A controlled trial of prostaglandin E1 precursor in chronic neuroleptic resistant schizophrenic patients Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Components of variance and intraclass correlations for the design of community-based surveys and intervention studies: data from the Health Survey for England 1994. Essential fatty acid supplementation in tardive dyskinesia. Eicosapentaenoic acid and arachidonic acid: collaboration and not antagonism is the key to biological understanding. A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Membrane fatty acids, niacin flushing and clinical parameters. Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia A double-blind trial of essential fatty acid supplementation in patients with tardive dyskinesia Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia. A RATING SCALE FOR EXTRAPYRAMIDAL SIDE EFFECTS Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia. A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials
The postulated deficiency of prostagl and in E1 series ( PGE1 ) in schizophrenia has been investigated in a controlled therapeutic trial . Twenty-one in patients with a schizophrenic illness resistant to neuroleptic drug treatments were r and omly assigned to one of three treatment conditions in a blind controlled trial of dihomo-gammalinolenic acid ( DHLA ) , a PGE1 precursor . Patients received depot neuroleptic medication and DHLA capsules , placebo depot medication and DHLA capsules , or placebo depot medication and placebo capsules .  No marked treatment effects were noticed on ratings of the patients ' behaviour or symptomatology , though some clinical effects were noted in dyskinetic patients . Abnormalities in red blood cell lipids were observed in the patients entering the trial , suggesting that further investigation of an EFA/prostagl and in deficiency hypothesis in schizophrenia is worth pursuing OBJECTIVE The study investigated the efficacy and tolerability of ethyl-eicosapentaenoic acid ( E-EPA ) as add-on treatment in chronic , severe schizophrenia . METHOD A r and omized , parallel-group , double-blind , placebo-controlled , fixed-dose , add-on study was conducted over 12 weeks . Forty patients with persistent symptoms after at least 6 months of stable antipsychotic treatment received E-EPA or placebo , in addition to their existing treatment . RESULTS At 12 weeks , the E-EPA group had significantly greater reduction of Positive and Negative Syndrome Scale total scores and of dyskinesia scores than the placebo group . CONCLUSIONS EPA may be an effective and well-tolerated add-on treatment in schizophrenia The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more .  ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Pre clinical and clinical observations suggest that enhancement of prostagl and in activity inhibits catecholamine release and may have antidyskinetic effects . A double-blind therapeutic trial with prostagl and in precursor essential fatty acids was conducted in 16 patients with tardive dyskinesia . No beneficial effects were seen Much of the literature on omega-3 and omega-6 fatty acids suggests that desirable effects of omega-3 fatty acids are in part related to depletion of arachidonic acid ( AA ) . However , in rats and humans , we have found that low doses of EPA actually elevate membrane AA phospholipid concentrations . In patients with schizophrenia , treatment with eicosapentaenoic acid ( EPA ) produced clinical improvement , but that improvement was greater at a dose of 2 g/day than at 4 g/day . The improvement was not significantly correlated with changes in either EPA or docosahexaenoic acid ( DHA ) but was highly significantly positively correlated with rises in red cell membrane AA . We suggest that elevation of concentrations of both AA and EPA in cell membranes may be important for health OBJECTIVE This study determined if augmentation of neuroleptics with 3 g/day of ethyl eicosapentaenoic acid ( EPA ) improves symptoms and cognition in patients with schizophrenia or schizoaffective disorder . METHOD Eighty-seven patients meeting criteria for schizophrenia or schizoaffective disorder who had residual symptoms despite neuroleptic treatment were r and omly assigned to receive either 3 g/day of ethyl EPA ( N=43 ) or placebo ( N=44 ) in a 16-week , double-blind supplementation trial . Assessment s were performed at baseline and at weeks 1 , 2 , 4 , 8 , 12 , and 16 ; a cognitive battery was administered at baseline and at week 16 . RESULTS No differences were found between groups in positive or negative symptoms , mood , cognition , or global impression ratings . Results were similar for the intention-to-treat ( N=87 ) and completer ( N=75 ) groups . CONCLUSIONS For schizophrenia patients treated with 3 g/day of ethyl EPA , improvement in residual symptoms and cognitive impairment was no greater than for schizophrenia patients treated with placebo Clinical definitions of schizophrenia are unreliable and difficult to use . The niacin flush test , which involves prostagl and in-induced vasodilatation , offers a method of exploring essential fatty acid metabolism in schizophrenic patients and may serve to define a subgroup of patients . In a multicentre study of schizophrenic patients with negative symptoms , we have examined the clinical accompaniments of the niacin response . Patients failing to flush with niacin showed significantly reduced levels of arachidonic and docosahexaenoic acids . Conversion from non-flushing to flushing during the 6 month supplementation period was predicted by an increase in arachidonic acid levels in red blood cell membranes irrespective of nature of supplementation . In this study , patients were selected for their negative symptoms and , therefore , it was not surprising that further measures of negative or positive symptoms did not predict flushing . However , an increased score for affective symptoms was significantly associated with a positive flush response . The stability of the niacin test needs to be examined in relation to the periodicity of symptoms in schizophrenia and manic depressive illness . New information on the an and amide system suggests that it may be associated with periodic phenomena and should be investigated in relation to the niacin test Evidence that the metabolism of phospholipids and polyunsaturated fatty acids ( PUFA ) is abnormal in schizophrenia provided the rationale for intervention studies using PUFA supplementation . An initial open label study indicating efficacy for n-3 PUFA in schizophrenia led to two small double-blind pilot studies . The first study was design ed to distinguish between the possible effects of two different n-3 PUFA : eicosapentaenoic acid ( EPA ) and docohexaenoic acid ( DHA ) .  Forty-five schizophrenic patients on stable antipsychotic medication who were still symptomatic were treated with either EPA , DHA or placebo for 3 months . Improvement on EPA measured by the Positive and Negative Syndrome Scale ( PANSS ) was statistically superior to both DHA and placebo using changes in percentage scores on the total PANSS . EPA was significantly superior to DHA for positive symptoms using ANOVA for repeated measures . In the second placebo-controlled study , EPA was used as a sole treatment , though the use of antipsychotic drugs was still permitted if this was clinical ly imperative . By the end of the study , all 12 patients on placebo  , but only eight out of 14 patients on EPA  , were taking antipsychotic drugs . Despite this , patients taking EPA had significantly lower scores on the PANSS rating scale by the end of the study . It is concluded that EPA may represent a new treatment approach to schizophrenia , and this requires investigation by large-scale placebo-controlled trials This study reports the results of a trial of essential fatty acid ( EFA ) supplementation in psychiatric patients ( predominantly schizophrenics ) with movement disorders . Evidence of EFA deficiency in these patients was observed . The antidyskinetic effect of EFA supplementation was marginally significant but not clinical ly important . However , active treatment produced highly significant improvements in total psychopathology scores and schizophrenia subscale scores , and a significant improvement in memory BACKGROUND It has been proposed that schizophrenia is associated with underactivity of brain glutamatergic neurotransmission , especially at the level of the N-methyl-D-aspartate ( NMDA ) subtype of glutamate receptor . Glycine potentiates NMDA receptor-mediated neurotransmission , indicating that it may serve as an effective therapeutic agent in the treatment of schizophrenia . METHOD Eleven treatment-resistant patients with chronic schizophrenia completed a double-blind , placebo-controlled , six-week , r and omly assigned , crossover treatment trial of 0.8 g/kg body weight/day of glycine , added to their prior antipsychotic treatment . RESULTS Glycine was well tolerated , result ed in significantly increased serum glycine levels and induced a mean 36 ( 7 % ) reduction in negative symptoms ( P < 0.0001 ) . Significant improvements were also induced in depressive and cognitive symptoms . The greatest reduction in negative symptoms was registered in the patients who had the lowest baseline serum glycine levels . CONCLUSIONS These results extend previous findings and suggest an additional approach to the pharmacotherapy of negative symptoms and cognitive deficits in schizophrenia A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales  were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials The objective was to test effects of ethyl eicosapentaenoate ( E-E ) on persistent ongoing symptoms in patients receiving different types of anti-schizophrenic drugs , typical antipsychotics , new atypical antipsychotics , and clozapine . 115 patients with DSM-IV-defined schizophrenia were studied , 31 on clozapine , 48 on new atypical drugs and 36 on typical antipsychotics . Placebo or 1 , 2 or 4 g/day of E-E was given for 12 weeks in addition to the background medication . The main assessment was change from baseline to 12 weeks on the PANSS and its sub-scales . There were no treatment-related side effects or adverse biochemical or haematological effects . Patients on 2 and 4 g/day E-E showed significant reductions in triglyceride levels which had been elevated by clozapine . In patients given 2 g/day E-E there were improvements on the PANSS and its sub-scales , but there was also a large placebo effect in patients on typical and new atypical antipsychotics and no difference between active treatment and placebo . In patients on clozapine , in contrast , there was little placebo response , but a clinical ly important and statistically significant effect of E-E on all rating scales . This effect was greatest at 2 g/day . There was a positive relationship between improvement on rating scales and rise in red blood cell arachidonic acid concentration To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results
BACKGROUND Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism .
This structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites .
OBJECTIVES To review the effects polyunsaturated fatty acids for people with schizophrenia .