human
***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: SUMMARY A controlled investigation was conducted to assess the relative effectiveness of amitriptyline and methylpheni date for treating hyperactive/aggressive behavior in children originally referred to a learning clinic .  Behavioral change was measured through parent and teacher ratings . Drug effects on attention , short term memory , and impulsivity were evaluated with laboratory tasks . It was found that both drugs were largely comparable in attenuating hyperactivity and aggression . Of the laboratory measures , only attention was improved by both drugs . However , neither medication interfered with functioning on the other laboratory tests . With the exception of and trip by line-induced sedation , side effects were of minor degree . Findings raised questions concerning measuring and improving attentiveness . Differences between results of this and other studies were discussed , as were issues regarding pharmacotherapy with amitriptyline in children BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement )  combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes OBJECTIVE This study examined the efficacy and safety of clonidine hydrochloride extended-release tablets ( CLON-XR ) in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD This 8-week , placebo-controlled , fixed-dose trial , including 3 weeks of dose escalation , of patients 6 to 17 years old with ADHD evaluated the efficacy and safety of CLON-XR 0.2 mg/day or CLON-XR 0.4 mg/day versus placebo in three separate treatment arms . Primary endpoint was mean change in ADHD Rating Scale-IV ( ADHD-RS-IV ) total score from baseline to week 5 versus placebo using a last observation carried forward method . Secondary endpoints were improvement in ADHD-RS-IV inattention and hyperactivity/impulsivity subscales , Conners Parent Rating Scale-Revised : Long Form , Clinical Global Impression of Severity , Clinical Global Impression of Improvement , and Parent Global Assessment from baseline to week 5 . RESULTS Patients ( N = 236 ) were r and omized to receive placebo ( n = 78 ) , CLON-XR 0.2 mg/day ( n = 78 ) , or CLON-XR 0.4 mg/day ( n = 80 ) . Improvement from baseline in ADHD-RS-IV total score was significantly greater in both CLON-XR groups versus placebo at week 5 . A significant improvement in ADHD-RS-IV total score occurred between groups as soon as week 2 and was maintained throughout the treatment period . In addition , improvement in ADHD-RS-IV inattention and hyperactivity/impulsivity subscales , Conners Parent Rating Scale-Revised : Long Form , Clinical Global Impression of Improvement , Clinical Global Impression of Severity , and Parent Global Assessment , occurred in both treatment groups versus placebo . The most common treatment-emergent adverse event was mild-to-moderate somnolence . Changes on electrocardiogram were minor and reflected the known pharmacology of clonidine . CONCLUSIONS Clonidine hydrochloride extended-release tablets were generally well tolerated by patients in the study and significantly improved ADHD symptoms in this pediatric population BACKGROUND Despite long-st and ing clinical concerns , relatively little is known about the comorbidity between attention-deficit/hyperactivity disorder ( ADHD ) and tic disorders . Therefore , we examined tic disorders in an ongoing prospect i ve follow-up study of male subjects with ADHD , a sample unselected for any comorbid disorder . METHODS One hundred twenty-eight male children and adolescents with ADHD and 110 male controls were comprehensively evaluated at baseline and 4 years later . We characterized tic disorders along with a wide range of neuropsychiatric correlates , including other comorbid disorders and indices of psychosocial function in multiple domains ( school , cognitive , social , and family ) . RESULTS Compared with controls , subjects with ADHD showed more tic disorders at baseline and more new onsets were reported at follow-up . Attention-deficit/hyperactivity disorder and tic disorders appeared to be independent in course : in contrast to low rates of ADHD remission , tic disorders mostly remitted . The age-adjusted rate of ADHD remission was 20 % and that of tic remission , 65 % . Tic disorders had little effect on the psychosocial functioning of subjects with ADHD . CONCLUSIONS These findings suggest that comorbidity with a tic disorder has a limited effect on ADHD outcome . However , because of the relatively small sample of subjects with tic disorders , our conclusions should be considered preliminary until confirmed in larger studies of medicated and unmedicated children with ADHD with and without tic disorders The objective of this study was to investigate the effects of methylpheni date ( MPH ) on attention and inhibition in children with Attention Deficit Hyperactivity Disorder ( ADHD ) and to establish what the relative contributions of the noradrenergic and dopaminergic systems to this effect were . In addition to MPH , two other drugs were administered in order to affect both transmitter systems more selectively , L-dopa ( dopamine ( DA ) agonist ) and desipramine ( DMI ) ( noradrenaline ( NA ) re-uptake inhibitor ) . Sixteen children with ADHD performed a stop-task , a laboratory task that measures the ability to inhibit an ongoing action , in a double-blind r and omized within-subjects design . Each child received an acute clinical dose of MPH , DMI , L-dopa , and placebo ;  measures of performance and plasma were determined . The results indicated that inhibition performance was improved under DMI but not under MPH or L-dopa . The response-time to the stop-signal was marginally shortened after intake of DMI . MPH decreased omission and choice-errors and caused faster reaction times to the trials without the stop-tone . No effects of L-dopa whatsoever were noted . Prolactin levels were increased and 5-HIAA levels were lowered under DMI relative to placebo . It is suggested that the effects of MPH on attention are due to a combination of noradrenergic and dopaminergic mechanisms . The improved inhibition under DMI could be serotonergically mediated BACKGROUND Four cases of  sudden death in children 12 years or younger during desipramine treatment were identified between 1986 and 1992 . We evaluated whether these events support the hypothesis that exposure to therapeutic doses of desipramine contributes to the risk for sudden death in otherwise healthy children . METHOD The National Center for Health Statistics provided the baseline number of sudden unexplained deaths in children 5 to 14 years old . Data from the National Disease and Therapeutic Index were used to estimate the exposure to desipramine in children in the same age group . Since two of the four deaths were identified by 1987 , we used the post-1987 experience as if it were a prospect i ve period in which a causal association could be examined . RESULTS The number of sudden deaths in  desipramine-exposed  children did not increase from 1986 to 1992 despite a marked increase in exposure . By using 4 to 6 months as the average lifetime of a desipramine prescription and a baseline rate of sudden death of 4.2 deaths/million/year in this population , the post-1987 period would account for 162,000 to 242,000 person-years of desipramine exposure . Although not statistically significant , this level of exposure corresponds to a relative risk of 2.1 ( 95 % CI = 0.5 to 15 ) to 3.1 ( 95 % CI = 0.8 to 22 ) . CONCLUSION Although , based on our estimates , the evidence for an association between desipramine and sudden death in children aged 5 to 14 years appears weak , replication of our findings is needed with a more precise numerator ( total number of deaths ) and denominator ( the appropriate conversion from drug appearance to actual exposure ) before a firm conclusion on this subject can be drawn . Until then , even if remote , the possibility of an association between desipramine and sudden death in children stresses the importance of assessing risks and benefits when desipramine is used in pediatric patients OBJECTIVES To study the efficacy and tolerability of nortriptyline ( NT ) in the treatment of pediatric attention deficit hyperactivity disorder ( ADHD ) . METHODOLOGY Subjects were outpatient children and adolescents with ADHD ascertained from clinical referrals . Subjects were enrolled in a 6-week open study in which NT was titrated to 2 mg/kg/day as tolerated over 2 weeks . Using either a 30 % reduction in the ADHD rating scale or a score of 1 or 2 on the Clinical Global Impression ( CGI ) scale for ADHD improvement , responders to treatment were then r and omized into a 3-week , controlled discontinuation phase . During this phase , subjects either continued on their current dose of NT or were tapered to placebo under double-blind conditions . Subjects were monitored for symptoms of ADHD , oppositionality , anxiety , and depression . RESULTS Of the 35 subjects enrolled in the study , 32 completed the open phase and 23 completed the discontinuation phase . The mean dose of NT was 80 mg ( 1.8 mg/kg/day ) , result ing in a serum level of 81 ng/ml . At the conclusion of the open 6-week study , NT was related to a significant reduction in ADHD ( p < 0.001 ) and oppositional symptoms ( p < 0.001 ) . At the conclusion of the discontinuation phase , the 12 subjects r and omized to NT had significantly lower scores on the DSM-IV ADHD symptom checklist than those 11 subjects r and omized to placebo ( 31 versus 21 ; t = 2.2 ; p < 0.04 ) . No significant adverse events were observed , and children were noted to have weight gain during the trial . CONCLUSIONS These data suggest that NT is effective in reducing symptoms not only of ADHD but also of oppositionality . This group of children and adolescents tolerated robust dosing of NT well , with few clinical or cardiovascular adverse events This community-based study was design ed to evaluate treatment outcomes with OROS ® methylpheni date ( MPH ) and atomoxetine in children with attentiondeficit/hyperactivity disorder ( ADHD ) , as assessed by physicians and parents in a setting that resembles clinical practice . In a multicenter , prospect i ve , open-label study , children 6 to 12 years of age with ADHD were r and omized ( 2:1 , respectively ) to 3 weeks of treatment with once-daily OROS MPH or atomoxetine . Investigatorrated measures of symptoms included the ADHD Rating Scale ( ADHD-RS ) and the Clinical Global Impression-Improvement of Illness scale ( CGI-I ) . Assessment s were made at baseline and during a telephone interview in week 1 , a clinic visit in week 2 , and a final clinic visit in week 3 . In total , 1323 patients received OROS MPH ( n=850 ) or atomoxetine ( n=473 ) . Significant reductions from baseline in investigator-evaluated ADHD-RS scores were observed among patients receiving OROS MPH and those receiving atomoxetine . At the end of the study , mean decreases from baseline ADHD-RS scores were 20.24 for OROS MPH and 16 for atomoxetine ( P < .001 ) . Between-treatment differences appeared to increase over time ( 2.77 , 3.44 , and 4.24 at weeks 1 , 2 , and 3 , respectively ; P < .001 ) . Treatment response ( ie , 25 % reduction from baseline ADHD-RS scores ) was significantly greater at each evaluation for patients taking OROS MPH than for those taking atomoxetine ( P < .001 ) . Similar percentages of patients taking OROS MPH ( 4.8 % ) and atomoxetine ( 5.5 % 
    Output:
    
agent
Desipramine appeared more efficacious than clonidine in reducing ADHD symptoms as rated by parents ( SMD -0.90 , 95 % CI -1.40 to -0.40 , 1 trial , 68 participants , very low quality evidence ) in participants with ADHD and comorbid tics or Tourette syndrome .
Although this Cochrane Review did not identify serious adverse effects in patients taking TCAs , it did identify mild increases in diastolic blood pressure and pulse rates .
Also , patients treated with desipramine had significantly higher rates of appetite suppression compared to placebo whilst nortriptyline result ed in weight gain .
Other reported adverse effects included headache , confusion , sedation , tiredness , blurred vision , diaphoresis , dry mouth , abdominal discomfort , constipation , and urinary retention .
AUTHORS ' CONCLUSIONS Most evidence on TCAs relates to desipramine .
Findings suggest that , in the short term , desipramine improves the core symptoms of ADHD , but its effect on the cardiovascular system remains an important clinical concern .
***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: SUMMARY A controlled investigation was conducted to assess the relative effectiveness of amitriptyline and methylpheni date for treating hyperactive/aggressive behavior in children originally referred to a learning clinic .  Behavioral change was measured through parent and teacher ratings . Drug effects on attention , short term memory , and impulsivity were evaluated with laboratory tasks . It was found that both drugs were largely comparable in attenuating hyperactivity and aggression . Of the laboratory measures , only attention was improved by both drugs . However , neither medication interfered with functioning on the other laboratory tests . With the exception of and trip by line-induced sedation , side effects were of minor degree . Findings raised questions concerning measuring and improving attentiveness . Differences between results of this and other studies were discussed , as were issues regarding pharmacotherapy with amitriptyline in children BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement )  combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes OBJECTIVE This study examined the efficacy and safety of clonidine hydrochloride extended-release tablets ( CLON-XR ) in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD This 8-week , placebo-controlled , fixed-dose trial , including 3 weeks of dose escalation , of patients 6 to 17 years old with ADHD evaluated the efficacy and safety of CLON-XR 0.2 mg/day or CLON-XR 0.4 mg/day versus placebo in three separate treatment arms . Primary endpoint was mean change in ADHD Rating Scale-IV ( ADHD-RS-IV ) total score from baseline to week 5 versus placebo using a last observation carried forward method . Secondary endpoints were improvement in ADHD-RS-IV inattention and hyperactivity/impulsivity subscales , Conners Parent Rating Scale-Revised : Long Form , Clinical Global Impression of Severity , Clinical Global Impression of Improvement , and Parent Global Assessment from baseline to week 5 . RESULTS Patients ( N = 236 ) were r and omized to receive placebo ( n = 78 ) , CLON-XR 0.2 mg/day ( n = 78 ) , or CLON-XR 0.4 mg/day ( n = 80 ) . Improvement from baseline in ADHD-RS-IV total score was significantly greater in both CLON-XR groups versus placebo at week 5 . A significant improvement in ADHD-RS-IV total score occurred between groups as soon as week 2 and was maintained throughout the treatment period . In addition , improvement in ADHD-RS-IV inattention and hyperactivity/impulsivity subscales , Conners Parent Rating Scale-Revised : Long Form , Clinical Global Impression of Improvement , Clinical Global Impression of Severity , and Parent Global Assessment , occurred in both treatment groups versus placebo . The most common treatment-emergent adverse event was mild-to-moderate somnolence . Changes on electrocardiogram were minor and reflected the known pharmacology of clonidine . CONCLUSIONS Clonidine hydrochloride extended-release tablets were generally well tolerated by patients in the study and significantly improved ADHD symptoms in this pediatric population BACKGROUND Despite long-st and ing clinical concerns , relatively little is known about the comorbidity between attention-deficit/hyperactivity disorder ( ADHD ) and tic disorders . Therefore , we examined tic disorders in an ongoing prospect i ve follow-up study of male subjects with ADHD , a sample unselected for any comorbid disorder . METHODS One hundred twenty-eight male children and adolescents with ADHD and 110 male controls were comprehensively evaluated at baseline and 4 years later . We characterized tic disorders along with a wide range of neuropsychiatric correlates , including other comorbid disorders and indices of psychosocial function in multiple domains ( school , cognitive , social , and family ) . RESULTS Compared with controls , subjects with ADHD showed more tic disorders at baseline and more new onsets were reported at follow-up . Attention-deficit/hyperactivity disorder and tic disorders appeared to be independent in course : in contrast to low rates of ADHD remission , tic disorders mostly remitted . The age-adjusted rate of ADHD remission was 20 % and that of tic remission , 65 % . Tic disorders had little effect on the psychosocial functioning of subjects with ADHD . CONCLUSIONS These findings suggest that comorbidity with a tic disorder has a limited effect on ADHD outcome . However , because of the relatively small sample of subjects with tic disorders , our conclusions should be considered preliminary until confirmed in larger studies of medicated and unmedicated children with ADHD with and without tic disorders The objective of this study was to investigate the effects of methylpheni date ( MPH ) on attention and inhibition in children with Attention Deficit Hyperactivity Disorder ( ADHD ) and to establish what the relative contributions of the noradrenergic and dopaminergic systems to this effect were . In addition to MPH , two other drugs were administered in order to affect both transmitter systems more selectively , L-dopa ( dopamine ( DA ) agonist ) and desipramine ( DMI ) ( noradrenaline ( NA ) re-uptake inhibitor ) . Sixteen children with ADHD performed a stop-task , a laboratory task that measures the ability to inhibit an ongoing action , in a double-blind r and omized within-subjects design . Each child received an acute clinical dose of MPH , DMI , L-dopa , and placebo ;  measures of performance and plasma were determined . The results indicated that inhibition performance was improved under DMI but not under MPH or L-dopa . The response-time to the stop-signal was marginally shortened after intake of DMI . MPH decreased omission and choice-errors and caused faster reaction times to the trials without the stop-tone . No effects of L-dopa whatsoever were noted . Prolactin levels were increased and 5-HIAA levels were lowered under DMI relative to placebo . It is suggested that the effects of MPH on attention are due to a combination of noradrenergic and dopaminergic mechanisms . The improved inhibition under DMI could be serotonergically mediated BACKGROUND Four cases of  sudden death in children 12 years or younger during desipramine treatment were identified between 1986 and 1992 . We evaluated whether these events support the hypothesis that exposure to therapeutic doses of desipramine contributes to the risk for sudden death in otherwise healthy children . METHOD The National Center for Health Statistics provided the baseline number of sudden unexplained deaths in children 5 to 14 years old . Data from the National Disease and Therapeutic Index were used to estimate the exposure to desipramine in children in the same age group . Since two of the four deaths were identified by 1987 , we used the post-1987 experience as if it were a prospect i ve period in which a causal association could be examined . RESULTS The number of sudden deaths in  desipramine-exposed  children did not increase from 1986 to 1992 despite a marked increase in exposure . By using 4 to 6 months as the average lifetime of a desipramine prescription and a baseline rate of sudden death of 4.2 deaths/million/year in this population , the post-1987 period would account for 162,000 to 242,000 person-years of desipramine exposure . Although not statistically significant , this level of exposure corresponds to a relative risk of 2.1 ( 95 % CI = 0.5 to 15 ) to 3.1 ( 95 % CI = 0.8 to 22 ) . CONCLUSION Although , based on our estimates , the evidence for an association between desipramine and sudden death in children aged 5 to 14 years appears weak , replication of our findings is needed with a more precise numerator ( total number of deaths ) and denominator ( the appropriate conversion from drug appearance to actual exposure ) before a firm conclusion on this subject can be drawn . Until then , even if remote , the possibility of an association between desipramine and sudden death in children stresses the importance of assessing risks and benefits when desipramine is used in pediatric patients OBJECTIVES To study the efficacy and tolerability of nortriptyline ( NT ) in the treatment of pediatric attention deficit hyperactivity disorder ( ADHD ) . METHODOLOGY Subjects were outpatient children and adolescents with ADHD ascertained from clinical referrals . Subjects were enrolled in a 6-week open study in which NT was titrated to 2 mg/kg/day as tolerated over 2 weeks . Using either a 30 % reduction in the ADHD rating scale or a score of 1 or 2 on the Clinical Global Impression ( CGI ) scale for ADHD improvement , responders to treatment were then r and omized into a 3-week , controlled discontinuation phase . During this phase , subjects either continued on their current dose of NT or were tapered to placebo under double-blind conditions . Subjects were monitored for symptoms of ADHD , oppositionality , anxiety , and depression . RESULTS Of the 35 subjects enrolled in the study , 32 completed the open phase and 23 completed the discontinuation phase . The mean dose of NT was 80 mg ( 1.8 mg/kg/day ) , result ing in a serum level of 81 ng/ml . At the conclusion of the open 6-week study , NT was related to a significant reduction in ADHD ( p < 0.001 ) and oppositional symptoms ( p < 0.001 ) . At the conclusion of the discontinuation phase , the 12 subjects r and omized to NT had significantly lower scores on the DSM-IV ADHD symptom checklist than those 11 subjects r and omized to placebo ( 31 versus 21 ; t = 2.2 ; p < 0.04 ) . No significant adverse events were observed , and children were noted to have weight gain during the trial . CONCLUSIONS These data suggest that NT is effective in reducing symptoms not only of ADHD but also of oppositionality . This group of children and adolescents tolerated robust dosing of NT well , with few clinical or cardiovascular adverse events This community-based study was design ed to evaluate treatment outcomes with OROS ® methylpheni date ( MPH ) and atomoxetine in children with attentiondeficit/hyperactivity disorder ( ADHD ) , as assessed by physicians and parents in a setting that resembles clinical practice . In a multicenter , prospect i ve , open-label study , children 6 to 12 years of age with ADHD were r and omized ( 2:1 , respectively ) to 3 weeks of treatment with once-daily OROS MPH or atomoxetine . Investigatorrated measures of symptoms included the ADHD Rating Scale ( ADHD-RS ) and the Clinical Global Impression-Improvement of Illness scale ( CGI-I ) . Assessment s were made at baseline and during a telephone interview in week 1 , a clinic visit in week 2 , and a final clinic visit in week 3 . In total , 1323 patients received OROS MPH ( n=850 ) or atomoxetine ( n=473 ) . Significant reductions from baseline in investigator-evaluated ADHD-RS scores were observed among patients receiving OROS MPH and those receiving atomoxetine . At the end of the study , mean decreases from baseline ADHD-RS scores were 20.24 for OROS MPH and 16 for atomoxetine ( P < .001 ) . Between-treatment differences appeared to increase over time ( 2.77 , 3.44 , and 4.24 at weeks 1 , 2 , and 3 , respectively ; P < .001 ) . Treatment response ( ie , 25 % reduction from baseline ADHD-RS scores ) was significantly greater at each evaluation for patients taking OROS MPH than for those taking atomoxetine ( P < .001 ) . Similar percentages of patients taking OROS MPH ( 4.8 % ) and atomoxetine ( 5.5 % 
    Output:
    