Bupropion for Adhd in Adults

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282 Am J Psychiatry 158:2, February 2001

A Controlled Clinical Trial of Bupropion

for Attention Deficit Hyperactivity Disorder in Adults

Timothy E. Wilens, M.D.

Thomas J. Spencer, M.D.

Joseph Biederman, M.D.

Kristine Girard, M.D.

Robert Doyle, M.D.

Jefferson Prince, M.D.

David Polisner, B.A.

Ramon Solhkhah, M.D.

Sharyn Comeau, M.D.

Michael C. Monuteaux, B.A.

Asha Parekh, M.D.

Objective: Despite the increasing recog-

nition of attention deficit hyperactivitydisorder (ADHD) in adults, there is a pau-

city of controlled pharmacological trials

demonstrating the effectiveness of com-

pounds used in treatment, particularly

nonstimulants. The authors report results

from a controlled investigation to deter-

mine the anti-ADHD efficacy of bupro-

pion in adult patients with DSM-IV ADHD.

Method: This was a double-blind, pla-

cebo-controlled, randomized, parallel, 6-

week trial comparing patients receiving

sustained-release bupropion (up to 200

mg b.i.d.) (N=21) to patients receiving pla-

cebo (N=19). The authors used standard-ized structured psychiatric instruments

for diagnosis of ADHD. To measure im-

provement, they used separate assess-

ments of ADHD, depression, and anxiety

symptoms at baseline and each weekly

visit.

Results: Of the 40 subjects (55% male)

enrolled in the study, 38 completed the

study. Bupropion treatment was associ-

ated with a significant change in ADHDsymptoms 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 aclinically 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)

There 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, scheduledprescribing 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



Am J Psychiatry 158:2, February 2001 283

WILENS, SPENCER, BIEDERMAN, ET AL.

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 braindisorders, 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 forSchool-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-

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 wereadministered 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 inthe 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-




BUPROPION FOR ADHD IN ADULTS

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 (somedata 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

TABLE 1. Characteristics of Adults With DSM-IV Attention Deficit Hyperactivity Disorder Who Were Treated With Either Sus-tained-Release Bupropion or Placebo

CharacteristicSubjects Treated With

Placebo (N=19)aSubjects Treated With

Bupropion (N=21)a Total (N=40)a

N % N % N %

Male 10 53 12 57 22 55Psychiatric disorders and smokingb

Major depressionc

Past 11 61 11 58 22 59Current 1 6 6 32 7 19

Two or more anxiety disordersPast 2 11 5 26 7 19Current 2 11 1 5 3 8

Substance abuse or dependencePast 7 39 6 32 13 35Current 0 0 0 0 0 0

SmokingPast 7 37 6 29 13 33Current 1 5 3 14 4 10

Alcohol abuse or dependencePast 7 39 7 37 14 38Current 0 0 0 0 0 0

Antisocial personality disorderPast 3 17 3 16 6 16Current 0 0 0 0 0 0

Any comorbid disorderPast 16 89 17 89 33 89Current 7 39 11 58 18 49

Mean SD Mean SD Mean SD

Age (years) 39.6 10.4 37.0 11.8 38.3 11.1Socioeconomic statusd 2.2 1.1 2.2 1.0 2.2 1.0Current Global Assessment of Functioning scale score 52.9 7.1 50.7 6.9 51.8 7.0Cognitive scores

WAIS IQFull-scale 104.1 11.2 107.1 15.2 105.7 13.4Freedom from distractibility 94.2 8.5 97.5 14.8 96.0 12.2

Wide-Range Achievement Test 3 scoreArithmetic 92.8 14.0 96.0 15.8 94.5 14.9Reading 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 9.1Hamilton Depression Rating Scale 6.7 4.3 7.8 5.1 7.3 4.7Hamilton 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.





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 si gnificantly 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 ti me

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 18DSM-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-

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.





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 tothat 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

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 todopamine (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





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;

[email protected] (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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