Module 2:CMN 554 Module 2: Study Guide (Developmental and Childhood Mental Health Disorders) Updated A+ Score Guide

Treating ADHD 1. Discontinuation syndrome with stimulants  Abrupt withdrawal after prolonged use may result in dysphoria, irritability or a rebound in symptoms of ADHD; increase in sleep and appetite reported  If a stimulant is taken in conjunction with an antipsychotic, sudden discontinuation of the stimulant may result in the emergence of extrapyramidal symptoms previously masked by the stimulant’s anticholinergic properties and competition for D 2 receptors  Case of priapism reported in 16-year-old each time he forgot to take his dose of extended-release methylphenidate (Concerta) 54 mg 2. MOA and general principles for atomoxetine  Mechanism of action:  Selectively blocks the reuptake of norepinephrine; increases dopamine and norepinephrine in the frontal cortex (without increasing dopamine in subcortical areas) – leads to cognitive enhancement without abuse liability; suggested to be important in regulating attention, impulsivity, and activity levels.  No stimulant or euphoriant activity – may be advantageous in patients with comorbid substance use disorder  General comments:  Most ADHD treatment guidelines list atomoxetine as a second-line agent. May be effective for some patients who have not responded to stimulant treatment, who have comorbid anxiety, or individuals who have an active comorbid substance use disorder. Benefits include a lack of euphoria, a lower risk of rebound, a lower risk of induction of tics or psychosis, low abuse potential, and increased somnolence  Available evidence indicates that stimulants and atomoxetine have both been found to be superior to placebo for reducing the severity of ADHD symptoms on average in the short term  Has a slow onset of action and response may take up to 4 weeks – titrate dose gradually to help mitigate adverse effects (especially in patients who may be poor CYP2D6 metabolizers: ~10% of the population). Response is seen at 4 weeks of full dose and full optimization of drug response requires at least 3 months  Ultrarapid metabolizers of CYP2D6 (28% of North Africans, Ethiopians, and Arabs; up to 10% of Caucasians; 3% of African Americans, and up to 1% of Hispanics, Chinese, and Japanese) would have reduced efficacy of atomoxetine  Reduces both the inattentive and hyperactive/impulsive symptom clusters of ADHD  Head-to-head studies show greater reductions in ADHD symptoms (net effect size difference = 0.3) and a greater percentage of responders with stimulants when compared to atomoxetine  A large head-to-head trial of OROS-methylphenidate (Concerta) vs. atomoxetine in over 600 children demonstrated that 40% of children who do not respond to methylphenidate are responders to atomoxetine, indicating a selective response. 3. Nonresponse to treatment strategies  Ascertain whether diagnosis is correct.  Ascertain if patient is adherent with therapy (speak with caregivers, check with pharmacy for late refills, count remaining pills in container and compare to prescription fill date)  Ensure dosage prescribed is therapeutically appropriate and tailor regimen to have peak serum levels occur at those times of the day when symptoms are most prominent.  Consider trying a stimulant from an alternate class (methylphenidate class or amphetamine class) if first trial was ineffective and the patient was adhering to therapy recommendations. 4. Indications for 2 agonists  ADHD (clonidine (Kapvay) and guanfacine (Intuniv/Intuniv XR)) – meta-analysis of studies suggests a moderate benefit in children and adolescents; reduced hyperarousal, agitation, aggression, impulsivity, and sleep disturbances; useful in patients with concurrent tic disorders or conduct disorder; minimal benefit on inattentive symptoms  Hypertension (guanfacine – USA only)  Some benefit apparent in combination with stimulants; may help ameliorate sleep disturbances caused by psychostimulants (Caution – see Drug Interactions p. 310)  May improve behavior or impulsivity when used alone or in combination with methylphenidate (Caution – see Drug Interactions p. 310)  Autism – reported to be effective for reducing hyperarousal and controlling some problematic behaviors in children and adults  Menopausal flushing  Generalized anxiety disorder (GAD), panic attacks, phobic disorders, and obsessive-compulsive disorders: Of some benefit; may augment effects of SSRIs and cyclic antidepressants in social phobia; helpful for symptoms of hyperarousal, hypervigilance, aggression, and irritability of PTSD  May relieve antipsychotic-induced asthenia and improve symptoms of tardive dyskinesia  May help decrease clozapine-induced sialorrhea