How atomoxetine works
Atomoxetine is an active ingredient used to treat attention-deficit/hyperactivity disorder (ADHD). It is chemically very similar in structure to the antidepressant fluoxetine. In fact, it occupies an intermediate position between ADHD medications and antidepressants. Like antidepressants, its effects are felt only after a few weeks, but atomoxetine does not have an antidepressant effect.
Studies in rats show that the effect of atomoxetine differs from brain area to brain area. Thus, in the prefrontal cortex – a brain area involved in attention and memory processes – a reuptake inhibition of dopamine was also demonstrated.
In addition, recent studies in monkeys demonstrate indirect stimulation of dopamine D1 as well as alpha-1 receptors by atomoxetine in the prefrontal cortex but not in the nucleus accumbens, an area in the forebrain associated with addictive behavior.
The serotonin balance is not affected by atomoxetine.
Another effect that still needs to be studied in detail, however, is the effect of atomoxetine on so-called NMDA receptors in the brain. These neurotransmitter binding sites occur primarily in the central nervous system and appear to be involved in the development of ADHD.
Atomoxetine differs considerably from the stimulants typically used in ADHD therapy (such as methylphenidate and amphetamine). In particular, the drug improves the core symptoms of hyperactivity, impulsivity, and attention deficit.
Atomoxetine, because of its lack of dependence potential and its similarity to fluoxetine, is the drug of choice for drug therapy of ADHD in the presence of concurrent anxiety, tic, or substance use disorders.
Absorption, degradation and excretion
In the liver, atomoxetine is degraded by the enzyme cytochrome 2D6, producing a potent intermediate. Both this metabolite and atomoxetine itself are ultimately excreted in the urine.
In patients with normal enzyme activity, about half of the active substance is excreted in the urine after three and a half hours, and after 21 hours in patients with impaired enzyme function.
When is atomoxetine used?
Atomoxetine is not approved for other uses. However, physicians sometimes use the active ingredient “off-label” (i.e., outside the stated scope of approval) for eating disorders, depression associated with ADHD, bedwetting in children, and weight loss.
How atomoxetine is used
In children and adolescents weighing over 70 kilograms, as well as adults, a dosage of 40 milligrams of atomoxetine is usually used at the beginning for at least one week. The dosage can be increased to 80 milligrams of atomoxetine depending on the effect (this only sets in completely after two to six weeks).
An atomoxetine solution is available for children with swallowing problems.
What are the side effects of atomoxetine?
More than one in ten patients experience adverse effects in the form of decreased appetite, headache, drowsiness, abdominal pain, nausea, vomiting, increased blood pressure, and accelerated heartbeat.
What should be considered when taking atomoxetine?
Contraindications
Atomoxetine must not be taken by:
- hypersensitivity to the active substance or to any of the ingredients
- concomitant treatment with monoamine oxidase inhibitors (MAO inhibitors; against depression)
- narrow-angle glaucoma (form of glaucoma)
- serious cardiovascular disease such as heart failure, arterial occlusive disease (smoker’s leg), angina pectoris
Interactions
When atomoxetine and other active ingredients that are broken down by the same enzyme (cytochrome 2D6) are used at the same time, there may be a mutual influence, since one active ingredient is usually preferentially broken down and the other therefore accumulates in the body.
Drugs that affect the heart rhythm in a certain way (cause QT time prolongation) should not be combined with atomoxetine. There are numerous examples of such agents, such as drugs for psychosis and schizophrenia, agents for cardiac arrhythmias, antibiotics and antidepressants.
Atomoxetine may attenuate the effect of antihypertensive drugs.
Drugs that affect norepinephrine concentrations (such as pseudoephedrine, phenylephrine) should be used with caution because synergistic effects are possible.
Age Limitation
Studies support safe and effective use of atomoxetine in children and adolescents six years of age and older and adults up to 65 years of age.
As with some antidepressants, use of atomoxetine may lead to increased suicidal behavior in adolescents. Adolescents at risk should be monitored accordingly.
Pregnancy and Lactation
Data on the use of atomoxetine during pregnancy are insufficient. Its use should therefore be avoided if possible.
How to obtain medication with the active ingredient atomoxetine
Atomoxetine requires a prescription in Germany, Austria, and Switzerland and is therefore only available from pharmacies upon presentation of a doctor’s prescription.
