Kelly Posner

The Columbia-suicide severity rating scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults

OBJECTIVE Research on suicide prevention and interventions requires a standard method for assessing both suicidal ideation and behavior to identify those at risk and to track treatment response. The Columbia-Suicide Severity Rating Scale (C-SSRS) was designed to quantify the severity of suicidal ideation and behavior. The authors examined the psychometric properties of the scale. METHOD The C-SSRSs validity relative to other measures of suicidal ideation and behavior and the internal consistency of its intensity of ideation subscale were analyzed in three multisite studies: a treatment study of adolescent suicide attempters (N=124); a medication efficacy trial with depressed adolescents (N=312); and a study of adults presenting to an emergency department for psychiatric reasons (N=237). RESULTS The C-SSRS demonstrated good convergent and divergent validity with other multi-informant suicidal ideation and behavior scales and had high sensitivity and specificity for suicidal behavior classifications compared with another behavior scale and an independent suicide evaluation board. Both the ideation and behavior subscales were sensitive to change over time. The intensity of ideation subscale demonstrated moderate to strong internal consistency. In the adolescent suicide attempters study, worst-point lifetime suicidal ideation on the C-SSRS predicted suicide attempts during the study, whereas the Scale for Suicide Ideation did not. Participants with the two highest levels of ideation severity (intent or intent with plan) at baseline had higher odds for attempting suicide during the study. CONCLUSIONS These findings suggest that the C-SSRS is suitable for assessment of suicidal ideation and behavior in clinical and research settings.

The Treatment of Adolescent Suicide Attempters Study (TASA): Predictors of Suicidal Events in an Open Treatment Trial

OBJECTIVE To identify the predictors of suicidal events and attempts in adolescent suicide attempters with depression treated in an open treatment trial. METHOD Adolescents who had made a recent suicide attempt and had unipolar depression (n =124) were either randomized (n = 22) or given a choice (n = 102) among three conditions. Two participants withdrew before treatment assignment. The remaining 124 youths received a specialized psychotherapy for suicide attempting adolescents (n = 17), a medication algorithm (n = 14), or the combination (n = 93). The participants were followed up 6 months after intake with respect to rate, timing, and predictors of a suicidal event (attempt or acute suicidal ideation necessitating emergency referral). RESULTS The morbid risks of suicidal events and attempts on 6-month follow-up were 0.19 and 0.12, respectively, with a median time to event of 44 days. Higher self-rated depression, suicidal ideation, family income, greater number of previous suicide attempts, lower maximum lethality of previous attempt, history of sexual abuse, and lower family cohesion predicted the occurrence, and earlier time to event, with similar findings for the outcome of attempts. A slower decline in suicidal ideation was associated with the occurrence of a suicidal event. CONCLUSIONS In this open trial, the 6-month morbid risks for suicidal events and for reattempts were lower than those in other comparable samples, suggesting that this intervention should be studied further. Important treatment targets include suicidal ideation, family cohesion, and sequelae of previous abuse. Because 40% of events occurred with 4 weeks of intake, an emphasis on safety planning and increased therapeutic contact early in treatment may be warranted.

A Laboratory School Comparison of Mixed Amphetamine Salts Extended Release (Adderall XR®) and Atomoxetine (Strattera®) in School-Aged Children With Attention Deficit/Hyperactivity Disorder

Mixed amphetamine salts extended release (MAS XR; Adderall XR®) and atomoxetine (Strattera®) were compared in children 6 to 12 years old with attention deficit/hyperactivity disorder (ADHD) combined or hyperactive/impulsive type in a randomized, double-blind, multicenter, parallel-group, forced-dose-escalation laboratory school study. Primary efficacy measure was the SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) behavioral rating scale. Changes in mean SKAMP deportment scores from baseline were significantly greater for MAS XR (n = 102) than for atomoxetine (n = 101) overall (-0.56 and -0.13, respectively; p < .0001) and at each week (p < .001). Adverse events were similar for both treatment groups. The extended time course of action and greater therapeutic efficacy of MAS XR suggests that it is more effective than atomoxetine in children with ADHD.

Analog Classroom Assessment of a Once-Daily Mixed Amphetamine Formulation, SLI381 (ADDERALL XR), in Children With ADHD

OBJECTIVES This investigation was conducted primarily to assess the safety and efficacy of SLI381 (Adderall XR), developed as a once-daily treatment for children with attention-deficit/hyperactivity disorder (ADHD). Secondary objectives included examination of the time course, pharmacokinetic, and pharmacodynamic properties of SLI381. METHOD This was a randomized, double-blind, crossover study of three doses of SLI381 (10, 20, and 30 mg), placebo, and an active control (Adderall 10 mg) given once daily to 51 children with ADHD. Weekly assessments in an analog classroom setting included blind ratings of attention and deportment and a performance measure (math test) obtained every 1.5 hours over a 12-hour period. RESULTS SLI381 was well tolerated. All active treatment conditions displayed significant time course effects and were superior to placebo in improving efficacy measures. Dose-dependent improvements were evident for SLI381. SLI381 20 and 30 mg and Adderall all showed rapid improvements by 1.5 hours, but only the SLI381 20- and 30-mg doses showed continued activity at 10.5 and 12 hours for classroom behavior and math test performance versus placebo. CONCLUSIONS These data provide support for the benefit of this novel, once-daily amphetamine preparation in the treatment of ADHD. The longer duration of action of SLI381 has the potential to simplify psychostimulant dosing, thus reducing dose diversion and eliminating the need for in-school administration. SLI381 appears to be a useful treatment option for many children with ADHD.

The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-Year Follow-Up

OBJECTIVE To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3 to 5 up to 9 to 12 years during a 6-year follow-up after the original Preschool ADHD Treatment Study (PATS). METHOD A total of 207 participants (75% male) from the original PATS, assessed at baseline (mean age, 4.4 years, when all met criteria for ADHD) and 3 months later (before medication treatment), were re-evaluated in three follow-up assessment visits (year 3, mean age 7.4 years; year 4, 8.3 years; and year 6, 10.4 years). Parents and teachers rated symptom severity, and clinicians established psychiatric diagnoses. Analyses examined longitudinal changes in symptom severity and ADHD diagnosis. RESULTS Parent- and teacher-rated symptom severity decreased from baseline to year 3 but remained relatively stable and in the moderate-to-severe clinical range through year 6. Girls showed generally steeper decreases in symptom T-scores. At year 6, 89% (160/180) of remaining participants met ADHD symptom and impairment diagnostic criteria. Comorbidity of oppositional defiant disorder and/or conduct disorder was associated with a 30% higher risk of having an ADHD diagnosis at year 6 in the multiple logistic model. Medication status during follow-up, on versus off, did not predict symptom severity change from year 3 to year 6 after adjustment for other variables. CONCLUSIONS ADHD in preschoolers is a relatively stable diagnosis over a 6-year period. The course is generally chronic, with high symptom severity and impairment, in very young children with moderate-to-severe ADHD, despite treatment with medication. Development of more effective ADHD intervention strategies is needed for this age group.

Insomnia and Sleep Duration as Mediators of the Relationship Between Depression and Hypertension Incidence

BACKGROUND Depression has been found to predict the incidence of hypertension and other adverse cardiovascular events in prospective studies. Insomnia and short sleep duration, which are typical symptoms of depression, have also been shown to increase the risk for hypertension incidence. Insomnia is associated with increased activation of the hypothalamic-pituitary-adrenal axis, and short sleep duration raises average 24-h blood pressure, which over time could lead to structural adaptations that gradually reset the entire cardiovascular system to operate at an elevated pressure equilibrium. No previous published population studies have examined whether insomnia and sleep duration mediate the relationship between depression and hypertension incidence. METHODS We conducted multivariate longitudinal (1982-1992) analyses stratified by age of the First National Health and Nutrition Examination Survey (NHANES I) (n = 4,913) using Cox proportional hazards models. RESULTS Middle-aged subjects who suffered from depression at baseline were 44% more likely to be diagnosed with hypertension over the follow-up period after controlling for covariates (hazard ratio (HR) = 1.44, 95% confidence interval (CI) 1.15-1.80). Both short sleep duration and insomnia were also significantly associated with hypertension incidence. Consistent with insomnia and sleep duration acting as mediators of the relationship between depression and hypertension incidence, the inclusion of these variables in the multivariate models appreciably attenuated the association (HR = 1.27, 95% CI 1.00-1.61). Depression, sleep duration, and insomnia were not significantly associated with hypertension incidence in elderly subjects. CONCLUSIONS These results suggest the hypothesis that treatment of sleep problems in middle-aged individuals suffering from depression could reduce their risk for developing hypertension, and its vascular and cardiac complications.

A Randomized, Double-Blind, Placebo-Controlled, Laboratory Classroom Assessment of Methylphenidate Transdermal System in Children with ADHD.

Objective: This study evaluates the efficacy, duration of action, and tolerability of methylphenidate transdermal system (MTS) in children with ADHD. Method: Participants were dose optimized over 5 weeks utilizing patch doses of 10, 16, 20, and 27 mg applied in the morning and worn for 9 hours. Following optimization, 80 participants were randomized to 1 week of MTS or placebo followed by 1 week of the opposite treatment. Laboratory classroom sessions conducted after each randomized week included blinded ratings of attention, behavior, and academic performance. Results: MTS was well tolerated and displayed significant improvement compared with placebo. Improvements were seen at the first postdose time point measured and continued through 12 hours. Conclusions: Treatment with MTS resulted in statistically significant improvements on all efficacy measures. Time course and therapeutic effects of MTS suggest that this novel methylphenidate delivery system is an efficacious once-daily treatment for ADHD.

Attention Deficit Hyperactivity Disorder in Preschool Children

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a childhood onset of symptoms and impairment. Although it is most frequently identified during elementary school years, epidemiologic data suggest that the onset of ADHD frequently occurs earlier, with presentation as young as 3 years of age. Early identification, however, allows consideration of appropriate interventions. Many data are available on safe and efficacious treatment options for school-aged children who have ADHD; however, little is known about the use of these modalities in preschoolers and, ultimately, the long-term effects of early treatment. Recognition of the preschool presentation of ADHD, appropriate differential diagnosis, and identification of comorbid conditions, and a developmental perspective on the course and potential outcomes of the disorder may guide treatment planning. Newly available data on the safety and efficacy of pharmacotherapy and psychosocial intervention for preschoolers who have ADHD may help clinicians make treatment decisions for these young children and their families.

Pharmacokinetics of SLI381 (ADDERALL XR), an Extended-Release Formulation of Adderall

OBJECTIVE To assess the pharmacokinetic (PK) properties of a single daily dose of Adderall (mixed amphetamine salts) and the extended-release formulation, SLI381 (ADDERALL XR), in pediatric attention-deficit/hyperactivity disorder (ADHD). METHOD Fifty-one children (aged 6-12 years) with ADHD participated in a 6-week, seven-visit, PK and pharmacodynamic study. PK sampling occurred during visit 1 and again at visit 7. At visit 1, subjects received an initial oral dose of SLI381, 20 mg. At visit 7 subjects completed 1 week of medication treatment following random assignment to once-daily orally dosed SLI381 10 mg, 20 mg, or 30 mg; Adderall 10 mg; or placebo. RESULTS PK parameters evidenced substantial intersubject variability (coefficients of variation = 28-56%). Time to maximum concentration (Tmax) for SLI381 versus Adderall showed average increases of 3.0 hours for dextroamphetamine (t = -2.35, p = .04, df = 8.6) and 3.2 hours for levoamphetamine (t = -2.39, p = .04, df = 9.2). The d- and l-isomer concentrations were highly correlated and approximated a 3:1 ratio. CONCLUSIONS SLI381 showed extended Tmax values compared with Adderall and appears suitable for once-daily dosing. Intersubject variability underscores the need for individual dose titration.

Factors in the assessment of suicidality in youth

Suicide remains a leading cause of death among youth, and suicide ideation and behavior are relatively common in both normal and clinical populations. Clinicians working with young people must assess for the presence of suicidal ideation, suicidal behavior, and other risk factors, in order to determine the level of risk. This paper provides the clinician with a summary of risk factors for youth suicide, as well as providing standardized terminology to enhance assessment of suicidal ideation and behavior.