There are many drugs other than psychostimulants that can be used to treat ADHD.

Nonstimulant therapy

Strattera® (atomoxetine) is the first nonstimulant medication approved by the Food and Drug Administration (FDA) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Strattera and all the other nonstimulants are generally considered to be less effective than psychostimulants in treating ADHD. The nonstimulants are usually considered second- and third-line medications.

Strattera works on the neurotransmitter (chemical in the brain that transmits nerve impulses) called norepinephrine. Like the stimulant drugs, Strattera is effective in treating and controlling ADHD symptoms. Unlike stimulant drugs, Strattera is not a controlled substance. Therefore, people are less likely to abuse or become dependent on it.

In addition, Strattera doesn't cause many of the potential side effects linked to psychostimulants, such as sleeplessness. Strattera can cause very significant abdominal pain, nausea and drowsiness, especially when starting the medication. Strattera tends to offset the effect of the stimulant starting to work and then wearing off. At times, it still should be taken more than once a day.

How does Strattera work?

This medication works by increasing the amount of norepinephrine, an important chemical in the brain. Doing this appears to help ADHD by increasing attention span and reducing impulsive behavior and hyperactivity.

Who should not take Strattera?

There are certain situations in which you shouldn't take Strattera. If you or your child has any of the following conditions, you should inform your healthcare provider before taking Strattera:

  • Allergy to Strattera or any of its components.
  • Narrow angle glaucoma (a condition that causes increased pressure in the eyes and can lead to blindness).
  • Treatment with a type of medication called monoamine oxidase inhibitors (MAOIs), such as Nardil® (phenelzine), Parnate® (tranylcypromine), Marplan® (isocarboxazid) or Emsam® (selegeline transdermal system) within 14 days of starting Strattera.
  • An adrenal problem called pheochromocytoma or a history of this condition.
  • Severe heart disease.

What are the side effects of Strattera?

The most common side effects in children and adolescents are:

  • Upset stomach (e.g., nausea, vomiting).
  • Decreased appetite, which may cause weight loss.
  • Nausea.
  • Dizziness.
  • Headache.
  • Mood swings.
  • Insomnia.
  • Drowsiness.
  • Abdominal pain.

The most common side effects in adults are:

These side effects can be significant and may require stopping the medication.

However in most cases, these side effects are generally not severe. Only a very small percentage of patients needed to stop Strattera due to side effects experienced during clinical trials.

Allergic reactions to Strattera are rare but do occur, usually as swelling or hives. Tell your provider right away if you or your family member taking Strattera develops a skin rash, swelling, hives or other allergic symptoms.

There have been reports of slightly decreased growth in children and teens taking Strattera. It's recommended that children and adolescents be observed, measured and weighed periodically while on Strattera.

Strattera should be stopped if you have signs of jaundice — yellowing of the skin or whites of the eyes. Jaundice is a sign of liver damage. Itching, right upper belly pain, dark urine and unexplained flu-like symptoms may also be signs of liver injury. If blood tests show evidence of liver damage, stop taking Strattera.

Strattera can increase suicidal thinking in teens who take the drug. Patients should be monitored for suicidal thoughts and actions while taking Strattera®.

Strattera can cause serious heart-related complications (e.g., heart attack, stroke), high blood pressure and increased heart rate especially if you have a history of heart and/or vessel disease and/or irregular heart rate. Therefore, patients should be evaluated for heart disease prior to starting Strattera and be monitored for changes in blood pressure and heart rate during therapy.

Strattera should be discontinued if symptoms of psychosis (such as hearing voices, believing things that are not true, being suspicious) or mania occur.

Aggressive or hostile behavior may occur. Therefore, monitoring for this type of behavior during Strattera therapy is recommended.

This is not a complete list of all side effects. If you have questions about side effects, please contact your healthcare provider.

Be sure to tell your healthcare provider:

  • If you are nursing, pregnant or plan to become pregnant.
  • If you are taking or plan to take any prescription drugs (especially antidepressants or other psychiatric medicines, blood pressure medicines, linezolid or methylene blue), dietary supplements, herbal medicines or nonprescription medications (especially cough and cold medicines that contain decongestants or nonsteroidal anti-inflammatory medicines like ibuprofen or naproxen).
  • If you have any past or present medical problems, including high blood pressure, seizures, heart disease, glaucoma or liver or kidney disease.
  • If you have a history of drug or alcohol abuse or dependency or if you have had mental health problems, including depression, manic depression or psychosis.
  • If you have had any liver problems or jaundice in the past.
  • If you become agitated or irritable or if you develop ideas of hurting yourself.

Take Strattera exactly as prescribed by your healthcare provider. It's usually taken once or twice a day and may be taken with or without food. Your physician may adjust the dose until it's correct for you or your child. No specific laboratory testing is required while taking Strattera. It may be used for extended or long-term treatment as long as there are periodic evaluations with your healthcare provider.

Is antidepressant therapy used to treat ADHD?

Several types of antidepressant drugs can be used to treat ADHD. Antidepressant therapy for ADHD is sometimes used as the treatment of choice for children or adults who have ADHD and depression.

Antidepressants, however, are generally not as effective as stimulants or Strattera at improving attention span and concentration.

Antidepressants used for treating ADHD include the following:

  • Tricyclic antidepressants, such as Pamelor™ (nortriptyline), Tofranil® (imipramine) and Norpramin® (desipramine) have been shown to be helpful in children and adults with ADHD, but they can cause some unpleasant side effects, such as dry mouth, constipation or urinary problems. They are also relatively inexpensive.
  • Wellbutrin® (bupropion), a different type of antidepressant, has been found to be effective in treating ADHD in adults and children. It's generally well-tolerated, but it also has some side effects that may be a problem for some people who have anxiety, headaches or seizures.
  • Effexor® (venlafaxine) and Effexor XR® (venlafaxine extended-release) are newer antidepressants that increase the levels of norepinephrine and serotonin in the brain. The drugs are effective at improving mood and concentration in adults as well as children and teens. They are occasionally used to treat ADHD.
  • Monoamine oxidase inhibitors (MAOIs) are a group of antidepressants that can treat ADHD with some benefit, but are rarely used because they have significant and sometimes serious side effects and can dangerously interact with certain foods and other medications. They may be of benefit in situations when other medications have failed. Examples include Nardil (phenelzine), Parnate (tranylcypromine), Marplan (isocarboxazid) or Emsam (selegeline transdermal system). Monoamine oxidase inhibitors are generally not prescribed for children or teens.

Note: The FDA has determined that antidepressant medications increase the risk of suicidal thinking and behavior in children and adolescents with depression and other psychiatric disorders. If you have questions or concerns, please discuss them with your healthcare provider.

How do antidepressants work?

Since most antidepressants work by increasing the levels of brain messenger chemicals (neurotransmitters), such as norepinephrine, serotonin and dopamine, it makes sense that they might have effects similar to other ADHD stimulant and nonstimulant treatments that appear to work by similar mechanisms.

Antidepressant treatment can have a small effect on attention span as well as impulse control, hyperactivity and aggressiveness. Children and adolescents treated with antidepressants are often more willing to take direction and may be less disruptive.

Antidepressants have the advantage of a low potential for abuse and there is no evidence that they suppress growth or contribute to significant weight loss.

Who should not take antidepressants?

Antidepressants should not be used in the following situations:

  • If you have a history or tendency toward manic behavior or manic depression (bipolar disorder).
  • Wellbutrin (bupropion) should not be taken if you have any history of seizures or epilepsy.
  • Treatment with antidepressants should not be initiated if you have taken a MAO inhibitor antidepressant, such as Nardil, Parnate. Marplan or Emsam within the last 14 days.

Each type of antidepressant has its own contraindications and usage warnings; you should discuss these with your healthcare provider.

The most common side effects experienced with tricyclic antidepressants include:

  • Stomach upset.
  • Constipation.
  • Dry mouth.
  • Blurred vision.
  • Drowsiness.
  • Dizziness.
  • Low blood pressure.
  • Weight gain.
  • Tremor.
  • Sweating.
  • Difficulty urinating.

Some tricyclic antidepressants are more likely to cause particular side effects than others.

Tricyclic antidepressants are potentially lethal in the event of an overdose of medication.

Tricyclic antidepressants also have the potential to cause serious heart conduction defects. Periodic electrocardiogram (EKG) monitoring is recommended during tricyclic antidepressant therapy to look for these heart problems.

Wellbutrin sometimes causes stomach upset, anxiety, headaches and rashes.

Effexor and Effexor XR can cause nausea, anxiety, sleep problems, tremor, dry mouth and sexual problems in adults.

Monoamine oxidase inhibitors can cause a wide variety of side effects, including dangerously increased blood pressure when combined with certain foods or medications. Prior to starting MAOI therapy, please consult a healthcare professional concerning potential food and drug interactions.

This is not a complete list of all side effects for antidepressants. If you have questions about side effects, please contact your healthcare provider.

When taking antidepressants for ADHD, be sure to tell your healthcare provider:

  • If you are nursing, pregnant or plan to become pregnant.
  • If you are taking or plan to take any prescription drugs, dietary supplements, herbal medicines or nonprescription medications.
  • If you have any past or present medical problems, including high blood pressure, seizures, heart disease and urinary problems.
  • If you have a history of drug or alcohol abuse or dependency or if you have had mental health problems, including depression, manic depression or psychosis.
  • If you develop any depressive symptoms or feelings that you might harm yourself.
  • If you develop irregular heartbeats (heart palpitations) or fainting spells.

The following are useful guidelines to keep in mind when taking antidepressants or giving them to your child for ADHD:

  • Always give the medication exactly as prescribed. If there are any problems or questions, call your healthcare provider.
  • Consult your physician prior to discontinuing antidepressant therapy.
  • Antidepressants usually take 2-4 weeks before the full effects are apparent. Be patient and don’t give up before giving them a chance to work.
  • Your provider will probably want to start your medication at a low dose and increase gradually until symptoms are controlled.
  • It's better not to miss doses of antidepressants. Most are given once or twice a day. If you miss a day or two of Effexor, it can cause an unpleasant withdrawal syndrome.
  • Taking bulk laxatives (fiber) and drinking lots of water is a good idea with tricyclic antidepressants, as they tend to cause constipation and hard stools.
  • Tell your provider if you notice any new or unusual side effects.

What other nonstimulant therapies are used to treat ADHD?

Two drugs, Kapvay® (extended-release clonidine) and Intuniv® (extended-release guanfacine), have been approved by the FDA for use alone or with stimulant drugs for the treatment of ADHD. These drugs can improve mental functioning as well as behavior in people with ADHD. However, they are usually reserved for those who respond poorly to and cannot tolerate stimulants or Strattera.

Clonidine is also available as a short-acting tablet and as a transdermal patch. Guanfacine is also available as a short-acting tablet. These dosage forms have also been used to treat ADHD, however they are not specifically approved by the FDA for this indication.

How do these drugs treat ADHD?

How these drugs work in treating ADHD is not yet known, but it is clear that they have a calming effect on certain areas of the brain.

Who should not take these drugs?

Kapvay should not be used in patients who are allergic to clonidine (e.g., Catapres®). Intuniv should not be used in patients who are allergic to guanfacine (e.g., Tenex®).

What are the side effects of these drugs?

The most common side effects include:

For Kapvay:

  • Drowsiness.
  • Headache.
  • Irritability.
  • Insomnia.
  • Nightmares.
  • Change in mood.
  • Dry mouth.

For Intuniv:

  • Drowsiness.
  • Headache.
  • Nausea.
  • Weakness.
  • Stomach pain.
  • Dizziness.

These drugs can rarely cause irregular heartbeats. They can lower blood pressure and slow heart rate.

Careful screening for heart rhythm irregularities and regular monitoring of blood pressure and EKGs is recommended.

Both drugs can cause significant drowsiness; use caution when operating dangerous equipment or driving until you know how these drugs affect you.

This is not a complete list of side effects. If you experience a potential side effect while taking these drugs, please consult a healthcare professional.

Are there tips and precautions for nonstimulant medications in ADHD treatment?

When taking one of these drugs for ADHD, be sure to tell your healthcare provider:

  • If you are nursing, pregnant or plan to become pregnant.
  • Consult your provider before discontinuing therapy; Kapvay and Intuniv should not be abruptly discontinued.
  • If you are taking or plan to take any prescription drugs, dietary supplements, herbal medicines or nonprescription medications.
  • If you have any past or present medical problems, including low blood pressure, seizures, heart rhythm disturbances and urinary problems.
  • If you develop irregular heartbeats (heart palpitations) or fainting spells.

The following are useful guidelines to keep in mind when taking clonidine or guanfacine or giving them to your child for ADHD:

  • Always take or give the medication exactly as prescribed. If there are any problems or questions, call your provider. It is best not to miss doses as this may cause the blood pressure to rise quickly, which may cause headaches and other symptoms.
  • Your health care provider will probably want to start the medication at a low dose and increase gradually until symptoms are controlled.
  • For very young children, clonidine short-acting tablets can be formulated into a liquid by a compounding pharmacy to make it easier to give the medication. Short-acting clonidine tablets can be crushed and mixed with food if necessary. However, Kapvay which is a long-acting clonidine tablet should not be chewed, crushed or broken.
  • Intuniv, which is a long-acting guanfacine, should not be chewed, crushed or broken.
  • Do not stop clonidine therapy, including Kapvay or guanfacine, including Intuniv, suddenly since this can cause a rebound increase in blood pressure. These medications must be tapered.

Last reviewed by a Cleveland Clinic medical professional on 01/07/2021.

References

  • U.S. Food & Drug Administration. Atomoxetine (Straterra) information. (https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/atomoxetine-marketed-strattera-information) Accessed 5/28/2021.
  • U.S. Food & Drug Administration. Kapvay (clonidine hydrochloride) extended-release tablets. (https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022331s001s002lbl.pdf) Accessed 5/28/2021.
  • The American Academy of Family Physicians. Guanfacine (Intuniv) for Attention-Deficit/Hyperactivity Disorder. (https://www.aafp.org/afp/2011/0215/p468.html) Accessed 5/28/2021.
  • Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Childhood disorders. In Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York, NY: McGraw-Hill;2008:1029-1040. Accesed 5/28/2021.

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