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What is the role of bupropion for the
management of adult patients with ADHD?

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Attention deficit hyperactive disorder
usually abbreviated as ADHD or ADD is a mental disorder which is commonly
diagnosed in children and teens and can continue into adulthood.  The prevalence of ADD is quite significance
the United States.1 According to the diagnoses and statistical
manual of mental disorders, between 3 to 7% of school- age children and 4.1% of
the adult population have ADD.1 People with ADD often show signs
ranging from being constantly distracted, unable to follow instructions,
forgets about daily activities and extreme difficulty in engaging in activity
that requires sitting still.1

Health care providers, such as
pediatricians, psychiatrists and child psychologists can diagnose ADHD after
giving a full physical exam including vision and hearing screenings on patients
who have shown some signs and symptoms.2 Also, the Foods and Drug
Administration has approved use of the Neuropsychiatric Electroencephalograph
-Based Assessment Aid (NEBA) System, a noninvasive scan that measures theta and
beta brain waves. The theta to beta ratio has been shown to be higher in
children and adolescents with ADHD than in children without it according to the
ADHD guidelines.2

Even though there are non-pharmacological
interventions such as behavioral therapy and Cognitive behavioral therapy, the
use medication is studied to be most effective way of treating ADHD. One
extensively studied medications for the treatment of ADHD in adults is

A randomized, double-blind,
placebo-controlled, parallel-design clinical trial hypothesized bupropion could
be effective in the treatment of adult ADHD. The trial used a sample size of 42
outpatient subjects between the ages of 20 and 60 years who were referred to a
psychiatrist for psychiatric evaluation. The subjects were visited by a
psychiatrist and when adult ADHD diagnosis was proven to exist according to the
DSM-IV-TR grading scale, they were asked to consent and participate in the study.
The trial was conducted over a 6week period with a one control arm and placebo
arm. Subjects in the control arm representing half of the sample size was given
a daily dose of 75 mg (150 mg max) of bupropion whiles the other half was given
a placebo. The trial was well organized because it adopted a rigorous inclusion
criteria which ensured patients with medically confirmed disease state were
included in the trial.  At the end of the
6th week, the bupropion group showed significant improvement in
their signs and symptons with the p value of 0.037 which indicates a significant
positive clinical impact in the management of ADHD with bupropion.

In spite of this, the trial recorded a
high incidence of side effects causing some of the subject to drop out
entirely. About 42% of patients reported insomnia upon taking the medication,
52% reported fatigue whiles another 43% also reported anxiety and palpitation.
In addition to these side effects, the trial had some limitations such as small
sample size which raises concerns about its external validity. Coupled with the
small sample size, it was stated in the results that significant improvement in
signs and symptoms was not recorded until the last week of the trial. Given the
serious side effect panel of the drug, many of the subjects withdrew from the
trial before the last week hence further reducing the amount of data that was
used in making efficacy conclusions about the medication. Furthermore, the
nature of the trial could not permit the researchers to observe patients in a
confined environment for a long period of time. There was no way to determine
if any of the subjects originally selected for the trial were still in
compliance with the inclusion criteria or not by the 6th week. This
also poses a serious threat to the consistency of the outcome and its external

The second
clinical trial is also a randomized, double-blind, placebo-controlled, parallel
design conducted over a period of 6 weeks with Fifty-nine patients (43 males,
16 female) who were evaluated for inclusion if they had at least moderate
impairment of both motor hyperactivity and attention difficulties. Patients who
were unable to complete tasks or disorganized, hot tempered, emotionally over
reactive with inability to tolerate stress and also impulsive were included
after the intensity of their symptoms was assessed using the Wender Utah Rating
Scale for the Attention Deficit Hyperactivity Disorder (WRAADDS) grading tool.
As a major strength of this trial, the researchers used a two stage inclusion
criteria which involved two grading scales for outpatient subjects.  Not only were they assessed by the DSM-IV
grading scale but also the more restrictive Utah Criteria for ADHD in adults
and to have a minimum score of 15 on the Wender-Reimherr Adult Attention
Deficit Disorder Scale. Patient with co- morbid conditions like cardiac
arrhythmias, seizures, recent drug or alcohol abuse, any bipolar disorder, and
current use of psychotropic medications were also excluded from the trial.

During the
trial, bupropion SR was initiated at 100 mg/day and titrated by 100-mg/day
increments based on clinical response and as tolerated to a maximum dose of 400
mg/day (200 mg twice daily). At the end of the trial, patients on bupropion SR
showed a 50% improvement in their WRAADDS scores from the screening visit to
the last visit in the double-blind period ,11% and 39% respectively, with a p
value less than 0.05 representing a significant portion of the patients.

Although the study showed that
bupropion was efficacious in improving symptoms of ADHD after the trial period,
the researchers relied on family members of the targeted patients for
information for initial assessment and inclusion of patients. There is the
tendency for misinformation and bias if the researchers rely solely on word of
mouth from patient’s family without doing further tests to confirm this
information. Since this forms the basis for the inclusion criteria of the
trial, it raises concerns about the internal validity of the trial which can
potentially affect its external validity.

There is evidence for the benefits of
bupropion in the management of ADHD as stated by the two trials however,
certain lapses in the set up of the trial, the selection of subjects and total
number of subjects considered for the trial raises some concerns about the
credibility of the outcomes and the conclusions of these trials.


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