60-80% of youth and adults with AD/HD gain significant relief from stimulants. However some individuals require other medications to treat their AD/HD symptoms. There are several reasons for choosing a non-stimulant medication.
- Stimulants do not relieve symptoms.
- Stimulants cause intolerable side effects.
- Medical problems make stimulant use difficult.
- Concern that the individual might abuse stimulant medication.
- The individual has another psychiatric diagnosis along with the AD/HD. In this case, we may need to treat both conditions.
In some cases, we will stop the stimulant and substitute another medication. In other cases, we add a second agent to the stimulant regimen.
Atomoxetine (Strattera, from Lilly Pharmaceuticals), was approved by the FDA for distribution in November 2002. It became available in US pharmacies in early 2003. Despite its hefty price tag, it has become widely used for adults and children with Attention Deficit Hyperactivity Disorder. (AD/HD) It is a non-stimulant medication approved for the treatment of AD/HD in both children and adults. It was the first medication that the FDA specifically approved for the treatment of ADHD in adults. Atomoxetine is a selective norepinephrine reuptake inhibitor. This means that it strengthens the chemical signal between those nerves that use norepinephrine to send messages. Atomoxetine does not appear to affect the dopamine systems as directly as do the stimulants. It appears to affect the dopamine system more indirectly. Common side effects are headache, abdominal pain, nausea, vomiting, weight loss anxiety, sleepiness and insomnia. It appears to cause less insomnia and appetite suppression than methylphenidate. However it may cause a higher incidence of sleepiness and nausea than methylphenidate. It is most commonly administered once a day. The clinical effect appears to last all day and even into the next morning. I sometimes prescribe it twice a day to minimize the nausea. It can be quite helpful to those who cannot tolerate stimulants. However, some patients say that it does not give as strong an effect as do the stimulants. Atomoxetine received a Black Box warning for possible risk for suicidal impulses. See our expanded article on Atomoxetine
Alpha-2A-adrenoceptor agonists: Clonidine (Catapress) and guanfacine (Tenex) have been used in adults for the control of high blood pressure. However, they are also useful in AD/HD, particularly for those with tics, impulsivity or aggression. Like clonidine, guanfacine can reduce tics for individuals with Tourette Syndrome. Because of its sedating properties, clonidine is sometimes used to help people with AD/HD fall asleep. Since both clonidine and guanfacine can affect blood pressure and heart rate, it is a good idea to monitor blood pressure. One might also consider an EKG. There have been a few reports of sudden death in children associated with the stimulant/clonidine combination, but some researchers have questioned whether some of those deaths were truly related to the medication. Because guanfacine lasts longer than clonidine, only one or two doses are needed each day. Recent research confirmed that it can be useful in children, especially the 30% who have difficulty tolerating stimulants. These medications can help all of the symptoms of AD/HD but often seem to help impulsivity motor hyperactivity and irritability more than attention.
For many years, we have used clonidine and guanfacine off label to treat individuals with AD/HD. Now there are two α-2 agonists which have FDA approval for the treatment of AD/HD.
Kapvay is a long acting form of clonidine. It was approved by the FDA in September 2009 for children and teens ages 6-17. It can be used by itself or in combination with a stimulant. Kapvay is usually prescribed twice a day. It is usually started at 0.1mg in the evening and can be increased up to 0.2 mg twice a day. If the individual is also taking a stimulant the dosing may need to be adjusted. Side effects may include lowered blood pressure, slower pulse, sleepiness, irritability, decreased sex drive, stomach pain constipation and nausea dizziness and fainting. It is important that blood pressure be monitored closely as the dose is increased and periodically after one reaches the optimal dose. Since it can affect heart rate, we may consider an EKG. Some individuals with AD/HD use short acting clonidine to help them fall asleep. Since Kapvay is a longer acting medication, it may not induce sleep as quickly.
Intuniv, a long acting form of guanfacine, was approved by the FDA in September 2010 for children and teens aged 6-17. It can be used by itself or in combination with a stimulant. It is commonly given once a day in the evening. Dosage usually starts at 1mg and can be increased to 4 mg per day. It has many of the same potential side effects as Kapvay. Some individuals do better on one and some on the other. Kapvay and Intuniv take longer than stimulants to show an effect. You may need to wait up to a month to see significant improvement. Since they are relatively new medications, they are much more expensive than generic guanfacine and clonidine. Longer term studies of Kapvay and Intuniv are needed. Although Intuniv and Kapvay are only FDA approved for ages 6-17, I have successfully used them then successfully used them for adults with AD/HD.
Modafinil (Provigil) has been approved for treatment of narcolepsy in adults. It is chemically unrelated to methylphenidate or amphetamine. It was to be marketed as Sparlon for children and adolescents with AD/HD. When compared to methylphenidate and amphetamine, it seems less likely to cause irritability and jitteriness. It appears to act on the frontal cortex and is more selective in its area of action than the traditional stimulants. In studies of adults with ADHD, there was a small, promising study suggesting that it might be effective for adults with AD/HD. However a larger study sponsored by Cephalon indicated that modafinil was no more effective than placebo. Some of their studies suggested a positive effect on children when larger doses are used. In the summer of 2006, the FDA announced that it would not approve modafinil for children with AD/HD. The FDA felt that the medication did not show significant advantages over existing ADHD medications, and expressed concern about side effects in the higher doses necessary to effectively treat AD/HD. There was a possible incidence of a severe rash, Stevens-Johnson Syndrome, in a child in the study group.
Bupropion SR and XL (Wellbutrin) has been used to treat AD/HD for several years. A recent controlled study showed that it is effective in the treatment of AD/HD symptoms in adults. Its structure is chemically similar to amphetamine, but does not have the same abuse potential. It should not be used in individuals with bulimia (repetitive self induced vomiting) or a seizure disorder. In my experience, it is not as powerful as the stimulants, but is useful for individuals who cannot tolerate stimulants or for whom a Schedule II drug is inadvisable. Bupropion is FDA approved for the treatment of depression in adults.
The tricyclic antidepressants, such as desipramine (Norpramine) imipramine (Tofranil) and nortryptiline (Pamelor) have been shown to effectively treat AD/HD. They can provide 24-hour coverage, and may not create the sleep difficulties sometimes associated with the stimulants. However, they have a number of potential drawbacks. Tricyclics can cause dry mouth, blurred vision, constipation, dizziness and sedation. The tricyclics, especially desipramine, can cause changes in cardiac conduction. Children are more sensitive to the cardiac effects than adults. When we use tricyclics with children and some adults, we may need to do blood tests and EKGs (a test of heart rhythm.)
The Selective Serotonin Reuptake Inhibitors (SSRIs) include paroxetine (Paxil) sertraline (Zoloft) fluvoxamine (Luvox) and others. They probably do not treat the core symptoms of AD/HD but may be helpful for irritability, anxiety or depression accompanying the AD/HD. These medications tend to have fewer side effects than the tricyclic antidepressants, and do not require as much medical monitoring. They occasionally cause jitteriness, headache, stomachache, appetite changes, sedation, apathy or irritability. They can interact with other types of medication, so it is necessary the physician to know all other medications or herbal remedies being taken. Any of the antidepressants, tricyclics, bupropion, or the SSRIs have the potential to precipitate a mania in individuals with undiagnosed Bipolar Disorder.
Selegiline (Eldepryl) is a monoamine oxidase inhibitor used to treat symptoms of Parkinson’s Disease. If one uses low doses, it may not be necessary to follow the restrictive diet associated with its cousins, the antidepressants Parnate and Nardil. A small controlled study showed that children with severe AD/HD and co-morbid conditions, demonstrated improvement in learning and classroom behavior on 5 mg twice a day. However there have been mixed results in adults with AD/HD.
Effexor and Effexor-XR (venlafaxine) An open trial (not a controlled study) with adults suggested that it might be helpful for some adults with AD/HD. In an open, 5-week study of children and adolescents with AD/HD, some individuals showed an improvement in behavioral but not cognitive measures. Several experienced worsening of their AD/HD symptoms and 25% could not tolerate the medication due to side effects. It is a good idea to monitor blood pressure since some individuals on Effexor show a rise in blood pressure. Sudden discontinuation of Effexor may lead to nausea and vomiting. Effexor may not be the best choice in some children and adolescents. It’s rapid elimination makes withdrawal symptoms a problem if the individual stops the medication or forgets pills. It can also be associated with irritability.
Mood Stabilizers are traditionally used for Bipolar Disorder. (Manic Depressive Disorder) These medications include Lithium and several anticonvulsant (seizure) medications such as Depakote (valproate) Tegretol (carbamazepine) Lamictal (lamotrigine) and others. There is debate among psychiatrists about the percentage of AD/HD individuals who also have Bipolar Disorder. Some see the mood swings as part of the AD/HD. Others see it as a sign of a separate, co-existing disorder. In either case, the mood stabilizers may be useful to help modulate irritability and rapid mood shifts. These medications require closer medical monitoring. Blood tests and sometimes an EKG may be required. If a child truly appears to have both AD/HD and Bipolar Disorder, one often treats the Bipolar Disorder first and then treats the AD/HD. Individuals with both conditions have a significantly increased incidence of substance abuse. Since illegal drugs can have dangerous interactions with some prescribed medications, drug screens may be advisable. A positive response to a mood stabilizer does not necessarily mean that the individual has the diagnosis of Bipolar Disorder.
The antipsychotics (haloperidol, risperidone and others) are not usually used to treat AD/HD. They may be useful for other disorders that may also be present. Such disorders include Bipolar Disorder, Pervasive Developmental Disorder, and Tourette Disorder. Risperdone has received FDA approval for the treatment of children with Autism who show agitation. Controlled studies have shown that children with Oppositional Defiant Disorder and other disruptive behavior disorders show short and long-term improvement when taking Risperdal. There may be a place for the atypical antipsychotics in some individuals with AD/HD and severe agitation. However the atypical antipsychotics can often cause weight gain in both children and adults. They can cause diabetes and problems with cholesterol and triglycerides. Abilify, (aripiprazole) is less likely to cause weight gain or metabolic problems. However children and adolescents are especially susceptible to the weight gain issues even with Abilify. It is generally a good idea to try behavioral treatment and other medications first.
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