***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: Thirty-one psychiatric out patients with tardive dyskinesia ( TD ) on neuroleptic medication were followed in a double-blind , r and omized trial comparing baclofen ( 30–90 mg per day ) to placebo . A repeated measures analysis of variance revealed no statistical difference between the baclofen-treated group and the placebo group for the group and the placebo group for the total Abnormal Involuntary Movement Scale ( AIMS ) scores . There was a trend ( P=0.09 ) for an initial improvement , then a worsening of frequency counts across four visits . The authors attempt to explain this finding on the basis of information obtained from animal research gamma-Aminobutyric acid ( GABA ) agonists have been proposed for the treatment of tardive dyskinesia , but their therapeutic potential has been limited by side effects and toxicity . To eluci date further the role of GABA in neuroleptic-induced dyskinesias , we evaluated tetrahydroisoxazolopyridinol ( THIP ) , a new , less toxic GABA analog and GABA receptor agonist , in both a dose-finding ( single-dose ) pilot study with five patients and a longer ( four-week ) placebo-controlled study with 13 patients . The patients were videotaped during a st and ardized examination ; tardive dyskinesia , parkinsonian symptoms , and eye-blinking rates were rated blindly and r and omly . The maximal short-term dose of THIP was 10 to 25 mg , whereas in the longer-term study the highest daily dose ranged from 20 to 120 mg . Tardive dyskinesia was unchanged during THIP treatment , but preexisting parkinsonism increased significantly and eye-blinking rates decreased . Psychiatric symptoms showed no significant changes , although tension and depression lessened . Side effects included sedation , confusion , dizziness , vomiting , and myoclonic jerks . Although THIP is not an effective new treatment for tardive dyskinesia , more specific GABA agonists should be evaluated in future studies of this syndrome As a treatment for tardive dyskinesia , sodium valproate was tested in a double-blind placebo-controlled  parallel group trial , with 6-week base-line observation period followed by 6 weeks of treatment . Sodium valproate was not found to be an effective treatment for either tardive dyskinesia or drug-induced Parkinsonism , and did not affect mental state or behaviour 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 A double-blind , placebo-controlled trial of gamma-vinyl gamma-aminobutyric acid ( GVG ) and 4,5,6,7-tetrahydroisoxazolo-(5,4-c ) pyridine-3-ol ( THIP ) was carried out in drug-free schizophrenic patients with tardive dyskinesia . A significant decrease in dyskinetic symptoms occurred with the administration of GVG , associated with a twofold increase in cerebrospinal fluid levels of GABA ; THIP produced a more moderate , yet consistent decrease in the involuntary movements . A pathophysiologic role for gamma-aminobutyric acid (GABA)-mediated neuronal transmission in tardive dyskinesia was explored by analyzing cerebrospinal fluid GABA concentrations in drug-free schizophrenic patients with and without tardive dyskinesia . A significant reduction in cerebrospinal fluid levels of GABA was observed in the dyskinetic schizophrenics compared with the nondyskinetic controls . These data compliment a growing body of experimental evidence suggesting a critical role for GABA-ergic neurons in the pathophysiology of tardive dyskinesia 24 hospitalized psychiatric patients with neuroleptic-induced tardive dyskinesia were treated with alpha-methyl-para-tyrosine ( AMPT ) , 4 g daily for 3 days , and biperiden , 12 mg daily for 3 weeks . The results were evaluated blindly by means of videotape technique . The frequency of tardive dyskinesia was significantly reduced by AMPT and significantly increased by biperiden . The amplitude was reduced by AMPT in ten cases , unchanged in 12 cases and increased in two cases . Biperiden significantly increased the amplitude . The duration of each separate tongue protrusion and /or mouth opening was significantly increased by AMPT and reduced or unchanged by biperiden . It is concluded that a reduced dopaminergic activity ( pharmacological or organic ) may constitute the primary pathogenetic background for tardive dyskinesia , but that dopaminergic hypersensitivity and /or cholinergic hypofunction is necessary before the hyperkinetic element of the movement disturbances can minifest itself The effect of sodium valproate , a drug which has been demonstrated to increase gamma-aminobutyric acid levels in the CNS , on tardive dyskinesia and psychiatric symptoms was investigated in a double-blind cross-over study on 32 chronic psychiatric patients . The oro-facial dyskinesias were totally or significantly relieved in 17 cases . During the active treatment period the involuntary movements of the extremities and dystonic spasms were also significantly relieved in 7 out of 9 patients . In two patients , however , the extrapyramidal symptoms became slightly worse . A significant improvement was noted in the psychiatric symptoms of 14 out of 32 patients during sodium valproate administration . The psychiatric state of 4 out of 32 patients deteriorated . Three was no correlation between the serum concentration of sodium valproate and its effect on the dyskinesia or on the psychiatric symptoms . Some of the elderly subjects showed a slight accumulation of the drug Saccadic distractibility , Stroop color-word scores , and serial dyskinesia assessment s were obtained on 10 schizophrenic patients with tardive dyskinesia during a pharmacologic challenge with placebo or 7 mg muscimol , a potent , direct-acting GABA agonist . Although no significant difference in the measures was evident between conditions , a significant correlation was found between GABA agonist-induced  changes in saccadic distractibility and dyskinesia scores where no correlation existed between these measures on placebo . Improvement in saccadic distractibility was also correlated with reduction in attention performance , as measured by Stroop . These effects are not due to sedation . The correlation between dyskinesia and saccadic distractibility is consistent with a model of parallel motor and oculomotor cortico-striatal-thalamic circuits in humans . This work supports the hypothesis that a dysfunction in GABA-mediated neurotransmission may be the basis for tardive dyskinesia A double‐blind cross‐over trial of the effects of baclofen and placebo was carried out in 20 female in patients suffering from neuroleptic‐induced tardive dyskinesia . After 14 days of treatment 15 patients showed improvement on baclofen , whereas none showed improvement on placebo ; baclofen was thus significantly more effective than placebo gamma-Vinyl GABA ( gamma-aminobutyric acid ) , a drug that increases brain GABA via GABA transaminase inhibition , was evaluated in a blind , placebo-controlled trial in 10 patients with stable tardive dyskinesia .  Drug effects during active treatment ( 2 to 6 g/day ) and during pre- and posttreatment placebo periods were determined by scoring r and omly sequenced videotapes of tardive dyskinesia and parkinsonian symptoms recorded weekly during st and ardized examinations . Tardive dyskinesia was significantly reduced , and correlated to increased parkinsonism . Eye blinking rates decreased , but psychiatric symptoms were unchanged during treatment Several short-term trials of baclofen for  tardive dyskinesia  have yielded conflicting results . We evaluated 33 patients maintained on a constant dose of neuroleptic during a r and omized 6-week double-blind placebo-controlled trial , followed by a 6-week open-label trial . During the double-blind part , 67 % of baclofen-treated patients and 47 % of placebo-treated patients showed a reduction of 25 % or more in their original dyskinesia score on the abnormal involuntary movement scale . In the open-labeled part , we further evaluated seven of nine baclofen responders and nine of nine placebo nonresponders . We found a 77 % baclofen response rate for the original placebo nonresponders , a loss of efficacy in 23 % of the original baclofen responders , and an attenuation of response in others . Patients with major depressive disorders were poorer responders to baclofen than those with schizophrenia . Side effects were infrequent and reversible , but dose limiting in several instances . Although baclofen may help some cases of mild tardive dyskinesia , its efficacy may attenuate with long-term administration Carroll BJ ( 1979 ) : Prediction of treatment outcome with lithium . Arch Gen Psychiatry 36:870 . Evrard JL , Banman P , Peru R , et al ( 1978 ) :  Lithium concentration in saliva , plasma and RBC of patients given lithium acetate .  Acta Psychiatr Sc and 58:67 . Mendels J , Frazer A ( 1974 ) : Alteration in cell membrane activity in depression . Am J Psychiatry 131:1240 . Mendels J , Frazer A ( 1973 ) : Intracellular lithium concentration and clinical response : Towards a membrane theory of depression . J Psychiatr Res 10:9 . Naylor GJ , McNamee liB , Moody JP ( 1971 ) : Changes in erythroeytic sodium and potassium on recovery from a depressive illness . Br J Psychiatry 118:212 . Naylor G J , Dick DAT , Dick EG ( 1976 ) : Erythroeytic membrane cation carrier relapse rate of manic depressive illness and response to lithium . Psychol Med 6:257 Sodium valproate , a GABAergic agent ( 800 mg ) , and placebo were administered orally , as a single dose , to nine chronic schizophrenics with tardive dyskinesia ( TD ) , seven chronic schizophrenics without TD and ten healthy controls , according to a double blind design . Blood sample s were collected before and after drug administration , to determine plasma prolactin concentrations . Sodium valproate decreased plasma prolactin levels in healthy subjects ( P<0.001 ) and in schizophrenic patients with TD ( P<0.001 ) , but not in chronic schizophrenics without TD . Moreover , in dyskinetic subjects , the maximum per cent decrease of plasma prolactin from basal value was positively correlated to the score of the abnormal involuntary movement scale ( r=0.724 , P<0.02 ) . Although the neural or biochemical substrate underlying the different responses of plasma prolactin to sodium valproate in schizophrenics with and without TD remains unclear , these results provide the first neuroendocrine evidence able to differentiate dyskinetic subjects from those without TD within a schizophrenic population 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 
    Output:
    
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