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.
