Does Guanfacine Work for Pediatric PTSD?
Kathryn G. Fort
Fellow, Child and Adolescent Psychiatry
NYU Child Study Center
Bellevue Hospital Center
Dr. Fort has disclosed that she has no relevant financial or other interests in any commercial companies pertaining to this educational activity.
Treatment options for pediatric PTSD and trauma symptoms are limited, and the symptoms are clearly detrimental to youths’ functioning, particularly in the presence of comorbid disorders. As recommended treatments, trauma-focused cognitive behavioral therapy (TF-CBT) and SSRIs rarely lead to a quick remission of symptoms, so child psychiatrists are in need of a larger pharmacologic toolbox.
A recent open-label pilot study was conducted investigating the tolerability and effectiveness of guanfacine XR (GXR) for children and adolescents with trauma symptoms, including re-experiencing, avoidance, and hyperarousal. (This study was sponsored by Shire Pharmaceuticals, the makers of Intuniv, a branded version of guanfacine.)
Seventeen subjects were enrolled, having been recruited through psychiatrists’ offices, advertisements, or word of mouth. Inclusion criteria included being six to 18 years old, having trauma symptoms as measured by standard rating instruments, and being free of other psychotropic medications.
Children were allowed to have comorbid conditions, and many did: 89.5% met criteria for ADHD, 68.4% for PTSD, 47.4% for GAD, 21.1% for depression, 10.6% for separation anxiety disorder, and 5.3% for reactive attachment disorder.
Subjects were started on 1 mg of GXR at bedtime during week one, which was titrated as needed by 1 mg weekly to maximum dose of 4 mg/day by week five. Thirteen of the original 17 children completed the trial, with an average does of GXR of 1.19 mg/day over the course of the 8 week trial. Four dropped out due to worsening depression, side effects (sedation/fatigue), lack of effectiveness, and transportation issues.
How well did the treatment work? Pretty well. Thirteen children completed the treatment: 70.6% were rated by clinicians as very much improved or much improved on the CGI, and 82.4% showed a greater than 30% reduction on the UCLA-RI, a measure of PTSD. Subjects also reported significant improvements in hyperactivity and inattention as well as anxiety symptoms. At study conclusion, 12 of the original 17 elected to continue GXR treatment (Connor D et al, J Child Adolesc Psychopharmacology 2013;23:244-251)
CCPR’s Take: Generalizability of these results is limited because this was not a double blind trial and the sample size was small. Nonetheless, given the paucity of treatment options for pediatric PTSD, low dose guanfacine—either as the branded XR or the cheaper immediate release generic—may be worth a try.
Are there Really Two Types of Antisocial Behavior in Children?
Sharon M. Kahler, MD
Clinical Instructor, Child and Adolescent Psychiatry
NYU Child Study Center
Dr Kahler has disclosed that she has no relevant financial or other interests in any commercial companies pertaining to this educational activity.
Two decades ago, Terrie Moffitt first proposed that there are two distinct kinds of antisocial behavior in children: one that starts when kids are young, is life-long and is neurobiologically-based, and one that develops in adolescence and that kids can grow out of. For those interested in the jargon of this field, the early onset version has been labeled “life-course persistent (LCP)” type, while the adolescent onset has been called “adolescent limited” (AL). This theory that these are distinct types of antisocial children has been influential and widely accepted over the years.
However, a recent research review suggests that the theory may need to be reformulated. The group conducted literature searches for relevant studies from 1993 through 2013, finding 61 applicable empirical studies that distinguished between LCP and AL antisocial behavior. The first major finding of the review is that children with LCP and those with AL antisocial behavior show similar neurobiological changes, contradicting the suggestion that AL is less biologically based.
Specifically, studies examining cortisol secretion and stress reactivity showed reduced HPA responses in both LCP and AL subtypes, with no significant differences between the two. Similarly, structural and functional neuroimaging studies demonstrated changes in the brains of both groups. And while genetic studies gave mixed results, the evidence did not clearly support the developmental taxonomic theory.
Other major findings of the review included the following:
• Both types have shown the same kinds of atypical personality traits;
• Both show similar neuropsychological impairments in facial emotion recognition, decision-making, and emotional reactivity;
• Perhaps most importantly, the epidemiologic research could not support a distinction between the outcomes of the two: antisocial behavior emerging in adolescence often persists into adulthood and prognosis is frequently poor, while a significant proportion of childhood onset cases will remit.
The authors concluded that there are no clear biological, clinical or epidemiological differences between early and late onset antisocial behavior. They are likely the same disorder, with differences in onset probably caused by differences in early childhood environment (Fairchild G et al, J Child Psychol Psychiatry 2013; July: online ahead of print).
CCPR’s Take: The authors cast considerable doubt on the validity of the developmental taxonomic theory, which may have significant implications for our understanding of antisocial behavior given the widespread influence the theory has had, including on prior research, and on the DSM-IV and 5.