Included as part of the PRECAUTIONS section.
Neuropsychiatric Symptoms And Suicide Risk In Smoking
Serious neuropsychiatric symptoms have been reported in
patients taking ZYBAN for smoking cessation. These have included changes in
mood (including depression and mania), psychosis, hallucinations, paranoia,
delusions, homicidal ideation, hostility, agitation, aggression, anxiety, and
panic, as well as suicidal ideation, suicide attempt, and completed suicide [see
BOXED WARNING, ADVERSE REACTIONS]. Observe patients for
the occurrence of neuropsychiatric reactions. Instruct patients to contact a
healthcare professional if such reactions occur.
In many of these cases, a causal relationship to
bupropion treatment is not certain, because depressed mood can be a symptom of
nicotine withdrawal. However, some of the cases occurred in patients taking
ZYBAN who continued to smoke.
The risks of ZYBAN should be weighed against the benefits
of its use. ZYBAN has been demonstrated to increase the likelihood of
abstinence from smoking for as long as 6 months compared with treatment with
placebo. The health benefits of quitting smoking are immediate and substantial.
Suicidal Thoughts And Behaviors In Children, Adolescents,
And Young Adults
Patients with MDD, both adult and pediatric, may
experience worsening of their depression and/or the emergence of suicidal
ideation and behavior (suicidality) or unusual changes in behavior, whether or
not they are taking antidepressant medications, and this risk may persist until
significant remission occurs. Suicide is a known risk of depression and certain
other psychiatric disorders, and these disorders themselves are the strongest
predictors of suicide. There has been a long-standing concern that
antidepressants may have a role in inducing worsening of depression and the
emergence of suicidality in certain patients during the early phases of
Pooled analyses of short-term placebo-controlled trials
of antidepressant drugs (selective serotonin reuptake inhibitors [SSRIs] and
others) show that these drugs increase the risk of suicidal thinking and
behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24)
with MDD and other psychiatric disorders. Short-term clinical trials did not
show an increase in the risk of suicidality with antidepressants compared with
placebo in adults beyond age 24; there was a reduction with antidepressants
compared with placebo in adults aged 65 and older.
The pooled analyses of placebo-controlled trials in
children and adolescents with MDD, obsessive compulsive disorder (OCD), or
other psychiatric disorders included a total of 24 short-term trials of 9
antidepressant drugs in over 4,400 subjects. The pooled analyses of placebo-controlled
trials in adults with MDD or other psychiatric disorders included a total of 295
short-term trials (median duration of 2 months) of 11 antidepressant drugs in
over 77,000 subjects. There was considerable variation in risk of suicidality
among drugs, but a tendency toward an increase in the younger subjects for
almost all drugs studied. There were differences in absolute risk of
suicidality across the different indications, with the highest incidence in
MDD. The risk differences (drug vs. placebo), however, were relatively stable
within age strata and across indications. These risk differences (drug-placebo
difference in the number of cases of suicidality per 1,000 subjects treated)
are provided in Table 1.
Table 1: Risk Differences in the Number of Suicidality
Cases by Age Group in the Pooled Placebo-Controlled Trials of
Antidepressants in Pediatric and Adult Subjects
||Drug-Placebo Difference in Number of Cases of Suicidality per 1,000 Subjects Treated
|Increases Compared with Placebo
| < 18
||14 additional cases
||5 additional cases
|Decreases Compared with Placebo
||1 fewer case
| ≥ 65
||6 fewer cases
No suicides occurred in any of the pediatric trials.
There were suicides in the adult trials, but the number was not sufficient to
reach any conclusion about drug effect on suicide.
It is unknown whether the suicidality risk extends to
longer-term use, i.e., beyond several months. However, there is substantial
evidence from placebo-controlled maintenance trials in adults with depression
that the use of antidepressants can delay the recurrence of depression.
All patients being treated with antidepressants for
any indication should be monitored appropriately and observed closely for
clinical worsening, suicidality, and unusual changes in behavior, especially
during the initial few months of a course of drug therapy, or at times of dose
changes, either increases or decreases [see BOXED WARNING].
The following symptoms, anxiety, agitation, panic
attacks, insomnia, irritability, hostility, aggressiveness, impulsivity,
akathisia (psychomotor restlessness), hypomania, and mania, have been reported
in adult and pediatric patients being treated with antidepressants for major depressive
disorder as well as for other indications, both psychiatric and nonpsychiatric.
Although a causal link between the emergence of such symptoms and either the
worsening of depression and/or the emergence of suicidal impulses has not been
established, there is concern that such symptoms may represent precursors to
Consideration should be given to changing the therapeutic
regimen, including possibly discontinuing the medication, in patients whose
depression is persistently worse, or who are experiencing emergent suicidality
or symptoms that might be precursors to worsening depression or suicidality,
especially if these symptoms are severe, abrupt in onset, or were not part of
the patient's presenting symptoms.
Families and caregivers of patients being treated with
antidepressants for MDD or other indications, both psychiatric and
nonpsychiatric, should be alerted about the need to monitor patients for the
emergence of agitation, irritability, unusual changes in behavior, and the
other symptoms described above, as well as the emergence of suicidality, and to
report such symptoms immediately to healthcare providers. Such monitoring
should include daily observation by families and caregivers. Prescriptions for
ZYBAN should be written for the smallest quantity of tablets consistent with
good patient management, in order to reduce the risk of overdose.
ZYBAN can cause seizure. The risk of seizure is
dose-related. The dose of ZYBAN should not exceed 300 mg per day [see DOSAGE
AND ADMINISTRATION]. Discontinue ZYBAN and do not restart treatment if the
patient experiences a seizure.
The risk of seizures is also related to patient factors,
clinical situations, and concomitant medications that lower the seizure
threshold. Consider these risks before initiating treatment with ZYBAN. ZYBAN
is contraindicated in patients with a seizure disorder, current or prior diagnosis
of anorexia nervosa or bulimia, or undergoing abrupt discontinuation of
alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see CONTRAINDICATIONS,
DRUG INTERACTIONS]. The following conditions can also increase
the risk of seizure: severe head injury; arteriovenous malformation; CNS tumor
or CNS infection; severe stroke; concomitant use of other medications that
lower the seizure threshold (e.g., other bupropion products, antipsychotics,
tricyclic antidepressants, theophylline, and systemic corticosteroids),
metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic
impairment, and hypoxia), use of illicit drugs (e.g., cocaine), or abuse or
misuse of prescription drugs such as CNS stimulants. Additional predisposing
conditions include diabetes mellitus treated with oral hypoglycemic drugs or
insulin; use of anorectic drugs; and excessive use of alcohol, benzodiazepines,
sedative/hypnotics, or opiates.
Incidence Of Seizure With Bupropion Use
Doses for smoking cessation should not exceed 300 mg per
day. The seizure rate associated with doses of sustained-release bupropion in
depressed patients up to 300 mg per day is approximately 0.1% (1/1,000) and
increases to approximately 0.4% (4/1000) at doses up to 400 mg per day.
The risk of seizure can be reduced if the dose of ZYBAN
for smoking cessation does not exceed 300 mg per day, given as 150 mg twice
daily, and titration rate is gradual.
Treatment with ZYBAN can result in elevated blood
pressure and hypertension. Assess blood pressure before initiating treatment
with ZYBAN, and monitor periodically during treatment. The risk of hypertension
is increased if ZYBAN is used concomitantly with MAOIs or other drugs that
increase dopaminergic or noradrenergic activity [see CONTRAINDICATIONS].
Data from a comparative trial of ZYBAN, nicotine
transdermal system (NTS), the combination of ZYBAN plus NTS, and placebo as an
aid to smoking cessation suggest a higher incidence of treatment-emergent
hypertension in patients treated with the combination of ZYBAN and NTS. In this
trial, 6.1% of subjects treated with the combination of ZYBAN and NTS had treatment-emergent
hypertension compared to 2.5%, 1.6%, and 3.1% of subjects treated with ZYBAN,
NTS, and placebo, respectively. The majority of these subjects had evidence of
preexisting hypertension. Three subjects (1.2%) treated with the combination of
ZYBAN and NTS and 1 subject (0.4%) treated with NTS had study medication
discontinued due to hypertension compared with none of the subjects treated
with ZYBAN or placebo. Monitoring of blood pressure is recommended in patients
who receive the combination of bupropion and nicotine replacement.
In a clinical trial of bupropion immediate-release in MDD
subjects with stable congestive heart failure (N = 36), bupropion was
associated with an exacerbation of pre-existing hypertension in 2 subjects,
leading to discontinuation of bupropion treatment. There are no controlled
trials assessing the safety of bupropion in patients with a recent history of
myocardial infarction or unstable cardiac disease.
Activation Of Mania/Hypomania
Antidepressant treatment can precipitate a manic, mixed,
or hypomanic episode. The risk appears to be increased in patients with bipolar
disorder or who have risk factors for bipolar disorder. There were no reports
of activation of psychosis or mania in clinical trials with ZYBAN conducted in
nondepressed smokers. Bupropion is not approved for use in treating bipolar depression.
Psychosis And Other Neuropsychiatric Reactions
Depressed patients treated with bupropion in depression
trials have had a variety of neuropsychiatric signs and symptoms, including
delusions, hallucinations, psychosis, concentration disturbance, paranoia, and
confusion. Some of these patients had a diagnosis of bipolar disorder. In some
cases, these symptoms abated upon dose reduction and/or withdrawal of
treatment. Instruct patients to contact a healthcare professional if such
In clinical trials with ZYBAN conducted in nondepressed
smokers, the incidence of neuropsychiatric side effects was generally
comparable to placebo. However, in the postmarketing experience, patients
taking ZYBAN to quit smoking have reported similar types of neuropsychiatric
symptoms to those reported by patients in the clinical trials of bupropion for depression.
The pupillary dilation that occurs following use of many
antidepressant drugs including bupropion may trigger an angle-closure attack in
a patient with anatomically narrow angles who does not have a patent
Anaphylactoid/anaphylactic reactions have occurred during
clinical trials with bupropion. Reactions have been characterized by pruritus,
urticaria, angioedema, and dyspnea requiring medical treatment. In addition,
there have been rare, spontaneous postmarketing reports of erythema multiforme,
Stevens-Johnson syndrome, and anaphylactic shock associated with bupropion.
Instruct patients to discontinue ZYBAN and consult a healthcare provider if
they develop an allergic or anaphylactoid/anaphylactic reaction (e.g., skin
rash, pruritus, hives, chest pain, edema, and shortness of breath) during
There are reports of arthralgia, myalgia, fever with rash
and other serum sickness-like symptoms suggestive of delayed hypersensitivity.
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (Medication Guide).
Although ZYBAN is not indicated for treatment of
depression, it contains the same active ingredient as the antidepressant
medications WELLBUTRIN, WELLBUTRIN SR, and WELLBUTRIN XL. Inform patients,
their families, and their caregivers about the benefits and risks associated
with treatment with ZYBAN and counsel them in its appropriate use.
A patient Medication Guide about “Quitting Smoking,
Quit-Smoking Medications, Changes in Thinking and Behavior, Depression, and
Suicidal Thoughts or Actions,” “Antidepressant Medicines, Depression and Other
Serious Mental Illnesses, and Suicidal Thoughts or Actions,” and “What Other
Important Information Should I Know About ZYBAN?” is available for ZYBAN.
Instruct patients, their families, and their caregivers to read the Medication
Guide and assist them in understanding its contents. Patients should be given
the opportunity to discuss the contents of the Medication Guide and to obtain
answers to any questions they may have. The complete text of the Medication
Guide is reprinted at the end of this document.
Advise patients regarding the following issues and to
alert their prescriber if these occur while taking ZYBAN.
Neuropsychiatric Symptoms and Suicide Risk in Smoking
Inform patients that quitting smoking, with or without
ZYBAN, may be associated with nicotine withdrawal symptoms (including
depression or agitation), or exacerbation of pre-existing psychiatric illness.
Furthermore, some patients have experienced changes in mood (including depression
and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation,
aggression, anxiety, and panic, as well as suicidal ideation, suicide attempt,
and completed suicide when attempting to quit smoking while taking ZYBAN. If
patients develop agitation, hostility, depressed mood, or changes in thinking
or behavior that are not typical for them, or if patients develop suicidal
ideation or behavior, they should be urged to report these symptoms to their
healthcare provider immediately.
Suicidal Thoughts and Behaviors
Instruct patients, their families, and/or their
caregivers to be alert to the emergence of anxiety, agitation, panic attacks,
insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor
restlessness), hypomania, mania, other unusual changes in behavior, worsening
of depression, and suicidal ideation, especially early during antidepressant
treatment and when the dose is adjusted up or down. Advise families and
caregivers of patients to observe for the emergence of such symptoms on a
day-to-day basis, since changes may be abrupt. Such symptoms should be reported
to the patient's prescriber or healthcare professional, especially if they are
severe, abrupt in onset, or were not part of the patient's presenting symptoms.
Symptoms such as these may be associated with an increased risk for suicidal
thinking and behavior and indicate a need for very close monitoring and
possibly changes in the medication.
Severe Allergic Reactions
Educate patients on the symptoms of hypersensitivity and
to discontinue ZYBAN if they have a severe allergic reaction to ZYBAN.
Instruct patients to discontinue ZYBAN and not restart it
if they experience a seizure while on treatment. Advise patients that the
excessive use or abrupt discontinuation of alcohol, benzodiazepines,
antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizure. Advise
patients to minimize or avoid use of alcohol.
Patients should be advised that taking ZYBAN can cause
mild pupillary dilation, which in susceptible individuals, can lead to an
episode of angle-closure glaucoma. Pre-existing glaucoma is almost always
open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated
definitively with iridectomy. Open-angle glaucoma is not a risk factor for
angle-closure glaucoma. Patients may wish to be examined to determine whether
they are susceptible to angle closure, and have a prophylactic procedure (e.g.,
iridectomy), if they are susceptible [see WARNINGS AND PRECAUTIONS].
Educate patients that ZYBAN contains the same active
ingredient (bupropion hydrochloride) found in WELLBUTRIN, WELLBUTRIN SR, and
WELLBUTRIN XL, which are used to treat depression and that ZYBAN should not be
used in conjunction with any other medications that contain bupropion (such as
WELLBUTRIN, the immediate-release formulation; WELLBUTRIN SR, the
sustained-release formulation; WELLBUTRIN XL or FORFIVO XL®, the
extendedrelease formulations; and APLENZIN®, the extended-release formulation
of bupropion hydrobromide). In addition, there are a number of generic
bupropion HCl products for the immediate-, sustained-, and extended-release
Potential for Cognitive and Motor Impairment
Advise patients that any CNS-active drug like ZYBAN may
impair their ability to perform tasks requiring judgment or motor and cognitive
skills. Advise patients that until they are reasonably certain that ZYBAN does
not adversely affect their performance, they should refrain from driving an
automobile or operating complex, hazardous machinery. ZYBAN may lead to decreased
Counsel patients to notify their healthcare provider if
they are taking or plan to take any prescription or over-the-counter drugs
because ZYBAN and other drugs may affect each others' metabolisms.
Advise patients to notify their healthcare provider if
they become pregnant or intend to become pregnant during therapy.
Precautions for Nursing Mothers
Advise patients that ZYBAN is present in human milk in small
Instruct patients to store ZYBAN at room temperature,
between 59°F and 86°F (15°C to 30°C) and keep the tablets dry and out of the
Instruct patients to swallow ZYBAN tablets whole so that
the release rate is not altered. Do not chew, divide, or crush tablets; they
are designed to slowly release drug in the body. When patients take more than
150 mg per day, instruct them to take ZYBAN in 2 doses at least 8 hours apart,
to minimize the risk of seizures. Instruct patients if they miss a dose, not to
take an extra tablet to make up for the missed dose and to take the next tablet
at the regular time because of the dose-related risk of seizure. ZYBAN can be
taken with or without food. Advise patients that ZYBAN tablets may have an
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Lifetime carcinogenicity studies were performed in rats
and mice at bupropion doses up to 300 and 150 mg per kg per day, respectively.
These doses are approximately 10 and 2 times the MRHD, respectively, on a mg
per m basis. In the rat study there was an increase in nodular proliferative
lesions of the liver at doses of 100 to 300 mg per kg per day (approximately 3
to 10 times the MRHD on a mg per m² basis); lower doses were not tested. The
question of whether or not such lesions may be precursors of neoplasms of the
liver is currently unresolved. Similar liver lesions were not seen in the mouse
study, and no increase in malignant tumors of the liver and other organs was
seen in either study.
Bupropion produced a positive response (2 to 3 times
control mutation rate) in 2 of 5 strains in the Ames bacterial mutagenicity
assay. Bupropion produced an increase in chromosomal aberrations in 1 of 3 in vivo rat bone marrow cytogenetic studies.
A fertility study in rats at doses up to 300 mg per kg
per day revealed no evidence of impaired fertility.
Use In Specific Populations
Pregnancy Category C.
Data from epidemiological studies of pregnant women
exposed to bupropion in the first trimester indicate no increased risk of
congenital malformations overall. All pregnancies, regardless of drug exposure,
have a background rate of 2% to 4% for major malformations, and 15% to 20% for
pregnancy loss. No clear evidence of teratogenic activity was found in
reproductive developmental studies conducted in rats and rabbits; however, in
rabbits, slightly increased incidences of fetal malformations and skeletal
variations were observed at doses approximately 2 times the maximum recommended
human dose (MRHD) and greater and decreased fetal weights were seen at doses
three times the MRHD and greater. ZYBAN should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus.
Pregnant smokers should be encouraged to attempt
cessation using educational and behavioral interventions before pharmacological
approaches are used.
Data from the international bupropion Pregnancy Registry
(675 first trimester exposures) and a retrospective cohort study using the
United Healthcare database (1,213 first trimester exposures) did not show an
increased risk for malformations overall.
No increased risk for cardiovascular malformations
overall has been observed after bupropion exposure during the first trimester.
The prospectively observed rate of cardiovascular malformations in pregnancies
with exposure to bupropion in the first trimester from the international
Pregnancy Registry was 1.3% (9 cardiovascular malformations/675 first trimester
maternal bupropion exposures), which is similar to the background rate of
cardiovascular malformations (approximately 1%). Data from the United
Healthcare database and a case-control study (6,853 infants with cardiovascular
malformations and 5,763 with non-cardiovascular malformations) from the
National Birth Defects Prevention Study (NBDPS) did not show an increased risk
for cardiovascular malformations overall after bupropion exposure during the
Study findings on bupropion exposure during the first
trimester and risk for left ventricular outflow tract obstruction (LVOTO) are
inconsistent and do not allow conclusions regarding a possible association. The
United Healthcare database lacked sufficient power to evaluate this association;
the NBDPS found increased risk for LVOTO (n = 10; adjusted OR = 2.6; 95% CI: 1.2,
5.7), and the Slone Epidemiology case control study did not find increased risk
for LVOTO. Study findings on bupropion exposure during the first trimester and
risk for ventricular septal defect (VSD) are inconsistent and do not allow
conclusions regarding a possible association. The Slone Epidemiology Study
found an increased risk for VSD following first trimester maternal bupropion
exposure (n = 17; adjusted OR = 2.5; 95% CI: 1.3, 5.0) but did not find
increased risk for any other cardiovascular malformations studied (including
LVOTO as above). The NBDPS and United Healthcare database study did not find an
association between first trimester maternal bupropion exposure and VSD.
For the findings of LVOTO and VSD, the studies were
limited by the small number of exposed cases, inconsistent findings among
studies, and the potential for chance findings from multiple comparisons in
case control studies.
In studies conducted in rats and rabbits, bupropion was
administered orally during the period of organogenesis at doses of up to 450
and 150 mg per kg per day, respectively (approximately 15 and 10 times the MRHD
respectively, on a mg per m basis). No clear evidence of teratogenic activity
was found in either species; however, in rabbits, slightly increased incidences
of fetal malformations and skeletal variations were observed at the lowest dose
tested (25 mg per kg per day, approximately 2 times the MRHD on a mg per m
basis) and greater. Decreased fetal weights were observed at 50 mg per kg and
When rats were administered bupropion at oral doses of up
to 300 mg per kg per day (approximately 10 times the MRHD on a mg per m basis)
prior to mating and throughout pregnancy and lactation, there were no apparent
adverse effects on offspring development.
Bupropion and its metabolites are present in human milk.
In a lactation study of 10 women, levels of orally dosed bupropion and its
active metabolites were measured in expressed milk. The average daily infant
exposure (assuming 150 mL per kg daily consumption) to bupropion and its active
metabolites was 2% of the maternal weight-adjusted dose. Exercise caution when
ZYBAN is administered to a nursing woman.
Safety and effectiveness in the pediatric population have
not been established [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
Of the approximately 6,000 subjects who participated in
clinical trials with bupropion sustained-release tablets (depression and
smoking cessation trials), 275 were aged > 65 years and 47 were aged > 75
years. In addition, several hundred subjects aged > 65 years participated in clinical
trials using the immediate-release formulation of bupropion (depression
trials). No overall differences in safety or effectiveness were observed
between these subjects and younger subjects. Reported clinical experience has
not identified differences in responses between the elderly and younger
patients, but greater sensitivity of some older individuals cannot be ruled out.
Bupropion is extensively metabolized in the liver to
active metabolites, which are further metabolized and excreted by the kidneys.
The risk of adverse reactions may be greater in patients with impaired renal
function. Because elderly patients are more likely to have decreased renal function,
it may be necessary to consider this factor in dose selection; it may be useful
to monitor renal function [see DOSAGE AND ADMINISTRATION, Use in
Specific Populations, CLINICAL PHARMACOLOGY].
Consider a reduced dose and/or dosing frequency of ZYBAN
in patients with renal impairment (Glomerular Filtration Rate: less than 90 mL
per min). Bupropion and its metabolites are cleared renally and may accumulate
in such patients to a greater extent than usual. Monitor closely for adverse
reactions that could indicate high bupropion or metabolite exposures [see
DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].
In patients with moderate to severe hepatic impairment
(Child-Pugh score: 7 to 15), the maximum dose of ZYBAN is 150 mg every other
day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6),
consider reducing the dose and/or frequency of dosing [see DOSAGE AND
ADMINISTRATION, CLINICAL PHARMACOLOGY].
Drug Abuse And Dependence
Bupropion is not a controlled substance.
Controlled clinical trials conducted in normal
volunteers, in subjects with a history of multiple drug abuse, and in depressed
subjects showed some increase in motor activity and agitation/excitement, often
typical of central stimulant activity.
In a population of individuals experienced with drugs of
abuse, a single oral dose of 400 mg of bupropion produced mild amphetamine-like
activity as compared with placebo on the Morphine-Benzedrine Subscale of the
Addiction Research Center Inventories (ARCI) and a score greater than placebo
but less than 15 mg of the Schedule II stimulant dextroamphetamine on the
Liking Scale of the ARCI. These scales measure general feelings of euphoria and
drug liking which are often associated with abuse potential.
Findings in clinical trials, however, are not known to
reliably predict the abuse potential of drugs. Nonetheless, evidence from
single-dose trials does suggest that the recommended daily dosage of bupropion
when administered orally in divided doses is not likely to be significantly reinforcing
to amphetamine or CNS stimulant abusers. However, higher doses (which could not
be tested because of the risk of seizure) might be modestly attractive to those
who abuse CNS stimulant drugs.
ZYBAN is intended for oral use only. The inhalation of
crushed tablets or injection of dissolved bupropion has been reported. Seizures
and/or cases of death have been reported when bupropion has been administered
intranasally or by parenteral injection.
Studies in rodents and primates demonstrated that
bupropion exhibits some pharmacologic actions common to psychostimulants. In
rodents, it has been shown to increase locomotor activity, elicit a mild
stereotyped behavior response, and increase rates of responding in several schedule-controlled
behavior paradigms. In primate models assessing the positive-reinforcing effects
of psychoactive drugs, bupropion was self-administered intravenously. In rats,
bupropion produced amphetamine-like and cocaine-like discriminative stimulus
effects in drug discrimination paradigms used to characterize the subjective
effects of psychoactive drugs.
The possibility that bupropion may induce dependence
should be kept in mind when evaluating the desirability of including the drug
in smoking cessation programs of individual patients.