of sustained muscle contraction that produces twisting and repetitive movements or abnormal postures. It usually involves the head and neck, producing torticollis, retrocollis, or anterocollis, but sometimes it involves back muscles, giving rise to opisthotonus and gait disturbances.1 The most common causes for development of tardive dystonia are exposure to neuroleptics or other medications like metaclorpromide, prochloroperazine, or amoxepine.1 Among the new generation of antipsychotics, aripiprazole has a unique receptor binding profile that combines partial agonistic activity at D2 and 5-HT2A receptors.2,3 The risk of movement disorder in people taking aripiprazole has to date been considered insignificant as there is no published report to our knowledge on association of tardive dystonia with aripiprazole. Case report. Ms. A, a 25-year-old woman, presented to the hospital in 2000 with schizoaffective disorder that included a past history of 2 psychotic episodes and 3 manic episodes. During the course of treatment, she developed skin rashes with the use of carbamazepine, experienced significant weight gain with the use of olanzapine, developed galactorrhea and severe extra-pyramidal symptoms with the use of risperidone, and experienced severe tremors and excessive daytime drowsiness with the use of valproate. These side effects led to frequent changes in medications. While treated with quetiapine, she developed recurrence of mania. She was also given a trial of lithium with which she complained of memory loss and vomiting. The lithium dosage was reduced to 450 mg/day, and she remained on treatment with that dosage for the 8 months preceding the current episode. For the current manic episode, in 2005, aripiprazole 10 mg/day was added to her lithium treatment, which she had been taking for the last 8 months without any significant problem. After 4 weeks, aripiprazole was increased to 15 mg/day. After 2 months of administration of aripiprazole, she developed backward arching of her body with spasm over the origin of latissimus dorsi muscle near vertebrae L1 and L2. These effects worsened while she was standing and lifting her arms. The arching increased when she was asked to engage in physical activity. These symptoms were absent during sleep, caused significant dysfunction in her occupation and embarrassment in public, and gradually worsened. She did not experience perioral tongue movements, facial grimacing, or difficulty in chewing or breathing. Ms. A had no history of head injury or loss of consciousness or a family history of movement disorders. A thorough neurologic examination, including neuroimaging, revealed no pathology. She was rated with the Extrapyramidal Symptom Rating Scale (ESRS)4 and was found to suffer from moderate to severe levels of extrapyramidal symptoms. Aripiprazole was stopped and tablet trihexyphenidyl 6 mg/day was started with continued lithium treatment (450 mg/day) in view of worsening dystonic symptoms. She showed improvement in dystonia, and after 2 weeks, her ESRS score was zero. Four weeks after the start of trihexyphenidyl treatment, in view of her mood and psychotic symptoms, she was started on treatment with clozapine, which was increased to 150 mg/day. Currently, 1 year after discontinuing aripiprazole, she is symptom free. This patient had several features suggestive of tardive dystonia following exposure to aripiprazole. The symptoms started after about 2 months of exposure to aripiprazole and worsened subsequently. They improved only after the stoppage of aripiprazole and addition of trihexyphenidyl. The neurologic examinations revealed no other causes of dystonia, and previous antipsychotic exposure was at least a year earlier. Association of lithium with tardive dystonia has been reported in literature,5 but in this case she took lithium for 8 months with no dystonic symptoms. Studies have reported no increase in incidence of extrapyra-midal symptoms in patients treated with aripiprazole compared with those treated with placebo.6,7 Moreover, treatment with aripiprazole has shown remarkable improvement in tardive dyskinesia.8 But, as seen in this case, the possibility of developing dystonia, though remote, is present even with a safe drug like aripiprazole. It is even more likely to occur in a patient who is vulnerable to side effects with other neuroleptics.

Aripiprazole-Related Tardive Dyskinesia

The low prevalence of extrapyramidal symptoms associated with atypical antipsychotics has led to their widespread use during the past decade. Aripiprazole, the newest medication in this class, has been associated with extrapyramidal symptoms (eg, akathisia) and with improvement of tardive dyskinesia (TD), but to date it has not been associated with the development of TD. We report a case of TD associated with the use of aripiprazole 15 mg/day for 18 months for refractory depression. Symptoms of TD resolved within several weeks of discontinuation of aripiprazole.

Improvement of tardive dyskinesia following amisulpride treatment

Tardive dyskinesia (TD) is a persistent, disturbing side effect of antipsychotic drug treatment. It is established that clozapine and other second generation agents cause less TD and may also improve pre-existing TD. We report a case of significant improvement of TD after the administration of amisulpride, a potential D 2/D 3 antagonist that has atypical properties. The possible effect of fast dissociation of D 2 receptors is being discussed.

Improvement in Tardive Dyskinesia with Aripiprazole Use

Improvement in Tardive Dyskinesia with Aripiprazole Use

Transient improvement of tardive dyskinesia induced with rTMS

Transcranial magnetic stimulation (TMS) has been effective in the treatment of psychiatric and movement disorders.1 Tardive dyskinesia (TD) is a persistent motor adverse event due to long-term neuroleptic exposure with a prevalence of about 30% among psychiatric patients. We describe a patient with resistant depression who underwent TMS of dorsolateral prefrontal cortex (DLPFC), a main target for stimulation in depression.1 This resulted in a complete yet transient improvement of the TD symptomatology. A 65-year-old woman had recurrent major depression of 30 years’ duration resulting in multiple hospitalizations and poor response to pharmacotherapy. During her last hospitalization, due to a depressive episode with psychotic symptoms, the patient was admitted with a therapy of amitriptyline 120 mg/day, lamotrigine 200 mg/day, and thioridazine 75 mg/day, to which she had not responded in the prior 5 months. Amitriptyline was increased up to 200 mg/day with …

Miscellaneous treatments for neuroleptic-induced tardive dyskinesia.

Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of neuroleptic medication. This review, one in a series examining the treatment of tardive dyskinesia, will cover miscellaneous treatments not covered elsewhere. The primary objective of this review was to determine whether the following interventions were associated with a reduction of TD in people with schizophrenia, or others chronic mental illnesses: botulin toxin, endorphin, estrogen, essential fatty acid, EX11582A, ganglioside, lithium, naloxone, periactin, phenylalanine, piracetam, stepholidine, tryptophan, neurosurgery, or ECT. Electronic searches of Biological Abstracts (1982-1995), Cochrane Schizophrenia Group's Register of trials (1995), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995), PsycLIT (1974-1995), and SCISEARCH (1995) were undertaken. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted. The inclusion criteria for all relevant randomised studies were that they should focus on people with schizophrenia or other chronic mental illnesses, with neuroleptic-induced TD and compare the use of the interventions listed above versus placebo or no intervention. Forty references describing 31 different trials were identified by the search strategy. Of 31 trials, 15 trials were excluded, six trials were included, eight awaiting assessment and a further two trials are pending (awaiting translation, unable to locate). Data were independently extracted by each reviewer and the odds ratio or the average differences were estimated. The reviewers assumed that people who dropped out had no improvement. Data were available about the efficacy and safety of cerultide, essential fatty acids, estrogen, lithium and insulin. There was a significant improvement in TD associated with the use of insulin compared to placebo (OR = 0.04, 95%CI 0.01-0.24). No significant differences between the other compounds and placebo were identified. There is no strong evidence to support the use of any of the agents included in this review, however because of the small sample sizes, all results must be considered inconclusive. The association between low dose insulin and improvement of TD requires replication.