If you or someone you love has been diagnosed with Attention Deficit Hyperactivity Disorder (ADHD), you may know that the most common treatment is stimulant medications such as Adderall, Ritalin, or Dexedrine. For many diagnosed with ADHD, stimulant medications increase concentration and focus, while reducing hyperactive and impulsive behaviors.
Researchers believe that stimulants work primarily because they increase dopamine and norepinephrine levels in regions of the brain that are involved in executive and attention function, particularly the cortex and striatum. Dopamine is a neurotransmitter (a chemical messenger made by brain cells to communicate with other cells in the brain and body) associated with motivation, pleasure, attention, and movement. Norepinephrine is a neurotransmitter that affects arousal, attention, mood, learning, memory and stress response. Given dopamine’s role in pleasure and reward behavior and stimulants’ role in increasing dopamine levels in the brain, there has been historical concern by doctors and patients regarding stimulants and their risk of misuse, abuse, and dependence.
In 2002, the Food and Drug Administration approved Strattera (atomoxetine [ATX]) as the first non-stimulant medication for use in the treatment of pediatric and adult ADHD, and also the first medicine to be approved to treat adult ADHD. After looking more closely at Strattera, I’ve concluded that it may be a reasonable first choice option for those seeking treatment for ADHD. Let’s take a look at the benefits as well as the side effects patients and clinicians need to be aware of.
Unlike stimulants, which primarily work by increasing levels of dopamine and norepinephrine in the brain, Strattera selectively increases only norepinephrine. Given dopamine’s role in reward and pleasure, and norepinephrine’s role in arousal, attention, memory, and impulse control, the idea is that Strattera has the potential to help symptoms of ADHD without abuse potential of stimulants.
Editor’s note: the pathophysiology of ADHD, and mechanism of action of atomoxetine and stimulants, are far more complex than stated in this blog post. For example, while the majority of the literature on the pathophysiology of ADHD has focused on dopamine and norepinephrine, ADHD has also been linked to dysfunction in serotonin, acetylcholine, opioid, and glutamate pathways. Alterations in all of these systems have been found to affect brain structures that moderate executive function, working memory, emotional regulation, and reward processing. Further, stimulants can also affect some of these pathways (beyond just the dopamine and norepinephrine pathways). Next, although Strattera selectively increases norepinephrine levels in the brain, its actions on norepinephrine metabolism cause it to indirectly increase dopamine levels in specific regions of the brain as well. I am adding this note not to confuse you, but to raise your awareness of the limitations of what a blog post can cover.
Understanding how Strattera works, let’s look at some of the benefits of this medication vs. stimulant medications.
Data from a Rhesus monkey trial as well as a human abuse study showed that, unlike many stimulant medications, Strattera does not have reinforcing effects. Reinforcing effects are what make drugs addictive. During one double-blind study, stimulant drug abusers did not prefer Strattera significantly more than the placebo. These results confirm that there is a reduced risk of abuse, lack of tolerance, and dependency with this drug vs. stimulants.
One of the challenges with most medications that take weeks and months of daily dosing in order to be effective, is that they typically need to be tapered over a period of weeks and months prior to discontinuation. Tapering helps patients avoid unpleasant and sometimes dangerous withdrawal symptoms. But, with Strattera, the available literature shows no acute side effects occur as a result of abrupt discontinuation.
Still, without a good reason not to taper, I generally prefer to taper all medications I prescribe, including Strattera. Typically, what this means is if a patient is taking 100mg daily, I will have them drop the dose by 20-40mg every three days until discontinuation is complete. Why risk the possibility of being the rare, undocumented patient who experiences side effects with an abrupt discontinuation of Strattera, if we can at least minimize that risk with a brief taper?
This is a key benefit for parents of children with ADHD to consider. Because stimulant medications can significantly disrupt sleep, we advise that parents not give children these medications after 2pm. But when a child or adolescent receives their last dose around lunchtime, the effectiveness may wear off by 5 or 6pm. Consequently, parents often have epic bedtime battles with their kids’ ADHD symptoms.
Unlike stimulants, Strattera is less likely to affect sleep patterns and essentially works 24 hours a day. Parents, whose kids participated in clinical trials, reported their children were less irritable, easier to get up and get ready in the morning, had less difficulty getting ready for bed, and had less difficulty falling asleep.
Stimulants show evidence of their maximum potential on the first day you take them and have absolutely no effectiveness on any day they are not taken. Strattera is unique, in that the maximum effect can take up to one year of daily dosing to achieve. This medicine takes time to build up in your brain, and the effects tend to linger even if you stop the medicine or skip doses. Although some improvement can be seen by the end of the first week of treatment, the median response time to reach 25% improvement in ADHD symptoms was 3.7 weeks.
Here are some other important statistics to note: the probability for a 40% reduction in symptoms is about 50% after one month, 75% at month three, 85% at six months, and 96% at one year. So, although it may take longer for Strattera, than for stimulants, to positively affect symptoms, Strattera is quite effective once it reaches full strength in the body.
This suggests that starting on Strattera could be a useful strategy for a patient who has concerns about ADHD, but for whom we don’t have enough information yet to warrant prescribing a stimulant. If during the course of treatment, we decide that a stimulant medication would be beneficial, then we can add it on later and fine tune the regimen from there.
Studies were also conducted to determine how long Strattera continues to be effective after a patient discontinues use. Researchers found that if someone discontinues Strattera after having taken it for at least 12 weeks and having shown at least a 25% reduction of symptoms at dose, then on average it would take 218 days before their symptoms “relapse” (i.e., return to 90% or higher in severity of their previous ADHD symptoms).
While these benefits make Strattera seem quite attractive for patients seeking an alternative ADHD treatment, it’s important to also consider the possible side effects.
The top five most common side effects for children:
The top five most common side effects for adults:
What affects the severity of experiencing side effects? One important factor is whether a patient is a rapid or slow metabolizer of this drug, since the longer the medication stays in your system, the more likely you will experience side effects. There is a lot of variability in how long Strattera stays in each person’s system and how long it takes your body to eliminate it from your blood. Also, drugs such as fluoxetine, paroxetine, and quinidine can decrease elimination of Strattera, which can lead to side effects.
If a patient experiences severe side effects, a clinician may want to consider giving them a lower dose. When this happens, one possibility is that the patient happens to be a slow metabolizer. So whereas someone who metabolizes Strattera rapidly may need a higher dose to see results, another individual may see results with a lower dose, which is also easier for their body to tolerate. There’s no way to know where you fall on the spectrum, so expect to go through a trial period in the beginning of treatment.
Another relevant factor here is whether a patient takes their dose as a single pill or as two pills. Adverse effects were quicker to occur in those who took Strattera once a day, rather than a smaller dose twice per day. This makes sense given that a higher concentration of the drug is more likely to cause side effects (e.g., taking 40mg at once as compared with 20mg in the morning and 20 mg in the afternoon).
One challenge is that some side effects are reduced and others are increased given different dosing. For example, while insomnia is more likely to occur with twice daily dosing, reduced appetite and nausea/vomiting are less likely to occur. A useful strategy would be to implement twice daily dosing, but instruct the patient to take each dose 4-6 hours apart (e.g., 8am and 12pm or 2am and 2pm) or to take the medication with food to see whether this will reduce the gastrointestinal side effects while also minimizing insomnia.
If you’re curious about non-stimulant treatments for ADHD, Strattera may be a good alternative to try. Contact our clinic today to explore what might work for you or your child.