***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: A single blind trial and a placebo controlled double blind trial of lithium were carried out in elderly patients with tardive dyskinesia . In the pilot study , neuroleptics were continued : in the controlled trial , neuroleptics were discontinued . The results of both studies were essentially negative . Thus , the suppression effect of neuroleptics is much more dramatic than anything seen in the two studies . Several reasons for this were discussed namely , the severity and chronicity of the symptoms Eleven patients with tardive dyskinesia were treated with lithium carbonate in a placebo-controlled double-blind crossover study . No significant effect of lithium on either tardive dyskinesia or blood prolactin concentrations was demonstrated , but 5 patients developed pseudo-Parkinsonian features Psychiatric in patients with tardive dyskinesia ( TD ) were treated with either lithium alone ( n = 9 ) or with a combination of lithium and lecithin ( n = 9 ) for 5 weeks in a double-blind , placebo-controlled experiment . A statistically significant but clinical ly unimportant improvement of TD occurred during both treatments . The addition of lecithin to lithium had no effect The effectiveness of a once-weekly i.m . injection of ceruletide ( 0.8 microgram/kg ) in suppressing the symptoms of neuroleptic-induced tardive dyskinesia ( TD )  was evaluated in a double-blind , placebo-controlled , matched-pairs study . Global evaluation of the severity of TD symptoms over the 8-week study period revealed a significant improvement with ceruletide as compared with placebo . Analysis of the therapeutic response to ceruletide over the course of treatment revealed a slow , but long-lasting improvement of TD symptoms . Side effects , which were mild and transient , consisted mainly of nausea and epigastric discomfort . The incidence of side effects did not differ between the  ceruletide- and placebo-treated groups . Ceruletide appears to be a novel and practical treatment that can substantially alleviate the symptoms of dyskinesia The beneficial effect of estrogens on L -dopa-induced dyskinesias and on tardive dyskinesia has recently been reported . In this open pilot study , conjugated estrogens ( CE ) were Eight psychiatric patients with tardive dyskinesia ( TD ) were treated with single doses of the synthetic met-enkephalin analogue FK 33 - 824 ( 1 , 2 , and 3 mg IM ) morphine ( 10 mg SC ) and naloxone , an opiate receptor antagonist ( 0.8 mg IM ) . The drug effects were assessed by blind evaluation of r and omly sequenced videotapes made before and during treatment . FK 33 - 824 ( 1,2 , and 3 mg IM ) slightly reduced TD ( P<0.05 ) and increased preexisting bradykinesia . The effect on TD , however , was pronounced only in patients concurrently treated with neuroleptics in relatively high doses . Morphine had a similar although weaker antihyperkinetic effect , whereas naloxone had no effect . Side effects of FK 33 - 824 included dizziness , heaviness in the extremities , slurred speech , and dryness of mouth .  Morphine caused drowsiness , dizziness , ataxia , and nausea , and naloxone had no side effects . The results do not point to a primary role of enkephalin in the pathophysiology of TD , but enkephalin may interact with dopamine functions and potentiate some of the effects of neuroleptic drugs The unique role of ganglioside GM1 in neuronal plasticity led two centers , New York University and McLean Hospital , to study the effect of GM1 or placebo in patients with tardive dyskinesia . Results from the NYU cohort have already been published . We now present data from the entire cohort , allowing us to evaluate the effects of GM1 in the elderly compared to young adults . Subjects with tardive dyskinesia were r and omly assigned to single-blind placebo injections for 1 week , followed by 1 month of double-blind intramuscular placebo or GM1100 mg .  The final sample included 29 patients : 12 younger than 55 years of age and 17 older . There was no GM1-versus-placebo difference observed in either-age group , or in the total group . However , whether on placebo or GM1 , repeated measures analysis of variance ( RANOVA ) found a significant difference in response between Abnormal Involuntary Movement Scale scores , taken baseline and week 4 , in the elderly compared to young adults . Scores for the young adults show initial improvement then deterioration back to baseline , and those for the elderly show continuing improvement during the 4-week trial . The importance of the placebo effect in the elderly and its meaning for studies of GM1 in tardive dyskinesia are discussed 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 Estrogen have been reported in animal studies to both enhance and block central dopaminergic activity and in one clinical report to improve tardive dyskinesia . In the present study estrogen ( Premarin , 2.5 mg per day ) administration caused varying degrees of improvement in less than one-third of 21 patients with chorea due to Huntington 's disease and tradive dyskinesia and had no effect in eight patients with dystonia .  Estrogens appear to have an antidopaminergic effect in humans but poses only limited efficacy in the treatment of dyskinetic disorders In an attempt to determine the role of serotoninergic mechanisms in the pathophysiology of tardive dyskinesia , the serotonin precursor 5-hydroxytryptophan ( 5HTP ) with carbidopa , a peripheral decarboxylase inhibitor , were given in a double-blind crossover design to seven patients with longst and ing tardive dyskinesia . In the five patients who completed the study , there was no change in dyskinetic movements . Most of the patients had worsening of psychotic symptoms with 5HTP . The data suggest that serotonin precursors have no therapeutic effects in tardive dyskinesia . The implication s for the role of serotonin in the pathophysiology of tardive dyskinesia are discussed Tardive dyskinesia ( TD ) is thought to result from nigrostriatal dopaminergic supersensitivity secondary to prolonged neuroleptic exposure . Pre clinical studies have demonstrated that the opiate antagonist naloxone can acutely reverse a haloperidol-induced hyperdopaminergic state . In a trial of high-dose naloxone , 20 patients with TD received i.v . naloxone ( 20 mg , 40 mg , and placebo ) under double-blind conditions . At baseline and at regular postdrug intervals , patients were evaluated using a battery of motor , clinical , and neuropsychological measures to study effects on neurological , behavioral , and cognitive functions . There was a significant improvement in involuntary movements at 30 min postnaloxone , together with improvement in clinical ratings at that time point , as well as some cognitive changes . The implication s of these findings for the putative functional relationship between dopaminergic and enkephalinergic systems in the nigrostriatal area are discussed 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 The subjects were 13 psychiatric in patients with tardive dyskinesia . Each subject participated in two sessions . Either naloxone ( 10 mg ) or placebo was administered intravenously during each session . In a subset of subjects ( n = 7 ) , blood sample s for beta-endorphin were drawn before and at 30 and 60 minutes after the injection . The Abnormal Involuntary Movement Scale was administered before and at 10 , 20 , 40 , 60 , 120 , and 360 minutes after the injection . Double-blind procedures were maintained throughout the experiment . Neither naloxone nor placebo had any appreciable effect on the involuntary movements . Naloxone elicited a significant increase in the plasma beta-endorphin Tardive dyskinesia ( TD ) induced by antipsychotic drugs represents a great concern for patients and psychiatrists . Considering its pathophysiological mechanisms , there exists a convergence towards the development of postsynaptic dopaminergic hypersensitivity as a possible cause of TD . Hypersensitivity following receptor blockade is the consequence of an increased number of receptors and such a synthesis is energy-dependent . In the brain , under normal conditions , energy is almost exclusively provided by glucose utilization . We thus hypothesized that , if glucose availability were reduced , the metabolically hyperactive structures should represent the best functional target of a reduction in fuel availability . Twenty chronic schizophrenic out patients ( 13 males , 7 females ) , aged 20 - 67 ( mean : 38.3 ) , accepted to participate in this double-blind , placebo-controlled study . They were r and omly assigned to either the insulin treatment group ( 10 patients ) or to the insulin-placebo group ( 10 patients ) . They received a subcutaneous injection of 10 units of st and ard insulin or placebo at 10 a.m. From day 1 to day 15 , injections were performed daily and , thereafter , every other week for 5 weeks totalizing 20 injections in 90 days . At day 7 , the insulin treatment group showed a sharp decrease in the intensity of TD symptoms which persisted throughout the duration of the study . By contrast , no change in TD symptomatology was observed in the insulin-placebo-treated group . Although a direct effect on DA neurones , or at least the participation of such an effect , can not be excluded , our data favor a role of decreased glucose availability in reversing receptor hypersensitivity Despite continued research , the influences that promote or exacerbate tardive dyskinesia ( TD ) symptoms remain incompletely understood . Recent findings ( Gardos et al. 1992 ; Richardson et al. 1989 ) suggest that ingestion of the dietary constituent , phenylalanine , might exacerbate TD symptoms , but a double-blind , placebo-controlled challenge had not previously been conducted in schizophrenic patients . On two different mornings , in counterbalanced order , 18 male schizophrenic patients with TD were challenged with either 100 mg/kg phenylalanine or placebo . Effects on abnormal involuntary movements , recall memory , and plasma phenylalanine were measured 90 minutes post-challenge . The results supported the hypothesis in that involuntary movements increased to a statistically and clinical ly meaningful degree after the phenylalanine challenge , but not after placebo . No effects on memory were detected . Significant order effects characterized the plasma findings but not the behavioral data . Results indicate that a dietary constituent , the amino acid phenylalanine , can potentially exacerbate tardive dyskinesia symptoms in schizophrenic patients . The influence of phenylalanine and other ingested substances on clinical symptomatology warrants further investigation A double-blind r and omized clinical trial was conducted among 10 post-menopausal women with tardive dyskinesia ( TD ) to test the effect of estrogen replacement of the severity of abnormal movements and other outcome variables . After 3 weeks of treatment , the mean Abnormal Involuntary Movement Scale ( AIMS ) score decreased by 38 % in the estrogen group and by 9 % in the placebo group ; the difference between groups was marginally significant ( p less than 0.10 ) . However , the small sample size and the imbalance between groups in baseline AIMS scores do not allow us to rule out the confounding effects of other pro 
    Output:
    
REVIEW ER 'S CONCLUSIONS There is no strong evidence to support the everyday use of any of the agents included in this review .