Adult ADHD Medications

Attention deficit/hyperactivity disorder (ADHD) is a mental health disorder that is usually diagnosed during childhood. According to The American Psychiatric Association, 5% of children in the U.S. have ADHD, although studies have reported rates as high as 11%. Childhood ADHD persists into adulthood ADHD for about 50% of individuals.

Adults with ADHD may have symptoms of restlessness, inattention, and impulsive behavior. Impairment in executive function, as well as social, emotional and vocational wellbeing is also common. Adults with ADHD often have difficulty with time management and prioritizing, completing, and focusing on tasks.

According to the National Comorbidity Survey Replication, a nationwide household survey of 18 to 44 year-olds, 4.4% of adults in the U.S. have ADHD. Surveys conducted by the National Institutes of Health report a prevalence of 3 to 5%, with comparable rates between men and women.

It's been noted that all adults with ADHD had ADHD as children, but not diagnosed. ADHD tends to be underdiagnosed in adults; fewer than 20% of adults with ADHD have been diagnosed or treated. This is due to a lack of awareness as well as the presence of certain disorders such as mood and anxiety in adults with ADHD. When ADHD symptoms are mistaken for these disorders, adults are more likely to be treated for the disorders rather than for ADHD.

Treatment options for ADHD include medications (stimulant and non-stimulant) and cognitive-behavioral therapy.

ADHD medications are drugs used to treat some of the characteristic behaviors associated with attention deficit hyperactivity disorder, including inattention, hyperactivity, and poor impulse control.

• Drugs used to treat ADHD target chemicals in the brain known as neurotransmitters.
• Most ADHD medications work by increasing levels of the neurotransmitters dopamine and norepinephrine.
• Another type of ADHD drug increases the level of norepinephrine only.

ADHD drug treatment should begin only after a specific diagnosis of ADHD has been made.

• A clinical diagnosis requires that symptoms have persisted for at least six months.
• In addition, diagnosis of adult ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) requires that some of the ADHD symptoms were present during childhood (before 12 years of age).
• There is no blood test or radiological scan that can diagnose ADHD.

Some stimulant ADHD medications are used for treating both ADHD and narcolepsy, a condition in which there is excessive daytime One non-stimulant medication, atomoxetine (Strattera), is indicated only for ADHD.

Other non-stimulant ADHD medications include Kapvay (extended-release clonidine) and Intuniv (extended-release guanfacine).

• Kapvay and Intuniv are FDA-approved to treat ADHD in children and adolescents 6 to 17 years old.
• However, they have not been studied extensively in adults and are therefore not FDA-approved for adult ADHD treatment. However, a small placebo-controlled, double-blinded crossover study showed a possible benefit of using immediate-release guanfacine to treat ADHD in adults.
• Immediate-release clonidine and guanfacine are indicated for high blood pressure.
• In addition, medications used to treat depression, including tricyclic antidepressants (amitriptyline, imipramine) as well as bupropion (Wellbutrin), may be used in ADHD treatment.

ADHD medications can generally be split into two categories:

• the stimulants and
• the non-stimulants.

Stimulant drugs used for ADHD include various amphetamines and methylphenidates.

• Amphetamines and methylphenidates increase the levels of the neurotransmitters, dopamine, and norepinephrine in the brain.
• Both drugs also inhibit monoamine oxidase (MAO), an enzyme that breaks down dopamine and norepinephrine.

Non-stimulant drugs such as Atomoxetine (Strattera) works by increasing levels of norepinephrine.

The tricyclic antidepressants and bupropion (Wellbutrin) are not FDA-approved for the treatment of ADHD but are often used off-label.

• The tricyclic antidepressants affect levels of norepinephrine while bupropion affects levels of both norepinephrine and dopamine.
• Imipramine and desipramine are the most commonly used tricyclic antidepressants.
• However, nortriptyline is also effective.

Atomoxetine (Strattera)

Antidepressants

• Tricyclic antidepressants (imipramine, desipramine, nortriptyline)
• buproprion (Wellbutrin)

Although just a handful of compounds specifically target ADHD, numerous dosage forms exist. The main variable between these is the duration of action- that is, how long the drug works.

• Short-acting stimulant drugs usually last four to five hours and are usually taken two to three times a day.
• Long-acting versions are effective from six to eight or even 12 hours.

Atomoxetine has a 24-hour duration of action. It also differs from stimulants in that it is not a potential drug of abuse and, therefore, not a controlled substance.

Selection of an ADHD medication selection depends on patient-specific factors as well as drug side effects, interactions, and existing conditions. However, stimulant medications have more evidence of use and are more effective than non-stimulants.

Stimulants have the fastest onset of effect, usually within 1 to 2 hours of an effective dose. If there is a poor response to one stimulant, for instance, methylphenidate, another stimulant such as dextroamphetamine may be tried.

Although non-stimulants are less effective than stimulants, they have no potential for abuse.

Atomoxetine has a slower onset of effect, about 2 to 4 weeks. However, the full effect may take 6 to 8 weeks to occur.

Guanfacine causes more sedation than stimulants and atomoxetine. Its duration of action is 18 hours.

The stimulants share common side effects. Most common among them is their potential for abuse. When doses of methylphenidate or amphetamines start low and are slowly increased, the result is a slow rise in brain dopamine levels. That pattern of therapeutic use is unlikely to trigger enticing side effects, such as euphoria. However, taken inappropriately, brain dopamine levels soar -- as does the risk for addiction.

To help prevent abuse, the government has put limits on how much of the medication can be dispensed at one time, and how often it can be dispensed.

The main side effects of stimulant medications are

• problems sleeping,
• decreased appetite, and
• headache.

Other side effects of methylphenidates and amphetamines include:

• Cardiac problems, including palpitations, increased heart rate, changes in blood pressure, chest pain, sudden death
• Neurologic problems including hallucinations, psychosis, tics, Tourette's syndrome, seizure
• Other effects such as skin rash, vision problems, and nausea

The side effects associated with atomoxetine (Strattera) include:

• Gastrointestinal effects such as dry mouth, nausea, abdominal pain, vomiting, and serious liver problems
• Suicidal thinking, headache, sleepiness, dizziness, irritability, change in libido, erectile and ejaculatory dysfunction, menstrual changes, decrease in appetite and, urinary dysfunction

Guanfacine (Tenex) can have the following side effects:

• Dry mouth
• Sleepiness
• Dizziness
• Constipation
• Fatigue

Side effects associated with tricyclic antidepressants include:

• Suicidal thoughts
• Dry mouth and nose
• Blurry vision
• Constipation
• Urinary retention
• Cognitive/memory impairment
• Low blood pressure, rapid heartbeat, and possibly arrhythmias
• Drowsiness, confusion, restlessness, dizziness
• Sexual dysfunction

Bupropion (Wellbutrin) may produce the following side effects:

• Suicidal thoughts
• Gastrointestinal problems, including dry mouth, constipation, nausea, vomiting, weight loss, weight gain, and anorexia
• Neurologic problems, including headache, insomnia, sedation, and agitation
• Blurry vision
• Tremor
• Excessive sweating
• Increased heart rate

Before starting any medication, a doctor should know a patient's full medical history such as drug allergies, medical conditions, current medication use, and whether the patient is pregnant, trying to get pregnant, or nursing.

• With stimulants, there is the risk of sudden cardiac death, especially in patients with existing structural abnormalities. These medications may exacerbate psychosis in patients. Stimulants, as mentioned earlier are potential drugs of abuse.
• Atomoxetine can also cause severe liver injury. Signs of liver injury include abnormal liver function tests, jaundice, dark urine, itching, and tenderness in the liver area of the abdomen. Patients with high blood pressure or cardiac abnormalities should be closely observed while on atomoxetine as it can increase blood pressure and heart rate.
• Painful and prolonged erections may occur in adult male patients using atomoxetine. Prompt medical attention is needed for this condition, known as priapism. Using atomoxetine may cause urinary retention or hesitancy. Patients taking atomoxetine should be monitored for possible drug-induced changes in perception and behavior, including hallucinations, delusions, mania, aggressiveness, or hostility.
• Caution is especially advised in patients with bipolar disorder.
• Guanfacine can cause drowsiness. Patients should use caution if driving or engaging in activities that require alertness. It should also be used in caution in patients with pre-existing cardiac or renal disease, or severe hepatic disease.
• Tricyclic antidepressants (TCAs) may increase suicidal thinking and behavior, and death may occur with an overdose of these drugs. TCAs should not be used in patients immediately following a heart attack and should always be used with caution in those with pre-existing cardiac issues. TCAs may affect blood sugar levels. Some TCAs heighten sensitivity to sunlight, and so patients should avoid excessive exposure.
• When taking bupropion, patients should be monitored for changes in behavior, worsening of their conditions, and/or suicidal thoughts. Bupropion may trigger seizures, especially at higher doses. It may also trigger seizures in normal doses in patients who have or have had anorexia nervosa or bulimia. Its use in those patients is contraindicated. Doses of bupropion should be reduced in patients with kidney or liver disease. Bupropion should not be used in patients abruptly stopping alcohol or sedative use.

Contraindications and Black Box Warnings for Stimulants

Contraindications

• Administration of stimulants can lead to physical and psychological drug dependence. Therefore methamphetamine is contraindicated in patients with a history of alcoholism.
• Dexmethylphenidate and methylphenidate are contraindicated in patients with anxiety since they can worsen this condition.
• Dextroamphetamine/amphetamine, dextroamphetamine, and methamphetamine are contraindicated for use in patients with arteriosclerosis due to the risk of sudden death.
• Methamphetamine and methylphenidate are contraindicated for use in patients with cardiac disease. These stimulants can cause an increase in blood pressure and heart rate and can lead to myocardial infarction and sudden unexplained death (SUD). Methamphetamine also has a Black Box Warning for this reason.
• Dextroamphetamine/amphetamine, dextroamphetamine, dexmethylphenidate, methamphetamine, and methylphenidate are contraindicated in people with glaucoma due to the risk of visual disturbances and blurred vision. This is because stimulants can block the outflow of aqueous humor (eye fluid) and increase intraocular pressure.
• Atomoxetine is contraindicated in closed-angle glaucoma due to the risk of mydriasis (pupil dilation).
• Methylphenidate (Metadate CD) contains sucrose and is contraindicated in patients with hereditary fructose intolerance, glucose-galactose malabsorption, and sucrase-isomaltase insufficiency.
• Stimulation of the sympathetic nervous system by dextroamphetamine/amphetamine, dextroamphetamine, methamphetamine, and methylphenidate can cause cardiac arrhythmias. Therefore, they are contraindicated for use in patients with hyperthyroidism.
• Atomoxetine, dextroamphetamine/amphetamine, dextroamphetamine, dexmethylphenidate, lisdexamfetamine, and methamphetamine are contraindicated with concurrent use or use within 14 days of MAOI therapy since the increase of norepinephrine in neuronal storage sites can cause hypertensive crisis. (MAOI – monoamine oxidase inhibitors) such as selegiline.
• Atomoxetine is contraindicated in patients with pheochromocytoma. Atomoxetine can cause serious reactions, including increased blood pressure and tachyarrhythmia in these patients.
• Dextroamphetamine/amphetamine, dextroamphetamine, and methamphetamine are contraindicated in patients with a history of substance abuse since stimulants can cause physical and psychological drug dependence. Dextroamphetamine/amphetamine and dextroamphetamine also have a Black Box Warning for this reason.
• Dexmethylphenidate and methylphenidate are contraindicated in patients with tics or Tourette's syndrome (including a family history of Tourette's syndrome) since they may worsen these conditions.

Black Box Warnings

• Dexmethylphenidate and methylphenidate should be used cautiously in patients with a history of alcoholism because prolonged administration can lead to physical and psychological drug dependence.
• Dextroamphetamine/amphetamine, dextroamphetamine, and methamphetamine should not be used in patients with cardiac disease. These stimulants can increase blood pressure and heart rate and lead to myocardial infarction and sudden unexplained death (SUD).
• Dextroamphetamine/amphetamine, dexmethylphenidate, lisdexamfetamine, and methylphenidate should be used cautiously in patients with a history of substance abuse because prolonged administration can lead to physical and psychological drug dependence. Dextroamphetamine/amphetamine has a high potential for abuse and is contraindicated for use in this setting.

General

• Methylphenidate and atomoxetine have been associated with priapism.
• Patients should be counseled on the signs and symptoms of priapism and seek immediate medical attention if an erection lasts more than 4 hours.

Adult patients with an anxiety disorder, as well as ADHD, should be first treated for the primary condition. ADHD symptoms should be treated if they still persist after the resolution of anxiety symptoms. However, it is important to first investigate whether the anxiety symptoms are a result of ADHD. In this case, effective treatment of ADHD would most likely resolve the anxiety as well. However, there is conflicting data on whether stimulant medications can improve anxiety symptoms.

• A study of 42 patients with ADHD and comorbid anxiety found that treatment with methylphenidate had a beneficial effect on anxiety symptoms.
• However other studies have shown that stimulants have no effect on anxiety.

ADHD medications such as methamphetamine, methylphenidate, and atomoxetine can increase blood pressure and heart rate and lead to myocardial infarction and sudden unexplained death (SUD). Although they are contraindicated for use in patients with cardiac disease, hypertension is a precaution, not an absolute contraindication.

• If the elevation of blood pressure occurs while taking these medications, the dose may need to be reduced or the medication may need to be discontinued.
• Treatment with an antihypertensive medication may also be necessary.
• Periodic blood pressure and heart rate monitoring are recommended in all patients taking methylphenidate.
• For atomoxetine, blood pressure and heart rate testing is recommended when starting therapy, after an increase in doses, and periodically throughout therapy.
• There are no specific guidelines recommending certain medications for adults with ADHD and high blood pressure.

Absorption and excretion of amphetamines -- and therefore blood levels --- are affected by pH. Fruit juices, vitamin C, and some drugs (guanethidine, reserpine) acidify the stomach, decreasing absorption. Alkalinizing agents, such as antacids, increase amphetamine absorption.

• Amphetamines should not be used along with tricyclic antidepressants or decongestants.

A 14-day clearing period is required between the use of a Monoamine Oxidase Inhibitor (MAOI) and amphetamine. Otherwise, severe hypertension may occur.

Methylphenidate should not be used within 14 days of using an MAOI. Otherwise, a hypertensive crisis might occur. Because it raises blood pressure and heart rate, methylphenidate should be used with caution with other drugs that can affect blood pressure and heart rate. Dosage adjustment may be necessary for:

• Warfarin (Coumadin)
• Phenytoin (Dilantin)
• Antidepressants (tricyclics and selective serotonin reuptake inhibitors)

Atomoxetine should not be used within 14 days of an MAOI, otherwise severe, possibly fatal reactions could occur. Increases in heart rate and blood pressure may occur if atomoxetine is administered with other medications that can increase heart rate or blood pressure.

The sedative effect of alcohol, barbiturates, or other drugs may be increased by guanfacine.

Bupropion should not be used within 14 days of an MAOI. Medications that can interact with bupropion include:

• Tricyclic and SSRI antidepressants (nortriptyline, desipramine, imipramine, norfluoxetine, sertraline, paroxetine, fluvoxamine)
• Atomoxetine (Strattera)
• Stimulants
• Anticonvulsants (carbamazepine, phenytoin, phenobarbital)
• Antipsychotics (haloperidol, risperidone, thioridazine)
• Beta-blockers (metoprolol, propranolol)
• Antiarrhythmics (propafenone, flecainide)
• Orphenadrine
• Thiotepa
• Cyclophosphamide
• Diabetes medications

Bupropion may increase adverse effects seen with levodopa and amantadine.

• Some medications increase the likelihood of seizures (antidepressants, theophylline, steroids) and should be used with caution in patients taking bupropion.
• Adverse events or reduced tolerance are possible when bupropion is combined with alcohol.
• Using bupropion with nicotine patches may increase the risk for high blood pressure.

Tricyclic antidepressants (TCAs) should not be used within 14 days of an MAOI. Severe, even fatal, reactions may occur. Many drugs may interact with TCAs. These include:

• Quinidine (Quinidex)
• Cimetidine (Tagamet)
• Phenothiazines
• Other antidepressants (such as fluoxetine, sertraline, paroxetine)
• Anticonvulsants (barbiturates, phenytoin)

TCAs may increase side effects from decongestants. TCAs can also increase the effects of anticholinergics, blood pressure-lowering drugs, and CNS depressants, including alcohol.

Amphetamines:

• Dextroamphetamine (Dexedrine, Dextrostat, Dexedrine Spansule, ProCentra)
• Lisdexamfetamine dimesylate (Vyvanse)
• Mixed amphetamine salts (Adderall, Adderal XR)
• Methamphetamine (Desoxyn)

Methylphenidate:

• Ritalin, Ritalin LA, Ritalin SR
• Methylin, Methylin ER
• Metadate ER, Metadate CD
• Concerta
• Daytrana
• Quillivant XR
• Dexmethylphenidate (Focalin, Focalin XR)

Atomoxetine:

• Strattera

Bupropion:

• Wellbutrin

Extended release clonidine:

• Kapvay

Extended release guanfacine:

• Intuniv

Tricyclic antidepressants:

• Imipramine
• Desipramine
• Nortriptyline