Introduction to Stimulants

Stimulants (prescription, not recreational) are a class of medications commonly used to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy. Class effects include increased alertness, attention, and energy.

There are two main classes of stimulant medications: amphetamines and methylphenidate. Both classes are available in short, intermediary and long-acting preparations.

• Methylphenidate blocks dopamine and norepinephrine transporters in the presynaptic neuron, thus inhibiting reuptake and resulting in increased synaptic concentrations of these neurotransmitters.
• Amphetamines stimulate release of dopamine and, to a lesser extent, norepinephrine from presynaptic sites. It also has secondary effects with inhibition of dopamine reuptake. Relative to methylphenidate, amphetamines stimulate up to 4× more dopamine release.

3,4-Methylenedioxymethamphetamine (MDMA) commonly known as ecstasy (E), is a psychoactive drug in the amphetamine classes of drugs with both stimulant and hallucinogenic properties. Under the DSM-5, it is officially classified as a hallucinogen.

• All stimulants regardless of class will start working within 30-60 mins.

• Amphetamines are thought to block the reuptake of norepinephrine (NE) and dopamine back into the presynaptic neuron and increase the release of these monoamines into the extra neuronal space, and increase the these neurotransmitters' availability in the synaptic cleft.^[1]
• Methylphenidate is also thought to block the reuptake of norepinephrine (NE) and dopamine back into the presynaptic neuron, with a preferential effect on dopamine, thereby increasing these neurotransmitters' availability in the synaptic cleft.^[2]

• Height
  • For children being treated for ADHD, if parents/guardians are exceedingly concerned about height loss, then a stimulant may not be the best option.
• Sudden Death
  • “Before prescribing an ADHD drug, it is important to be aware of whether the patient: has a family history of sudden death or death related to cardiac problems; participates in strenuous exercise; or takes other sympathomimetic drugs; as these are thought to be additional risk factors. In patients with relevant risk factors, and based on the physician’s judgement, further evaluation of the cardiovascular system may be considered before starting on the drug.”
• Cardiac Assessment Checklist
  • Discuss with families the issue of very rare cases of sudden death in individuals taking stimulants
  • Ask in detail about the child’s cardiac history
  • Take a careful family history of cardiac disease and sudden unexplained death
  • Ask about other medications, especially sympathomimetics
  • Ask about “strenuous exercise”
  • Ensure that a physical examination (either by yourself or another physician) has been performed, including a careful cardiac examination
  • Measure baseline HR & BP
  • For patients with cardiac risk factors, pursue further evaluation or consultation (ideally with a pediatric cardiologist) before starting a stimulant
  • See also: Cardiac Risk Assessment Before the Use of Stimulant Medications in Children and Youth, A Joint Position Statement by the CPS, CCS, and CACAP (Bélanger et al., 2009)

• Baseline ECGs in children without cardiac risk factors are generally considered unnecessary (AAP, AACAP, CPS, CACAP, CCS)
• However, a history and physical exam has low sensitivity, and it is often not useful in identifying cardiac pathology. As a result, an ECG may be a more cost-effective solution than a history and physical.
• BP, HR (may increase)
• Priapism
• Growth retardation
• Peripheral vasculopathy including Raynaud’s Phenomenon

• Treatment with MAO inhibitors and for up to 14 days after discontinuation
• Symptomatic cardiovascular disease or cardiac issues
• Glaucoma
• Advanced arteriosclerosis
• Untreated hyperthyroidism
• Known hypersensitivity or allergy to the stimulant medication
• Acute psychiatric conditions such as mania or psychosis
• Moderate to severe hypertension

• History of substance abuse
• Anxiety
• Renal impairment
• Tic disorders and Tourette's (to be used cautiously)
• Epilepsy
• Peripheral vasculopathy including Raynaud’s Phenomenon
• Autism spectrum disorder

• Sympathomimetics
  • Stimulants potentiate other sympathomimetics (e.g. - Beta2-agonists)
• Benzodiazepines and antihistamines
  • Stimulants may counteract sedative effects
• Lithium
  • Stimulatory effects of amphetamines may be inhibited
• SSRIs and SNRIs – possible increased risk of serotonin syndrome
• Tricyclic antidepressants
  • The combination may enhance the effects of both the TCA and the stimulant
• Phenytoin and phenobarbital
  • AMPH may act synergistically to increase anticonvulsant activity
• Antipsychotics
  • May reduce the effect of amphetamines
• MAOIs
  • Contraindicated! Can cause hypertensive crisis
• Anticonvulsants
  • Methylphenidate may increase the level of phenytoin, primidone and phenobarbital
• St. John’s Wort
  • Has some MAOI activity
• Warfarin
  • Methylphenidate may increase serum concentrations of warfarin