CMN 554 Module 2 Study Guide Developmental and
Childhood Mental Health Disorders
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 istaken 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 priapism reported in 16-year-old each time he forgot to take his dose of extended-release methylphenidate (Concerta) 54
of 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 leads to cognitive enhancement without abuse liability; suggested to be important in regulating
areas) –
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 listatomoxetine as a second-line agent. May be effective for some patients who have Benefits includetoa
not responded
stimulant treatment, who have comorbid anxiety, or individuals who have an active comorbid substance use disorder.
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 Response is seen at 4 weeks of full dose and full optimization
population). 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
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▪ ADHD (clonidine (Kapvay) and guanfacine (Intuniv/Intuniv XR)) – meta-analysis of studies suggests a moderate benefit in
useful in patients with
children and adolescents; reduced hyperarousal, agitation, aggression, impulsivity, and sleep disturbances;
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
Autism – reported to be effective for reducing hyperarousal and controlling some problematic behaviors in children and adults
Menopausal flushing
Interactions p. 310)
▪ 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
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▪ Heroin, cocaine, and nicotine withdrawal: Used to reduce agitation, tremor, and diaphoresis, and to increase patient
comfort. Opioid antagonists (e.g., naltrexone) as well as dicyclomine (for stomach cramps) and cyclobenzaprine (for
muscle cramps) often given concomitantly
5. Target symptoms for 2 agonists
Both clonidine and guanfacine stimulate ↵ 2 -adrenergic receptors in the brain stem. This reduces sympathetic outflow from the CNS
and decreases peripheral resistance, renal vascular resistance, heart rate, and blood pressure.
6. Treating rebound symptoms from stimulants
The extended-release, sustained-release, or controlled-release formulations may decrease inter dose dysphoria or “wear off”
phenomenon (“rebound” hyperactivity). Supplementation with short-acting preparations may be needed in the morning (to speed
up onset) or in the afternoon (to extend duration of action) for some extended-release preparations with a relatively lower
proportion of immediate-release stimulant such as Concerta (all others are active within 30–60 min)
7. Baseline and Monitoring for patients on stimulants
Baseline: Height, weight, blood pressure, and pulse and repeat regularly throughout treatment. Patients with a prior or family
history of cardiac disease should be further evaluated via ECG and cardiology consult, including echocardiogram as necessary.
Cardiac evaluation recommended if patient experiences excessive increase in blood pressure or pulse, exertional chest pain, or
unexplained syncope
8. Treating ADHD medication-induced insomnia
Drug-induced insomnia [can be managed by changing dose timing or formulation based on expected duration of action; addition
of melatonin, sedating antihistamines or trazodone (25–50 mg) at bedtime or clonidine 100 micrograms given 2 h before bedtime.
When stimulants wear off at the end of the day, patient may experience rebound or a period of irritability and return of ADHD
symptoms in excess of baseline – this may cause difficulty in falling asleep
9. Treating comorbid Tic disorder and ADHD
▪ Tic disorders: research investigating increased risk of tics with the use of stimulants has yielded contradictory results.
Tics tend to wax and wane, often independent of therapy, though clinicians have commented that stimulants can
unmask tics.
▪ 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
Child and Adolescent Development
1. Five developmental domains
There are five (5) developmental domains.
The mnemonic PILES can help to remember them.
Review Sadock (2017) chapters 35.2 and 35.3 for overview of Normal Child and Adolescent Development.
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