17.5.1 Pharmacological interventions in children and young people Comparisons Included in this Clinical Question Antidepressant (Desipramine) vs. Antidepressant (Imipramine) vs. Atomoxetine (Continued on Effective Atomoxetine + Fluoxetine vs. Placebo Placebo dose) vs. Atomoxetine (Decreased Atomoxetine alone dose) BIEDERMAN1989 KRATOCHVIL2005 DONNELLY1986 NEWCORN2006 SPENCER2002C Atomoxetine vs. Placebo Bupropion vs. Placebo Clonidine + Clonidine vs. Placebo Methylphenidate/Dexamphetamine vs. ALLEN2005 CASAT1987 KURLAN2002 Placebo + BOHNSTEDT2005 CONNERS1996B Methylphenidate/Dexamphetamine BROWN2006 HAZELL2003 KELSEY2004 MICHELSON2001 MICHELSON2002 MICHELSON2004 SPENCER2002A SPENCER2002B WEISS2005 WERNICKE2004A Dexmethylphenidate vs. Placebo Methylphenidate + Clonidine vs. Methylphenidate + Thioridazine vs. Methylphenidate + Thioridazine vs. Placebo Methylphenidate Placebo WIGAL2004 KURLAN2002 GITTELMANKLEIN1976A GITTELMANKLEIN1976A Methylphenidate + Thioridazine vs. Methylphenidate 0.3mg/kg vs. Methylphenidate 0.3mg/kg vs. Methylphenidate 0.4mg/kg vs. Thioridazine Methylphenidate 0.5mg/kg Methylphenidate 0.7mg/kg Methylphenidate 0.8mg/kg GITTELMANKLEIN1976A KUPIETZ1988 KUPIETZ1988 IALONGO1994 Methylphenidate 0.7mg/kg vs. Methylphenidate vs. Bupropion Methylphenidate vs. Clonidine Methylphenidate vs. Methylphenidate 0.5mg/kg Dexmethylphenidate BARRICKMAN1995 KURLAN2002 KUPIETZ1988 WIGAL2004 Methylphenidate vs. Pemoline CONNERS1980 Methylphenidate vs. Placebo Methylphenidate vs. Thioridazine Modafinil vs. Placebo Nicotine vs. Placebo BUTTER1983 GITTELMANKLEIN1976A BIEDERMAN2005 SHYTLE2002 CONNERS1980 BIEDERMAN2006B FINDLING2006 GREENHILL2006A GITTELMANKLEIN1976A RUGINO2003 GREENHILL2002 SWANSON2006 GREENHILL2006 IALONGO1994 KOLLINS2006 KUPIETZ1988 KURLAN2002 LERER1977 PLISZKA2000 WIGAL2004 WILENS2006A WOLRAICH2001 Pemoline vs. Placebo Stimulants (+ Placebo) vs. Placebo Sustained-release methylphenidate vs. TCAs vs. Clonidine Immediate-release methylphenidate CONNERS1980 SINGER1995 WOLRAICH2001 TCAs vs. Placebo Thioridazine vs. Placebo SINGER1995 GITTELMANKLEIN1976A Characteristics of Included Studies Methods Participants Outcomes Interventions Notes ALLEN2005 Study Type: RCT n= 148 Data Used Group 1N= 76 Research from Lilly ADHDRS Inattentive (Change from BL: Research Laboratories Study Description: Comorbidity (Specific: Tic Age: Mean 11 Range 7-17 Atomoxetine. Mean dose 1.33mg/kg/day - means, SDs) Disorder, & non-specific). Sex: 131 males 17 females INITIAL WASHOUT:10-18 day(screening) Sample consisted of 'Children' and ADHDRS Total (Change from Baseline: DOSE: 3wk titration phase- 'Adolescents' (percentages not reported). Diagnosis: means, SDs) began:0.5mg/kg/day,titrated to 30% Chronic Motor Tic Disorder by YGTSS >5, ADHDRS Hyper/Impuls.(Change from BL: 1.0mg/kg/day at end of wk 1, then titrated Type of Analysis: ITT (P's:prov.data @ BL & 1 K-SADS-PL & Clinical Interview means, SDs) up/down (final range 0.5-1.5 mg/kg/day, post-BL assessment) Data Not Used max daily dose 110mg) ADMIN:Daily as divided dose (morning & Blindness: Double blind 22% Oppositional defiant disorder by DSM-IV Yale Global Tic Severity Scale (YGTSS) - late afternoon) Duration (days): Mean 140 outcome not relevant Group 2N= 72 3% ADHD Hyperactive/Impulsive subtype by CGI-ADHD/Psych-S - outcome not relevant Setting: Recruited from 14 sites in USA, DSM-IV, K-SADS-PL, ADHDRS-IV-Parent-Inv CGI-Tic/Neuro-S - outcome not relevant Placebo - INITIAL WASHOUT:10-18 day primarily hospitals and clinics. ADMIN:Daily as divided dose(morning & Tic Symptom Self Report (TSSR) - outcome late afternoon) Notes: Randomisation carried out by a not relevant 36% ADHD Inattentive subtype by DSM-IV, K- NB.: No mention of form/appearance of computerised Interactive Voice Response SADS-PL, ADHDRS-IV-Parent-Inv CGI-Overall-S - outcome not relevant either Placebo or Atomoxetine - assume System. Notes: TAKEN AT:Baseline & Endpoint (Not tablet form, identical?? Info on Screening Process: 10-18 day 7% Major depression, GAD, or OCD by DSM-IV clear when assesments were made between screening and washout period - physical exam, these times) vital sign measurements, medical history etc. LOST TO F.U.: ATX 2/76, PLB 1/72 (Not incl.in 79% Tourette's Syndrome by YGTSS >5, K- 166 patients entered screening, 148 randomly ITT analysis) SADS-PL & Clinical Interview assisgned, 145 provided data at baseline and at least one postbaseline assesment. 61% ADHD Combined subtype by DSM-IV, K- SADS-PL, ADHDRS-IV-Parent-Inv 18% Chronic Vocal Tic Disorder by YGTSS >5, K-SADS-PL & Clinical Interview Exclusions: Weight<20 kg, or >80kg; Children's Yale-Brown Obsessive Compulsive Scale (C-YBOCS) >15, or diagnosis of OCD severe enough to require medication; Children's Depression Rating Scale-Revised (CDRS-R) >40, or diagnosis of depression severe enough to require medication; history of bipolar disorder/psychosis; seizure disorder; current use of any psychotropic medication other than study drug. Notes: YGTSS= Yale Global Tic Severity Scale ADHDRS-IV-Parent:Inv = Attention deficit/hyperactivity disorder Rating Scale-IV-Parent Version: Investigator administered and scored (NB. Needed to be >1.5 SDs above age and sex norm) Baseline: Mean (SD) YGTSS = 22 (8) (mild to moderate level of tic severity) NB: ATX group:significantly greater impairment in their mean ADHDRS-IV-Parent:Inv total and hyperactivity sub- scale scores (Change scores extracted). ADHDRS Total Mean (SD): ATX: 38.9 (9.1); PLB: 35.0 (9.5) ADHDRS Inattentive: ATX: 21.6 (4.1); PLB: 20.5 (5.0) ADHDRS Hyperactive/Implusive: ATX: 17.2 (6.8) PLB: 14.6 (7.2) Results from this paper: Internal validity: 1.1 Well covered 1.2 Well covered 1.3 Well covered 1.4 Well covered 1.5 Adequately addressed 1.6 Adequately addressed 1.7 Well covered 1.8 ATX 65% (49/76), PLB 72% (52/72) 1.9 Well covered 1.10 Not addressed Overall assessment of the study: 2.1: 1+ BARRICKMAN1995 Study Type: RCT crossover n= 15 Data Used Group 1N= 9 Funding: NR IOWA-Conners Abb.Teacher Rating Study Description: Comorbidity (Non-specific: Age: Range 7-17 Methylphenidate. Mean dose 0.8 +/- 0.1 Scale(mean change) CD, ODD, developmental learning disorders). Sex: 12 males 3 females mg/kg/day - WASHOUT: 14days Sample consisted of 'Children' and Data Not Used DOSE: Wk1 0.4mg/kg/day; Wk2-3 titrated 'Adolescents' (percentages not reported). Diagnosis: WISC-R - Baseline only; not relevant outcome to 0.7+/-0.2mg/kg/day-fixed wks4-6. 100% ADHD by DSM-III-R K-SADS-E - Baseline only ADMIN: 3 Type of Analysis: Completer capsules/day(morn,noon,4pm)[MPH Conner's Continous Performance Test - active morn & noon, & active 4pm if Blindness: Double blind Baseline only; not relevant outcome Exclusions: IQ<70; any other Axis I, II, or III diagnoses required]. Duration (days): Mean 42 (screened with Schedule for Affectiveness Disorders and Children's Manifest Anxiety Scale - Baseline Schizophrenia for School-Age Children-Epidemiologic only; not relevant outcome Setting: Outpatient clinic; USA. Version (K-SADS-E); any seizure history; eating disorders; Clinical Global Impression Scale (NIMH) - Notes: RANDOMISATION: No detail; only current use of MOAI Baseline only 'randomised'. NB. Assume equal n's Children's Depression Inventory - Baseline randomised to each group. Baseline: Several scales (Iowa-Conners, CGI, Children's only; not relevant outcome NB. Duration is to point of crossover only Depression Inventory, Revised Children's Manifest Anxiety Matching Familiar Figures Task - Baseline Group 2N= 9 Scale, etc.) administered at baseline, but baseline scores only; not relevant outcome Info on Screening Process: Consecutive Bupropion. Mean dose 2.6 +/- 0.5 not reported. recruitment of p's willing to participate. No Rey Auditory-Verbal Learning Test - Baseline mg/kg/day - WASHOUT: 14days information reported re. No's only; not relevant outcome DOSE: Wk1 1.5mg/kg/day; Wk2 screened/excluded/turn-down trial. IOWA-Conners Abb.Parent Rating Scale - no 2.0mg/kg/day; 3wk titrated to 3.3+/- NB. 18 p's randomised into trial, paper only pre-cross-over data 1.2mg/kg/day-fixed wks4-6. reported demographics for n=15 (reported Notes: TAKEN AT: All outcomes taken at ADMIN: 3 here). baseline; at endpoint: only history, physical capsules/day(morn,noon,4pm)[BUP examinations and Conners scales repeated. active morn & 4pm, & active noon if LOST TO FOLLOW-UP: 3/18 (unknown required]. allocation); completer analysis. Results from this paper: Internal validity 1.1 Well covered 1.2 Not reported adequately 1.3 Not reported adequately 1.4 Well covered 1.5 Not reported- crossover trial 1.6 Adequately assessed 1.7 Adequately assessed 1.8 17% from whole sample (3/18 dropped out at some point, unclear whether this before crossover or after) 1.9 Poorly addressed 1.10 Not applicable Overall assessment of the study 2.1: 1+ BIEDERMAN1989 Study Type: RCT n= 62 Data Used Group 1N= 31 Funding: Supported in part AE: Decreased appetite (dichotomous data) by grants from Merrell-Dow Study Description: Comorbidity: 'Non-specific' Age: Range 6-17 Placebo - WASHOUT: see excl.'s Pharmaceutical Company; comorbidity. AE: Abdominal pain (dichotomous data) DOSE/ADMIN: Increased to nearest Sex: 58 males 4 females Charlupski Foundation; Sample: 67% 'Children'; 33% 'Adolescents'. AE: Loss of >=5% body weight (dichot data) conveniant no.of pills(identical DSI)to USPHS (NIMH) award and Diagnosis: yield dose >=0.5mg/kg by wk3 & resulted Type of Analysis: ? (P's who completed >=3wks Leaving the Study Early due to Adverse Event grants. 37% Conduct disorder by Unspecified