Article

A Controlled Clinical Trial of Bupropion

for Attention Deficit Hyperactivity Disorder in Adults

Timothy E. Wilens, M.D. Objective: Despite the increasing recog-
nition of attention deficit hyperactivity
disorder (ADHD) in adults, there is a pau-
Thomas J. Spencer, M.D. city of controlled pharmacological trials
demonstrating the effectiveness of com-
Joseph Biederman, M.D. pounds used in treatment, particularly
nonstimulants. The authors report results
Kristine Girard, M.D. from a controlled investigation to deter-
mine the anti-ADHD efficacy of bupro-
pion in adult patients with DSM-IV ADHD.
Robert Doyle, M.D.
Method: This was a double-blind, pla-
cebo-controlled, randomized, parallel, 6-
Jefferson Prince, M.D. week trial comparing patients receiving
sustained-release bupropion (up to 200
David Polisner, B.A. mg b.i.d.) (N=21) to patients receiving pla-
cebo (N=19). The authors used standard-
Ramon Solhkhah, M.D. ized structured psychiatric instruments
for diagnosis of ADHD. To measure im-
provement, they used separate assess-
Sharyn Comeau, M.D. ments of ADHD, depression, and anxiety
symptoms at baseline and each weekly
Michael C. Monuteaux, B.A. visit.
Results: Of the 40 subjects (55% male)
Asha Parekh, M.D. enrolled in the study, 38 completed the
study. Bupropion treatment was associ-
ated with a significant change in ADHD
symptoms at the week-6 endpoint (42%
reduction), which exceeded the effects of
placebo (24% reduction). In analyses us-
ing a cutoff of 30% or better reduction to
denote response, 76% of the subjects re-
ceiving bupropion improved, compared
to 37% of the subjects receiving placebo.
Similarly, in analyses using Clinical Global
Impression scale scores, 52% of the sub-
jects receiving bupropion reported being
“much improved” to “very improved,”
compared to 11% of the subjects receiv-
ing placebo.
Conclusions: These results indicate a
clinically and statistically significant effect
of bupropion in improving ADHD in
adults. The results suggest a therapeutic
role for bupropion in the armamentar-
ium of agents for ADHD in adults, while
further validating the continuity of phar-
macological responsivity of ADHD across
the lifespan.

(Am J Psychiatry 2001; 158:282–288)

T here is an increasing awareness of the presence of at-

tention deficit hyperactivity disorder (ADHD) in adults.
Despite controversy (1), studies of clinical correlates, neu-
ropsychology, familial aggregation, and neuroimaging
have supported the validity of this disorder in adults (2).
Adults with ADHD have high rates of psychopathology,
substance abuse, social dysfunction, and academic and
occupational underachievement (3–5). Conversely, adults
with ADHD are overrepresented among those seeking
treatment for substance abuse (6, 7) and depression (8).
Although ADHD was initially conceptualized as a child-
hood disorder, follow-up studies have documented that
approximately one-half of affected youth continue to have
ADHD into adulthood (3, 9–11). Although epidemiological
data are limited, a relatively recent study suggests that up
to 4.7% of adults may meet criteria for ADHD (12).
Despite the emerging recognition of adult ADHD, there
is a paucity of data on the treatment of this disorder (13).
For instance, in contrast to the more than 200 controlled
studies of stimulant use in children with ADHD (14–16),
we are aware of only nine controlled studies of the use of
stimulants in adults with ADHD (14). Although this work
has demonstrated the efficacy of stimulants for the treat-
ment of adult ADHD, the multiple daily doses, scheduled
prescribing restrictions, anxiogenic properties, and liabil-
ity for abuse limit their usefulness in treating subgroups of
adults with ADHD (14, 17). Moreover, the co-occurrence of
mood and substance use disorders in patients with ADHD
supports the development of safe and effective nonstimu-
lant alternatives.
Tricyclic antidepressants and bupropion have emerged
as second-line agents for treating pediatric ADHD (16).
Bupropion is a novel aminoketone antidepressant related
to the phenylisopropylamines and pharmacologically dis-
tinct from available antidepressants (18, 19). Bupropion
has been shown in preclinical studies to manifest antide-
pressant properties with indirect dopaminergic and nora-
drenergic agonist effects, although the clinical relevance
of these findings remains unclear (19). Bupropion at doses
of up to 6 mg/kg per day has been shown in controlled
clinical trials in youth to be effective in reducing ADHD
symptoms, albeit less robustly than stimulants (16, 20–22).
Data on ADHD in adults, however, are restricted to one
open trial of 19 adults treated with an average of 360 mg/
day of bupropion for 6–8 weeks (23). In this 1990 study,
Wender and Reimherr (23) observed that 74% of patients

282 Am J Psychiatry 158:2, February 2001


completing the trial manifested a positive and sustained
response. Although this information was helpful, the high
dropout rate (27%), the open nature of the study, and the
recent availability of a sustained-release preparation of
bupropion necessitate a reexamination of the role of this
compound in the treatment of adults with ADHD. To this
end, we conducted a placebo-controlled trial of the sus-
tained-release preparation of bupropion in a well-charac-
terized group of adults with ADHD. On the basis of the
available pediatric and adult literature, we hypothesized
that bupropion would be superior to placebo in the treat-
ment of adults with ADHD.
Method
Subjects
Subjects were outpatient adults with ADHD who were between
20 and 59 years of age and who were recruited from advertise-
ments and clinical referrals to a clinical psychopharmacology
clinic. We excluded potential subjects if they had any clinically
significant chronic medical conditions, a history of cardiac ar-
rhythmias or seizures, mental retardation (IQ <75), organic brain
disorders, clinically unstable psychiatric conditions, bipolar dis-
order, drug or alcohol abuse or dependence within the 6 months
preceding the study, or current use of psychotropics. This study
was approved by the institutional review board of our facility; all
subjects completed written informed consents before inclusion
in the study.
Assessment Measures
Subjects underwent a standard clinical assessment comprising
a psychiatric evaluation, a structured diagnostic interview, a cog-
nitive battery, a medical history, physical and neurological exami-
nations, an ECG, and an SGOT test. The diagnostic interview used
was the Structured Clinical Interview for DSM-III-R and DSM-IV,
supplemented for childhood disorders by unmodified modules
from the Schedule for Affective Disorders and Schizophrenia for
School-Age Children—Epidemiologic Version (24). To obtain a full
diagnosis of adult ADHD, the subject had to have 1) fully met the
DSM-IV criteria for a diagnosis of ADHD by the age of 7 as well as
currently (within the past month), 2) described a chronic course of
ADHD symptoms from childhood to adulthood, and 3) endorsed a
moderate or severe level of impairment attributed to those symp-
toms. The diagnostic reliability between raters and board-certified
psychiatrists was excellent. A kappa of 1.0 was obtained for ADHD
diagnosis, with a 95% confidence interval of 0.8–1.0.
To assess intellectual functioning, we administered subtests of
the WAIS-R and the Wide-Range Achievement Test 3 (25). Socio-
economic status was measured by use of the Hollingshead Four-
Factor Index of Social Status; low values indicated high socioeco-
nomic status.
To assess change during treatment, we examined ADHD, de-
pression, and anxiety symptoms. As in previous reports (26, 27),
overall severity in each of these domains was assessed with the
Clinical Global Impression (CGI) scale (28). The CGI includes glo-
bal severity (1=“not ill” to 7=“extremely ill”) and global improve-
ment (1=“very much improved” to 7=“very much worse”) scales.
The intraclass correlation coefficient for the CGI was 0.91. In ad-
dition, the following domain-specific rating scales were used. To
assess ADHD improvement, we used the ADHD Rating Scale (29–
31), which has been shown to be sensitive to drug effects in pedi-
atric (29) and adult groups (26, 27, 32, 33). This scale, updated for
DSM-IV (31), assesses each of 18 individual criteria symptoms by
using an identical severity grid (0=“not present,” 3=“severe”; over-
Am J Psychiatry 158:2, February 2001
WILENS, SPENCER, BIEDERMAN, ET AL.
all minimum score=0, overall maximum score=54) that has been
shown to be correlated with ADHD in adults (34, 35) and is medi-
cation-sensitive (26, 27, 32, 33). An intraclass correlation of 0.85
was obtained for the ADHD symptom checklist. For depression
we used the Hamilton Depression Rating Scale (minimum=0,
maximum=64) (36) and the Beck Depression Inventory (mini-
mum=0, maximum=63) (37). For anxiety we used the Hamilton
Anxiety Rating Scale (minimum=0, maximum=56) (38). In addi-
tion, adverse experiences were systematically recorded at each
visit. Although the ADHD symptom checklists and the CGI were
administered at baseline and at each follow-up visit, the Hamil-
ton Anxiety Rating Scale, Hamilton Depression Rating Scale, and
Beck Depression Inventory were administered only at baseline
and at the end of the study.
Procedures
This was a double-blind, placebo-controlled, randomized, par-
allel 6-week trial comparing the results obtained with sustained-
release bupropion (up to 200 mg b.i.d.) to those obtained with
placebo in adults with DSM-IV ADHD. Weekly supplies of bupro-
pion or placebo were dispensed by the pharmacy in identically
appearing 100-mg capsules. Subjects were instructed to take their
medication on rising and again approximately 6 hours later.
Compliance was monitored by means of pill counts at each phy-
sician visit. The study medication dose was begun with 100 mg in
the morning and increased by 100 mg weekly in twice-a-day
doses up to 200 mg twice daily (week 4), unless adverse events
emerged or the subject noted optimal improvement at a lower
dose. Vital signs were assessed at baseline and each week.
Statistical Analysis
On the basis of our projected group size of 20 subjects per treat-
ment arm, a bupropion response rate of 60%, a placebo response
rate of 10%, and an alpha level of 0.05, we calculated our statisti-
cal power to be 0.89. Thus, the probability of a type II error in our
analysis was 0.11. Improvement in ADHD symptoms was defined
as a reduction in the ADHD Rating Scale score of 30% or better.
For analyses of CGI and ADHD Rating Scale scores, we used the
intent-to-treat method with the last observation carried forward.
To compare the proportion of subjects improving while taking
bupropion versus the number improving while taking placebo,
we used Fisher’s exact test. To compare ordinal data between two
time points, we used the Wilcoxon signed-rank test for paired
data. To compare ordinal and continuous data at baseline or end-
point, we used the Wilcoxon rank-sum test. To compare study
groups on binary outcomes, we used Fisher’s exact test. For con-
tinuous variables, we tested for group differences using linear re-
gression and generalized estimation equations that estimated the
main effects of drug (bupropion versus placebo) and time (week
in study), as well as any interactions among variables. The model
assumed a subject-specific residual that differed between sub-
jects but was constant over time (39, 40). All statistical analyses
were performed by using Stata (Stata Corporation, College Park,
Tex.). All statistical tests were two-tailed, with statistical signifi-
cance at 0.05. Data are expressed as means and standard devia-
tions unless otherwise specified.
Results
Of the 154 subjects screened, 40 (26%) subjects were en-
rolled in the study (30 were not interested, 27 did not re-
turn for follow-up, 17 had current substance abuse, 11
were receiving exclusionary psychotropics, 10 had no
ADHD, nine had bipolar or psychotic disorder, six had
medical contraindications, and four had previous expo-
283
BUPROPION FOR ADHD IN ADULTS

TABLE 1. Characteristics of Adults With DSM-IV Attention Deficit Hyperactivity Disorder Who Were Treated With Either Sus-
tained-Release Bupropion or Placebo
Subjects Treated With Subjects Treated With
Characteristic Placebo (N=19)a Bupropion (N=21)a Total (N=40)a
N % N % N %

Male 10 53 12 57 22 55
Psychiatric disorders and smokingb
Major depressionc
Past 11 61 11 58 22 59
Current 1 6 6 32 7 19
Two or more anxiety disorders
Past 2 11 5 26 7 19
Current 2 11 1 5 3 8
Substance abuse or dependence
Past 7 39 6 32 13 35
Current 0 0 0 0 0 0
Smoking
Past 7 37 6 29 13 33
Current 1 5 3 14 4 10
Alcohol abuse or dependence
Past 7 39 7 37 14 38
Current 0 0 0 0 0 0
Antisocial personality disorder
Past 3 17 3 16 6 16
Current 0 0 0 0 0 0
Any comorbid disorder
Past 16 89 17 89 33 89
Current 7 39 11 58 18 49

Mean SD Mean SD Mean SD

Age (years) 39.6 10.4 37.0 11.8 38.3 11.1

Socioeconomic statusd 2.2 1.1 2.2 1.0 2.2 1.0
Current Global Assessment of Functioning scale score 52.9 7.1 50.7 6.9 51.8 7.0
Cognitive scores
WAIS IQ
Full-scale 104.1 11.2 107.1 15.2 105.7 13.4
Freedom from distractibility 94.2 8.5 97.5 14.8 96.0 12.2
Wide-Range Achievement Test 3 score
Arithmetic 92.8 14.0 96.0 15.8 94.5 14.9
Reading 105.1 11.0 105.4 9.3 105.2 10.0
Psychiatric rating scale scores
Beck Depression Inventory 9.4 9.5 11.5 8.9 10.5 9.1
Hamilton Depression Rating Scale 6.7 4.3 7.8 5.1 7.3 4.7
Hamilton Anxiety Rating Scale 8.5 4.4 7.8 5.1 8.2 4.7
a Data for some variables were missing for up to three subjects.
b Not mutually exclusive.
c Cases with at least moderate impairment.
d Measured by means of the Hollingshead Four-Factor Index of Social Status scale, in which low values indicate high status.

sure to bupropion). The final study group consisted of 18
women and 22 men who ranged in age from 20 to 59 years
(mean=38, SD=11). Thirty-eight subjects completed the
protocol; two subjects dropped out because of noncom-
pliance (both receiving bupropion).
Demographics and Comorbidity
Subjects were most frequently diagnosed with the inat-
tentive subtype of ADHD (N=23, 58%), followed by the
combined (N=14, 35%) and hyperactive or impulsive sub-
types (N=3, 8%). As depicted in Table 1, 89% of the subjects
with ADHD had at least one past comorbid psychiatric dis-
order; for 49% (data were missing for three subjects), the
comorbid disorder was also present within the past month.
The results did not differ significantly between the placebo
and bupropion groups (past ADHD: p=1.00, Fisher’s exact
test; current ADHD: p=0.33, Fisher’s exact test). Before en-
tering this study, 11 subjects had been taking medications
for ADHD, seven had received counseling, and seven had
received both medication and counseling. Despite this
group of adults with ADHD possessing average to above-
average intelligence, 17 (46%) had required tutoring in
school, and 11 (30%) had repeated at least one grade (some
data were missing). The rate of past smoking status did not
differ between the patients in the bupropion and placebo
arms (p=0.74, Fisher’s exact test). Likewise, there were also
no significant differences in terms of current smoking sta-
tus (p=0.61, Fisher’s exact test).
Outcome Assessment
By using categorical definitions of ADHD improvement
(with last observation carried forward), bupropion was

284 Am J Psychiatry 158:2, February 2001


found to be clinically and statistically superior to placebo
in adult patients. By using a predefined criteria of a CGI
improvement rating of 1 or 2 (“much improved” to “very
much improved”), a significantly higher proportion of
subjects were considered improved while receiving bu-
propion than while receiving placebo (N=11, 52%; N=2,
11%) (p=0.007, Fisher’s exact test). A similar result was ob-
tained by using a preestablished definition of improve-
ment of 30% or more reduction in scores on the DSM-IV
ADHD symptom checklist (N=16, 76%; N=7, 37%) (p=0.02,
Fisher’s exact test). The same pattern of results was ob-
served when the group was stratified by past and current
smoking status, although statistical significance was not
reached because of reduced group size.
Although the subjects with ADHD who were randomly
selected for the active treatment arm had a baseline mean
score of 32.9 (SD=7.8, range=21–47) on the ADHD symp-
tom checklist, week-6 endpoint analysis (with last observa-
tion carried forward) revealed a 42% reduction in scores
(week 6: mean=19.2, SD=11.0, range=0–41). Comparatively,
placebo group baseline scores (mean=31.3, SD=8.5, range=
19–47) decreased by only 24% by week 6 (mean=23.8, SD=
11.8, range=7–46), resulting in a significant difference be-
tween groups (t=–2.02, df=39, p=0.05, linear regression).
Results from the generalized estimation equations model,
using ADHD symptom checklist scores from all time
points, indicated a significant effect of time (z=–4.66,
p<0.001), no significant main effect of drug (bupropion or
placebo) (z=0.69, p=0.49), and no drug-by-time interaction
for ADHD symptoms (z=–1.29, p=0.20). The bulk of im-
provement in ADHD symptom profiles occurred in weeks 5
and 6.
We also evaluated the impact of treatment on the 18
DSM-IV specific symptoms of ADHD (with last observa-
tion carried forward). These analyses showed that com-
pared to baseline, a significantly greater number of ADHD
symptoms improved in subjects receiving bupropion
compared to those receiving placebo: all 18 symptoms im-
proved significantly in the bupropion-treated group,
whereas only eight (44%) of 18 of the symptoms improved
in the placebo group (p<0.001, Fisher’s exact test). Re-
sponse to treatment was not significantly related to DSM-
IV ADHD subtype (inattentive versus combined).
Baseline ratings of depression (mean Hamilton depres-
sion scale score and mean Beck Depression Inventory
score) and anxiety (mean Hamilton anxiety scale score)
were relatively low and did not differ between groups (all
p>0.05, Wilcoxon rank-sum test). When using standard
cutoff points for depression (Hamilton depression scale
score: >16, Beck Depression Inventory score: >19, and CGI
severity scale score: 4) and anxiety (Hamilton anxiety scale
score: >21 and CGI severity scale score: 4), eight subjects
had scores indicative of depression at baseline per the CGI
severity scale (three taking placebo and five taking bupro-
pion), five had scores above the Beck Depression Inven-
Am J Psychiatry 158:2, February 2001
WILENS, SPENCER, BIEDERMAN, ET AL.
tory cutoff (two taking placebo and three taking bupro-
pion), and eight had scores indicative of anxiety per the
CGI severity scale (three taking placebo and five taking bu-
propion). There was no significant medication effect
(medication versus placebo at endpoint) on the Hamilton
depression scale, Beck Depression Inventory, or Hamilton
anxiety scale, including analyses of all subjects stratified
by the presence of abnormal baseline scores (all p>0.05,
Wilcoxon rank-sum test). There was no difference in
ADHD symptom checklist scores or CGI ADHD scores
(improvement or severity) in adults with past or current
anxiety or major depression (placebo or bupropion group,
p>0.05, Wilcoxon rank-sum test). Similarly, there was no
effect of gender or socioeconomic status on response to
bupropion, although we lacked adequate statistical power
to fully evaluate the impact of treatment on comorbidity,
socioeconomic status, or gender.
There was no relationship between response and bu-
propion daily dose (t=–0.11, df=19, p=0.91). Average daily
doses of placebo and bupropion at the end of the trial
(week 6) were 379 mg/day and 362 mg/day, respectively. At
the conclusion of the study, 16 bupropion subjects (76%)
were receiving the full dose of 400 mg/day, two (10%) were
receiving 300 mg/day, and three (14%) were receiving 200
mg/day. A total of 57% (12 out of 21) of the bupropion re-
sponders opted to continue with bupropion treatment at
the conclusion of the study.
Adverse Effects
No serious adverse drug effects were observed during
the trial. Adverse effects reported in at least two (5%) of the
subjects included headache (bupropion: 19%; placebo:
16%), gastrointestinal problems (19% versus 16%), insom-
nia (38% versus 16%), aches or pains (10% versus 5%), dry
mouth (10% versus 0%), and chest pain (10% versus 0%).
There were no statistically significant differences between
the study groups in the rates of any single adverse event or
in the rate of at least one adverse event (bupropion: N=14,
67%; placebo: N=11, 58%) (all p>0.05, Fisher’s exact test).
Not including the two bupropion dropouts, five subjects
taking bupropion and three subjects taking placebo low-
ered their dose because of adverse effects.
Evaluation of vital signs failed to reveal any differences
between the subjects in the bupropion and placebo arms.
Specifically, there were no statistically significant effects of
bupropion compared to placebo on heart rate at week 6
(mean=78.4, SD=14.4; mean=72.7, SD=12.0, respectively)
(z=–1.35, p=0.18, Wilcoxon rank-sum test). Likewise, there
were no significant differences between the treatment
groups at endpoint on systolic (mean=127.9, SD=13.2;
mean=124.6, SD=18.2) (z=–0.83, p=0.41, Wilcoxon rank-
sum test) or diastolic (mean=73.5, SD=10.2; mean=73.1,
SD=9.0 (z=–0.15, p=0.88, Wilcoxon rank-sum test) blood
pressure.
285
BUPROPION FOR ADHD IN ADULTS
Discussion
In this randomized, double-blind, placebo-controlled
trial, our results demonstrated the clinical efficacy and tol-
erability of sustained-release bupropion for the treatment
of ADHD in adults. By clinical impression, 52% of adults
with ADHD who received bupropion were considered
“much improved” to “very much improved,” whereas only
11% of those receiving placebo were so classified (p=0.007,
Fisher’s exact test). This modest therapeutic effect was
seen after several weeks, which suggests an apparent de-
layed onset of action in these adults with ADHD.
The current results confirm and extend previous open
findings in adults (23) and adolescents (41), as well as con-
trolled studies in juveniles (20–22), that found bupropion
to be effective in reducing ADHD symptom profiles. Our
response rate (30% or more reduction in ADHD symptom
checklist score) is identical to that reported in an open
study by Wender and Reimherr (23) using the immediate-
release preparation of bupropion. Moreover, the magni-
tude of response observed in the current study is similar to
that found in previous controlled investigations in chil-
dren and adolescents with ADHD employing similar
weight-corrected doses of bupropion (20–22). Hence, as in
results found in children and adolescents, our data indi-
cate that adults with ADHD respond favorably to bupro-
pion treatment.
The relatively low placebo response noted in the current
study is consistent with data from our previous studies
documenting the low placebo response in adult ADHD
(26, 27, 32, 42). The 52% response rate (per the CGI scale)
observed with bupropion in this study was somewhat
lower than the response rate observed in our prior, meth-
odologically similar trials of methylphenidate (87%) (26),
desipramine (89%) (27), and amphetamine compounds
(75%) (43). However, the response rate to bupropion was
similar to that achieved with pemoline (50%) (42), an ex-
perimental cognition-enhancing agent (40%) (33), and the
nonstimulant investigational agent tomoxetine (52%)
(32). Hence, given the current results, bupropion appears
to follow stimulants and desipramine in terms of efficacy
for treating ADHD in adults. It remains unknown whether
a longer study at higher doses could lead to better results.
The study was only 6 weeks long; that may have been in-
sufficient time for the full clinical benefit of bupropion to
unfold. In support of this notion, our data suggest that the
therapeutic value of bupropion was most striking in the fi-
nal 2 weeks of the study, after the subjects had achieved
their highest dose of bupropion. Our current data mirror
previous data with desipramine in adults with ADHD,
which indicated a delayed onset of maximal efficacy, with
the largest improvement occurring after the dose was
maximally titrated (i.e., between the 2-week end of titra-
tion and 6-week endpoint) (27).
This study was not a dose-response evaluation; our re-
sults did not identify statistically significant associations
286
between clinical effect and bupropion dose, which is con-
sistent with findings in pediatric studies of bupropion and
other antidepressants (16). Consistent with our previous
controlled studies in adults with ADHD, response to bu-
propion was not affected by gender or social class. More-
over, our lack of a significant association of past or current
depression or anxiety influencing ADHD symptoms sug-
gests that bupropion is effective in the presence of anxiety
or depression in reducing the symptoms of ADHD.
As part of its mechanism of action, bupropion has been
shown to potentiate dopaminergic neurotransmission
(19). The current findings support the notion that phar-
macological agents that are effective in reducing ADHD
symptoms have similar catecholaminergic properties (16,
44). Agents such as stimulants and antidepressants appear
to facilitate directly norepinephrine and dopamine neu-
rotransmission, whereas nicotinic cognitive enhancers
may indirectly affect such systems (33, 45, 46). For exam-
ple, research suggests that recently described polymor-
phisms in the postsynaptic D4 receptor in youth (47) and
adults (48) with ADHD may result in a blunted response to
dopamine (49). If substantiated, these findings would fur-
ther the hypotheses linking ADHD with catecholaminer-
gic dysregulation in general and dopaminergic systems in
particular (44).
The results of this study should be viewed in light of its
methodological limitations. Only 26% of the subjects
screened were enrolled in the study. The majority of sub-
jects were from relatively high socioeconomic strata;
hence, the results of the current study may not generalize
to lower socioeconomic strata. Despite subjects meeting
criteria for a lifetime diagnosis of depression or anxiety
per structured psychiatric interview, the majority had low
current scores on depression and anxiety rating scales,
which limited our ability to evaluate the efficacy of bupro-
pion in these comorbid conditions. Other limitations in-
cluded the use of a relatively short exposure to a full dose
of medication, which may not have allowed adequate time
for the full therapeutic benefit of bupropion treatment to
emerge.
Although our results are based on self-reports from af-
fected individuals, it has been suggested that subjects with
ADHD may not be ideal reporters of their disorder (29). Al-
though this places some limits on the interpretation of our
results, the significant effects on ADHD symptoms ob-
served in this and previous studies (26, 27, 32, 33, 42, 50)
suggest that adults with ADHD are acceptable reporters of
their own condition. In addition, self-reports of ADHD
symptoms have been shown to be a reliable and valid
method of assessing ADHD in adults (51, 52).
Despite these limitations, the results of this study show
that bupropion significantly improved ADHD symptoms
in adults. Bupropion may have a delayed onset of action of
from 4 to 6 weeks in treating ADHD. Given that it has less
efficacy for ADHD compared to stimulants (26, 43), bupro-
pion appears to be useful as a second-line agent for the
Am J Psychiatry 158:2, February 2001

treatment of uncomplicated ADHD in adults. However,
because of its freedom from the liability of abuse, bupro-
pion may be considered a first-line therapy in special
groups of individuals with ADHD, such as those with
substance abuse (53) or co-occurring prominent mood la-
bility (54). Since some stimulants (methylphenidate,
pemoline, and amphetamine compounds) and some anti-
depressants (desipramine and bupropion) have now been
shown in controlled trials to be effective in treating both
pediatric and adult forms of ADHD, the present results
further support the validity of ADHD in adults and the
continuity of treatment responsivity across the lifespan.
Presented in part at the 39th annual meeting of the New Clinical
Drug Evaluation Unit, Boca Raton, Fla., June 1–4, 1999, the 152nd
annual meeting of the American Psychiatric Association, Washing-
ton, D.C., May 15–20, 1999, and the 46th annual meeting of the
American Academy of Child Psychiatry, Chicago, Oct. 20–24, 1999.
Received Sept. 1, 1999; revision received March 16, 2000; accepted
April 14, 2000. From the Pediatric Psychopharmacology Clinic,
Massachusetts General Hospital, Harvard Medical School. Address
reprint requests to Dr. Wilens, Pediatric Psychopharmacology Clinic,
ACC 725, Massachusetts General Hospital, Boston MA 02114;
wilens@helix.mgh.harvard.edu (e-mail).
Supported by grants from Glaxo Wellcome Incorporated, the NIH
(MH-011175), and the National Institute on Drug Abuse (DA-11315)
(Dr. Wilens).
The authors thank John Vetrano, Harold Demonaco, and the phar-
macy staff at Massachusetts General Hospital for their help.
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