The effects of eicosapentaenoic acid in tardive dyskinesia: a randomized, placebo-controlled trial.

OBJECTIVE: Worldwide, conventional antipsychotic medication continues to be used extensively, and tardive dyskinesia (TD) remains a serious complication. The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD. METHOD: This was a 12-week, double-blinded, randomized study of ethyl-EPA 2g/day versus placebo as supplemental medication, in patients with schizophrenia or schizoaffective disorder, with established TD. RESULTS: Eighty-four subjects were randomized, of whom 77 were included in the analysis. Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores, but there were no significant between-group differences (p=0.4). Response rates (>or=30% improvement in TD symptoms) also did not differ significantly between EPA-treated subjects (45%) and placebo-treated subjects (32%) (p=0.6). However, a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD. The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially, although this was not sustained beyond 6 weeks. CONCLUSIONS: This trial failed to demonstrate an anti-dyskinetic effect for ethyl-EPA 2g/day on the primary efficacy measure. However, a modest and transient benefit is suggested in patients with more recent onset of TD. The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low, the study being underpowered, TD being too chronic in the majority of cases, differences in dietary fatty acid intake, or that EPA lacks an anti-dyskinetic action.

Remission in first-episode psychosis: predictor variables and symptom improvement patterns.

BACKGROUND: Previous attempts to identify clinically useful predictors of treatment outcome in schizophrenia have been hampered by methodological inconsistencies, including a lack of standardized outcome measures. Recently proposed operationally defined criteria for remission provide an opportunity to readdress this topic. METHOD: We applied the remission criteria to a sample of 57 subjects with first-episode psychosis (DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder), treated according to a fixed protocol in a prospective study. Subjects were recruited between April 1999 and January 2000 and were followed for 2 years. Various demographic, baseline clinical, and early-response variables were subjected to discriminant analysis for their ability to predict remission or nonremission. We also assessed the symptom improvement patterns over time and compared endpoint psychopathology in the remitters and nonremitters. RESULTS: A model incorporating neurologic soft signs, 6-week treatment response, duration of untreated psychosis, marital status, and Positive and Negative Syndrome Scale excited factor baseline score was able to correctly predict 89% of the remitters and 86% of the nonremitters. Symptom reduction at 6 weeks, including core psychotic symptoms, was significant in both groups (remitters, p < .0001; nonremitters, p < .0001), although reduction was substantially greater in the remission group (p = .004). Thereafter, the remission group continued to improve (p < .01), while the nonremitting group failed to do so (p = .55). Considerable overlap of endpoint symptoms was observed, and depressive symptom scores were similar in remitters and nonremitters. CONCLUSION: A combination of demographic, baseline clinical, and acute treatment response variables may accurately predict treatment outcome. Persistent noncore psychotic symptoms in subjects meeting proposed remission criteria require further investigation.

Neurological abnormalities in first-episode schizophrenia: temporal stability and clinical and outcome correlates.

OBJECTIVE: Neurological abnormalities in subjects with schizophrenia have been regarded as diagnostically non-specific and non-localising. This study assessed the temporal stability of neurological abnormalities in subjects with first-episode schizophrenia over the course of 12 months. We also examined their relationships with psychiatric symptoms, medication effects and treatment outcome. METHOD: The sample comprised 66 largely medication-naive subjects who were treated according to a fixed protocol. We performed a factor analysis of the Neurological Evaluation Scale (NES) items, and relationships between the NES factors and various clinical and outcome measures were explored. RESULTS: Five NES factors were identified, explaining 68.4% of the variance. While the NES total scores did not change significantly over time, poor performance on motor sequencing tests was related to longer duration of untreated psychosis, and showed a tendency to improve as psychiatric symptoms resolved. The most interesting finding was that high scores on the motor sequencing factor predicted the emergence of persistent dyskinesia at 24 months (ANCOVAR F(1, 20) = 19.287, p = 0.0002). CONCLUSIONS: Two NES factors (motor sequencing and attention) are reasonably replicable across samples, and have potential relevance for the further exploration of the pathogenesis of schizophrenia, as well as possible clinical applications.

Effects of quetiapine and haloperidol on body mass index and glycaemic control: a long-term, randomized, controlled trial.

The topic of antipsychotic-induced weight-gain and its relationship to glucose metabolism is under-studied. We evaluated the long-term effects of a new-generation antipsychotic, quetiapine and a conventional antipsychotic, haloperidol on body mass index (BMI) and glycaemic control in patients with schizophrenia previously treated with conventional antipsychotics. Forty-five clinically stable patients with schizophrenia participated in this randomized, investigator-blinded, parallel-group comparison of flexible doses of quetiapine and haloperidol treatment over 52 wk. Primary outcome measures were change from baseline in BMI and glycosylated haemoglobin (HBA1c) levels. There were no between-group differences at any of the time-points for BMI (F = 1.90, p = 0.1) and HBA1c (F = 1.17, p = 0.3) values, and there were no significant changes in BMI from baseline for either group. HBA1c levels decreased significantly at end-point for the haloperidol group (-1.5%, p = 0.04), but not for the quetiapine group (-0.3%, p = 0.5). Although the sample was not generally obese (mean baseline BMI 25.5 +/- 6.3 kg/m2), a large proportion exhibited evidence of abnormal glycaemic control prior to randomization (mean HBA1c 6.7 +/- 1.9%), with 48% having values that were at least mildly elevated (HBA1c > 6.1%) and 19% markedly elevated (HBA1c > 7%). The number of subjects with elevated HBA1c values decreased from baseline in both the haloperidol and quetiapine treatment groups. These findings suggest that switching treatment from a conventional antipsychotic to quetiapine is not associated with weight gain or worsening of glycaemic control, even in the long term. The study also highlights the high incidence of unrecognized glucose dysregulation in patients with schizophrenia receiving conventional antipsychotic treatment.

A single-blind, randomized trial comparing quetiapine and haloperidol in the treatment of tardive dyskinesia.

BACKGROUND: While the atypical antipsychotics should ultimately reduce the prevalence of tardive dyskinesia, it is likely to remain a significant clinical problem for a long time to come. No strategy has clearly emerged as the treatment of choice for tardive dyskinesia. Atypical antipsychotics have reduced propensities for producing acute extrapyramidal symptoms (EPS) and possibly tardive dyskinesia and may be effective in treating patients with established tardive dyskinesia. METHOD: This 12-month, randomized, investigator-blinded study compared the efficacy of quetiapine (N = 22) and haloperidol (N = 23) in treating patients with DSM-IV schizophrenia or schizoaffective disorder and established tardive dyskinesia. Dyskinesia was assessed using the Extrapyramidal Symptom Rating Scale (ESRS) dyskinesia subscale scores and the Clinical Global Impression (CGI) dyskinesia scores. Other EPS, weight, serum prolactin level, and glycosylated hemoglobin level were also assessed. Subjects were enrolled in the study between April 2000 and March 2002. RESULTS: Mean endpoint doses were 400 mg/day of quetiapine and 8.5 mg/day of haloperidol. Compared with the haloperidol group, the quetiapine group showed significantly greater improvements in ESRS dyskinesia (6 and 9 months [p or= 50% symptom reduction) was greater with quetiapine than haloperidol (64% [9/14] and 37% [6/16] at 6 months; 55% [6/11] and 28% [4/14] at 12 months). Other EPS decreased significantly with quetiapine at 3 (p =.01), 6 (p =.01), and 9 (p =.002) months. Serum prolactin levels decreased with quetiapine but increased with haloperidol, differing significantly between the groups at endpoint (p =.005). No significant changes in weight or glucose metabolism were recorded in either group. CONCLUSION: Quetiapine effectively reduces the severity of tardive dyskinesia and is well tolerated in patients with established tardive dyskinesia.