Service use and costs of care for depressed adolescents: who uses and who pays?

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.

An exploratory analysis of the impact of family functioning on treatment for depression in adolescents.

This article explores aspects of family environment and parent-child conflict that may predict or moderate response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive behavioral therapy, their combination, or placebo. Outcomes were Week 12 scores on measures of depression and global impairment. Of 20 candidate variables, one predictor emerged: Across treatments, adolescents with mothers who reported less parent-child conflict were more likely to benefit than their counterparts. When family functioning moderated outcome, adolescents who endorsed more negative environments were more likely to benefit from fluoxetine. Similarly, when moderating effects were seen on cognitive behavioral therapy conditions, they were in the direction of being less effective among teens reporting poorer family environments.

Research knowledge among the participants in the Treatment for Adolescents With Depression Study (TADS).

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.

Factors associated with recruitment and screening in the Treatment for Adolescents With Depression Study (TADS).

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.

A manual-based intervention to address clinical crises and retain patients in the Treatment of Adolescents With Depression Study (TADS).

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.

Attention-deficit hyperactivity disorder: recent advances in paediatric pharmacotherapy.

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.

Treatment response in depressed adolescents with and without co-morbid attention-deficit/hyperactivity disorder in the Treatment for Adolescents with Depression Study.

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 .

Suicidal events in the Treatment for Adolescents With Depression Study (TADS).

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.