Bupropion
Treatment
Paul
of Attention-Deficit Disorder in Adults
H. Wender,
M.D.,
and Fred W. Reimherr,
The authors treated I 9 adults with attention-deficit hyperactivity disorder with an open trial of bupropion. These patients had received maintenance stimulant medication or monoamine oxidase inhibitors for an average of 3. 7 years. Fourteen of the patients experienced moderate to marked benefit from bupropion; ten of these patients chose to continue bupropion rather than their former medication. These results suggest that bupropion may be an alternative to stimulants in treating some adults with attention-deficit hyperactivity disorder. (Am J Psychiatry 1990; 147:1018-1020)
D
uning cally
the past 14 years we have been systematiinvestigating attention-deficit hyperactivity disorder in adults. We have established diagnostic cmiteria, constructed rating scales, and conducted controlled drug trials (1). As in children, a number of drugs have been tried in adults, including stimulants, lithium, and various antidepressants. To date, the most efficacious drugs have been the stimulants. Although the tricyclic antidepressants appear to be of little or no value, the monoamine oxidase inhibitors (MAOIs) appear to be of some use. In placebo-controlled trials of pemohine and methylphenidate (2-4) and in open trials of pargyline and L-deprenyl (5, 6), we have found that 60% of adults with attention-deficit hyperactivity disorder manifest a moderate to marked improvement when treated with these agents. Since the MAOIs are of some use, theme is a possibihity that other antidepressants might be effective in the treatment of adults with attention-deficit hyperactivity disorder. Bupropion has been found to be an effective antidepressant in adults (7, 8), and the rationale for its use in the treatment of attention-deficit hyperactivity disorder in adults is that at least some of its effects are similar to those of the stimulants in that they appear to be dopaminergically mediated (9). Further-
Received Feb. 16, 1989; revisions received Sept. 20, 1989, Jan. 24, 1990; accepted March 8, 1990. From the Department Psychiatry,
requests Center,
University
84182. Copyright
1018
of Utah
School
to Dr. Wender, Department University of Utah School © 1990
American
of Medicine.
Address
of Psychiatry, 5R154 of Medicine, Salt Lake
Psychiatric
Association.
Hyperactivity
and of
reprint
Medical City, UT
M.D.
more, two clinical trials (10, 11) suggested that bupropion is effective in the treatment of attention-deficit hyperactivity disorder in children. Our purpose in the current study was not to cornpare the relative efficacy of stimulants and bupropion in the treatment of attention-deficit hyperactivity disorder but to determine if a drug with a long duration of action and no known abuse potential could be substituted for standard drug treatment. (This would be analogous to evaluating the effectiveness of lithium in neuroleptic-responsive schizophrenic patients in order to determine if a drug that does not produce tardive dyskinesia could be substituted for one that does.) In this paper we report an open trial of bupropion to determine its effectiveness in adults with attention-deficit hyperactivity disorder who had demonstrated mesponsiveness to either stimulant drugs or MAOIs.
METHOD Informed consent was obtained from all subjects participating in the study. The sample was composed of 14 men and five women with a mean±SD age of 39±6 years who had been in continuous treatment with us for attention-deficit hyperactivity disorder. All patients met the Utah Diagnostic Criteria for attention-deficit hyperactivity disorder in adults. The Utah criteria, which are more stringent than those of DSMIII-R, are as follows. 1) A childhood history chamactenized by clear-cut hyperactivity and attentional probhems together with one of the following symptoms (signs): behavior problems at school, impulsivity, overexcitability, and temper outbursts. 2) The continuing presence in adulthood of hyperactivity and inattentiveness together with two of the following five characteristics: affective lability, disorganization and inability to complete tasks, hot temper, impulsivity, and stress intolerance. The affective disturbance seen in adults with attention-deficit hyperactivity disorder has a distinctive pattern. It is described by patients as antedating adolescence and in some instances extending as far back as the patient can remember. It is manifested by definite shifts from a normal mood to depression or mild euphonia or excitement. The depression is described as being “down,” “bored,” or “discontented.” The mood
Am
J
Psychiatry
147:8,
August
1990
PAUL
shifts usually last for hours or a few days at most and do not have substantial physiological concomitants. They may occur spontaneously or be reactive. The diagnoses excluded by the Utah criteria are current unipolar affective disorder and current or past bipolar affective disorders, schizophrenia, and schizoaffective disorder. Individuals with the following charactemistics of schizotypah on borderline personality disorden are excluded: magical thinking, ideas of reference, odd communication, inadequate rapport in face-toface interactions, suspiciousness or paranoid ideation, prolonged anger, identity disturbances, inability to tolemate being alone, and physically self-damaging acts. Nineteen patients meeting the Utah criteria for adult attention-deficit hyperactivity disorder participated in the bupropion trial. They had been followed and treated by us for an average of 3.7 years: three patients for 4-9 months, eight for 1-3 years, five for 4-8 years, and three for 9-1 1 years. Before the bupropion trial the patients had been receiving the following drugs: 12 patients received 40-80 mg/day of methylphenidate, two received 20-30 mg/day of d-amphetamine, one received 40 mg/day of tranylcypromine, two meceived 30-150 mg/day of pargyline, one received 100 mg/day of benzphetamine, and one received 75 mg/day of pemohine. The severity of the signs and symptoms of attentiondeficit hyperactivity disorder was mated on the Clinical Global Impression Scale (CGI) and on the Targeted Attention Deficit Disorder Symptoms Scale. CGI ratings of change in attention-deficit hyperactivity disorder aften the bupropion trial were compared with functioning before bupropion administration (2 weeks after discontinuation of the maintenance drug) and scored as improvement or deterioration on a 4-point scale: 0=no change, 1 =slight change, 2=moderate change, and 3 = marked change. The Targeted Attention Deficit Disorder Symptoms Scale has seven items: hypemactivity, attentional difficulties, affective lability, disorganization and inability to complete tasks, hot temper, impulsivity, and stress intolerance. Each item is rated on a 4-point scale: 0=not present, 1 =slight, 2=moderate, 3=marked. Thus, the maximum score is 21. The subjects’ previous medications were gradually decreased over a 2-week period; in all instances the patients’ symptoms returned to their pretreatment level. After this 2-week washout, treatment with bupropion was begun. The medication was dispensed in 75-mg tablets starting at a dose of 150 mg/day and increasing every 2-3 days by 75 mg. The total dose was increased to the highest level that could be administered without side effects or to the maximum of 450 mg/day.
RESULTS Five patients bupropion (150 tion; bupropion
Am
]
Psychiatry
could not tolerate mg/day), primarily was discontinued
147:8,
August
the lowest dose of because of agitain these patients af-
1990
H.
WENDER
AND
FRED
W.
REIMHERR
ten a few weeks. The mean±SD dose of bupropion for the 14 patients who continued to take the drug was 359±118 mg/day (range=1S0-450 mg/day). The mean pretreatment Targeted Attention Deficit Disorden Symptoms Scale score of these 14 patients 2 weeks after discontinuation of their maintenance drug was 14.8±2.4, indicating an average rating of moderate on each of the seven items; following 6-8 weeks of bupropion treatment, their mean score was 3.9±2.5, representing an average rating of not present or slight on each of the seven scales. The scores before and after treatment differed significantly (t=4.6, df=18, p< 0.001). Of the 14 patients who responded to bupropion, eight had scores of 3 (marked response) and six had scores of 2 (moderate response) on the CGI after bupropion treatment. Ten of the patients who responded to bupropion chose to continue that drug; four did not. The mean Targeted Attention Deficit Disorder Symptoms Scale scores of the four patients who chose to return to their previous treatment were 5.3 while taking bupropion and 2.8 while taking their best previous medication. Although their symptom scores were virtually the same as the scores of the patients who continued to take bupropion, they chose to return to treatment with damphetamine or methylphenidate because they perceived the benefit-to-side-effect ratio of stimulants to be better.
DISCUSSION All of the subjects in this study have participated in trials of several stimulant and antidepressant medications. As a result of these trials, they have selected the drug therapy that they judged most satisfactory. With this background, 10 of the 19 subjects chose to remain on bupropion therapy, which has lasted for periods ranging from 10 to 17 months. These results, however, can only suggest that bupropion is effective in the treatment of attention-deficit hyperactivity disorder because the study suffers from all of the limitations of any open trial. Nevertheless, the positive findings warrant a placebo-controlled, double-blind study. Such a study is further warranted because there is a need for new drugs in the treatment of attention-deficit hyperactivity disorder; all of the available agents have serious therapeutic shortcomings. For example, the stimulants methylphenidate and amphetamine are potentially abusable, and this property represents a major obstacle to the acceptance of attention-deficit hyperactivity disorder as a legitimate psychiatric disorder, thereby denying many individuals beneficial drug thenapy. In addition, in some patients, the stimulants have a very short duration of effectiveness: 2-3 hours for methylphenidate and 3-4 hours for amphetamine. This necessitates repeated daily doses, which is an obvious limitation to any therapy. Unfortunately, some of the stimulant effects are not short-lived, most notably the effect on wakefulness. Because this effect is
1019
BUPROPION
FOR
HYPERACTIVITY
IN ADULTS
relatively persistent, these drugs must not be given late in the day in order to avoid interference with sleep. Thus, the stimulants do not provide 24-hour benefits. There are also problems with the MAOI drugs. Most importantly, they do not appear to be as generally effective as are the stimulants. They also cause untoward effects in the presence of certain drugs on foods, cause weight gain, and interfere with sexual function. Bupropion does not appear to manifest any of the himitations of either the stimulants or the MAOIs. There is a theoretical basis for a therapeutic effect of bupropion in attention-deficit hyperactivity disorder. The drug has dopaminergic activity (9), and attentiondeficit hyperactivity disorder has been proposed to be the result of a deficiency in dopaminengic function (12, 13). Considerable data exist to support this hypothesis. First, the drugs that are therapeutically effective in attention-deficit hyperactivity disorder are all capable of enhancing dopaminergic activity; these drugs indude not only methylphenidate and amphetamine but also the MAOIs, pargyhine, and L-deprenyl, which decrease the catabolism of dopamine. Second, levels of the dopamine metabohite homovanilhic acid (HVA) are low in the CSF of adult patients with attention-deficit hyperactivity disorder (14), ostensibly reflecting less dopaminergic activity. Finally, the administration of L-tymosine, the immediate precursor of dopamine, also produces a therapeutic effect in attention-deficit hypenactivity disorder (15). Clearly, more efficacious drugs are needed, and bupropion appears to be a potentially useful agent. A note of caution should be added. Although the stimulants have their limitations, they are efficacious and they are safe. Adults with attention-deficit hyperactivity disorder do not develop tolerance to the therapeutic effect of stimulants, and so there is no necessity to escalate the dose, and, in general, these patients do not abuse the stimulants. Furthermore, stimulants have proven to be remarkably safe when administered within a prescribed dose range. It must also be remembered that attention-deficit hyperactivity disorder is a chronic disorder; therefore, the ultimate consideration is the long-term safety and efficacy of any drug therapy.
1020
REFERENCES 1. Wender
PH, Wood
ment
of
attention
“minimal
brain
Bull
DR.
Wood treatment
diagnosis
Pharmacological
residual
type
treat-
(ADD,
RT,
in adults.
Psy-
21:222-231
brain
Wender
PH,
dysfunction
et at: Diagnosis
and
in
Gen
adults.
Arch
33:1453-1461
Reimherr
FW,
brain
dysfunction”)
der (“minimal of
1985;
minimal
PH,
FW:
“hyperactivity”)
FW,
1976;
Wender
disorder,
Reimherr of
Psychiatry
3.
Reimherr
dysfunction,”
chopharmacot 2.
DR. deficit
and
drug
Wood
DR:
Attention
in adults:
treatment.
Arch
FW,
D, et at:
deficit
dison-
a replication
study
Psychiatry
1981;
A controlled
study
Gen
38:449-456 4.
Wender
PH,
Reimherr
of methylphenidate
der,
Wood
in the
residual
type,
treatment
in adults.
of attention deficit disorPsychiatry .1985; 142:547-
J
Am
552 S. Wender pargyline type.
PH, Wood in the Psychiatry
6. Wood the
DR.
Res
FW,
of attention
1983;
DR. Reimherr
treatment
Reimherr
treatment
et al: An open deficit
of attention
Chouinard
G:
depressed 129
PH: The use of L-deprenyl
deficit
Bupropion
J
patients.
9. Cooper
BR, Hester
ical
of
effects
disorder,
dence
residual
Casat of
Exp Ther CD,
bupropion
Simeon in
1980;
Pleasants
chopharmacol
11.
blockade
1986;
Van
Wyck
in children
with
Bull
23:120-122
1987;
of
2):121-
and
biochem-
(Wellbutnin): uptake
FleetJ:
cvi-
in vivo.
J
Phar-
and
A double-blind
attention
HB, Van Wyck
deficit
31:58
bupropion of dopamine
treatment
45(section
RA: Behavioral
J
bupropion.
in the
1983;
in
(ADD,
215:127-134
DZ,
JG, Ferguson
attention
type
with
amitriptyline
Psychiatry
antidepressant
for selective
macol 10.
and Clin
TJ, Maxwell
the
of
residual
9:329-336
FW, Wender
RT). Psychopharmacol Bull 1983; 19:627-629 7. Zung W: Review of placebo-controlled trials Clin Psychiatry 1983; 45(section 2):104-114 8.
trial
disorder,
conduct
deficit
J:
Fleet
disorders.
trial
disorder.
Bupropion Can
J
Psy-
effects Psychiatry
1-585
12.
Wender
13.
York, John Wiley & Sons, 1971 Wender PH: The minimal brain dysfunction syndrome dren, I: the syndrome and its relevance for psychiatry;
in chilII: a
psychological
J
Ment
14.
PH:
and
Dis
Reimherr
1972;
chiatry Reimherr
Res
L-tyrosine type.
Brain
Am
Dysfunction
biochemical
model
in
for
the
Children.
syndrome.
PH, Ebert
MH,
et at: Cerebrospinal
acid and 5-hydroxyindole deficit disorder, residual
acetic acid type (ADD,
1984; 11:71-78 FW, Wender PH, Wood DR, et at: An open in the treatment of attention deficit disorder,
J
New
Nerv
155:55-71
FW, Wender
homovanillic with attention 15.
Minimal
1987;
Psychiatry
Am
J
fluid
in adults RT). Psytrial of residual
144:1071-1073
Psychiatry
147:8,
August
1990
Treatment
Paul
of Attention-Deficit Disorder in Adults
H. Wender,
M.D.,
and Fred W. Reimherr,
The authors treated I 9 adults with attention-deficit hyperactivity disorder with an open trial of bupropion. These patients had received maintenance stimulant medication or monoamine oxidase inhibitors for an average of 3. 7 years. Fourteen of the patients experienced moderate to marked benefit from bupropion; ten of these patients chose to continue bupropion rather than their former medication. These results suggest that bupropion may be an alternative to stimulants in treating some adults with attention-deficit hyperactivity disorder. (Am J Psychiatry 1990; 147:1018-1020)
D
uning cally
the past 14 years we have been systematiinvestigating attention-deficit hyperactivity disorder in adults. We have established diagnostic cmiteria, constructed rating scales, and conducted controlled drug trials (1). As in children, a number of drugs have been tried in adults, including stimulants, lithium, and various antidepressants. To date, the most efficacious drugs have been the stimulants. Although the tricyclic antidepressants appear to be of little or no value, the monoamine oxidase inhibitors (MAOIs) appear to be of some use. In placebo-controlled trials of pemohine and methylphenidate (2-4) and in open trials of pargyline and L-deprenyl (5, 6), we have found that 60% of adults with attention-deficit hyperactivity disorder manifest a moderate to marked improvement when treated with these agents. Since the MAOIs are of some use, theme is a possibihity that other antidepressants might be effective in the treatment of adults with attention-deficit hyperactivity disorder. Bupropion has been found to be an effective antidepressant in adults (7, 8), and the rationale for its use in the treatment of attention-deficit hyperactivity disorder in adults is that at least some of its effects are similar to those of the stimulants in that they appear to be dopaminergically mediated (9). Further-
Received Feb. 16, 1989; revisions received Sept. 20, 1989, Jan. 24, 1990; accepted March 8, 1990. From the Department Psychiatry,
requests Center,
University
84182. Copyright
1018
of Utah
School
to Dr. Wender, Department University of Utah School © 1990
American
of Medicine.
Address
of Psychiatry, 5R154 of Medicine, Salt Lake
Psychiatric
Association.
Hyperactivity
and of
reprint
Medical City, UT
M.D.
more, two clinical trials (10, 11) suggested that bupropion is effective in the treatment of attention-deficit hyperactivity disorder in children. Our purpose in the current study was not to cornpare the relative efficacy of stimulants and bupropion in the treatment of attention-deficit hyperactivity disorder but to determine if a drug with a long duration of action and no known abuse potential could be substituted for standard drug treatment. (This would be analogous to evaluating the effectiveness of lithium in neuroleptic-responsive schizophrenic patients in order to determine if a drug that does not produce tardive dyskinesia could be substituted for one that does.) In this paper we report an open trial of bupropion to determine its effectiveness in adults with attention-deficit hyperactivity disorder who had demonstrated mesponsiveness to either stimulant drugs or MAOIs.
METHOD Informed consent was obtained from all subjects participating in the study. The sample was composed of 14 men and five women with a mean±SD age of 39±6 years who had been in continuous treatment with us for attention-deficit hyperactivity disorder. All patients met the Utah Diagnostic Criteria for attention-deficit hyperactivity disorder in adults. The Utah criteria, which are more stringent than those of DSMIII-R, are as follows. 1) A childhood history chamactenized by clear-cut hyperactivity and attentional probhems together with one of the following symptoms (signs): behavior problems at school, impulsivity, overexcitability, and temper outbursts. 2) The continuing presence in adulthood of hyperactivity and inattentiveness together with two of the following five characteristics: affective lability, disorganization and inability to complete tasks, hot temper, impulsivity, and stress intolerance. The affective disturbance seen in adults with attention-deficit hyperactivity disorder has a distinctive pattern. It is described by patients as antedating adolescence and in some instances extending as far back as the patient can remember. It is manifested by definite shifts from a normal mood to depression or mild euphonia or excitement. The depression is described as being “down,” “bored,” or “discontented.” The mood
Am
J
Psychiatry
147:8,
August
1990
PAUL
shifts usually last for hours or a few days at most and do not have substantial physiological concomitants. They may occur spontaneously or be reactive. The diagnoses excluded by the Utah criteria are current unipolar affective disorder and current or past bipolar affective disorders, schizophrenia, and schizoaffective disorder. Individuals with the following charactemistics of schizotypah on borderline personality disorden are excluded: magical thinking, ideas of reference, odd communication, inadequate rapport in face-toface interactions, suspiciousness or paranoid ideation, prolonged anger, identity disturbances, inability to tolemate being alone, and physically self-damaging acts. Nineteen patients meeting the Utah criteria for adult attention-deficit hyperactivity disorder participated in the bupropion trial. They had been followed and treated by us for an average of 3.7 years: three patients for 4-9 months, eight for 1-3 years, five for 4-8 years, and three for 9-1 1 years. Before the bupropion trial the patients had been receiving the following drugs: 12 patients received 40-80 mg/day of methylphenidate, two received 20-30 mg/day of d-amphetamine, one received 40 mg/day of tranylcypromine, two meceived 30-150 mg/day of pargyline, one received 100 mg/day of benzphetamine, and one received 75 mg/day of pemohine. The severity of the signs and symptoms of attentiondeficit hyperactivity disorder was mated on the Clinical Global Impression Scale (CGI) and on the Targeted Attention Deficit Disorder Symptoms Scale. CGI ratings of change in attention-deficit hyperactivity disorder aften the bupropion trial were compared with functioning before bupropion administration (2 weeks after discontinuation of the maintenance drug) and scored as improvement or deterioration on a 4-point scale: 0=no change, 1 =slight change, 2=moderate change, and 3 = marked change. The Targeted Attention Deficit Disorder Symptoms Scale has seven items: hypemactivity, attentional difficulties, affective lability, disorganization and inability to complete tasks, hot temper, impulsivity, and stress intolerance. Each item is rated on a 4-point scale: 0=not present, 1 =slight, 2=moderate, 3=marked. Thus, the maximum score is 21. The subjects’ previous medications were gradually decreased over a 2-week period; in all instances the patients’ symptoms returned to their pretreatment level. After this 2-week washout, treatment with bupropion was begun. The medication was dispensed in 75-mg tablets starting at a dose of 150 mg/day and increasing every 2-3 days by 75 mg. The total dose was increased to the highest level that could be administered without side effects or to the maximum of 450 mg/day.
RESULTS Five patients bupropion (150 tion; bupropion
Am
]
Psychiatry
could not tolerate mg/day), primarily was discontinued
147:8,
August
the lowest dose of because of agitain these patients af-
1990
H.
WENDER
AND
FRED
W.
REIMHERR
ten a few weeks. The mean±SD dose of bupropion for the 14 patients who continued to take the drug was 359±118 mg/day (range=1S0-450 mg/day). The mean pretreatment Targeted Attention Deficit Disorden Symptoms Scale score of these 14 patients 2 weeks after discontinuation of their maintenance drug was 14.8±2.4, indicating an average rating of moderate on each of the seven items; following 6-8 weeks of bupropion treatment, their mean score was 3.9±2.5, representing an average rating of not present or slight on each of the seven scales. The scores before and after treatment differed significantly (t=4.6, df=18, p< 0.001). Of the 14 patients who responded to bupropion, eight had scores of 3 (marked response) and six had scores of 2 (moderate response) on the CGI after bupropion treatment. Ten of the patients who responded to bupropion chose to continue that drug; four did not. The mean Targeted Attention Deficit Disorder Symptoms Scale scores of the four patients who chose to return to their previous treatment were 5.3 while taking bupropion and 2.8 while taking their best previous medication. Although their symptom scores were virtually the same as the scores of the patients who continued to take bupropion, they chose to return to treatment with damphetamine or methylphenidate because they perceived the benefit-to-side-effect ratio of stimulants to be better.
DISCUSSION All of the subjects in this study have participated in trials of several stimulant and antidepressant medications. As a result of these trials, they have selected the drug therapy that they judged most satisfactory. With this background, 10 of the 19 subjects chose to remain on bupropion therapy, which has lasted for periods ranging from 10 to 17 months. These results, however, can only suggest that bupropion is effective in the treatment of attention-deficit hyperactivity disorder because the study suffers from all of the limitations of any open trial. Nevertheless, the positive findings warrant a placebo-controlled, double-blind study. Such a study is further warranted because there is a need for new drugs in the treatment of attention-deficit hyperactivity disorder; all of the available agents have serious therapeutic shortcomings. For example, the stimulants methylphenidate and amphetamine are potentially abusable, and this property represents a major obstacle to the acceptance of attention-deficit hyperactivity disorder as a legitimate psychiatric disorder, thereby denying many individuals beneficial drug thenapy. In addition, in some patients, the stimulants have a very short duration of effectiveness: 2-3 hours for methylphenidate and 3-4 hours for amphetamine. This necessitates repeated daily doses, which is an obvious limitation to any therapy. Unfortunately, some of the stimulant effects are not short-lived, most notably the effect on wakefulness. Because this effect is
1019
BUPROPION
FOR
HYPERACTIVITY
IN ADULTS
relatively persistent, these drugs must not be given late in the day in order to avoid interference with sleep. Thus, the stimulants do not provide 24-hour benefits. There are also problems with the MAOI drugs. Most importantly, they do not appear to be as generally effective as are the stimulants. They also cause untoward effects in the presence of certain drugs on foods, cause weight gain, and interfere with sexual function. Bupropion does not appear to manifest any of the himitations of either the stimulants or the MAOIs. There is a theoretical basis for a therapeutic effect of bupropion in attention-deficit hyperactivity disorder. The drug has dopaminergic activity (9), and attentiondeficit hyperactivity disorder has been proposed to be the result of a deficiency in dopaminengic function (12, 13). Considerable data exist to support this hypothesis. First, the drugs that are therapeutically effective in attention-deficit hyperactivity disorder are all capable of enhancing dopaminergic activity; these drugs indude not only methylphenidate and amphetamine but also the MAOIs, pargyhine, and L-deprenyl, which decrease the catabolism of dopamine. Second, levels of the dopamine metabohite homovanilhic acid (HVA) are low in the CSF of adult patients with attention-deficit hyperactivity disorder (14), ostensibly reflecting less dopaminergic activity. Finally, the administration of L-tymosine, the immediate precursor of dopamine, also produces a therapeutic effect in attention-deficit hypenactivity disorder (15). Clearly, more efficacious drugs are needed, and bupropion appears to be a potentially useful agent. A note of caution should be added. Although the stimulants have their limitations, they are efficacious and they are safe. Adults with attention-deficit hyperactivity disorder do not develop tolerance to the therapeutic effect of stimulants, and so there is no necessity to escalate the dose, and, in general, these patients do not abuse the stimulants. Furthermore, stimulants have proven to be remarkably safe when administered within a prescribed dose range. It must also be remembered that attention-deficit hyperactivity disorder is a chronic disorder; therefore, the ultimate consideration is the long-term safety and efficacy of any drug therapy.
1020
REFERENCES 1. Wender
PH, Wood
ment
of
attention
“minimal
brain
Bull
DR.
Wood treatment
diagnosis
Pharmacological
residual
type
treat-
(ADD,
RT,
in adults.
Psy-
21:222-231
brain
Wender
PH,
dysfunction
et at: Diagnosis
and
in
Gen
adults.
Arch
33:1453-1461
Reimherr
FW,
brain
dysfunction”)
der (“minimal of
1985;
minimal
PH,
FW:
“hyperactivity”)
FW,
1976;
Wender
disorder,
Reimherr of
Psychiatry
3.
Reimherr
dysfunction,”
chopharmacot 2.
DR. deficit
and
drug
Wood
DR:
Attention
in adults:
treatment.
Arch
FW,
D, et at:
deficit
dison-
a replication
study
Psychiatry
1981;
A controlled
study
Gen
38:449-456 4.
Wender
PH,
Reimherr
of methylphenidate
der,
Wood
in the
residual
type,
treatment
in adults.
of attention deficit disorPsychiatry .1985; 142:547-
J
Am
552 S. Wender pargyline type.
PH, Wood in the Psychiatry
6. Wood the
DR.
Res
FW,
of attention
1983;
DR. Reimherr
treatment
Reimherr
treatment
et al: An open deficit
of attention
Chouinard
G:
depressed 129
PH: The use of L-deprenyl
deficit
Bupropion
J
patients.
9. Cooper
BR, Hester
ical
of
effects
disorder,
dence
residual
Casat of
Exp Ther CD,
bupropion
Simeon in
1980;
Pleasants
chopharmacol
11.
blockade
1986;
Van
Wyck
in children
with
Bull
23:120-122
1987;
of
2):121-
and
biochem-
(Wellbutnin): uptake
FleetJ:
cvi-
in vivo.
J
Phar-
and
A double-blind
attention
HB, Van Wyck
deficit
31:58
bupropion of dopamine
treatment
45(section
RA: Behavioral
J
bupropion.
in the
1983;
in
(ADD,
215:127-134
DZ,
JG, Ferguson
attention
type
with
amitriptyline
Psychiatry
antidepressant
for selective
macol 10.
and Clin
TJ, Maxwell
the
of
residual
9:329-336
FW, Wender
RT). Psychopharmacol Bull 1983; 19:627-629 7. Zung W: Review of placebo-controlled trials Clin Psychiatry 1983; 45(section 2):104-114 8.
trial
disorder,
conduct
deficit
J:
Fleet
disorders.
trial
disorder.
Bupropion Can
J
Psy-
effects Psychiatry
1-585
12.
Wender
13.
York, John Wiley & Sons, 1971 Wender PH: The minimal brain dysfunction syndrome dren, I: the syndrome and its relevance for psychiatry;
in chilII: a
psychological
J
Ment
14.
PH:
and
Dis
Reimherr
1972;
chiatry Reimherr
Res
L-tyrosine type.
Brain
Am
Dysfunction
biochemical
model
in
for
the
Children.
syndrome.
PH, Ebert
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