Focus on Guanfacine Extended-release: A Review of its Use in Child and Adolescent Psychiatry.

OBJECTIVE: To review the basic pharmacology and published literature regarding use of guanfacine extended-release (GXR) for the treatment of attention deficit/hyperactivity disorder in children and adolescents. METHODS: A LITERATURE REVIEW WAS CONDUCTED USING THE SEARCH TERMS: 'guanfacine', with limits set to: Human trials, English Language, and All Child (Age 0-18). Articles pertaining to guanfacine immediate-release or for indications other than attention deficit/hyperactivity disorder (ADHD) were not included for analysis. Additional articles were identified from reference information and poster presentation data. RESULTS: Six prospective, randomized controlled trials (RCT) and four open-label trials (including two long-term safety extension trials) were identified for GXR in the treatment of ADHD. All published RCTs showed superiority over placebo on the primary outcome measure. Subgroup analysis of available RCT data showed no efficacy of GXR at any dose in adolescents. Adverse effects in GXR trials were generally mild to moderate. High rates of early discontinuation were observed in long-term open-label extension trials. CONCLUSION: GXR is an effective option for treatment of ADHD in patients 6-12 years of age as monotherapy, or as adjunctive treatment to psychostimulants.

OBJECTIF: Effectuer une revue de la pharmacologie de base et de la littérature publiée sur l'utilisation de la guanfacine à action prolongée (GXR) pour le traitement du trouble de déficit de l'attention avec hyperactivité (TDAH) chez les enfants et les adolescents. MÉTHODES: Une revue de la littérature a été menée à l'aide des mots clés « guanfacine ¼', et des limites suivantes: essais sur des humains, langue anglaise, et tous les enfants (0­18 ans). Les articles traitant de la guanfacine à action immédiate ou pour indications autres que le TDAH n'ont pas été inclus dans l'analyse. Les articles additionnels ont été repérés dans des bibliographies et les données de présentations par affiches. RÉSULTATS: Six essais randomisés contrôlés (ERC) prospectifs, et quatre essais ouverts (y compris deux essais prolongés d'innocuité à long terme) ont été retenus pour la GXR dans le traitement du TDAH. Tous les ERC publiés montraient la supériorité sur le placebo à la première mesure du résultat. L'analyse par sous-groupe des données d'ERC disponibles n'indiquait aucune efficacité de la GXR à n'importe quelle dose chez les adolescents. Les effets indésirables des essais de la GXR étaient généralement de faibles à modérés. Des taux élevés d'interruption précoce ont été observés dans les essais ouverts prolongés du long terme. CONCLUSION: La GXR est une option efficace de monothérapie pour le traitement du TDAH chez les patients de 6 à 12 ans, ou comme traitement d'appoint des psychostimulants.

Focus on Lisdexamfetamine: A Review of its use in Child and Adolescent Psychiatry.

OBJECTIVE: To summarize and review published literature regarding lisdexamfetamine and its use in child and adolescent psychiatry. METHOD: A LITERATURE REVIEW WAS CONDUCTED USING THE PUBMED SEARCH TERM: 'lisdexamfetamine' with limits: Human trials, English language, All Child (aged 0-18 years). Additional articles were identified from reference information and poster presentation data. RESULTS: Lisdexamfetamine (Vyvanse®) is a prodrug formulation of dextroamphetamine used for the treatment of Attention Deficit/Hyperactivity Disorder (ADHD). Conversion of lisdexamfetamine to active dextroamphetamine occurs via hydrolytic enzymes located on erythrocytes, and leads to an onset of action within 1-2 hours post-dose, and duration of up to 13 hours. Administration of lisdexamfetamine via nasal or intravenous routes did not result in significant elevation of drug liking scores in known stimulant abusers, suggesting low potential for abuse. Lisdexamfetamine has been available in the United States since 2007, but was only recently approved by Health Canada for use in children 6 to 12 years of age. There are five randomized controlled trials with lisdexamfetamine in children and adolescents showing efficacy for treatment of ADHD. In addition, several open-label trials and case reports were identified. The adverse effect profile of lisdexamfetamine is similar to that observed with other long-acting amphetamine formulations. CONCLUSION: Lisdexamfetamine is a novel long-acting stimulant formulation with efficacy for treatment of ADHD and low abuse potential due to its prodrug formulation.

The human dimension: how the prefrontal cortex modulates the subcortical fear response.

Numerous studies suggest that the amygdala is critical for the acquisition and expression of fear. Conditioned fear in animals has been considered a good model for human anxiety disorders, but animal models of anxiety have several limitations. Conditioned fear in animals can be directed to a specific stressor and is easily extinguished. Furthermore, animals do not seem to be able to develop the capacity to worry excessively about the future. While animal models are useful and can demonstrate psychiatric illnesses, they do not completely mimic the complex cognitive processes that occur in anxious humans. Thus, we hypothesize that human anxiety disorders are caused at least in part by differential activity in the prefrontal cortex, the brain region that most separates us from our nearest genetic neighbors. The human prefrontal cortex has not only been shown to be more developed than that of other mammals, but it also has unique morphology and gene expression. Neuroimaging studies repeatedly show abnormalities in the prefrontal cortex in anxious individuals. Thus, we suggest that the very same cortical complexity that allows us to produce a vibrant culture is also the seat of anxiety disorders. Interestingly, preclinical studies have shown that the prefrontal cortex inhibits the amygdala. There appears to be a distinction between two classes of anxiety disorders. Those disorders involving intense fear and panic--panic disorder, post-traumatic stress disorder, and phobias--seem to be characterized by an underactivity of the prefrontal cortex, thus disinhibiting the amygdala. Disorders such as generalized anxiety disorder and obsessive-compulsive disorder, which involve worry and rumination, on the other hand, seem to be characterized by an overactivity of the prefrontal cortex. Studies of prefrontal cortical function in psychiatric illness should be a fruitful method for identifying effective treatment approaches.