Objective: In the Treatment for Adolescents with Depression Study (TADS), fluoxetine (FLX) and the combination of fluoxetine with cognitive-behavioral therapy (COMB) had superior improvement trajectories compared to pill placebo (PBO), whereas cognitive–behavioral therapy (CBT) was not significantly different from PBO. Because attention-deficit= hyperactivity disorder (ADHD) and major depressive disorder (MDD) frequently co-exist, we examined whether ADHD moderated these outcomes in TADS. Method: A total of 439 adolescents with MDD, 12–17 years old, were randomized to FLX, CBT, COMB, or PBO. Random coefficients regression models examined depression improvement in 377 depressed youths without ADHD and 62 with ADHD, including 20 who were treated with a psychostimulant. Results: Within the ADHD group, the improvement trajectories of the three active treatments were similar, all with rates of improvement greater than PBO. For those without ADHD, only COMB had a rate of improvement that was superior to PBO. Conclusions:Co-morbidADHDmoderated treatment ofMDD.CBTalone or FLXalonemay offer benefits similar toCOMB in the treatment of MDD in youths with co-morbid MDD and ADHD, whereas monotherapy may not match the benefits of COMB for thosewithout ADHD. TheADHD subgroup analysis presented in this paper is exploratory in nature because of the small number of youths with ADHD in the sample. Clinical Trial Registry:www.clinicaltrials.gov Identifier: NCT00006286. The TADS protocol and all of the TADSmanuals are available on the Internet at https:==trialweb.dcri.duke.edu=tads=index.html.

Throughout this decade, there has been significant research into pharmacotherapies for attention-deficit hyperactivity disorder (ADHD). This article considers the efficacy and safety of five of the more novel long-acting pharmacological treatments recently approved by the FDA for marketing in the US for paediatric ADHD, along with an α 2 -adrenoceptor agonist in preparation. Reviewed treatments include the non-stimulant atomoxetine, three novel extended-release (XR) stimulant preparations: dexmethylphenidate, lisdexamfetamine dimesylate and the methylphenidate transdermal system (TDS), and the recently approved XR α 2 -adrenoceptor agonist, guanfacine. Dexmethylphenidate XR is a stimulant treatment in a single isomer form, and has an efficacy and tolerability similar to two doses of immediate-release (IR) dexmethylphenidate when taken 4 hours apart, but is dosed at half of the usual d,l -methylphenidate dose. Dexmethylphenidate XR utilizes a beaded bimodal release, with 50% initially released and another 50% released 4 hours later to provide benefit lasting up to 10–12 hours. Lisdexamfetamine was the first stimulant treatment approved as a prodrug, whereby the single isomer d -amfetamine remains pharmacologically inactive until activated by cleaving the lysine. Its efficacy and tolerability are generally consistent with that of XR mixed amfetamine salts, with this activation method and more consistent absorption generally resulting in up to an 11- to 13-hour benefit. The methylphenidate TDS patch utilizes skin absorption to provide predictable and uniform delivery of methylphenidate when worn for 9 hours/day. The efficacy and tolerability of the methylphenidate TDS patch is generally consistent with that of osmotic-controlled release oral system (OROS®) methylphenidate, providing benefit for about 11–12 hours. Because of their formulation, lisdexamfetamine and methylphenidate each have an onset of effect at about 2 hours after administration. An adjustable wear time for the methylphenidate TDS patch accommodates related adverse effects, but its disadvantages are frequent skin irritation and the need to remember to take the patch off. Atomoxetine is the first non-stimulant treatment approved by the FDA and employs weight-based dosing up to 1.4 mg/kg/day. Benefit is generally observed within 2–8 weeks of initiation and is considered to have a lesser therapeutic effect than that of stimulants. A recent parallel-group controlled study found that atomoxetine (up to 1.8 mg/kg/day) and OROS® methylphenidate both improved ADHD symptoms, although subjects receiving OROS® methylphenidate had a significantly better response. Interestingly, treatment-naive children had a similar beneficial response to atomoxetine as those receiving OROS® methylphenidate. Subsequent crossover treatment revealed a subgroup of youths who did not respond well to OROS® methylphenidate but did respond to atomoxetine. Also identified was a larger than expected subgroup who did not respond well to either active treatment, confirming the need to continue the pursuit of novel treatments. As of September of 2009, guanfacine in XR form is the first α 2 -adrenoceptor agonist to gain approval to treat ADHD, approved for the treatment of 6- to 17-year olds. A second α 2 -adrenoceptor agonist, clonidine, is in development as a potential XR treatment for paediatric ADHD. IR clonidine has a fast onset and short half-life, with its use historically limited by somnolence. Although early formulations did not improve inattention well, recent evidence suggests that clonidine XR may have potential use as monotherapy or in extending benefit when taken with a stimulant. Guanfacine has a more specific neuronal action and a longer action than that of clonidine. The approved dosing of guanfacine XR 1 to 4 mg daily generally provides symptom benefit lasting 8–14 hours, and up to 24 hours in some children and adolescents receiving a higher dose. Such recent developments and ongoing study of additional potential pharmacological interventions may lead to additional future treatment options for children with ADHD.

OBJECTIVE:This study tested whether positive response to short-term treatment for adolescent major depressive disorder (MDD) would have the secondary benefit of preventing subsequent alcohol use disorders (AUD) or substance use disorders (SUD). METHOD:For 5 years, we followed 192 adolescents (56.2% female; 20.8% minority) who had participated in the Treatment for Adolescents with Depression Study (TADS; TADS Team, 2004) and who had no prior diagnoses of AUD or SUD. TADS initial treatments were cognitive behavior therapy (CBT), fluoxetine alone (FLX), the combination of CBT and FLX (COMB), or clinical management with pill placebo (PBO). We used both the original TADS treatment response rating and a more restrictive symptom count rating. During follow-up, diagnostic interviews were completed at 6- or 12-month intervals to assess onset of AUD or SUD as well as MDD recovery and recurrence. RESULTS:Achieving a positive response to MDD treatment was unrelated to subsequent AUD but predicted a lower rate of subsequent SUD, regardless of the measure of positive response (11.65% vs. 24.72%, or 10.0% vs. 24.5%, respectively). Type of initial MDD treatment was not related to either outcome. Prior to depression treatment, greater involvement with alcohol or drugs predicted later AUD or SUD, as did older age (for AUD) and more comorbid disorders (for SUD). Among those with recurrent MDD and AUD, AUD preceded MDD recurrence in 24 of 25 cases. CONCLUSION:Effective short-term adolescent depression treatment significantly reduces the rate of subsequent SUD but not AUD. Alcohol or drug use should be assessed prior to adolescent MDD treatment and monitored even after MDD recovery.

CONTEXTMajor depressive disorder in adolescents is common and impairing. Efficacious treatments have been developed, but little is known about longer-term outcomes, including recurrence.OBJECTIVESTo determine whether adolescents who responded to short-term treatments or who received the most efficacious short-term treatment would have lower recurrence rates, and to identify predictors of recovery and recurrence.DESIGNNaturalistic follow-up study.SETTINGTwelve academic sites in the United States.PARTICIPANTSOne hundred ninety-six adolescents (86 males and 110 females) randomized to 1 of 4 short-term interventions (fluoxetine hydrochloride treatment, cognitive behavioral therapy, their combination, or placebo) in the Treatment for Adolescents With Depression Study were followed up for 5 years after study entry (44.6% of the original Treatment for Adolescents With Depression Study sample).MAIN OUTCOME MEASURESRecovery was defined as absence of clinically significant major depressive disorder symptoms on the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version interview for at least 8 weeks, and recurrence was defined as a new episode of major depressive disorder following recovery.RESULTSAlmost all participants (96.4%) recovered from their index episode of major depressive disorder during the follow-up period. Recovery by 2 years was significantly more likely for short-term treatment responders (96.2%) than for partial responders or nonresponders (79.1%) (P < .001) but was not associated with having received the most efficacious short-term treatment (the combination of fluoxetine and cognitive behavioral therapy). Of the 189 participants who recovered, 88 (46.6%) had a recurrence. Recurrence was not predicted by full short-term treatment response or by original treatment. However, full or partial responders were less likely to have a recurrence (42.9%) than were nonresponders (67.6%) (P = .03). Sex predicted recurrence (57.0% among females vs 32.9% among males; P = .02).CONCLUSIONSAlmost all depressed adolescents recovered. However, recurrence occurs in almost half of recovered adolescents, with higher probability in females in this age range. Further research should identify and address the vulnerabilities to recurrence that are more common among young women.

Throughout this decade, there has been significant research into pharmacotherapies for attention-deficit hyperactivity disorder (ADHD). This article considers the efficacy and safety of five of the more novel long-acting pharmacological treatments recently approved by the FDA for marketing in the US for paediatric ADHD, along with an alpha(2)-adrenoceptor agonist in preparation. Reviewed treatments include the non-stimulant atomoxetine, three novel extended-release (XR) stimulant preparations: dexmethylphenidate, lisdexamfetamine dimesylate and the methylphenidate transdermal system (TDS), and the recently approved XR alpha(2)-adrenoceptor agonist, guanfacine. Dexmethylphenidate XR is a stimulant treatment in a single isomer form, and has an efficacy and tolerability similar to two doses of immediate-release (IR) dexmethylphenidate when taken 4 hours apart, but is dosed at half of the usual d,l-methylphenidate dose. Dexmethylphenidate XR utilizes a beaded bimodal release, with 50% initially released and another 50% released 4 hours later to provide benefit lasting up to 10-12 hours. Lisdexamfetamine was the first stimulant treatment approved as a prodrug, whereby the single isomer d-amfetamine remains pharmacologically inactive until activated by cleaving the lysine. Its efficacy and tolerability are generally consistent with that of XR mixed amfetamine salts, with this activation method and more consistent absorption generally resulting in up to an 11- to 13-hour benefit. The methylphenidate TDS patch utilizes skin absorption to provide predictable and uniform delivery of methylphenidate when worn for 9 hours/day. The efficacy and tolerability of the methylphenidate TDS patch is generally consistent with that of osmotic-controlled release oral system (OROS) methylphenidate, providing benefit for about 11-12 hours. Because of their formulation, lisdexamfetamine and methylphenidate each have an onset of effect at about 2 hours after administration. An adjustable wear time for the methylphenidate TDS patch accommodates related adverse effects, but its disadvantages are frequent skin irritation and the need to remember to take the patch off. Atomoxetine is the first non-stimulant treatment approved by the FDA and employs weight-based dosing up to 1.4 mg/kg/day. Benefit is generally observed within 2-8 weeks of initiation and is considered to have a lesser therapeutic effect than that of stimulants. A recent parallel-group controlled study found that atomoxetine (up to 1.8 mg/kg/day) and OROS methylphenidate both improved ADHD symptoms, although subjects receiving OROS methylphenidate had a significantly better response. Interestingly, treatment-naive children had a similar beneficial response to atomoxetine as those receiving OROS methylphenidate. Subsequent crossover treatment revealed a subgroup of youths who did not respond well to OROS methylphenidate but did respond to atomoxetine. Also identified was a larger than expected subgroup who did not respond well to either active treatment, confirming the need to continue the pursuit of novel treatments. As of September of 2009, guanfacine in XR form is the first alpha(2)-adrenoceptor agonist to gain approval to treat ADHD, approved for the treatment of 6- to 17-year olds. A second alpha(2)-adrenoceptor agonist, clonidine, is in development as a potential XR treatment for paediatric ADHD. IR clonidine has a fast onset and short half-life, with its use historically limited by somnolence. Although early formulations did not improve inattention well, recent evidence suggests that clonidine XR may have potential use as monotherapy or in extending benefit when taken with a stimulant. Guanfacine has a more specific neuronal action and a longer action than that of clonidine. The approved dosing of guanfacine XR 1 to 4 mg daily generally provides symptom benefit lasting 8-14 hours, and up to 24 hours in some children and adolescents receiving a higher dose. Such recent developments and ongoing study of additional potential pharmacological interventions may lead to additional future treatment options for children with ADHD.

Major depressive disorder is common in adolescence and is associated with significant morbidity and family burden. Little is known about service use by depressed adolescents. The purpose of this article is to report the patterns of services use and costs for participants in the Treatment for Adolescents with Depression Study sample during the 3 months before randomization. Costs were assigned across three categories of payors: families, private insurance, and the public sector. We examined whether costs from payors varied by baseline covariates, such as age, gender, insurance status, and family income. The majority (71%) of depressed youth sought services during the 3-month period. Slightly more than one-fifth had contact with a behavioral health specialist. The average participant had just under $300 (SD = $437.67, range = $0 $3,747.71) in treatment-related costs, with most of these costs borne by families and private insurers.

OBJECTIVE:In the Treatment for Adolescents with Depression Study (TADS), fluoxetine (FLX) and the combination of fluoxetine with cognitive-behavioral therapy (COMB) had superior improvement trajectories compared to pill placebo (PBO), whereas cognitive-behavioral therapy (CBT) was not significantly different from PBO. Because attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) frequently co-exist, we examined whether ADHD moderated these outcomes in TADS.METHOD:A total of 439 adolescents with MDD, 12-17 years old, were randomized to FLX, CBT, COMB, or PBO. Random coefficients regression models examined depression improvement in 377 depressed youths without ADHD and 62 with ADHD, including 20 who were treated with a psychostimulant.RESULTS:Within the ADHD group, the improvement trajectories of the three active treatments were similar, all with rates of improvement greater than PBO. For those without ADHD, only COMB had a rate of improvement that was superior to PBO.CONCLUSIONS:Co-morbid ADHD moderated treatment of MDD. CBT alone or FLX alone may offer benefits similar to COMB in the treatment of MDD in youths with co-morbid MDD and ADHD, whereas monotherapy may not match the benefits of COMB for those without ADHD. The ADHD subgroup analysis presented in this paper is exploratory in nature because of the small number of youths with ADHD in the sample.CLINICAL TRIAL REGISTRY:www.clinicaltrials.gov Identifier: NCT00006286. The TADS protocol and all of the TADS manuals are available on the Internet at https://trialweb.dcri.duke.edu/tads/index.html .

OBJECTIVE:The Treatment for Adolescents With Depression Study (TADS) evaluates the effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), and their combination in adolescents with major depressive disorder. The authors report effectiveness outcomes across a 1-year naturalistic follow-up period.METHOD:The randomized, controlled trial was conducted in 13 academic and community sites in the United States. Stages I, II, and III consisted of 12, 6, and 18 weeks of acute, consolidation, and continuation treatment, respectively. Following discontinuation of TADS treatments at the end of stage III, stage IV consisted of 1 year of naturalistic follow-up. The participants were 327 subjects between the ages of 12 and 17 with a primary DSM-IV diagnosis of major depressive disorder. No TADS treatment was provided during the follow-up period; treatment was available in the community. The primary dependent measures, rated by an independent evaluator blind to treatment status, were the total score on the Children's Depression Rating Scale-Revised and the rate of response, defined as a rating of much or very much improved on the Clinical Global Impressions improvement measure.RESULTS:Sixty-six percent of the eligible subjects participated in at least one stage IV assessment. The benefits seen at the end of active treatment (week 36) persisted during follow-up on all measures of depression and suicidality.CONCLUSIONS:In contrast to earlier reports on short-term treatments, in which worsening after treatment is the rule, the longer treatment in the TADS was associated with persistent benefits over 1 year of naturalistic follow-up.

OBJECTIVE:The Treatment for Adolescents with Depression Study (TADS) database was analyzed to determine whether suicidal events (attempts and ideation) occurred early in treatment, could be predicted by severity of depression or other clinical characteristics, and were preceded by clinical deterioration or symptoms of increased irritability, akathisia, sleep disruption, or mania. METHOD:TADS was a 36-week randomized, controlled clinical trial of pharmacologic and psychotherapeutic treatments involving 439 youths with major depressive disorder (DSM-IV criteria). Suicidal events were defined according to the Columbia Classification Algorithm of Suicidal Assessment. Patients were randomly assigned into the study between spring 2000 and summer 2003. RESULTS:Forty-four patients (10.0%) had at least 1 suicidal event (no suicide occurred). Events occurred 0.4 to 31.1 weeks (mean +/- SD = 11.9 +/- 8.2) after starting TADS treatment, with no difference in event timing for patients receiving medication versus those not receiving medication. Severity of self-rated pretreatment suicidal ideation (Suicidal Ideation Questionnaire adapted for adolescents score > or = 31) and depressive symptoms (Reynolds Adolescent Depression Scale score > or = 91) predicted occurrence of suicidal events during treatment (P < .05). Patients with suicidal events were on average still moderately ill prior to the event (mean +/- SD Clinical Global Impressions-Severity of Illness scale score = 4.0 +/- 1.3) and only minimally improved (mean +/- SD Clinical Global Impressions-Improvement scale score = 3.2 +/- 1.1). Events were not preceded by increased irritability, akathisia, sleep disturbance, or manic signs. Specific interpersonal stressors were identified in 73% of cases (N = 44). Of the events, 55% (N = 24) resulted in overnight hospitalization. CONCLUSIONS:Most suicidal events occurred in the context of persistent depression and insufficient improvement without evidence of medication-induced behavioral activation as a precursor. Severity of self-rated suicidal ideation and depressive symptoms predicted emergence of suicidality during treatment. Risk for suicidal events did not decrease after the first month of treatment, suggesting the need for careful clinical monitoring for several months after starting treatment.

Throughout this decade, there has been significant research into pharmacotherapies for attention-deficit hyperactivity disorder (ADHD). This article considers the efficacy and safety of five of the more novel long-acting pharmacological treatments recently approved by the FDA for marketing in the US for paediatric ADHD, along with an α2-adrenoceptor agonist in preparation. Reviewed treatments include the non-stimulant atomoxetine, three novel extended-release (XR) stimulant preparations: dexmethylphenidate, lisdexamfetamine dimesylate and the methylphenidate transdermal system (TDS), and the recently approved XR α2-adrenoceptor agonist, guanfacine.

Objective To examine factors associated with eligibility and randomization and consider the efficiency of recruitment methods. Method Adolescents, ages 12 to 17 years, were telephone screened (N = 2,804) followed by in-person evaluation (N = 1,088) for the Treatment for Adolescents With Depression Study. Separate logistic regression models, controlling for site, examined whether sex, age, race, or source of recruitment was associated with eligibility, providing written consent, or randomization. Efficiency was calculated from the number of completed telephone screens per each enrolled participant. Results Older adolescents were less likely to be eligible at telephone screening (odds ratio [OR]; 0.81). Regardless of race, eligible adolescents who were referred by a professional had higher odds of presenting in-person for consent (OR 1.56). African Americans had statistically lower odds of providing consent (OR 0.67), particularly if recruited by advertisement (OR 0.54). Females were more likely to be diagnosed with major depressive disorder (OR 1.69). No significant differences were found between randomized participants and eligible adolescents who withdrew from the study before randomization. Conclusions These findings underscore the importance of using multiple strategies to recruit adolescents for clinical trial participation and enhancing sensitivity to cultural variations, especially when reaching out to depressed African Americans.

OBJECTIVE To describe a manual-based intervention to address clinical crises and retain participants in the Treatment for Adolescents With Depression Study (TADS). METHOD The use of adjunct services for attrition prevention (ASAP) is described for adolescents (ages 12-17 years) during the 12-week acute treatment in TADS, from 2000 to 2003. Logistic regression, controlling for site, was used to predict use. RESULTS Of 439 enrolled participants, 17.8% (n = 78) used ASAP primarily for suicidality or worsening of depression. Of these, 46.2% continued in their assigned treatment through week 12, 47.4% received out-of-protocol treatment but continued participating in assessments, and 10.3% withdrew consent, including 3 who terminated treatment and withdrew consent on the same date. ASAP use did not differ between treatments (p =.97) and typically occurred early in treatment. At the end of the 12 weeks, 37.2% of participants using ASAP remained in their assigned treatment, although 80.8% continued participating in assessments. ASAP was associated with, at baseline, a higher severity of depression (p <.01), substance use (p <.01), and precontemplation level of change (p <.02). CONCLUSIONS ASAP may be useful to retain adolescent participants and as a safety intervention in placebo-controlled trials. In clinical practice ASAP-like procedures may be useful to encourage adherence in patients engaging in long-term treatment. Clinical trial registration information-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006286.

Objective We examined the extent to which parents and adolescents participating in the Treatment for Adolescents With Depression Study (TADS) understood key aspects of the study. Method TADS was a clinical trial comparing the effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), their combination, and placebo in 439 adolescents (12-17 years old) with major depressive disorder. Six weeks after starting treatment, adolescents and their parents were asked to complete a questionnaire about critical elements of the trial. Results Completion rate was 67.2% for adolescents (N = 295) and 73.6% for parents (N = 323). More than 90% of the completers knew of the main purpose of the trial, possible assignment to placebo, and their right to withdraw participation at any time. However, about one third overall (and 49% in the CBT group) described TADS as “education” rather than “research.” Of 12 questions, the mean number of correct answers was 10.3 (SD 1.7) among adolescents and 11.2 (SD 1.2) among parents (p <.0001). The most frequently stated reason for TADS participation was the pursuit of high-quality care. Conclusions Most parents and adolescents were well-informed research participants. Difficulties in appreciating the research nature of the trial, however, emerged, especially among participants assigned to psychotherapy. Parents were overall better informed than adolescents.

OBJECTIVETo examine the time to response for both pharmacotherapy and psychotherapy in the Treatment for Adolescents with Depression Study (TADS).METHODAdolescents (N = 439, ages 12 to 17 years) with major depressive disorder were randomized to fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or pill placebo (PBO). Defining response as very much improved or much improved on the Clinical Global Impression-Improvement Scale (CGI-I), survival analyses using Cox proportional hazards models, and Kaplan-Meier curves were conducted to evaluate time to first response and time to stable response for subjects receiving pharmacotherapy (COMB, FLX, PBO) as well as for subjects receiving CBT (COMB, CBT). Direct comparisons between pharmacotherapy and CBT were not made because of differences in visit schedules.RESULTSBased on pharmacotherapist CGI-I scores, COMB and FLX showed faster onset of benefit than PBO on time to response and time to stable response (p < .001), and COMB was faster than FLX on time to stable response (p = .034). The probability of sustained early response was approximately threefold greater for COMB than PBO, twofold greater for FLX than PBO, and 1.5-fold greater for COMB than FLX. On the psychotherapist CGI-I scores, both first response and stable response occurred faster in COMB than CBT (p < .001), with a probability of sustained early response approximately threefold greater for COMB than CBT.CONCLUSIONSIn the acute treatment of depressed adolescents, FLX and COMB accelerate response relative to PBO, and COMB accelerates response relative to CBT alone.

OBJECTIVES A rapidly growing empirical literature on the treatment of major depressive disorder (MDD) in youth supports the efficacy of short-term treatment with depression-specific cognitive-behavioral therapy or medication management with a selective serotonin reuptake inhibitor. These studies also identify a substantial probability of partial response and of relapse, which might be addressed by more intensive, longer-term treatments. METHOD Funded by the National Institute of Mental Health, the Treatment for Adolescents With Depression Study (TADS) is a multicenter, randomized, masked effectiveness trial designed to evaluate the short-term (12-week) and long-term (36-week) effectiveness of four treatments for adolescents with MDD: fluoxetine, cognitive-behavioral therapy, their combination, and, acutely, pill placebo. A volunteer sample of 432 subjects aged 12-17 years (inclusive) with a primary DSM-IV diagnosis of MDD who are broadly representative of patients seen in clinical practice will enter the study. The primary dependent measures rated blindly by an independent evaluator are the Children's Depression Rating Scale and, for responder analysis, a dichotomized Clinical Global Impressions-Improvement score. Consistent with an intent-to-treat analysis, all patients, regardless of treatment status, return for all scheduled assessments. RESULTS This report describes the design of the trial, the rationale for the design choices made, and the methods used to carry out the trial. CONCLUSION When completed, TADS will improve our understanding of how best to initiate treatment for adolescents with MDD.

OBJECTIVETo collect pilot data assessing the safety, tolerability, and efficacy of tomoxetine, a nonstimulant norepinephrine enhancer, in pediatric attention deficit hyperactivity disorder (ADHD).METHODSAn open-label trial of tomoxetine in pediatric ADHD was conducted as part of a multisite clinical trial. Following a baseline assessment, an ascending dose titration was completed during 10 weekly visits.RESULTSTen subjects were enrolled at baseline, with eight completing the study. Seven of the eight remaining subjects met efficacy criteria. Significant decreases in symptom severity ratings by parents and study investigators were found. The medication was well tolerated, with transient appetite suppression the most frequently reported side effect. However, subjects' weights remained stable across study visits.DISCUSSIONThese preliminary findings suggest that tomoxetine may hold promise as a treatment for pediatric ADHD.