Hybrid particles of polystyrene and carboxymethyl cellulose as substrates for copper ions.

The synthesis of hybrid particles was carried out by emulsion polymerization of styrene in complexes formed by carboxymethyl cellulose (CMC), a polyanion, and a cationic surfactant, cetyltrimethylammonium bromide (CTAB). CMC chains with variable molecular weights and degrees of substitution were tested. The polymerization condition chosen was that corresponding to CMC chains fully saturated with CTAB and to the onset of pure surfactant micelle formation, namely, at the critical aggregation concentration. The hybrid particles were characterized by zeta potential and light scattering measurements. The period of colloidal stability in the ionic strength of 2.0 mol L(-)(1) NaCl was observed visually. Upon increasing the CMC chain length, the particle characteristics remained practically unchanged, but the colloid stability was increased. The increase in the CMC degree of substitution led to particles with more negative zeta potential values. The adsorption of copper ions (Cu(2+)) on the surface of hybrid particles could be described by the Langmuir model, as determined by potentiometric measurements. The increase in the mean zeta potential values and X-ray absorption near-edge spectra evidenced the immobilization of Cu(2+) ions on the hybrid particles.

Benzodiazepines for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Tardive dyskinesia (TD) is a potentially disfiguring movement disorder of the orofacial region often caused by the use of neuroleptic drugs. A wide range of strategies have been used to help manage tardive dyskinesia and, for those who are unable to have their antipsychotic medication stopped or substantially changed, the benzodiazepine group of drugs has been suggested as a useful adjunctive treatment. OBJECTIVES: To determine the effects of benzodiazepines for people with neuroleptic-induced tardive dyskinesia and schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-2002), the Cochrane Schizophrenia Group's Register of trials (February 2002), EMBASE (1980-2002), LILACS (1982-2002), MEDLINE (1966-2002), PsycLIT (1974-2002), SCISEARCH (2002), hand searching the references of all identified studies and contacting the first author of each included trial. SELECTION CRITERIA: All randomised clinical studies focusing on people with both schizophrenia or other chronic mental illnesses and neuroleptic-induced tardive dyskinesia and comparing benzodiazepines with placebo or no intervention. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes a fixed effects risk ratio (RR) and its 95% confidence interval (CI) was calculated. Where possible, the weighted number needed to treat/harm statistic (NNT/H), and its 95% confidence interval (CI), was also calculated. For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were synthesised using a weighted mean difference (WMD). If statistical heterogeneity was found by Mantel-Haenszel chi-square test, random effects models were used. MAIN RESULTS: Two small trials (total n=32) were included. Using benzodiazepines as adjunctive treatment did not result in any clear changes for a series of tardive dyskinesia medium term outcomes (RR not improved to a clinically important extent 1.08 CI 0.57 to 2.05, n=30, 2 RCTs; RR not improved at all 1.19 CI 0.3 to 5.3, n=30, 2 RCTs; RR deterioration 1.85 CI 0.3 to 10.1, n=30, 2 RCTs). Adverse effects were not reported. REVIEWER'S CONCLUSIONS: The 2002 update has added almost no extra data. This is clearly not an area of active research. Benzodiazepines may have something to contribute to the care of people with tardive dyskinesia but the use of this group of compounds should be considered experimental. Large definitive studies are indicated.

Vitamin E for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. However, it is associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD). Vitamin E has been proposed as a treatment to prevent or decrease the severity of TD. OBJECTIVES: To determine the clinical effects of vitamin E for people with schizophrenia or other chronic mental illnesses who also developed neuroleptic-induced tardive dyskinesia. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-2001), The Cochrane Schizophrenia Group's Register (January 2001), EMBASE (1980-2001), LILACS (1982-2001), MEDLINE (1966-2001), PsycLIT (1974-2001), SCISEARCH (1997), hand searching the references of all identified studies and contacting the first author of each included trial. SELECTION CRITERIA: Reports identified in the search were included 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 vitamin E or to a placebo or no intervention. DATA COLLECTION AND ANALYSIS: Data were independently extracted from these trials by each reviewer and relative risks (RR) or weighted mean differences (WMD), with 95% confidence intervals (CI) were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Ten studies were included. The overall results for 'clinically relevant improvement' found no benefit of vitamin E against placebo (6 trials, 256 people, RR 0.95 CI 0.89 to 1.02). For the outcome of 'any improvement in TD symptoms', again, no clear difference in favour of vitamin E was found (7 trials, 311 people, RR 0.86 CI 0.75 to 1.00). However, people who had not been allocated vitamin E, showed more deterioration of their symptoms (5 trials, 98 people, RR 0.38 CI 0.16 to 0.9). There was no difference in the incidence of adverse effects (8 trials, 163 people, RR 1.3 CI 0.5 to 3.2) or leaving the study early (medium term 5 trials, 133 people, RR 1.5 CI 0.8 to 2.7). There is no trial-based information regarding the effect of vitamin E for those with early onset of TD. REVIEWER'S CONCLUSIONS: Small trials with uncertain quality of randomisation indicate that vitamin E protects against deterioration of TD but there is no evidence that vitamin E improves symptoms of TD.

Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. The gamma-aminobutyric acid (GABA) agonist drugs have been trialed as a treatment for TD, but these drugs have intense sedative properties and may exacerbate psychotic symptoms. OBJECTIVES: To determine the effects of GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide, muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP)) for people with neuroleptic-induced tardive dyskinesia (TD) and schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-2000), The Cochrane Library (Issue 4, 2000), Cochrane Schizophrenia Group's Register of Trials (2000), EMBASE (1980-2000), LILACS (1982-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), and SCISEARCH were undertaken. References of all identified studies were searched for further trial citations. First authors of each included trial were contacted. SELECTION CRITERIA: 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 non-benzodiazepine GABA agonist drugs to placebo or no intervention. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and the relative risk (RR) and its 95% confidence interval (CI) or the weighted mean difference with 95% CI were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Eight small, short, poorly reported studies were included. For the outcome of 'no clinically important improvement in tardive dyskinesia' GABA agonist drugs were not clearly better than placebo (n=108, RR 0.83 CI 0.6 to 1.1). Deterioration in mental state was more likely to occur for people receiving GABA medication (n=95, RR 2.55 CI 1.17 to 5.59), but this effect was influenced by the decision to assign a negative outcome to those who dropped out 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, RR 1.99 CI 0.84 to 4.68). There is a suggestion of an increase in ataxia for both baclofen and sodium valproate (n=95, RR 3.26 CI 0.4 to 30), and in sedation (n=113, RR 2.12 CI 0.8 to 5.4) compared with placebo. Withdrawal of THIP may cause seizures. REVIEWER'S CONCLUSIONS: Currently, evidence of effect of baclofen, progabide, sodium valproate, or THIP for people with neuroleptic-induced TD is inconclusive and unconvincing. Any possible benefits are likely to be outweighed by the adverse effects associated with the use of these drugs.

Calcium channel blockers for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Tardive dyskinesia (TD) is a potentially disfiguring movement disorder of the orofacial region often caused by use of neuroleptic drugs. A wide range of strategies has been used to help manage TD and, for those who are unable to have their antipsychotic medication stopped or substantially changed, the calcium-channel blocking group of drugs (diltiazem, nifedipine, nimodipine, verapamil) has been suggested as a useful adjunctive treatment. OBJECTIVES: To determine the effects of calcium-channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced TD in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-2000), Cochrane Library (Issue 4, 2000), Cochrane Schizophrenia Group's Register of trials (November 2000), EMBASE (1980-2000), LILACS (1982-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), and SCISEARCH were undertaken. References of all identified studies were searched for relevant citations. Principal authors of trials were contacted. SELECTION CRITERIA: Randomised clinical trials comparing calcium-channel blockers to placebo or no intervention for people with both TD and schizophrenia or serious mental illness were reliably selected. DATA COLLECTION AND ANALYSIS: Data were to have been independently extracted and analysed on an intention-to-treat basis. The relative risk (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data were to have been calculated using a random effects model, and, where possible, the number needed to treat calculated. Weighted mean differences (WMD) were to have been calculated for continuous data. MAIN RESULTS: No trials were included. Seven studies were excluded; five were not randomised and two small randomised crossover studies provided no usable data. Two more small randomised controlled trials await assessment. The authors have been contacted for relevant information. REVIEWER'S CONCLUSIONS: Based on currently available information, no confident statement can be made about the effectiveness of calcium-channel blockers for treating people with neuroleptic-induced tardive dyskinesia. Before evaluation of these drugs in larger randomised controlled trials, clinicians should carefully weigh up the possible benefits against their potential adverse effects.

Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. The gamma-aminobutyric acid (GABA) agonist drugs have been trialed as a treatment for TD, but these drugs have intense sedative properties and can possibly exacerbate psychotic symptoms. OBJECTIVES: To determine the effects of GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide, muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP)) in people with neuroleptic-induced tardive dyskinesia (TD) and schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1998), The Cochrane Library CENTRAL (1998), Cochrane Schizophrenia Group's Register of Trials (1998), EMBASE (1980-1998), LILACS (1982-1996), MEDLINE (1966-1998), PsycLIT (1974-1998), and SCISEARCH were undertaken. References of all identified studies were searched for further trial citations. First authors of each included trial were contacted. SELECTION CRITERIA: 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 GABA agonist drugs to placebo or no intervention. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and the odds ratio (OR) and its 95% confidence interval (CI) or the weighted mean difference with 95% CI were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Eight studies were able to be included. Results were equivocal, showing only a tendency for clinical improvement for those using GABA agonist drugs but, when analysis of any improvement (rather than clinical improvement) was performed, a significant reduction was noted in the GABA group (OR 0.36 CI 0.15-0.85). This suggests that for every 10 people treated with GABA drugs one person would benefit with a reduction in TD symptoms. People using the interventions had more confusion (OR 7.4 CI 1.3-40.9) and sedation (OR 3.0 CI 1.2-7.6). The numbers of people needed to treat to cause one extra person to experience these side effects were three and six, respectively. Tendency for more deterioration of the TD symptoms (OR 1.72 CI 0. 54-5.5), deterioration of the mental state (OR 3.07 CI 0.78-12.05), and to drop out before the end of the trial (OR 2.05 CI 0.8-5.21) were also observed in those using GABA agonists. REVIEWER'S CONCLUSIONS: No clear statement about the efficacy of GABA agonist drugs could be provided. From the combined data, GABA agonist drugs tend to be associated with some degree of improvement in TD symptoms, but also with side effects such as confusion and sedation and a deterioration of the person's mental state.

Anticholinergic medication for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Neuroleptic medication is used extensively to treat people with chronic mental illnesses. However, it is associated with a wide range of adverse effects, including movement disorders. Because of this, many acutely psychotic patients being treated with neuroleptic medication also receive anticholinergic drugs in order to reduce some of the associated movement side-effects. OBJECTIVES: To determine whether the use or the withdrawal of anticholinergic drugs (benzhexol or benztropine or biperiden or orphenadrine or procyclidine or scopolamine or trihexylphenidyl) were clinically effective for the treatment of people with both neuroleptic-induced TD and schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: 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. Principle authors of trials were contacted. SELECTION CRITERIA: Reports identified in the search were included 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 an anticholinergic agent or to a placebo (or no intervention). DATA COLLECTION AND ANALYSIS: No data could be extracted from the seven randomised controlled trials identified. MAIN RESULTS: No data were synthesized. The authors have been contacted to provide the relevant information. Two studies were excluded because no data are available and six others are still awaiting further information from the authors. REVIEWER'S CONCLUSIONS: Based on currently available information, no confident statement can be made about the effectiveness of anticholinergics to treat people with neuroleptic-induced tardive dyskinesia. The same applies for the withdrawal of such medications. Whether the withdrawal of anticholinergics may benefit people with neuroleptic-induced TD, this should be evaluated in a parallel-group, placebo-controlled randomised trial, with adequate sample size and at least 6 weeks of follow up.

Benzodiazepines for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Tardive dyskinesia (TD) is a potentially disfiguring movement disorder of the orofacial region often caused by use of neuroleptic drugs. A wide range of strategies have been used to help manage TD and, for those who are unable to have their antipsychotic medication stopped or substantially changed, the benzodiazapine group of drugs has been suggested as a useful adjunctive treatment. OBJECTIVES: To determine the clinical efficacy of benzodiazepines for people with neuroleptic-induced tardive dyskinesia (TD) schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1995), the Cochrane Schizophrenia Group's Register of trials (1995), EMBASE (1980-1995), LILACS (1982-1995), MEDLINE (1966-1995), PsycLIT (1974-1995), SCISEARCH (1995) and handsearching the references of all identified studies. SELECTION CRITERIA: The inclusion criteria for all randomised studies were that they should focus on people with schizophrenia or other chronic mental illnesses and neuroleptic-induced TD and compare the use of benzodiazepines to placebo or no intervention. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and the odds ratio (95% CI) or the average difference (95% CI) were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Two trials were able to be included in this review. The results of this review do not allow any confident interpretations on the clinical utility of benzodiazepines for the treatment of neuroleptic-induced TD. From the data combined in this review, benzodiazepines have no distinct advantages over placebo in the treatment of TD. Data on side effects were not reported in the included trials. REVIEWER'S CONCLUSIONS: No clear statement about the efficacy of benzodiazepines drugs, to treat neuroleptic-induced TD, could be provided.

Diltiazem, nifedipine, nimodipine or verapamil for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Tardive dyskinesia (TD) is a potentially disfiguring movement disorder of the orofacial region often caused by use of neuroleptic drugs. A wide range of strategies have been used to help manage TD and, for those who are unable to have their antipsychotic medication stopped or substantially changed, the calcium-channel blocking group of drugs (diltiazem, nifedipine, nimodipine, verapamil) has been suggested as a useful adjunctive treatment. OBJECTIVES: To determine the clinical efficacy of calcium-channel blockers in people with neuroleptic-induced tardive dyskinesia (TD) and schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: 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 were undertaken. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted. SELECTION CRITERIA: 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 calcium-channel blockers to placebo or no intervention. DATA COLLECTION AND ANALYSIS: No data could be extracted from the two randomised controlled trials that are currently awaiting assessment. The authors have been contacted to provide the relevant information. MAIN RESULTS: No studies met the entry criteria. No data were synthesized. REVIEWER'S CONCLUSIONS: Based on currently available information, no confident statement can be made about the effectiveness of calcium-channel blockers for treating people with neuroleptic-induced tardive dyskinesia. Before evaluation of these drugs in larger randomised controlled trials, clinicians should carefully weigh up their possible benefits against their potential adverse effects.

Cholinergic medication for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Since the 1950's neuroleptic medication has been extensively used to treat people with chronic mental illnesses, such as schizophrenia. These may cause tardive dyskinesia (TD), abnormal, repetitive and involuntary movements, in up to 20% of those using the medication for longer than three months. One theory of causation supports the use of cholinergic drugs for the management of TD. OBJECTIVES: To determine whether the use of cholinergic agents (arecoline, choline, deanol, lecithin, meclofenoxate, physostigmine, RS 86) were associated with clinical improvement in neuroleptic-induced TD in people with schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: 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. SELECTION CRITERIA: Reports identified in the search were included if they were controlled trials dealing with people with neuroleptic-induced TD and schizophrenia or other chronic mental illnesses who had been randomly allocated to either a cholinergic agent or to a placebo (or no intervention). DATA COLLECTION AND ANALYSIS: Seven different studies (8 references) were included in this review, and another ten trials are currently awaiting further data from authors. Data were independently extracted from these trials by each reviewer and odds ratios (OR) or average differences, with the 95% confidence intervals (95% CI) were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: The studies failed to detect any significant advantage of deanol or lecithin when compared to placebo. Data from two deanol trials demonstrated an excess of side effects in the active treatment group. People on cholinergic compounds report a range of gastrointestinal adverse effects (anorexia, nausea, vomiting, diarrhea, abdominal pain), sedation, and undesirable body odour. One person died of acute aspiration in a deanol versus placebo cross-over study. REVIEWER'S CONCLUSIONS: This review provides no strong evidence for the use of cholinergic agents in the treatment of neuroleptic-induced tardive dyskinesia. While people receiving cholinergic treatment had a marginal benefit compared to placebo, because of the small sample size, the cumulative data must be interpreted as inconclusive. Clinicians and trialists considering using cholinergic agents to treat TD should balance the lack of evidence for the efficacy against the excess of side effects associated with these compounds.

Miscellaneous treatments for neuroleptic-induced tardive dyskinesia.

BACKGROUND: 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. OBJECTIVES: 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. SEARCH STRATEGY: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. REVIEWER'S CONCLUSIONS: 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.

Vitamin E for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Neuroleptic (antipsychotic) medication is used extensively to treat people with chronic mental illnesses. However, it is associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD). Vitamin E has been proposed as a treatment to prevent or decrease the severity of TD. OBJECTIVES: To determine the clinical effects of vitamin E for people with schizophrenia or other chronic mental illnesses who also developed neuroleptic-induced tardive dyskinesia. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1998), The Cochrane Schizophrenia Group's Register (September 1998), EMBASE (1980-98), LILACS (1982-96), MEDLINE (1966-98), PsycLIT (1974-98), SCISEARCH, handsearching the references of all identified studies and contacting the first author of each included trial. SELECTION CRITERIA: Reports identified in the search were included 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 vitamin E or to a placebo or no intervention. DATA COLLECTION AND ANALYSIS: Data were independently extracted from these trials by each reviewer and Peto odds ratios (OR) or average differences, with the 95% confidence intervals (CI) were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Eight studies were included, and another three are currently awaiting further data from authors. The overall results for both, 'clinically relevant improvement' and 'any improvement' of TD symptoms, were in favour of vitamin E (OR 0.16, CI 0.04-0.7, NNT 5 CI 2.-32 and OR 0.23, CI 0.10-0.55, NNT 4 CI 2. 5-12 respectively). People who had not used vitamin E showed more deterioration of their symptoms (OR 0.20, CI 0.04-0.93). No difference could be found regarding the presence of adverse effects or leaving the study early before the end of study. There is no trial-based information regarding the effect of vitamin E for those with early onset of TD. REVIEWER'S CONCLUSIONS: Small trials with uncertain quality of randomisation, tend to suggest that vitamin E improves the symptoms of TD. Methodological problems such as small sample size, short term interventions, and inappropriate use of crossover design need to be dealt with in any future studies. The results of a recently completed trial involving 158 participants are eagerly awaited.

Neuroleptic reduction and/or cessation and neuroleptics as specific treatments for tardive dyskinesia.

BACKGROUND: Since the 1950s neuroleptic medication has been extensively used to treat people with chronic mental illnesses, such as schizophrenia. These drugs, however, have been also associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD). Various strategies have been examined to reduce a person's cumulative exposure to neuroleptics. These studies include dose reduction, intermittent dosing strategies, such as drug holidays, and neuroleptic cessation. OBJECTIVES: To determine whether, for those people with both schizophrenia (or other chronic mental illnesses) and tardive dyskinesia (TD), a reduction or cessation of neuroleptic drugs was associated with reduction in TD symptoms. A secondary objective was to determine whether the use of specific neuroleptics for similar groups of people could be a treatment for already established TD. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1997), Cochrane Schizophrenia Group's Register of trials (1997), EMBASE (1980-1997), LILACS (1982-1996), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were undertaken. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted. SELECTION CRITERIA: Reports were included if they assessed the treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia or other chronic mental illnesses and already established TD, who had been randomly allocated to (a) neuroleptic cessation (placebo or no intervention) versus neuroleptic maintenance; b. neuroleptic reduction (including intermittent strategies) versus neuroleptic maintenance; or c. specific neuroleptics for the treatment of TD versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and the Odds Ratio (95% CI) or the average difference (95% CI) were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Two trials were able to be included in this review. Sixty two were excluded and 16 are awaiting assessment. Seven trials are still pending classification. No randomised controlled trial-derived data were available to clarify the role of neuroleptics as treatments for TD. This includes the atypical antipsychotics including clozapine. Despite neuroleptic cessation being a frequently first-line recommendation, there were no RCT-derived data to support this. Two studies ( approximately approximately Cookson 1987 approximately approximately , approximately approximately Kane 1983 approximately approximately ) found a reduction in TD associated with neuroleptic reduction. REVIEWER'S CONCLUSIONS: The lack of evidence to support the efficacy of neuroleptic cessation as a treatment for TD, combined with the accumulating evidence of an increased risk of relapse should antipsychotic drugs be reduced, makes this intervention a hazardous treatment for TD. Dose reduction may offer some benefit as a treatment for TD compared to standard levels of neuroleptic use. There is a need to evaluate the utility of clozapine and the 'atypical' antipsychotics as treatments for established TD.

The treatment of tardive dyskinesia--a systematic review and meta-analysis.

This systematic review aimed to collate randomized controlled trials (RCTs) of various interventions used to treat tardive dyskinesia (TD) and, where appropriate, to combine the data for meta-analysis. Clinical trials were identified by electronic searches, handsearches and contact with principal investigators. Data were extracted independently by two reviewers, for outcomes related to improvement, deterioration, side-effects and drop out rates. Data were pooled using the Mantel-Haenzel Odds Ratio (fixed effect model). For treatments that had significant effects, the number needed to treat (NNT) was calculated. From 296 controlled clinical trials, data were extracted from 47 trials. For most interventions, we could identify no RCT-derived evidence of efficacy. A meta-analysis showed that baclofen, deanol and diazepam were no more effective than a placebo. Single RCTs demonstrated a lack of evidence of any effect for bromocriptine, ceruletide, clonidine, estrogen, gamma linolenic acid, hydergine, lecithin, lithium, progabide, seligiline and tetrahydroisoxazolopyridinol. The meta-analysis found that five interventions were effective: L-dopa, oxypertine, sodium valproate, tiapride and vitamin E; neuroleptic reduction was marginally significant. Data from single RCTs revealed that insulin, alpha methyl dopa and reserpine were more effective than a placebo. There was a significantly increased risk of adverse events associated with baclofen, deanol, L-dopa, oxypertine and reserpine. Meta-analysis of the impact of placebo (n=485) showed that 37.3% of participants showed an improvement. Interpretation of this systematic review requires caution as the individual trials identified tended to have small sample sizes. For many compounds, data from only one trial were available, and where meta-analyses were possible, these were based on a small number of trials. Despite these concerns, the review facilitated the interpretation of the large and diverse range of treatments used for TD. Clinical recommendations for the treatment of TD are made, based on the availability of RCT-derived evidence, the strength of that evidence and the presence of adverse effects.

Violent death in young people in the city of São Paulo, 1991-1993.

This paper aims to describe the principal causes of violent deaths among young people in the city of São Paulo, Brazil. Data from routine mortality statistics were used in the analysis. Young males were found to have a dramatically increased risk of death from violent causes especially those resident in lower income areas of the city. Possible explanations for these findings include economic instability generating social and cultural inequalities.