Non-Stimulant Medication for Children, Adolescents and Adults with ADHD

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.

  • 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 is becoming 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 is often prescribed once per day, but those who

have trouble with gastrointestinal upset, can take a

smaller dose twice a day.

Common side effects are headache, abdominal pain,

nausea, vomiting, weight loss anxiety, sleepiness

and insomnia. It appeared to cause less insomnia and

appetite suppression than methylphenidate. However

it may cause a higher incidence of sleepiness and

vomiting 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 what they

get from the stimulants. Atomoxetine received a

Black Box warning for possible risk for suicidal

impulses. See our expanded article on

Atomoxetine

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 ADHD. 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 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. 

Alpha-2A-adrenoceptor agonist:

  Clonidine (Catapress) and guanfacine (Tenex)

have been used in adults for the contol 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 ADHD fall asleep. Since both clonidine and guanfacine

can affect blood pressure and heart rate, it is a good idea to monitor blood

pressure and get an EKG to check the heart rhythm. 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. In some cases, clonidine or guanfacine is combined with a stimulant

if the stimulant does not have enough effect on irritability and

impulsivity. Shire Pharmaceuticals is working on a long-acting form of

guanfacine (Connexyn) which it will market as a non-stimulant drug for

ADHD for children aged 6-17 years.

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 this effect than are 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) 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 agitation. The

atypical antipsychotics can often cause weight gain in both children and adults.

Abilify, (aripiprazole) is less likely to cause weight gain or metabolic

problems.

Selected References:

Wilens TE, Biederman

J, Prince J, et al. Six-week, double-blind,

placebo-controlled study of desipramine for adult

attention deficit hyperactivity disorder. Am J

Psychiatry. 1996;153:1147-1153.

Findling, RL, Aman, MG, Erdeknes, M, Lyons, B, 

 Long-Term, Open-Label Study of Risperidone in Children With Severe

Disruptive Behaviors and Below-Average IQ,  Am J Psychiatry 2004;

161: 677-684.

Biederman J. Efficacy and safety of modafinil

film-coated tablets in children and adolescents with

attention-deficit/hyperactivity disorder: results of a randomized, double-blind,

placebo-controlled, flexible-dose study. Pediatrics. 01-DEC-2005; 116(6):

e777-84.

Wilens, TE, Haight, BR, Horrigan, JP, Bupropion

XL in adults with attention-deficit hyperactivity disorder: a randomized,

placebo-controlled study: Biological Psychiatry 2005: 57(7) 793-801.

 

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