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Chapter 29: Psychopharmacological Treatment
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29.10 Bupropion
Bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban)
is an antidepressant drug that inhibits the reuptake of norepi-
nephrine and, possibly, dopamine. Most significantly, it does
not act on the serotonin system like SSRI antidepressants. This
results in a side effect profile characterized by a low risk of
sexual dysfunction and sedation and with modest weight loss
during acute and long-term treatment. No withdrawal syndrome
has been linked to discontinuation of bupropion. Although
increasingly used as first-line monotherapy, a significant per-
centage of bupropion use occurs as add-on therapy to other
antidepressants, usually SSRIs. Bupropion has been marketed
under the name Zyban for use in smoking cessation regimens.
Pharmacologic Actions
Three formulations of bupropion are available: immediate
release (taken three times daily), sustained release (taken twice
daily), and extended release (taken once daily). The different
versions of the drug contain the same active ingredient but
differ in their pharmacokinetics and dosing. There have been
reports of inconsistencies in bioequivalence between various
branded and generic versions of bupropion. Any changes with
this drug in tolerability or clinical efficacy in a patient who had
been doing well should prompt an inquiry about whether these
changes correspond to a switch to a new formulation.
Immediate-release bupropion is well absorbed from the
GI tract. Peak plasma concentrations of bupropion are usually
reached within 2 hours of oral administration, and peak levels
of the sustained-release version are seen after 3 hours. The mean
half-life of the compound is 12 hours, ranging from 8 to 40 hours.
Peak levels of extended-release bupropion occur 5 hours after
ingestion. This provides a longer time to maximum plasma con-
centration (t
max
) but comparable peak and trough plasma concen-
trations. The 24-hour exposure occurring after administration of
the extended-release version of 300 mg once daily is equivalent
to that provided by sustained release of 150 mg twice daily. Clini-
cally, this permits the drug to be taken once a day in the morn-
ing. Plasma levels are also reduced in the evening, making it less
likely for some patients to experience treatment-related insomnia.
The mechanism of action for the antidepressant effects of
bupropion is presumed to involve the inhibition of dopamine
and norepinephrine reuptake. Bupropion binds to the dopamine
transporter in the brain. The effects of bupropion on smoking
cessation may be related to its effects on dopamine reward path-
ways or to inhibition of nicotinic acetylcholine receptors.
Therapeutic Indications
Depression
Although overshadowed by the SSRIs as first-line treatment
for major depression, the therapeutic efficacy of bupropion in
depression is well established in both outpatient and inpatient
settings. Observed rates of response and remission are compa-
rable to those seen with the SSRIs. Bupropion has been found
to prevent seasonal major depressive episodes in patients with a
history of seasonal pattern or affective disorder.
Smoking Cessation
As the brand name Zyban, bupropion is indicated for use in
combination with behavioral modification programs for smok-
ing cessation. It is intended to be used in patients who are highly
motivated and who receive some form of structured behavioral
support. Bupropion is most effective when combined with nico-
tine substitutes (Nico-Derm, Nicotrol).
Bipolar Disorders
Bupropion is less likely than tricyclic antidepressants to pre-
cipitate mania in persons with bipolar I disorder and less likely
than other antidepressants to exacerbate or induce rapid-cycling
bipolar II disorder; however, the evidence about use of bupro-
pion in the treatment of patients with bipolar disorder is limited.
Attention-Deficit/Hyperactivity Disorder
Bupropion is used as a second-line agent, after the sympatho-
mimetics, for treatment of attention-deficit/hyperactivity dis-
order (ADHD). It has not been compared with proven ADHD
medications such as methylphenidate (Ritalin) or atomox-
etine (Strattera) for childhood and adult ADHD. Bupropion is
an appropriate choice for persons with comorbid ADHD and
depression or persons with comorbid ADHD, conduct disorder,
or substance abuse. It may also be considered for use in patients
who develop tics when treated with psychostimulants.
Cocaine Detoxification
Bupropion may be associated with a euphoric feeling; thus, it
may be contraindicated in persons with histories of substance
abuse. However, because of its dopaminergic effects, bupro-
pion has been explored as a treatment to reduce the cravings
for cocaine in persons who have withdrawn from the substance.
Results have been inconclusive, with some patients showing
a reduction in drug craving and others finding their cravings
increased.
Hypoactive Sexual Desire Disorder
Bupropion is often added to drugs such as SSRIs to counteract
sexual side effects and may be helpful as a treatment for non-
depressed individuals with hypoactive sexual desire disorder.
Bupropion may improve sexual arousal, orgasm completion,
and sexual satisfaction.
Precautions and Adverse Reactions
Headache, insomnia, dry mouth, tremor, and nausea are the
most common side effects. Restlessness, agitation, and irritabil-
ity may also occur. Patients with severe anxiety or panic disor-
der should not be prescribed bupropion. Most likely because
of its potentiating effects on dopaminergic neurotransmission,
bupropion can cause psychotic symptoms, including hallucina-
tions, delusions, and catatonia, as well as delirium. Most nota-
ble about bupropion is the absence of significant drug-induced
orthostatic hypotension, weight gain, daytime drowsiness, and
anticholinergic effects. Some persons, however, may experience
