***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: Background The treatment of children with attention deficit hyperactivity disorder ( ADHD ) and Tourette syndrome ( TS ) has been problematic because methylpheni date (MPH)—the most commonly used drug to treat ADHD — has been reported to worsen tics and because clonidine (CLON)—the most commonly prescribed alternative — has unproven efficacy . Methods The authors conducted a multicenter , r and omized , double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were r and omly administered CLON alone , MPH alone , combined CLON + MPH , or placebo ( 2 × 2 factorial design ) . Each subject participated for 16 weeks ( weeks 1–4 CLON/placebo dose titration , weeks 5–8 added MPH/placebo dose titration , weeks 9–16 maintenance therapy ) . Results Thirty-seven children were administered MPH alone , 34 were administered CLON alone , 33 were administered CLON + MPH , and 32 were administered placebo . For our primary outcome measure of ADHD ( Conners Abbreviated Symptom Question naire – Teacher ) , significant improvement occurred for subjects assigned to CLON ( p < 0.002 ) and those assigned to MPH ( p < 0.003 ) . Compared with placebo , the greatest benefit occurred with combined CLON + MPH ( p < 0.0001 ) . CLON appeared to be most helpful for impulsivity and hyperactivity ; MPH appeared to be most helpful for inattention . The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH ( 20 % ) than those being administered CLON alone ( 26 % ) or placebo ( 22 % ) . Compared with placebo , measured tic severity lessened in all active treatment groups in the following order : CLON + MPH , CLON alone , MPH alone . Sedation was common with CLON treatment ( 28 % reported moderate or severe sedation ) , but otherwise the drugs were tolerated well , including absence of any evident cardiac toxicity . Conclusions Methylpheni date and clonidine ( particularly in combination ) are effective for ADHD in children with comorbid tics . Prior recommendations to avoid methylpheni date in these children because of concerns of worsening tics are unsupported by this trial Ten years ago deep brain stimulation ( DBS ) has been introduced as an alternative and promising treatment option for patients suffering from severe Tourette syndrome ( TS ) . It seemed timely to develop a European guideline on DBS by a working group of the European Society for the Study of Tourette Syndrome ( ESSTS ) . For a narrative review a systematic literature search was conducted and expert opinions of the guidelines group contributed also to the suggestions . Of 63 patients reported so far in the literature 59 had a beneficial outcome following DBS with moderate to marked tic improvement . However , r and omized controlled studies including a larger number of patients are still lacking . Although persistent serious adverse effects ( AEs ) have hardly been reported , surgery-related ( e.g. , bleeding , infection ) as well as stimulation-related AEs ( e.g. , sedation , anxiety , altered mood , changes in sexual function ) may occur . At present time , DBS in TS is still in its infancy . Due to both different legality and practical facilities in different European countries these guidelines , therefore , have to be understood as recommendations of experts . However , among the ESSTS working group on DBS in TS there is general agreement that , at present time , DBS should only be used in adult , treatment resistant , and severely affected patients . It is highly recommended to perform DBS in the context of controlled trials Objective : To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder ( ADHD ) and comorbid tic disorders . Methods : Study subjects were 7 to 17 years old , met Diagnostic and Statistical Manual of Mental Disorders – IV criteria for ADHD , and had concurrent Tourette syndrome or chronic motor tic disorder . Patients were r and omly assigned to double-blind treatment with placebo ( n = 72 ) or atomoxetine ( 0.5 to 1.5 mg/kg/day , n = 76 ) for up to 18 weeks . Results : Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo , approaching significance on the Yale Global Tic Severity Scale total score ( –5.5 ± 6.9 vs –3.0 ± 8.7 , p = 0.063 ) and Tic Symptom Self-Report total score ( –4.7 ± 6.5 vs –2.9 ± 5.2 , p = 0.095 ) and achieving significance on the Clinical Global Impressions ( CGI ) tic/neurologic severity scale score ( –0.7 ± 1.2 vs –0.1 ± 1.0 , p =  0.002 ) . Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score ( –10.9 ± 10.9 vs –4.9 ± 10.3 , p < 0.001 ) and CGI severity of ADHD/psychiatric symptoms scale score ( –0.8 ± 1.1 vs –0.3 ± 1.0 , p = 0.015 ) . Discontinuation rates were not significantly different between treatment groups . Atomoxetine patients had greater increases in heart rate and decreases of body weight , and rates of treatment-emergent decreased appetite and nausea were higher . No other clinical ly relevant treatment differences were seen in any other vital sign , adverse event , or electrocardiographic or laboratory measures . Conclusions : Atomoxetine did not exacerbate tic symptoms . Rather , there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms . Atomoxetine treatment appeared safe and well tolerated To evaluate the feasibility and efficacy of behavioral relaxation therapy as treatment for Tourette syndrome , 23 patients were recruited from a university-based pediatric Tourette syndrome referral clinic . Individuals were r and omized and stratified according to initial tic severity and the presence of attention-deficit hyperactivity disorder into either relaxation therapy or a minimal therapy ( control ) group .  Sixteen patients , mean age 11.8 years ( S.D. 2.8 years ) , completed the 3-month study , which included weekly , hour-long , individual training sessions for 6 weeks . Individuals ( n = 7 ) in the relaxation therapy group demonstrated a significantly increased ability to relax , compared with the minimal therapy ( awareness and quiet time training ) group . At 6 weeks , tic findings , based on five established tic severity scales , revealed greater improvement in the relaxation treatment group , but values failed to reach statistical significance . No difference between therapy groups was apparent at the 3-month evaluation . The acquired ability to relax did not significantly affect behavioral measures on the Child Behavioral Checklist . On the basis of this pilot study , relaxation therapy appears to have a limited role in the treatment of tics in Tourette syndrome BACKGROUND Dopamine agonists could theoretically normalize the suspected central dopamine hypersensitivity in Tourette 's syndrome . METHODS There was a multicenter r and omized , placebo-controlled , double-blind clinical trial of pramipexole given for 6 weeks in 63 children and adolescents with Tourette 's syndrome . RESULTS There were no significant differences in the adjusted mean change in the Total Tic Score of the Yale Global Tic Severity Scale for patients treated with pramipexole ( -7.16 ) and placebo ( -7.17 ) . There were no significant treatment effects on change from baseline in the Global Severity score of the Yale Scale and parent- and investigator-scored Clinical Global Impression of Improvement . In patients with attention deficit hyperactivity disorder , there was improvement in DuPaul ADHD scale scores for patients receiving pramipexole compared with placebo . CONCLUSIONS There was no evidence that pramipexole has efficacy in suppressing tics .  Pramipexole may decrease symptoms of associated attention deficit hyperactivity disorder Clonidine has been suggested to be effective in Gilles de la Tourette 's syndrome ( GTS ) , but no double‐blind study has ever evaluated its effects using objective measures . Thirty patients with GTS completed a 6‐month placebo‐controlled crossover study of the effectiveness of clonidine . Videotapes were obtained at each 3‐week visit and were evaluated r and omly at the end of the study for distribution , frequency , and severity of motor and vocal tics . Quantifiable psychometric examinations were performed as well . The use of clonidine did not significantly ( p < 0.05 ) reduce motor tics , vocalizations , or behavior . The effect of a low dose ( 0.0075 mg/kg/day ) was no different from that of a high dose ( 0.015 mg/kg/day ) ; children 's responses were no different from adults ' ; and those also receiving neuroleptic agents showed the same lack of efficacy as seen in patients on no other medication . Dosing schedule did not affect the objective ratings ; scores from clonidine given twice a day were equivalent to those for three times a day BACKGROUND Case studies and a placebo-controlled study previously suggested the effectiveness of immunomodulatory therapy in patients with tic or related disorders whose symptoms show a relationship with streptococcal infections . No data are available on the effectiveness of intravenous immunoglobulins ( IVIG ) on tic severity in unselected tic disorder patients . METHOD Thirty patients with a DSM-IV tic disorder were r and omly assigned to IVIG  ( 1 g/kg on 2 consecutive days ; mean age = 28.71 years ; range , 14 - 53 years ) or  placebo ( mean age = 30.73 years ; range , 14 - 63 years ) . Symptoms were rated with the Yale Global Tic Severity Scale , the Yale-Brown Obsessive Compulsive Scale , and the Clinical Global Impressions scale of symptom change with regard to tic severity . These were used at baseline and on weeks 2 , 4 , 6 , 10 , and 14 posttreatment , after which blinding was broken . The study was conducted from March through August 2002 . RESULTS We observed no significant differences between both treatment groups regarding posttreatment changes in tic severity . Severity of obsessions and compulsions , which was in the sub clinical range , decreased significantly in the IVIG group compared with the placebo group at week 6 ( p = .02 ) . Then , there was a 32.3 % improvement in the IVIG group compared with baseline . Though this improvement was maintained over the following 8 weeks , no statistically significant differences between the IVIG and the placebo group with regard to improvements in obsessions and compulsions were detected at subsequent assessment s. IVIG treatment was associated with significantly more side effects than placebo , most notably headache . CONCLUSION Based on the present results , IVIG can not be recommended in tic disorders This clinical guideline provides recommendations for the behavioural and psychosocial interventions ( BPI ) of children and adolescents with tic disorders prepared by a working group of the European Society for the Study of Tourette Syndrome ( ESSTS ) . A systematic literature search was conducted to obtain an up date on the efficacy of BPI for tics . Relevant studies were identified using computerised search es of the Medline and PsycINFO data bases and the Cochrane Library for the years 1950–2010 . The search identified no meta-analyses , yet twelve ( systematic ) review s and eight r and omised controlled trials provided evidence for the current review . Most evidence was found for habit reversal training ( HRT ) and the available but smaller evidence also supports the efficacy of exposure with response prevention ( ERP ) . Both interventions are considered first line behavioural treatments for tics for both children and adults and should be offered to a patient , taking into account his preference . Treatments that are considered second line or add-on behavioural treatments are  contingency management , function based interventions and relaxation training . Neurofeedback is still experimental . Almost no research was identified that examined the efficacy of psychosocial interventions , e.g. , psychoeducation and group work . Based on clinical practice , this guideline recommends behavioural treatment as first line offer to patients in most cases . It should be embedded within a psychoeducational and supportive context and can be combined with drug treatment Objective : To evaluate the efficacy and safety of risperidone in children and adults with Tourette syndrome . Methods : This was an 8-week , r and omized , double-blind , placebo-controlled trial . The primary outcome measure was the Total Tic score of the Yale Global Tic Severity Scale ( YGTSS ) . Results : Thirty-four medication-free subjects ( 26 children and 8 adults ) ranging in age from 6 to 62 years ( mean = 19.7 ± 17.0 years ) participated . YGTSS Total Tic scores were similar at baseline ( 26.0 ± 5.1 for risperidone vs 27.4 ± 8.5 for placebo ) . After 8 weeks of treatment ( mean daily dose of 2.5 ± 0.85 ) , the 16 subjects on risperidone showed a 32 % reduction in tic severity from baseline , compared to a 7 % reduction for placebo patients ( n = 18 ) ( F[2,64 ] = 6.07 ; p = 0.004 ) . The 12 children r and omized to risperidone showed a 36 % reduction in tic symptoms compared to an 11 % decrease in the 14 children on placebo ( F[2,48 ] = 6. 
    Output:
    
When medication is considered appropriate for the treatment of tics , the balance of clinical benefits to harm favours α2-adrenergic receptor agonists ( clonidine and guanfacine ) as first-line agents .
Antipsychotics are likely to be useful but carry the risk of harm and so should be reserved for when α2-adrenergic receptor agonists are either ineffective or poorly tolerated .
There is evidence that HRT/CBIT is effective , but there is no evidence for HRT/CBIT alone relative to combining medication and HRT/CBIT .
There is currently no evidence to suggest that the physical and dietary interventions review ed are sufficiently effective and safe to be considered as treatments