***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 Tardive dyskinesia ( TD ) is a serious , often disabling , movement disorder that is caused by medications that block dopamine receptors ( i.e. , neuroleptics , anti-emetics ) . There is currently no st and ard treatment approach for physicians confronted with such patients . This may be the result of notions that TD is disappearing because of the switch to second-generation antipsychotic agents and that it is largely reversible . In this article we demonstrate that second-generation antipsychotics do , indeed , cause TD and , in fact , the frequency is likely higher than expected because of growing off-label uses and a tripling of prescriptions written in the last 10 years . In addition , studies demonstrate that TD actually remits in only a minority of patients when these drugs are withdrawn . Furthermore , neuroleptic agents are often utilized to treat TD , despite prolonged exposure being a risk factor for irreversibility . The outcome of these trends is a growing population afflicted with TD . We review non-neuroleptic agents that have shown positive results in small , early-phase , blinded trials , including tetrabenazine , amantadine , levetiracetam , piracetam , clonazepam , propranolol , vitamin B6 , and Ginkgo biloba . Other options , such as botulinum toxin and  deep brain stimulation  , will also be discussed , and a suggested treatment algorithm is provided . While these agents are reasonable treatment options at this time there is a need , with a concerted effort between neurology and psychiatry , for full-scale drug development , including multicenter , r and omized , blinded trials to confirm the effectiveness of the agents that were positive in phase 2 trials and the development of newer ones Twenty patients with signs of tardive dyskinesia secondary to antipsychotic medication participated in a double blind , controlled , parallel group study comparing codergocrine mesylate 4.5 mg once daily with a placebo . After 6 weeks medication a reduction in dyskinetic scores occurred in both groups , but at the end of a further 6-week period the patients on active treatment maintained their improvement while those on placebo did not . This may be due to a slow onset of action and a hangover of activity associated with the drug 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 OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate 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 Despite the plethora of clinical drug trials in tardive dyskinesia , few consistent findings have emerged . One possible reason for this is that there have been no serious attempts to define the role of major neurotransmitter systems ( dopamine , norepinephrine , acetylcholine , serotonin , GABA ) in one specific population of tardive dyskinesia patients . This study reports a series of five controlled drug trials in a population of patients with persistent tardive dyskinesia ; each drug probed one of four neurotransmitter systems . The intra- and interpatient responses are analyzed and the implication s of the pharmacologic response profiles for the clinical management of tardive dyskinesia are discussed 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 BACKGROUND Antipsychotics remain the mainstay of drug intervention in the management of schizophrenia . However , long-term treatment with antipsychotics is associated with a variety of movement disorders , the most disabling of which is tardive dyskinesia ( TD ) , which occurs in up to 50 % of patients hospitalized with chronic schizophrenia . The pathophysiology of TD is still unclear and no definite treatment exists . Both dopamine receptor supersensitivity and oxidative stress-induced neurotoxicity in the nigrostriatal system are apparently implicated . The pineal hormone melatonin is a potent antioxidant and attenuates dopaminergic activity in the striatum and dopamine release from the hypothalamus . Thus , it may have a beneficial effect for both the treatment and prevention of TD . METHODS Using a double-blind , placebo-controlled , crossover study , we evaluated the efficacy of 10 mg/d of melatonin for 6 weeks in 22 patients with schizophrenia and TD . The primary outcome measure was the change from baseline in Abnormal Involuntary Movement Scale ( AIMS ) score . RESULTS The decrease ( mean + /- SD ) in AIMS score was 2.45 + /- 1.92 for the melatonin and 0.77 + /- 1.11 for the placebo treatment groups ( P<.001 ) . No adverse events or side effects were noted . CONCLUSION This is the first clinical evidence for efficacy of melatonin in the treatment of TD 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 , r and omized 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 r and omized , 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 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 199 
    Output:
    
AUTHORS ' CONCLUSIONS This review has found that the use of valbenazine or extract of Ginkgo biloba may be effective in relieving the symptoms of tardive dyskinesia .