The data suggest that effects of maternal PTSD related to cortisol can be observed very early in the life of the offspring and underscore the relevance of in utero contributors to putative biological risk for PTSD.
In both the United States and the Netherlands, SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents.
Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2-3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid antiobsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n ¼ 15) with nearconstant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine's effects within the crossover design showed significant (po0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n ¼ 8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n ¼ 7). One-week post-infusion, 50% of those receiving ketamine (n ¼ 8) met criteria for treatment response (X35% Y-BOCS reduction) vs 0% of those receiving placebo (n ¼ 7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.
Objectives
To determine long-term effects on substance use and substance use disorder (SUD), up to 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the multisite Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA; n=436); to test whether (a) medication at follow-up, (b) cumulative psychostimulant treatment over time, or (c) both relate to substance use/SUD; to compare substance use/SUD in the ADHD sample to the non-ADHD childhood classmate comparison group (n=261).
Method
Mixed-effects regression models with planned contrasts were used for all tests except the important cumulative stimulant treatment question, for which propensity score matching analysis was used.
Results
The originally randomized treatment groups did not differ significantly on substance use/SUD by the 8 year follow-up or earlier (M age = 17 years). Neither medication at follow-up (mostly stimulants) nor cumulative stimulant treatment was associated with adolescent substance use/SUD. Substance use at all time points, including use of two or more substances and SUD, were each greater in the ADHD than non-ADHD samples, regardless of sex.
Conclusions
Medication for ADHD did not protect from, nor contribute to, visible risk of substance use or SUD by adolescence, whether analyzed as randomized treatment assignment in childhood, as medication at follow-up, or as cumulative stimulant treatment over an 8 year follow-up from childhood. These results suggest the need to identify alternative or adjunctive adolescent-focused approaches to substance abuse prevention and treatment for boys and girls with ADHD, especially given their increased risk for use and abuse of multiple substances that is not improved with stimulant medication. Clinical trial registration information—Multimodal Treatment Study of Children with Attention Deficit and Hyperactivity Disorder (MTA); http://clinical trials.gov/; NCT00000388.
Objective: To compare delinquent behavior and early substance use between the children in the Multimodal Treatment Study of Children With ADHD (MTA; N = 487) and those in a local normative comparison group (n = 272) at 24 and 36 months postrandomization and to test whether these outcomes were predicted by the randomly assigned treatments and subsequent self-selected prescribed medications. Method: Most MTA children were 11 to 13 years old by 36 months.Delinquency seriousness was coded ordinally from multiple measures/reporters; child-reported substance use was binary.Results: Relative to local normative comparison group, MTA children had significantly higher rates of delinquency (e.g., 27.1% vs. 7.4% at 36 months; p = .000) and substance use (e.g., 17.4% vs. 7.8% at 36 months; p = .001). Children randomized to intensive behavior therapy reported less 24-month substance use than other MTA children (p = .02).Random effects ordinal growth models revealed no other effects of initial treatment assignment on delinquency seriousness or substance use. By 24 and 36 months, more days of prescribed medication were associated with more serious delinquency but not substance use. Conclusions: Cause-and-effect relationships between medication treatment and delinquency are unclear; the absence of associations between medication treatment and substance use needs to be re-evaluated at older ages. Findings underscore the need for continuous monitoring of these outcomes as children with attentiondeficit/hyperactivity disorder enter adolescence.
Additional application of a "three-protein" biomarker model to current diagnostic criteria may provide an objective biomarker pattern to help identify patients with ALS.
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