13.5: CNS Stimulants and Nonstimulants
By the end of this section, you should be able to:
- 13.5.1 Identify the characteristics of drugs used to treat attention deficit disorders and narcolepsy.
- 13.5.2 Explain the indications, actions, adverse reactions, contraindications, and interactions of drugs used to treat attention deficit disorders and narcolepsy.
- 13.5.3 Describe nursing implications for drugs used in the treatment of attention deficit disorders and narcolepsy.
- 13.5.4 Explain the client education related to drugs used in the treatment of attention deficit disorders and narcolepsy.
Attention deficit hyperactivity disorder (ADHD) is the most common psychiatric or neurobehavioral disorder in children. ADHD is more prevalent among males than females (NIMH, 2022). Various theories have been proposed regarding the actual etiology; however, no single theory has been accepted. This condition is characterized by persistent behavior demonstrating inattention, impulsivity, and/or hyperactivity that generally presents during childhood but can persist into adulthood (American Psychiatric Association, 2022). ADHD can be divided into three subcategories: predominantly inattentive type, predominantly hyperactive-impulsive type, or combined type (NIMH, 2022).
The goal of drug therapy is to control symptoms, facilitate learning, and promote social development. Commonly used agents are CNS stimulants, which are considered the first-line treatments for ADHD. These work by increasing the brain chemicals dopamine and norepinephrine, which play essential roles in thinking and attention. If a client is unable to tolerate the stimulant agents, nonstimulating drugs can be tried. Treatment includes a combination of medications, cognitive behavioral therapy , support groups and other therapies, stress management, and academic accommodations (NIMH, 2022).
Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness and sudden periods of sleep attacks at inopportune times. The cause is not completely understood but is possibly caused by several factors including autoimmune disorders, family history, or brain trauma (National Institute of Neurological Disorders and Stroke, n.d.). This condition affects males and females equally and usually begins during the teenage or young adult years. Most clients verbalize that the excess sleepiness substantially interferes with their daily lives, including work, school, home, and social life. Cataplexy is another common feature of narcolepsy. This condition is exhibited by loss of muscle function, ranging from slight weakness to complete body collapse. These episodes are frequently triggered by strong emotional reactions, such as laughing, anger, surprise, or fear, and last a duration of a few seconds to minutes. Cataplexy can occur several times per day to a few times a year. Other clinical manifestations of narcolepsy include hypnagogic hallucinations (sleep-related hallucinations that occur when falling asleep) and sleep paralysis (temporary inability to move when falling asleep or waking). Medications and lifestyle changes can manage the symptoms of narcolepsy (National Institute of Neurological Disorders and Stroke, n.d.).
Central Nervous System Stimulants
CNS stimulants are the mainstay of ADHD therapy. Although treating ADHD with a stimulant seems paradoxical, these drugs give the client the ability to maintain attention and focus on one activity for a longer period of time. These drugs redirect and excite the arousal stimuli from the RAS. They also help clients increase goal-oriented behavior. The impulsiveness and hyperactivity decline because clients are now able to concentrate on the task at hand. These drugs work by increasing the release of catecholamines from presynaptic neurons. In addition, amphetamines block the reuptake of NE and dopamine, which further increases their concentration so more of the drug can bind to the postsynaptic neuron. It is valuable to know that if one stimulant is ineffective, another should be tried before considering a nonstimulant.
The dosing schedule is important and is determined by the time course of the formulation selected. Most of these are available in immediate-release (IR), sustained release (SR), and 24-hour formulations. Most are controlled substances, and education should be provided to ensure these are not inappropriately used or distributed.
The most common CNS stimulants are:
- Methylphenidate (Class II controlled substance): This medication is a first-line treatment for ADHD and a second-line treatment for narcolepsy.
- Amphetamine/dextroamphetamine (Class II controlled substance): This is a mixed-salt drug available in IR and ER formulations. The mechanism of action is to mediate CNS stimulation through the release of norepinephrine and dopamine. This is the only FDA-approved stimulant for use in children under age 3.
- Dextroamphetamine: This drug releases NE from nerve terminals and increases the amounts of NE, dopamine, and serotonin.
- Lisdexamfetamine: This is a prodrug of dextroamphetamine. It is used only in the treatment of ADHD and, recently, binge-eating disorders among adults. It is not approved for use in narcolepsy or as a weight-loss measure.
- Methamphetamine: This is a highly addictive drug used to treat ADHD and narcolepsy. It is frequently used recreationally, and it is at high risk of being obtained and distributed for nontherapeutic uses.
- Dexmethylphenidate: This drug is used to treat ADHD in clients age 6 and older. As with all stimulants, pediatric clients taking this medication should be monitored for evidence of hindered growth and development.
- Modafinil (Class IV controlled substance): This drug improves wakefulness in clients with excessive daytime sleepiness associated with narcolepsy or shift-work sleep disorder and is used as an adjunctive therapy for obstructive sleep apnea/hypopnea syndrome. The drug can also be used to treat ADHD. Clients need to be aware that this drug can decrease the effectiveness of oral contraceptives.
- Pitolisant: This is an H3 (histamine) blocker, not a controlled substance. It is used to treat excessive daytime sleepiness caused by narcolepsy and to treat cataplexy in adults with narcolepsy.
Table 13.23 lists common CNS stimulants and typical routes and dosing for adult and pediatric clients .
| Drug | Routes and Dosage Ranges |
|---|---|
|
Methylphenidate
( Concerta , Ritalin , Daytrana ) |
ADHD:
Adults: Immediate release: Initial dose: 10–60 mg daily in 2–3 divided doses. Extended release: Initial dose: 20 mg in the morning; maximum dose: 60 mg/day. Transdermal: Apply 10 mg patch to hip 2 hours before effect is needed. Remove 9 hours after application. Children ≥6 years: Immediate release: 5 mg twice daily. Narcolepsy: Immediate release: Initial dose: 10 mg 2–3 times/day. Maximum dose: 60 mg/day. |
|
Amphetamine and dextroamphetamine
( Adderall ) |
ADHD:
Adults: Immediate release: Initial dose: 5 mg 1–2 times/day. Maximum dose: 40 mg/day. Extended release: Initial dose: 20 mg in the morning. Maximum dose: 60 mg/day. Children 3 –5 years: Immediate-release: 2.5 mg/day; maximum dose: 30 mg/day. Children ≥6 years: Immediate-release : 5 mg 1–2 times per day. Extended-release: 5–10 mg/day; maximum dose: 30 mg/day. Narcolepsy: Adults and children >12 years: Immediate release: Initial dose: 10 mg/day; maximum dose: 60 mg/day. Children 6 –12 years: Initial dose: 5 mg/day. |
|
Dextroamphetamine
( Xelstrym ) |
ADHD:
Adults: Initial dose: 9 mg/9 hours transdermally. Maximum dose: 18 mg/9 hours. Apply transdermally 2 hours before an effect is needed and remove within 9 hours. Children (6–17 years): Initial dose: 4.5 mg/9 hours transdermally. Titrate dosage in weekly increments of 4.5 mg up to a maximum recommended dose of 18 mg/9 hours. |
|
Lisdexamfetamine
( Vyvanse ) |
ADHD:
Adults and children ≥6 years: Initial dose: 30 mg/day in the morning; may increase by 10–20 mg at weekly intervals until optimal response is reached. Maximum dose: 70 mg/day. |
|
Methamphetamine
( Desoxyn ) |
ADHD:
Adults and children ≥6 years: Initial dose: 5 mg 1–2 times daily. Usual effective dose: 20–25 mg/day in 2 divided doses. |
|
Dexmethylphenidate
( Focalin ) |
ADHD:
Adults and children ≥6 years: Initial dose: 2.5 mg orally twice daily, 4 hours apart; maximum dose: 10 mg twice daily. |
|
Serdexmethylphenidate and dexmethylphenidate
( Azstarys ) |
ADHD:
Adults and children 13– 17 years: Initial dose: 39.2 mg/7.8 mg/day in the morning; dosage may be increased after 1 week to 52.3 mg/10.4 mg/day. Children 6– 12 years: Initial dose: 39.2 mg/7.8 mg orally once daily in the morning; dosage may be increased to 52.3 mg/10.4 mg daily or decreased to 26.1 mg/5.2 mg daily after 1 week. Maximum dose: 52.3 mg/10.4 mg/day. |
|
Modafinil
( Provigil ) |
ADHD:
Initial dose: 100–300 mg/day. Narcolepsy and obstructive sleep apnea/hypopnea syndrome: Initial dose: 200 mg/day taken in the morning. Shift-work sleep disorder: Initial dose: 200 mg/day taken 1 hour prior to shift work. Dose must be reduced by 50% in clients with severe hepatic impairment. |
|
Pitolisant
( Wakix ) |
Narcolepsy:
Adults and children ≥ 13 years: Administer once daily in the morning. Recommended dose: 17.8–35.6 mg/day orally. Week 1: Initiate with 8.9 mg/day orally. Week 2: Increase dose to 17.8 mg/day orally. Week 3: May increase to the maximum recommended dosage of 35.6 mg/day orally. |
Safety Alert
Similarly Named Drugs Associated with CNS Stimulants
Do not confuse Adderall (CNS stimulant) with Inderal ( beta blocker ).
(Source: ISMP, 2023)
Adverse Effects and Contraindications
A client must use CNS stimulants with caution when pregnant and taking stimulants. Premature delivery and low birth weight have occurred in infants born to a parent taking these drugs.
Stimulants are contraindicated in glaucoma, hyperthyroidism, and the spectrum of cardiovascular diseases because they can exacerbate these conditions. Individuals with a history of drug or alcohol use disorder/dependence should avoid these drugs because they have a high potential for physical and psychological dependence. Sudden cardiac arrest has occurred with the use of CNS stimulants. Studies have shown that the majority of these cases occurred in children with an undocumented cardiac defect. It is now recommended to obtain a baseline electrocardiogram (ECG, EKG) before beginning this therapy. To reduce the risk of insomnia, these medications should be taken in the morning or early afternoon. If a client has been diagnosed with a psychiatric disorder, they should avoid the CNS stimulants because they can worsen the preexisting psychiatric disorder. Motor and verbal tics can be intensified with the CNS stimulants, so it is essential to identify if there is a family history or personal diagnosis of Tourette syndrome.
The effects of phenytoin and tricyclic antidepressants (TCAs) are increased by the CNS stimulants. Also, lisdexamfetamine should not be used concurrently with TCAs or meperidine because it can potentiate the effects of these drugs, increasing the risk of adverse effects. MAOIs are contraindicated if currently taking or within 14 days of receiving the last dose because both CNS stimulants and MAOIs can drastically increase blood pressure. The effects of alpha-1 adrenergic blockers can be reduced or negated by the CNS stimulants.
Table 13.24 is a drug prototype table for CNS stimulants featuring methylphenidate. It lists drug class, mechanism of action, adult and pediatric dosage , indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
CNS stimulant (Class II controlled substance) Mechanism of Action Blocks the reuptake of norepinephrine and dopamine in specific areas of the brain |
Drug Dosage
ADHD: Adults: Immediate release: Initial dose: 10–60 mg daily in 2–3 divided doses. Extended release: Initial dose: 20 mg in the morning; maximum dose: 60 mg/day. Transdermal: Apply 10 mg patch to hip 2 hours before effect is needed. Remove 9 hours after application. Children ≥6 years: Immediate release: 5 mg twice daily. Narcolepsy: Immediate release: Initial dose: 10 mg 2–3 times/day. Maximum dose: 60 mg/day. |
|
Indications
ADHD Narcolepsy Traumatic brain injury (TBI) Therapeutic Effects Enhances dopamine and NE actions in certain brain regions to improve attention, concentration, and wakefulness Enhancement of dopamine in the basal ganglia may improve hyperactivity |
Drug Interactions
Concomitant use of MAOIs or within 14 days of MAOI use Alpha-1 adrenergic blockers Phenytoin Tricyclic antidepressants Meperidine Food Interactions Alcohol Caffeine |
|
Adverse Effects
Insomnia Headaches/seizures Heart palpitations/tachyarrhythmias Angina Sudden cardiac death CVA Hypertension Leukopenia and anemia Hyperhidrosis Irritability/nervousness Anorexia/weight loss Potential for dependence and misuse Suppression of growth in children with long-term use Exacerbation of preexisting or emergence of new psychiatric disorders such as psychosis or mania Contact dermatitis with transdermal application |
Contraindications
Advanced arteriosclerosis Symptomatic cardiovascular disease Congenital cardiac structural abnormalities Recent MI or angina Severe hypertension Heart failure Arrhythmias Hyperthyroidism Glaucoma History of substance use History of psychiatric disorders Family history or personal diagnosis of Tourette syndrome Caution: Pregnancy/breastfeeding Seizures |
CNS Nonstimulants
These alternative drugs for ADHD and narcolepsy are not associated with the many cardiac and systemic stimulatory effects experienced with the CNS stimulants. They are preferable in clients who are unable to tolerate the stimulatory effects of the other drugs. The most common CNS nonstimulant s are:
- Atomoxetine: This is an SNRI with anticholinergic effects used to treat ADHD. It inhibits reuptake of NE in nerve synapses. It has little risk for abuse and dependence; therefore, it is not a controlled substance.
- Guanfacine: This is a selective alpha-2 adrenergic agonist. It is not a controlled substance. Guanfacine does not produce CNS stimulation but instead can cause significant CNS depression. As an alpha-2 agonist, sympathetic nerve impulses are reduced. Furthermore, it binds specifically to postsynaptic alpha-2A adrenoreceptors in the prefrontal cortex. As a result, working memory and behavioral inhibitions are affected, which improves symptoms associated with ADHD.
- Clonidine: This is an alpha-2 adrenergic agonist. The mechanism of action in ADHD is unknown.
- Viloxazine: This drug is a selective NE reuptake inhibitor for the treatment of ADHD in adults and pediatric clients age 6 and older.
- Solriamfetol: This drug is a dopamine and norepinephrine reuptake inhibitor (DNRI) that improves daytime wakefulness in adult clients with narcolepsy or obstructive sleep apnea (OSA).
- Sodium oxybate (Class III controlled substance): This is the first once-at-bedtime medication for people with narcolepsy. The extended-release formulation treats cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy. It has not been tested in children or pregnant individuals; therefore, it must be avoided in these populations. This CNS depressant drug is the sodium salt of gamma-hydroxybutyrate (GHB). Abuse or misuse of illicit GHB is associated with CNS adverse reactions, including seizure, respiratory depression, decreased consciousness, coma, and death. It is available only through a restricted program called the Lumryz REMS. It is contraindicated in combination with sedative-hypnotics or alcohol. Adverse effects include depression and suicidality, confusion/anxiety, and parasomnias . Ingesting high sodium content while taking this drug can exacerbate heart failure or hypertension or further impair renal function.
Table 13.25 lists common CNS nonstimulants and typical routes and dosing for adult and pediatric clients .
| Drug | Routes and Dosage Ranges |
|---|---|
|
Atomoxetine
( Strattera ) |
Adults and children >70 kg:
40 mg/day orally. Gradually increase to a target daily dose of 80 mg. Maximum dose: 100 mg/day.
Children ≤70 kg: Initial dose: 0.5 mg/kg/day; target dose: 1.2 mg/kg/day; maximum dose: 1.4 mg/kg/day. |
|
Guanfacine
( Intuniv ) |
Adults and children ≥6 years: Extended-release tablet: Initial dose: 1 mg/day; maximum dose: 4–7 mg/day. |
|
Clonidine
( Kapvay ) |
Adults and children >6 years: Initial dose: 0.1 mg/day tablet at bedtime for 1 week. Increase daily dosage in increments of 0.1 mg/day each week until desired response is achieved. |
|
Viloxazine
( Qelbree ) |
Adults:
Initial dose: 200 mg/day orally; increase dose as needed and tolerated; maximum dose: 600 mg/day.
Children 12–17 years: Initial dose: 200 mg/day orally; increase dose as needed and tolerated; maximum dose: 400 mg/day. Children 6–11 years: Initial dose: 100 mg/day orally; increase dose as needed and tolerated; maximum dose: 400 mg/day. Children <6 years: Use and dose must be determined by the provider. |
|
Solriamfetol
( Sunosi ) |
Narcolepsy:
Initial dose: 75 mg/day orally; maximum dose: 150 mg/day orally. Sleep apnea: Initial dose: 37.5 mg/day orally; maximum dose: 150 mg/day orally. Adults: Administer once daily upon awakening. Avoid administration within 9 hours of planned bedtime due to potential to interfere with sleep. Children: Safety and effectiveness have not yet been established. |
|
Sodium oxylate
( Lumryz ) |
Narcolepsy:
Initial dose: 4.5 g orally once nightly; titrate in increments of 1.5 g per night at weekly intervals. Recommended dose: 6–9 g once per night orally. |
Adverse Effects and Contraindications
Adverse effects seen with atomoxetine are mainly related to its anticholinergic effects. These include dry mouth, blurred vision, nausea, constipation, and urine retention. Guanfacine and clonidine can cause sedation, severe hypotension, and bradycardia. Antihypertensives and CNS depressants are contraindicated with these due to the additive effects they can have on blood pressure and sedation. Taking guanfacine with a high-fat meal can cause increased absorption of the drug.
TCAs can increase blood pressure and may counteract clonidine’s hypotensive effects. Monitor blood pressure and adjust as needed. Antihypertensive agents will potentiate the hypotensive effects of clonidine. CNS depressants can potentiate sedating effects. It is recommended to avoid concomitant use. Digoxin, calcium channel blockers, and beta blockers should not be used in conjunction with clonidine because they can exacerbate bradycardia and AV block.
Safety Alert
Similarly Named Drugs Associated with CNS Nonstimulants
Do not confuse Intuniv (CNS nonstimulant) with Invega ( antipsychotic ).
(Source: ISMP, 2023)
Table 13.26 is a drug prototype table for CNS nonstimulants featuring clonidine. It lists drug class, mechanism of action, adult and pediatric dosage , indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
CNS nonstimulant, alpha-2 adrenergic agonist Mechanism of Action Unknown |
Drug Dosage
Adults and children >6 years: Initial dose: 0.1 mg/day tablet at bedtime for 1 week. Increase daily dosage in increments of 0.1 mg/day each week until desired response is achieved. |
|
Indications
ADHD as a monotherapy or as an adjunct to a CNS stimulant Therapeutic Effects Reduces sympathetic outflow from the CNS |
Drug Interactions
Tricyclic antidepressants Antihypertensive agents CNS depressants Drugs that affect sinus node function or AV node conduction (digoxin, calcium channel blockers, and beta blockers) Food Interactions No significant interactions |
|
Adverse Effects
Hypotension Bradycardia/syncope Sedation Rebound hypertension with abrupt withdrawal Allergic reactions (generalized rash, angioedema) |
Contraindications
Hypersensitivity to any of the ingredients Caution: Heart block Cardiovascular disease Cerebrovascular disease Chronic renal failure |
Nursing Implications
The nurse should do the following for clients who are taking CNS stimulants and nonstimulants:
- Screen and monitor client’s cardiovascular risk factors, such as family history, smoking, elevated lipids, hypertension, diabetes mellitus, and obesity.
- Assess client’s psychiatric history.
- Measure and document blood pressure readings, heart rate, weight, food intake, and amount of uninterrupted sleep.
- Obtain a baseline ECG prior to beginning therapy and during episodes of chest pain or palpitations.
- Provide drug holidays to children for the purpose of determining the need for continued treatment and allow for “catch-up” growth.
- Monitor for improved attention span and task performance in both children and adults.
- Observe for a decrease in hyperactivity in children along with functioning appropriately during social interactions with other children.
- Assess for fewer sleep episodes during normal waking hours.
- Ensure nutritional needs are being met.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking a CNS stimulant or nonstimulant should:
- Report chest pain, difficulty breathing, fainting, abnormal thinking or behavior, increased aggression, hallucinations, and unintended weight loss.
- Take immediate-release tablets, chewable tablets, and solution 30–45 minutes before meals.
- Drink at least 8 oz of water with chewable tablets to avoid choking.
- Weigh self at least once a week.
- Be cognizant of caloric and nutrient intake to avoid excessive weight loss.
The client taking a CNS stimulant or nonstimulant should not:
- Chew or crush sustained- or extended-release formulations.
- Take a CNS stimulant after 6 p.m or less than 6 hours before bedtime.
- Take less than 1 tablet per day.
- Take guanfacine with a high-fat meal.
- Take more than prescribed or distribute to others.
- Drive or participate in any activities that require alertness until the effects of nonstimulants are known.
FDA Black Box Warning
CNS Stimulants and Nonstimulants
Atomoxetine, viloxazine: In clinical studies, higher rates of suicidal thoughts and behavior were reported in clients with ADHD treated with atomoxetine or viloxazine than in clients treated with placebo.
Dextroamphetamine, lisdexamfetamine , and dexmethylphenidate have a high misuse potential.
Sodium oxybate has a risk of causing clinically significant respiratory depression. This medication also has a high risk of abuse or misuse.