This article provides answers to several common questions associated with the use of Strattera® (atomoxetine HCl) to treat patients with ADHD. Strattera is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children age 6 and older, adolescents, and adults.
This article provides answers to several common questions associated with the use of Strattera® (atomoxetine HCl) to treat patients with ADHD. Strattera is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children
age 6 and older, adolescents, and adults.
Is atomoxetine an efficacious medication for ADHD?
There have been more than a dozen double-blind, randomized
controlled ADHD trials of atomoxetine in children, adolescents,
and adults with ADHD and all clinical studies have had a positive
efficacy outcome. Each of these studies demonstrates a very
clear statistically significant and clinically meaningful advantage
of atomoxetine over placebo.
Why do many clinicians report not having the same clinical success with atomoxetine that they might with stimulants or other medications?
A number of factors may be contributing to the differential perception
of efficacy between stimulants and atomoxetine. The most
basic explanation is that the magnitude of benefit for many patients
may be greater with stimulants and there is some research to support
this from head-to-head studies.8,9 However, other factors can
also contribute to the perception of an efficacy gap. Central to these
factors, I believe, is the fact that atomoxotine works via a different
mechanism of action compared to the stimulants, and therefore
exhibits a different therapeutic time-course. Atomoxetine is a selective
norepinephrine reuptake inhibitor. ADHD symptom reduction
begins early but accrues slowly and steadily over many weeks
before marked benefits are achieved.1 In fact, data suggests that it
may require 4-6 weeks before marked benefits are seen. As a result,
changes in patients are gradual and subtle and therefore can be
more easily overlooked by patients compared to the rapid symptomatic
improvement experienced by some patients taking stimulant
medications every morning. In essence, patients may report that
atomoxetine is not having any effect, when indeed it may be. This
could be because it produces symptom improvement that grows
slowly and steadily over time in contrast to the more apparent daily
onset associated with stimulants.
One possible explanation for a perceived less apparent response
with atomoxetine is that patients who had experienced the more
dramatic response to stimulants previously may be less able to
recognize the more subtle therapeutic benefits of atomoxetine.
What can clinicians do to help patients recognize the therapeutic effects of atomoxetine?
A potential gap in perceived versus actual benefit of atomoxetine
may often be mitigated if clinicians take a more rigorous approach
to evaluating the therapeutic effects of atomoxetine. This means
not relying solely on nebulous, open-ended questions to assess a
patient’s response to the medication (eg, “how are you doing?” or
“do you think the medication is working?”). Given the extremely
subtle course of atomoxetine’s therapeutic effects, patients will,
not infrequently, answer in the negative to such questions. The
clinician must, in those cases, pursue a more meticulous line of
questioning aimed at a patient’s specific target symptoms. Prior to
starting treatment, the clinician and patient should create a short
list of frequently occurring and debilitating ADHD target symptoms.
If a treatment is successful, these target symptoms would
decrease noticably. By doing this, clinicians and patients themselves
may be surprised how often an apparent lack of effect by
“Gestalt” assessment yields to recognition of improvement upon
specific target symptom assessment. Atomoxetine can produce
therapeutic benefits even before a patient is aware of it, especially
if they are a patient who has previously experienced the salient,
rapid therapeutic effects of a stimulant.
What are some of the considerations that go intomedication selection?
There is some evidence now that can inform this decision. For
example, a recent double-blind study of children with ADHD and
co-morbid anxiety confirms the experience of many physicians
that atomoxetine may be a good choice in this population, as it
demonstrated significant reduction in ADHD for patients with
ADHD and co-morbid anxiety symptoms.10 However, in general, I
don’t think we know enough in this regard to reliably categorize
patients as optimal candidates for one ADHD medication or the
other. The reality is that neither the physician nor the patient
can, a priori, predict which patient will respond well or poorly
to any given medication option. As a result, I take a very different
approach, which can be considered the antithesis of trying to
match a patient with a medication.
The first priority, and perhaps the most important thing to do in
this approach, is to establish the appropriate context and expectations.
I educate newly diagnosed adult patients or parents of child
patients that ADHD is a chronic condition requiring long-term treatment.
The good news, I tell them, is that medications are generally
highly efficacious and that there is a strong likelihood that one or
more of the available treatments will make a significant positive
impact on the patient’s quality of life. I explain to them that the
chronic nature of the illness combined with the general efficacy
of available medications mean that it is likely that they or their
child will be receiving treatment for many years. In my experience,
once a medication regimen has been established patients tend to
go on with their lives, and do not continually revisit whether the
established regimen they are taking is the optimal one. Therefore,
I explain to newly diagnosed patients that the initial period after a
diagnosis has been made, the period they are now in, is the time to
identify the optimal treatment regimen.
During this educational process, I admit to my patients that
I cannot reliably predict what medication will be best for them
and likewise, that they cannot predict this either. As such, I
encourage them to consider trying one of the first-line treatment
options available: one of the long-acting stimulant preparations,
on the one hand, and atomoxetine on the other. This is important
because many patients with ADHD, or parents of children with
ADHD, want a complete resolution of ADHD instantaneously,
and they will gravitate toward a stimulant simply for this reason
when selecting a treatment. This logic can thereby preclude the
opportunity to discover the potential benefits of atomoxetine.
One such benefit is 24-hour symptom coverage; atomoxetine can
provide ADHD coverage beyond the work and school day in a
once-daily dosing regimen. In addition, atomoxetine is the only
FDA-approved, non-scheduled medication for ADHD. With atomoxetine,
clinicians should also be familiar with the safety information
associated with ADHD treatments and share that with their
patients. This would be a discussion about the boxed warning
and other safety considerations. [Please see Important Safety
Information, including Boxed Warning and information regarding
the potential for Strattera to increase suicidal ideation, on page 6
and accompanying Full Prescribing Information on pages 7-13.]
How do patients generally respond to the suggestion of not simply seeking out the most rapid treatment for their ADHD?
My patients respond to this with varying degrees of acceptance.
I would concede that it is frequently the case that an urgent
therapeutic intervention is needed. For example, often by the
time they seek treatment they may be facing severe, imminent
consequences in school. Unless some reason for hope is provided
to teachers or school administrators, “the other shoe is going
to drop”. In those cases, I am usually in agreement with the
parent that a stimulant is the appropriate choice to stabilize the
situation. Nevertheless, I still present information about both
stimulants and atomoxetine. By laying down the mental ground
work, I’ve opened the possibility of revisiting atomoxetine when
the situational crisis has settled down.
More perplexing are adult ADHD patients, many of whom
have recently been diagnosed with ADHD for the first time in
their lives. Sometimes they have been struggling with the symptoms
for decades, and they find it hard to tolerate another day of
impairment now that the cause is identified. With such patients,
I try hard to change the mindset from a perceived need for an
immediate, impulsive fix, which is often part of ADHD, toward acceptance of a more systematic long-term approach to finding
the optimal treatment regimen. This is important because their
ADHD often impacts not only work but their family, friends, and
Once the context of expectations is set, how do you proceed?
I proceed to explain the risks and benefits of stimulants and
atomoxetine, as well as the potential advantages and disadvantages
of both. I explain that stimulants, while effective
in most patients, have a rapid onset of therapeutic benefit, and
they tend to wear off later in the day. This makes stimulants
a highly timing-dependant treatment; they work for “X”
number of hours a day, “X” being dependent on the specific
formulation of the medications available to treat ADHD and
the patient’s unique metabolism. This requires patients to
be very deliberate about timing in the use of stimulants.11 If
a patient misses a dose after a period of regular compliance,
they may typically experience the re-emergence of the full
effect of ADHD symptoms.
In contrast, atomoxetine takes a lot longer than stimulants
to reach its optimal therapeutic benefit, typically 4-6 weeks,
and sometimes, in my experience, even as long as 8-12 weeks,1
which could be viewed by some patients as a disadvantage.
However, if the patient responds to atomoxetine, he or she may
find convenience with the once-a-day dosing regimen. As with
other medications that are commonly utilized in psychiatry
that have delayed onset of optimal therapeutic benefit, the
therapeutic benefits of atomoxetine do not depend on which
time of day the medication is taken. In fact, it is not uncommon
for patients to take their atomoxetine in the evening or
even right before bedtime, something rarely done by patients
taking stimulants. Therefore, the benefits of atomoxetine are
not limited to “X” hours” after ingestion.2 Similarly, the therapeutic
effects produced by atomoxetine are typically much
more forgiving of missed doses. Patients who miss a dose typically
do not notice any loss of therapeutic benefit right away.3
Thus, the longer time needed for the benefits of atomoxetine
to manifest is often redeemed by the benefit of the 24-hour
ADHD symptom coverage.
Finally, one cannot overlook a difference between stimulants
and atomoxetine. Stimulants, unlike atomoxetine, are
scheduled medications. They are controlled drugs requiring a
special prescription form. For some patients, the requirement
of obtaining a new prescription each time they need more
stimulant medication may be an inconvenience.
Once you have set the appropriate context, educated patients about the chronic nature of treatment, described the main medication options, and discussed safety considerations, what comes next?
At that point I, as all clinicians should do, it is important to take a
thorough medical history and discuss safety considerations in order
to ensure appropriate medication selection. With appropriate screening,
there would be a discussion about important risk information.
One consideration with atomoxetine would be to discuss suicidal
ideation. A more complete summary of safety information can be
found on page 6. I ask them what they think about the medication
options I just described. If they have a strong desire for a medication
that is likely going to work rapidly, they will request a stimulant, at
which point I describe to them the options among the stimulants. If
they are amenable to trying both classes of medications in sequence,
or if they ask my opinion, then I will typically suggest beginning
with a trial of atomoxetine, if this treatment option is right for them.
Patients who have not experienced a stimulant effect may be more
likely to recognize the benefits of atomexetine than those who have
previously experienced a stimulant effect.
If appropriate and the patient agrees to a trial of atomoxetine,
I will initiate therapy, which includes setting appropriate expectations
with patients and titrating to a target dose of 1.2mg/kg
per day for four to six weeks before evaluating full efficacy. It is
important to set appropriate expectations with my patients because,
unlike stimulants, patients on atomoxetine do not have a noticeable
feeling associated with the medication that is common to stimulant
medications, and often do not notice the more gradual onset of atomoxetine.
As result, I will often select and track one or two specific
symptoms that are most troublesome to a patient and then revisit
these symptoms to help gauge the more gradual onset of action