***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: Our previous studies in Parkinson 's disease have shown that both levodopa and expectancy of receiving levodopa reduce cortical excitability . We design ed this study to evaluate how degree of expectancy and other individual factors modulate placebo response in Parkinson 's patients . Twenty-six Parkinson 's patients were r and omized to 1 of 3 groups : 0 % , 50 % , and 100 % expectancy of receiving levodopa . All subjects received placebo regardless of expectancy group . Subjects completed the NEO-Five Factor Inventory , General Perceived Self-Efficacy Scale , and Perceived Stress Scale . Cortical excitability was measured by the amplitude of motor-evoked potential ( MEP ) evoked by transcranial magnetic stimulation . Objective physical fatigue of extensor carpi radialis before and after placebo levodopa was also measured . Responders were defined as subjects who responded to the placebo levodopa with a decrease in MEP . Degree of expectancy had a significant effect on MEP response ( P < .05 ) . Subjects in the 50 % and 100 % expectancy groups responded with a decrease in MEP , whereas those in the 0 % expectancy group responded with an increase in MEP ( P < .05 ) . Responders tended to be more open to experience than nonresponders . There were no significant changes in objective physical fatigue between the expectancy groups or between responders and nonresponders . Expectancy is associated with changes in cortical excitability . Further studies are needed to examine the relationship between personality and placebo effect in Parkinson 's patients . © 2013 Movement Disorder Society The age-related response to placebo and active antihypertensive treatment was evaluated in 742 elderly hypertensive patients who were followed in the double-blind placebo-controlled trial conducted by the European Working Party on High blood pressure in the Elderly ( EWPHE ) . In the two treatment groups , the fall in systolic and diastolic blood pressures after 3 months was negatively correlated with age ( P less than 0.02 ) , indicating that the hypotensive effect of placebo and active treatment was more pronounced in older patients . Further comparison of the two treatment groups failed to demonstrate any statistical differences in the slopes of the hypotensive effect on age . These conclusions were not altered by cumulative adjustments for baseline blood pressure , pulse rate , serum creatinine and the presence of cardiovascular complications at entry . In conclusion , in the present study , a similar blood-pressure-lowering action which increased with age was observed on active and placebo treatment ; thus , proof that an observed age-related hypotensive effect is caused by a particular drug requires comparison with a control group on placebo OBJECTIVES Our prior work has shown that there is improvement in self-reported sleep in persons receiving placebo in hypnotic clinical trials . We examined the components of the " placebo response " in a hypnotic clinical trial . METHODS This was an exploratory analysis of a r and omized , double-blind clinical trial of eszopiclone versus placebo in the treatment of persons with depression and insomnia who were also receiving fluoxetine at a clinic of a teaching hospital . Sixty adults with both depression and insomnia symptoms , who were free of significant primary sleep disorders , received open-label fluoxetine for 9weeks . Patients were further r and omized 1:1 to receive either masked eszopiclone 3 mg or placebo at bedtime after the first week of fluoxetine . We examined the respective contributions of three factors associated with the " placebo effect " : ( 1 ) regression to the mean , ( 2 ) expectancy , and ( 3 ) social desirability . RESULTS There was evidence for regression to the mean for the continuous measurement of the Insomnia Severity Index ( ISI ) and the Hamilton Depression Rating Scale . There was evidence for expectancy in self-reported Wake After Sleep Onset , continuous measurement of ISI , and dichotomous remission/non-remitter measurement of ISI . There was evidence of social desirability affecting self-reported Total Sleep Time . CONCLUSIONS Factors that have been associated with the " placebo effect " are operating in hypnotic clinical trials . However , the role of each factor differs depending upon which self-reported variable is being considered . The findings have implication s for clinical trial design in insomnia Objective : To examine the frequency , temporal development , and stability of objective ly derived motor changes during placebo treatment in PD and to define the clinical domains and demographic groups most affected . Background : Placebo effects are documented in neurology , but the timing and specific disabilities most susceptible to changes during placebo treatment in PD have not been examined . Methods : The authors examined the  placebo-treated group from a r and omized , multicenter , placebo-controlled clinical trial of monotherapy ropinerole in PD patients without motor fluctuations . In 105 patients , they evaluated placebo-associated effects on the motor section of the Unified Parkinson ’s Disease Rating Scale ( UPDRS ) , dividing the motor examination into four categories : tremor , bradykinesia , rigidity , and gait/balance/midline functions . The motor UPDRS and its subscales were compared over time ( at baseline and at 4 , 12 , and 24 weeks ) using Wilcoxon ’s signed rank test . They applied a rigorous definition of placebo-associated improvement as an improvement over baseline score in motor UPDRS of at least 50 % or a change in at least two motor items at any one visit by ≥2 points . Results : During the 6-month study , 16 % of subjects improved on placebo treatment . The prevalence of response was steady ( 8 to 9 % ) at any one visit without a predominance of an early effect . No patient showed a placebo-associated improvement on all visits . All domains of parkinsonian disability were subject to placebo-associated improvement , with a trend toward more response in bradykinesia and rigidity than in tremor or gait/balance/midline function . Gender , age , disease duration , and baseline disability score did not influence the likelihood of improvement in association with placebo treatment . Conclusion : Based on a rigorous definition of placebo-associated improvement , prominent improvements in objective measures of PD disability occur during clinical trials . Because placebo-associated improvements occur throughout a 6-month trial , placebo-controlled studies in PD should be at least 6 months to capture early as well as late improvements OBJECTIVE  Placebo response and the rate of failed clinical trials are increasing in schizophrenia , resembling previous experience with antidepressant clinical trials . In depression , the percent of patients r and omized to placebo was shown to be strongly associated with drug-placebo differences ( signal detection).We hypothesized that this factor would also be important in recent schizophrenia clinical trials . To test this hypothesis a data base of acute schizophrenia placebo-controlled studies conducted between 1997 and 2008 was constructed . The data base contained 27 studies , with 79 active treatment arms . As percentage of patients r and omized to placebo increased , mean placebo improvement decreased ( p = 0.047 ) and mean drug-placebo differences tended to increase ( p = 0.166 ) . The frequency of significant contrasts from studies with ≥ 25 % r and omized to placebo was 83.3 % , compared with 58.3 % in studies with < 25 % r and omized to placebo . Caveats to these findings include limited data and confounding of potentially influential factors . These limitations prevent definitive conclusions . However , results are consistent with previous findings in depression where having a higher percent of patients r and omized to placebo increased drug-placebo differences Placebo may yield beneficial effects that are indistinguishable from those of active medication , but the factors underlying proneness to respond to placebo are widely unknown . Here , we used functional neuroimaging to examine neural correlates of anxiety reduction result ing from sustained placebo treatment under r and omized double-blind conditions , in patients with social anxiety disorder .  Brain activity was assessed during a stressful public speaking task by means of positron emission tomography before and after an 8 week treatment period .  Patients were genotyped with respect to the serotonin transporter-linked polymorphic region ( 5-HTTLPR ) and the G-703 T polymorphism in the tryptophan hydroxylase-2 ( TPH2 ) gene promoter . Results showed that placebo response was accompanied by reduced stress-related activity in the amygdala , a brain region crucial for emotional processing . However , attenuated amygdala activity was demonstrable only in subjects who were homozygous for the long allele of the 5-HTTLPR or the G variant of the TPH2 G-703 T polymorphism , and not in carriers of short or T alleles . Moreover , the TPH2 polymorphism was a significant predictor of clinical  placebo  response , homozygosity for the G allele being associated with greater improvement in anxiety symptoms . Path analysis supported that the genetic effect on symptomatic improvement with placebo is mediated by its effect on amygdala activity . Hence , our study shows , for the first time , evidence of a link between genetically controlled serotonergic modulation of amygdala activity and placebo-induced anxiety relief OBJECTIVE To search for predictors of placebo response in clinical trials of lisdexamfetamine dimesylate for the treatment of DSM-IV-TR-defined attention-deficit/hyperactivity disorder ( ADHD ) in children and adults . METHOD We used data from 2 clinical trials : ( 1 ) a 4-week , phase 3 , multicenter , r and omized , double-blind , forced-dose , parallel-group study of children aged 6 to 12 years with ADHD ( n = 290 ) and ( 2 ) a 4-week , r and omized , double-blind , placebo-controlled  , parallel-group , forced-dose titration study in adult subjects , aged 18 - 55 years with ADHD ( n = 420 ) .  Response and remission were defined using the ADHD Rating Scale-IV and the Clinical Global Impressions-Improvement scale . RESULTS Symptom remission was inversely correlated with baseline severity in both children and adults ( P < .001 ) , with less robust effects seen for response . The time to response and remission was delayed in adult subjects prescribed placebo versus lisdexamfetamine dimesylate , while response time in children was also significantly slower with placebo versus lisdexamfetamine dimesylate ( P < .01 ) . We found little evidence that demographic factors , prior pharmacotherapy , the emergence of adverse events during the trial , or changes in ADHD symptoms from the screening to baseline assessment s predicted placebo response . Certain comorbid medical symptoms reduced the response and remission rates to placebo in children ( P < .001 ) and adults ( P < .001 ) . CONCLUSIONS In both children and adults , baseline symptom severity was the most consistent predictor of remission with placebo while the temporal profile of response reliably differentiated placebo from medication responders . Placebo effects are most likely to be minimized in shorter trials enrolling more severely impaired subjects . The impact of medical and psychiatric comorbidities on placebo response merits further investigation . TRIAL REGISTRATION clinical trials.gov identifiers NCT00556296 and NCT00334880 BACKGROUND Placebos are hypothesized to exert positive effects on medical conditions by enhancing patient expectancies . Recent review s suggest that placebo benefits are restricted to subjective responses , like pain , but might be ineffective for objective physiologic outcomes . Nevertheless , mind-body links and placebo responsivity in asthma are widely believed to exist . OBJECTIVE We carried out a r and omized , double-blind investigation to ( 1 ) determine whether placebo can suppress airway hyperreactivity in asthmatic subjects , ( 2 ) quantify the placebo effect , ( 3 ) identify predictors of the placebo response , and ( 4 ) determine whether physician interventions modify the placebo response . METHODS In a double-blind , crossover design investigation , 55 subjects with mild intermittent and persistent asthma with stable airway hyperreactivity were r and omized to placebo or salmeterol before serial methacholine challenges . Subjects were additionally r and omized to physician interactions that communicated either positive or neutral expectancies regarding drug effect . RESULTS Placebo bronchodilator administration significantly reduced bronchial hyperreactivity compared with baseline ( the calculated concentration of methacholine required to induce a 20 % decrease in FEV(1 ) nearly doubled ) ; 18 % of subjects were placebo responders by using conservative definitions . Experimental manipulation of physician behavior altered perceptions of the physician but not the magnitude or frequency of the placebo response . CONCLUSIONS Objective placebo effects exist in asthma . These responses are of significant magnitude and likely to be meaningful clinical ly . The placebo response was not modulated by alterations in physician behavior in this study . CLINICAL IMPLICATION S The placebo response in patients with asthma is important in underst and ing the limitations of clinical research studies and in maximizing safe and effective therapies . This article confirms the existence of a strong placebo response in an objective and clinical ly relevant measure of disease activity OBJECTIVE There has been concern about a high rate of placebo response and a substantial failure rate in recent clinical trials in major depressive disorder ( MDD ) . This report explores differences in efficacy data from placebo-controlled MDD trials su bmi tted in support of new drug applications ( NDAs ) over a 25-year period . METHOD We compiled efficacy data from 81 r and omized , double-blind clinical trials , with 21,611 evaluable patients , that were su bmi tted to the US Food and Drug Administration as part of NDAs for an antidepressant cl aim between 1983 and 2008 . Trial data were limited to completed , r and omized , multicenter , 
    Output:
    
While younger age may contribute to the PR in some conditions , sex does not .
There is currently no evidence that the PR is different in the elderly .
PR are , however , markedly influenced by the symptom severity at baseline , and by the likelihood of receiving active treatment in placebo-controlled trials