Atomoxetine: New Treatment For AD/HD

Atomoxetine: A New Medication for AD/HD

Carol

Watkins, M.D.

 

Atomoxetine,

brand name, Strattera, 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. The

stimulants include methylphenidate (Ritalin, Concerta and Metadate CD) and

amphetamine (Dexedrine, Dexedrine Spansules, and Adderall XR). Stimulants are

FDA approved for the treatment of AD/HD in children and adolescents, but most

physicians consider them the first line medication treatment for AD/HD in adults

too.

 

How Does It Work?

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.  Atomoxetine does not seem to cause an increase in brain dopamine

levels in the nucleus accumbens or the striatum areas of the brain. The

stimulants appear to cause an increase in the availability of dopamine in these

areas. The effect on the nucleus accumbens is believed to cause euphoria and to

be responsible for the stimulants’ abuse liability. Dopamine increases in the

striatum may be associated with the risk of motor tics.

(1)

 

Although Atomoxetine’s direct

effect only seems to be with norepinephrine, it appears to cause a secondary

increase in dopamine levels in the prefrontal cortex area of the brain. (the

brain area behind the eyes.) This part of the brain is associated with the

ability to mentally rehearse responses, and inhibit impulsivity. The area is

also associated with working memory.

 

Atomoxetine’s chemical

structure bears some similarities to the tricyclic antidepressants although it

is actually a phenylpropanolamine derivative.  The tricyclic antidepressants

include desipramine and imipramine. These two medications have been shown to be

effective treatments for AD/HD in adults and children but do not have FDA

approval for this use. The tricyclics affect norepinephrine but are not as

specific as atomoxetine.  It is the tricyclics’ effect on neurotransmitters

other than dopamine and norepinephrine that appear to cause their drawbacks.

Their anticholinergic effects can cause constipation, dry mouth and dry eyes.

Their antihistaminergic effects can cause weight gain and tiredness. Their alpha

adrenergic effects can cause tremor and changes in blood pressure.

The tricyclics can cause a delay in cardiac conduction. This effect can cause

minor—and in rare cases—serious changes in heart rhythm. Investigators have

evaluated atomoxetine carefully for cardiac rhythm and blood pressure changes.

Minor, but insignificant, increases in pulse and blood pressure were noted.

Atomoxetine did not appear to cause changes in cardiac conduction.  (2) 

 

Can you abuse atomoxetine?

Some

physicians have been reluctant to prescribe stimulants for adults because they

are Schedule II and are officially listed as having a significant potential for

addiction. Although stimulants can indeed be abused, their use does not seem to

cause abuse individuals who do not already have a substance abuse problem.

(3)

However

there are other ways in which stimulants can be abused. Because they decrease

sleepiness and cut appetite, individuals might use them to cram for exams or

lose weight.  Atomoxetine appears to have minimal abuse potential. Thus, it is

not as highly controlled as the stimulants. It can inhibit sleep or appetite but

does so much less than the stimulants. Thus, it is less likely to be passed

around.

 

Does atomoxetine have side effects?

The

side effects of atomoxetine may include many of the side effects seen with

stimulants. These common effects include appetite suppression, sleep

disturbance  jitteriness and irritability. Since there is a small increase in

pulse and blood pressure, these should be monitored in patients with cardiac

disease. However, these effects are often milder than those of the stimulants.

However atomoxetine can cause a significant problem with nausea. In my

experience, this is the most common reason for individuals stopping the drug.

Taking it with meals or splitting the dose may help. Atomoxetine is most

commonly given as a single dose in the morning. However there are some

individuals who cannot tolerate this because they actually find the medication

to be sedating.  Atomoxetine can lead to urinary retention in some individuals.

It can also cause problems with sexual functioning. About 7 % of men experienced

problems with erections and 3% experienced impotence.

(4) Stimulants often

cause the individual to feel more alert and less sleepy. Atomoxetine can

occasionally do this to a milder degree. In some individuals, however,

Atomoxetine can actually cause sleepiness. I have several patients who prefer to

take it at night. Atomoxetine does not usually have a rebound effect. Although

the compound is metabolized quickly, the clinical effects appear to last all day

and even into the following morning. This can be a good thing for individuals

who find that stimulants make them feel irritable in the evenings. However,

people who need to stimulant “kick” to help them focus may be disappointed in

the new drug.  

 

How Strong and How Fast?

Stimulants start to work in less than an hour. Because of this, one can rapidly

determine the best dose. Atomoxetine has a more subtle, gradual onset. One must

increase the dose over several days or weeks. One may not see the maximum effect

of a given dose for about three weeks. In some cases, I may do a cross over in

which the individual takes a lower dose of the stimulant while waiting for the

atomoxetine to take its full effect. Limited studies have suggested that

atomoxetine is equally effective to methylphenidate (Ritalin) for a variety of

AD/HD symptoms.  (2)

In my own experience, this is not always true. Some individuals experience even

the highest recommended doses of the drug as less effective than the

conventional stimulants.

 

Atomoxetine is metabolized through the cytochrome  P-450 2D6 pathway. However

the major metabolite is also active. The activity of the CYP 2D6 system can vary

widely in perfectly healthy people. Individuals who metabolize it slowly will

build up a higher level faster than those who metabolize it rapidly. We often

use blood levels to help us determine the proper dose of a tricyclic

antidepressant. However we do not have such a test widely available for

atomoxetine. Because of this, we may not be able to achieve an effective dose in

some individuals within the FDA dosage guidelines. Fluoxetine (Prozac) and

paroxetine (Paxil),, as well as other drugs affect the metabolism of

atomoxetine. If one is taking atomoxetine it is important to check with the

doctor or pharmacist to make sure that they are not taking any other drugs that

affect its metabolism.

 

A

Double Edged Sword?

Some

of the advantages of atomoxetine may be a double edged sword. Its lower abuse

potential might make us more willing to prescribe it for individuals with a

substance abuse problem. Its weak antidepressant effect might make us more

comfortable prescribing it for individuals who might have co-morbid depression.

However this should not relieve clinicians from the responsibility for assessing

and treating co-morbid substance abuse and mood problems. Atomoxetine is more

convenient because you can call in refills. However, one of the major reasons

for failure for AD/HD medication treatment failure is inadequate follow up with

infrequent dosage monitoring and adjustments. Medication management visits can

be therapeutic. Frequent visits also help pick up changes in the patient’s

clinical condition.

 

So, Where Does Atomoxetine Fit In?

I

still recommend the stimulants as the first-line drugs for AD/HD.  They have

stood the test of time. We are familiar with their strengths and their side

effects. Their quick onset enables the clinician to more rapidly adjust the

dose. The stimulants—even the newer ones—are less expensive than atomoxetine. I

have found a number of patients who feel that even the higher doses of

atomoxetine are not as effective as the stimulants. However there are many

people who do not respond to stimulants or who cannot tolerate the side effects.

I have achieved excellent results in a number of individuals who felt jumpy or

irritable on stimulants. For these people, atomoxetine can be an excellent

medication.

 

 

  1. Bymaster FP,

    Katner JS, Nelson DL, et al.

    Atomoxetine increases extracellular levels of norepinephrine and dopamine in

    prefrontal cortex of rat: A potential mechanism for efficacy in attention

    deficit/hyperactivity disorder. Neuropsychopharmacology 2002;

    27:699-711.

  2. Kratochvil

    CJ, Heiligenstein JH, Dittmann R, et al. Atomoxetine and

    methylphenidate treatment in children with ADHD: A prospective, randomized,

    open-label trial. J Am Acad Child Adolesc Psychiatry 2002;41:776-84.

  3. Biederman, J, WIlens, T,

    Mick, E, Spencer, T, Faraone, SV, Pharmacotherapy of

    Attention-Deficit/Hyperactivity Disorder Reduces Risk for Substance Use

    Disorder, Pediatrics, 104:2 1999 pe20.

  4. Michelson D, Adler I,

    Spencer T, et al. Atomoxetine in adults with ADHD: two randomized,

    placebo-controlled studies. Biol Psychiatry 2003;53:112-20.

  5. Michelson, D, Faries, D, Wernicke, J, Kelsey, D,

    Kendrick, K, Sallee, FR, Spencer, T., Atomoxetine in the Treatment of Children

    and Adolescents with Attention-Deficit Disorder: A Randomized,

    Placebo-Controlled, Dose-Response Study, Pediatrics 2001, 108:5. 


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Northern County Psychiatric

Associates 

Our practice has experience in the treatment of Attention

Deficit disorder

(ADD or ADHD), Depression, Separation Anxiety Disorder, Obsessive-Compulsive

Disorder, and other

psychiatric conditions. We are located in Northern Baltimore County and serve the

Baltimore County, Carroll County and Harford County areas in Maryland. Since we are near

the Pennsylvania border, we also serve the York County area.   Our

services include psychotherapy, psychiatric evaluations, medication management, and

family therapy. We treat children, adults, and the elderly.


Contact Us:

Telephone:410-329-2028

Fax: 410-343-1272

Postal address: We have two locations in Baltimore County

      Monkton Office16829 York Road/PO Box 544/Monkton, MD 21111

      Lutherville Office: 2360 West Joppa Road Suite 223/

Lutherville, MD

Email: [email protected]

Please use telephone for appointments or medical questions.

Carol Watkins, M.D.

Glenn Brynes, Ph.D., M.D.

Rita Preller, LCSW-C

Copyright © 2006  Northern County

Psychiatric Associates

Last modified:

September 30, 2006

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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