Usefulness of ADHD stimulant medications for rehabilitation

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Attention Deficit/ Hyperactive Disorder (ADHD) is a complex neuropsychiatric condition which causes changes in functional and structural aspects as well as altered neurochemistry of brain. It is characterized by a persistent pattern of inattention and/or hyperactivity or impulsivity that interferes with functioning or development of skills in child. ADHD symptoms begin to show in childhood but later it can continue through adolescence and adulthood.

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ADHD is diagnosed based on DSM-5 criterias:

• A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development and have persisted for at least 6 months to a degree that is inconsistent with developmental level and that negatively impacts directly on social and academic/occupational activities.
• Several inattentive or hyperactive-impulsive symptoms were present prior to age 12 years.
• Several inattentive or hyperactive-impulsive symptoms are present in two or more settings (e.g., at home, school, or work; with friends or relatives; in other activities).
• There is clear evidence that the symptoms interfere with, or reduce the quality of, social, academic, or occupational functioning.
• The symptoms do not occur exclusively during the course of schizophrenia or another psychotic disorder and are not better explained by another mental disorder (e.g., mood disorder, anxiety disorder, dissociative disorder, personality disorder, substance intoxication or withdrawal).

The most commonly prescribed medicine category for ADHD problems in children and adults are stimulant drugs. These medicines consists of amphetamine or methylphenidate, which is a central nerves system stimulant. Non-stimulant medicines namely Atomoxetine, alpha-2 adrenergic are given to patients who don't tolerate or show benefits from stimulant medications. Some frequently used stimulant medications for ADHD are Adderall XR, Concerta, Retalin, etc. 

What is the reason behind inattention, hyperactivity or impulsivity in ADHD patients? We need to first understand the neurophysiology of ADHD brains. 

1) Brain is a highly complex structure of our body with many neural pathways that are continuously sending and receiving signals from one part of the body to brain and vice versa, thus maintaining proper functioning and balance of our body with environment. These signals are carried and transferred between nerve cells with help of neurotransmitters or chemical messenger. 

2) Research has shown that the ADHD symptoms are caused due to low levels of following neurotransmitters namely dopamine, serotonin and norepinephrine in synaptic clefts. All three are modulatory neurotransmitters. Although the exact cause is unknown, alteration in the dopamine pathway are hypothesized to play an important role. Function of these neurotransmitters are:

• Dopamine (DA) : It regulates emotional responses and take actions to achieve specific rewards. It is responsible for feeling of pleasure and rewards. DA in the brain, especially the prefrontal cortex, helps in improving working memory, attention, executive function, problem solving.
• Norepinephrine (NE) : centrally acting  NE helps to maintain and increase overall arousal (in fight or flight response), contribute to affect regulation related to excitability and response to danger or opportunity, and contribute in memory storage and retrieval, especially affect-related or emotionally intense events. 

• Serotonin (5-HT) : it regulates memory processing, sleep and wakefulness, mood, circadian rhythms, appetite, body temperature, level of aggression and anxiety.

3)  In one of the ADHD medical review panel by ADDitude, its member Larry Silver (M.D.) mentioned that ADHD brain has impaired activity in four regions of brain:

• Frontal Cortex mainly the prefrontal cortex: it control high level function  namely, attention executive function and organization.
• Limbic system: it regulates emotions and attention
• Basal Ganglia: deficiency of neurotransmitters in this region can cause inattention or impulsivity.
• Reticular Activating System: deficiency here can cause inattention, impulsivity and hyperactivity.

4) Research has shown association of  presynaptic Dopamine transporter gene (DAT1) with ADHD symptoms. Increase in number or over-expression of DAT results in lower concentration of dopamine in synaptic cleft. This leads to less number of dopamine concentration in synaptic cleft due to quick and increased re-uptake of dopamine i.e. excessively efficient dopamine- removal system. Similarly, the presynaptic norepinephrine transporter (NET) control the level of norepinephrine neurotransmitter in the synaptic cleft.

Mechanism of action of stimulant medications:

1) Methylphenidate (MPH) targets  the presynaptic dopamine transporter (DAT) and norepinephrine transporter (NET) and blocks their action of dopamine and norepinephrine re-uptake, thus maintaining and increasing their levels in synaptic clefts for more duration. Its effect on brain will depend on duration of action i.e. short-acting, intermediate-acting or long-acting type. Methylphenidate actions include dopamine and norepinephrine transporter inhibition, agonist activity at serotonin type 1A receptors. It is a pure re-uptake inhibitors. 

Fig: DAT blocking action of Methylphenidate. Increase in number and availability  of dopamine neurotransmitter for binding to postsynaptic DRD4 receptors.

2) Amphetamine (AMP) also functions similarly to methylphenidate medicine but the only difference is that amphetamine additionally functions to release dopamine and norepinephrine from the presynaptic vesicles.  A significant proportion of AMP is directly excreted in the urine (especially acidic urine), while MPH is completely metabolized.

How these medications will be beneficial for ADHD rehabilitation?

Prefrontal cortex abilities are impaired when dopamine and norepinephrine levels are too little or too high, which will lead to fatigued or stressed state respectively in patients. 

For optimal functioning of prefrontal cortex, moderate level of dopamine and norepinephrine is necessary. This will keep the patient in alert state. 

ADHD patients have too little levels of dopamine and norepinephrine in synaptic clefts, thus causing inefficient functioning of prefrontal cortex. ADHD patients face difficulties in regulating and controlling their attention, behaviour and emotions  thus showing the symptoms of inattentiveness, distractibility and impulsivity. These patients show difficulties in learning new skills, inefficient working memory, ineffective social expression, anger outburst, risk of injury while working, difficulty in recalling memory etc.

  

For patients (children/adult) with moderate to severe or uncontrollable ADHD symptoms, initially should start by taking medications. This will keep the patient in optimal functioning and alert state. Rehabilitation given in alert state will enable ADHD patients to: 

• Receive, collect and process appropriate sensory information from the environment which is required for the task completion during the therapy sessions.(Sensory Integration). 
• Be attentive in the therapy sessions and focus on the instructions of the game or task. It gives scope for patient to learn new behaviour and skills.
• Improve his gross-motor and fine-motor skills which is required to complete any daily living tasks. It allows patient to success in activities of daily living & occupations, improve quality of life.

Thankyou for reading!!!

(Dr. Sheetal Tatar-Dhande, Dr. Ashwini Sangar, Dr. Pallavi Khadse-Kolhe)

References:

• Willard and Spackman's Occupational Therapy. (11th edition)
• ADDitude: Inside the ADHD mind by Larry Silver, M.D. (2020)
• Sensory Processing Problems in Children with ADHD, a Systematic Review by Ahmad Ghanizadeh : Research Center for Psychiatry and Behavioral Sciences, 2Department of Psychiatry, Shiraz University of Medical Sciences, Hafez Hospital, Shiraz, Iran (2011)
• Arnsten, A. F., & Berridge, C. W. (2014). Catecholamine influences on prefrontal cortex circuits and function. Attention-Deficit Hyperactivity Disorder in Adults and Children, 161.
• Wilens, T. E. (2006). Mechanism of action of agents used in attention-deficit/hyperactivity disorder. Journal of Clinical Psychiatry, 67, 32.,
• Katzman M. A., & Sternat, T. (2014). A Review of OROS Methylphenidate (Concerta®) in the Treatment of Attention-Deficit/Hyperactivity Disorder. CNS drugs, 28(11), 1005–1033.
• The Roles of Dopamine and Noradrenaline in the Pathophysiology and Treatment of Attention-Deficit/Hyperactivity Disorder. Natalia del Campo, Samuel R. Chamberlain. ( BIOL Psychiatry 2011).
• Occupational Therapy for Children and Adolescents by Jane Case-Smith