Long-Term Assessment of the Effects of COVID-19 and Isolation Care on Survivor Disability and Anxiety.

We conducted an assessment of disability, anxiety, and other life impacts of COVID-19 and isolation care in a unique cohort of individuals. These included both community admissions to a university hospital as well as some of the earliest international aeromedical evacuees. Among an initial 16 COVID-19 survivors that were interviewed 6-12 months following their admission into isolation care, perception of their isolation care experience was related to their reporting of long-term consequences. However, anxiety and disability assessed with standard scores had no relationship with each other. Both capture of the isolation care experience and caution relying on single scoring systems for assessing long-term consequences in survivors are important considerations for on-going and future COVID-19 and other pandemic survivor research.

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.

Relative cost-effectiveness of treatments for adolescent depression: 36-week results from the TADS randomized trial.

OBJECTIVE: The cost-effectiveness of three active interventions for major depression in adolescents was compared after 36 weeks of treatment in the Treatment of Adolescents with Depression Study. METHOD: Outpatients aged 12 to 18 years with a primary diagnosis of major depression participated in a randomized controlled trial conducted at 13 U.S. academic and community clinics from 2000 to 2004. Three hundred twenty-seven participants randomized to 1 of 3 active treatment arms, fluoxetine alone (n = 109), cognitive-behavioral therapy (n = 111) alone, or their combination (n = 107), were evaluated for a 3-month acute treatment and a 6-month continuation/maintenance treatment period. Costs of services received for the 36 weeks were estimated and examined in relation to the number of depression-free days and quality-adjusted life-years. Cost-effectiveness acceptability curves were also generated. Sensitivity analyses were conducted to assess treatment differences on the quality-adjusted life-years and cost-effectiveness measures. RESULTS: Cognitive-behavioral therapy was the most costly treatment component (mean $1,787 [in monotherapy] and $1,833 [in combination therapy], median $1,923 [for both]). Reflecting higher direct and indirect costs associated with psychiatric hospital use, the costs of services received outside Treatment of Adolescents with Depression Study in fluoxetine-treated patients (mean $5,382, median $2,341) were significantly higher than those in participants treated with cognitive-behavioral therapy (mean $3,102, median $1,373) or combination (mean $2,705, median $927). Accordingly, cost-effectiveness acceptability curves indicate that combination treatment is highly likely (>90%) to be more cost-effective than fluoxetine alone at 36 weeks. Cognitive-behavioral therapy is not likely to be more cost-effective than fluoxetine. CONCLUSIONS: These findings support the use of combination treatment in adolescents with depression over monotherapy.

iPLEDGE allegiance to the pill: evaluation of year 1 of a birth defect prevention and monitoring system.

The United States Food and Drug Administration (FDA), in collaboration with pharmaceutical manufacturers, have recently implemented a heavily revised risk-management program for patients on isotretinoin (Accutane), a drug with known and pronounced teratogenic effects. This revised risk management plan places significant burdens on both providers and patients in the hopes of achieving its goal of reducing fetal exposure to isotretinoin. The main focus of this paper is to discuss the burdens of various aspects of the program in relationship to potential corresponding benefits. In particular, we evaluate the pregnancy rates of women on isotretinoin therapy compared with that of the general population and the rate changes based on the risk management programs. Additionally, we investigate whether the benefits of the program for women have increased as the benefits have risen. We devote special attention to the ethical implications of the intent of the program and to an analysis of the ethical justification of the restrictions placed on women of childbearing potential (WCP) as it compares to the risk-benefit relationship of using isotretinoin.

Assessment of safety and long-term outcomes of initial treatment with placebo in TADS.

OBJECTIVE: The authors examined whether initial assignment to receive placebo for 12 weeks followed by open active treatment as clinically indicated was associated with different levels of benefit and risk of harm across 36 weeks as compared with initial assignment to receive active treatments. METHOD: Adolescents with major depressive disorder (N=439) were randomly assigned to receive an initial 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy (CBT), combination treatment with fluoxetine and CBT, or clinical management with placebo; those assigned to placebo received open active treatment as clinically indicated after 12 weeks of placebo. Assessments were conducted every 6 weeks for 36 weeks. The primary outcome measures were response and remission based on scores on the Children's Depression Rating Scale-Revised and the Clinical Global Impression improvement subscale. RESULTS: At week 36, the response rate was 82% in the placebo/open group and 83% in the active treatment groups. The remission rate was 48% in the placebo/open group and 59% in the active treatment groups, a difference that approached statistical significance. Patients who responded to placebo generally retained their response. Those who did not respond to placebo subsequently responded to active treatment at the same rate as those initially assigned to active treatments. There were no differences between groups in rates of suicidal events, study retention, or symptom worsening. CONCLUSIONS: Remission rates at 9 months were lower in patients treated initially with placebo, but 3 months of placebo treatment was not associated with any harm or diminished response to subsequent treatment.

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.

Cost-effectiveness of treatments for adolescent depression: results from TADS.

OBJECTIVE: While the evidence base for treatments for adolescent depression is building, little is known about the relative efficiency of such treatments. Treatment costs are a relevant concern given the competing demands on family and health care budgets. The authors evaluated the cost-effectiveness of three active treatments among adolescents with major depressive disorder. METHOD: Volunteers (N=439) ages 12 to 18 with a primary diagnosis of major depressive disorder participated in a randomized, controlled trial conducted at 13 U.S. academic and community clinics from 2000 to 2004. Subjects included those participants who did not drop out and had evaluable outcome and cost data at 12 weeks (N=369). Subjects were randomly assigned to 12 weeks of either fluoxetine alone (10-40 mg/day), CBT alone, CBT combined with fluoxetine (10-40 mg/day), or placebo (equivalent to 10-40 mg/day). Both placebo and fluoxetine were administered double-blind; CBT alone and CBT in combination with fluoxetine were administered unblinded. Societal cost per unit of improvement on the Children's Depression Rating Scale-Revised and cost per quality-adjusted life year (QALY) were compared. RESULTS: Results ranged from an incremental cost over placebo of $24,000 per QALY for treatment with fluoxetine to $123,000 per QALY for combination therapy treatment. The cost-effectiveness ratio for CBT treatment was not evaluable due to negative clinical effects. The models were robust on a variety of assumptions. CONCLUSIONS: Both fluoxetine and combination therapy are at least as cost-effective in the short-term as other treatments commonly used in primary care (using a threshold of $125,000/QALY). Fluoxetine is more cost-effective than combination therapy after 12 weeks of treatment.

Ethics and the prescription pad.

This article reviews the considerations that inform ethical psychotropic medication prescription processes at the clinical level with child and adolescent patients and their families or guardians. Physician attributes, cultural and religious factors, and the psychodynamic aspects of psychopharmacology are reviewed, in addition to the applications of basic ethical principles and concepts to the act of dispensing psychotropic medications. Attention is given to the processes of informed consent, assent, and challenges encountered to ethical prescribing for special populations such as children in foster care and juvenile justice systems. Ramifications of black box warnings and off label prescribing are discussed. Finally, the authors offer practical tips to guide clinicians in ethical psychopharmacologic management of their child and adolescent patients.

Ethnic Differences in Attributions and Treatment Expectancies for Adolescent Depression.

Studies suggest that ethnicity and socioeconomic factors may relate to differences in treatment expectancies and the attributions made for emotional or behavioral problems. We examined ethnic differences in (1) parents' attributions about the causes of adolescent behavioral and emotional problems and (2) treatment expectancies among 236 adolescent participants who enrolled in a 36-week randomized controlled trial for depression. Controlling for education and income, European American parents were more likely to endorse beliefs reflecting physical causes of depression than African American parents. There were no ethnic differences for beliefs reflecting external, familial, or community factors. Ethnic differences were observed in the treatment expectancies reported by parents, but not adolescents, with African American parents more likely than European Americans and Other minorities to endorse positive expectations for CBT. These findings may have implications for understanding discrepancies in mental health service use.

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.

The assessment of attention-deficit/hyperactivity disorder in rural primary care: the portability of the American Academy of Pediatrics guidelines to the "real world".

OBJECTIVE: To examine the implementation of a protocol for the assessment of attention-deficit/hyperactivity disorder (ADHD) in rural pediatric practices. The protocol was designed to provide an efficient means for pediatricians to learn and use the ADHD guidelines put forth by the American Academy of Pediatrics (AAP). METHODS: Primary care staff (physicians, nurses, etc) from 2 rural pediatric practices were trained to use the ADHD-assessment protocol. Medical records for 101 patients were reviewed from 1 to 2 years before the introduction of the protocol and for 86 patients during the subsequent 2 to 3 years to assess compliance with the AAP guidelines. In addition, 34% of the scales scored by the staff were rescored to check for scoring accuracy. RESULTS: Before the availability of the AAP guidelines and the implementation of the assessment protocol, neither primary care site was consistently collecting the comprehensive information that is now recommended for an ADHD assessment. Parent and/or teacher rating scales were collected for only 0% to 21% of assessments across sites. When provided with brief training and supporting materials, medical records reflected significant improvement in the ascertainment of clinically necessary ADHD information, with parent and teacher rating scales present 88% to 100% of the time. Staff demonstrated an ability to score rating scales with a high degree of accuracy. The integrity of protocol collection and management was maintained 2 to 3 years after training. CONCLUSIONS: An efficient system for conducting ADHD assessments according to AAP guidelines in rural pediatrics clinics can be initiated and maintained with integrity. Additional research is needed to determine if this system improves diagnostic decision-making and patient outcomes.