From the Guidelines
The primary mechanism of action of stimulant medications in ADHD is the inhibition of dopamine and norepinephrine transporters, leading to an increase in the levels of these neurotransmitters in the brain, particularly in the prefrontal cortex, thereby enhancing executive and attentional function. This is achieved through the actions of medications like methylphenidate and amphetamine, which not only inhibit the reuptake of dopamine and norepinephrine but also, in the case of amphetamines, inhibit vesicular monoamine transporter 2 and monoamine oxidase activity 1. By enhancing the impact of dopamine and norepinephrine, psychostimulants increase the efficiency of prefrontal cortex activity, which is crucial for executive functions such as attention, impulse control, and working memory, typically impaired in ADHD 1.
The specific actions of methylphenidate include dopamine and norepinephrine transporter inhibition, agonist activity at the serotonin type 1A receptor, and redistribution of the vesicular monoamine transporter 2 1. Amphetamine's actions, on the other hand, include the inhibition of dopamine and norepinephrine transporters, vesicular monoamine transporter 2, and monoamine oxidase activity 1. These mechanisms collectively contribute to the therapeutic effects of stimulant medications in ADHD, allowing for improved focus, reduced impulsivity, and better control over symptoms.
Key aspects of stimulant medications in ADHD management include their formulation, with both short-acting and long-acting options available, each with its own advantages and considerations regarding medication adherence, flexibility, and potential for rebound effects 1. The choice of formulation should be tailored to the individual patient's symptom profile and needs, taking into account the pharmacokinetic profiles of different formulations 1.
While stimulant medications are generally well-tolerated, they can be associated with adverse effects such as decreased appetite, sleep disturbances, and increases in blood pressure and heart rate 1. Monitoring of pulse and blood pressure is recommended, especially for patients with preexisting cardiovascular diseases 1. Additionally, there is evidence suggesting that long-term treatment with psychostimulants may be associated with reductions in height and weight gain, although these effects are typically minor and dose-related 1.
In clinical practice, the benefits of stimulant medications in managing ADHD symptoms often outweigh the risks, particularly when carefully monitored and managed by a healthcare professional. The primary goal is to improve the patient's quality of life, reduce morbidity, and minimize mortality risks associated with untreated or undertreated ADHD. Therefore, the use of stimulant medications, when appropriately prescribed and monitored, is a crucial component of ADHD management, offering significant benefits in terms of symptom control and improvement in executive and attentional functions.
From the FDA Drug Label
Methylphenidate hydrochloride is a central nervous system (CNS) stimulant. ... Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases the release of these monoamines into the extraneuronal space The primary mechanism of action of stimulant medications like methylphenidate in ADHD is:
- Blocking the reuptake of certain neurotransmitters, specifically:
- Norepinephrine
- Dopamine
- Increasing the release of these neurotransmitters into the extraneuronal space 2
From the Research
Mechanism of Action of Stimulant Medications in ADHD
The primary mechanism of action of stimulant medications in ADHD involves the increase of central dopamine and norepinephrine activity, which impacts executive and attentional function 3. This is achieved through various pharmacologic effects, including:
- Dopamine and norepinephrine transporter inhibition 3, 4, 5
- Vesicular monoamine transporter 2 (VMAT-2) inhibition and redistribution 3, 4
- Monoamine oxidase activity inhibition 3
- Agonist activity at the serotonin type 1A receptor 3
Key Findings
Key findings from studies on the mechanism of action of stimulant medications in ADHD include:
- Methylphenidate exhibits a multimodal mechanism of action, working primarily as a dopamine and noradrenaline reuptake inhibitor 4
- Amphetamine actions include dopamine and norepinephrine transporter inhibition, VMAT-2 inhibition, and monoamine oxidase activity inhibition 3
- Stimulant medications produce symptomatic improvement via both common and divergent neurophysiologic actions in frontoparietal regions implicated in the pathophysiology of ADHD 6
Neurochemical Basis of ADHD
The neurochemical basis of ADHD is thought to involve a dopamine/norepinephrine deficit, with medications such as methylphenidate, amphetamine, and atomoxetine indicating this deficit 7. However, the etiology of ADHD is more complex, and the exact mechanisms of action of these medications are not fully understood.