29.10 Bupropion
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dry mouth or constipation and weight loss. Hypertension may
occur in some patients, but bupropion causes no other signifi-
cant cardiovascular or clinical laboratory changes. Bupropion
exerts indirect sympathomimetic activity, producing positive
inotropic effects in human myocardium, an effect that may
reflect catecholamine release. Some patients experience cogni-
tive impairment, most notably word-finding difficulties.
Concern about seizure has deterred some physicians from
prescribing bupropion. The risk of seizure is dose dependent.
Studies show that at dosages of 300 mg a day or less of sus-
tained-release bupropion, the incidence of seizures is 0.05 per-
cent, which is no worse than the incidence of seizures with other
antidepressants. The risk of seizures increases to about 0.1 per-
cent with dosages of 400 mg a day.
Changes in electroencephalographic (EEG) waveforms have
been reported to be associated with bupropion use. About 20
percent of individuals treated with bupropion exhibit spike
waves, sharp waves, and focal slowing. The likelihood of
women having sharp waves is higher than for men. The presence
of these waveforms in individuals taking a medication known
to lower the seizure threshold may be a risk factor for develop-
ing seizures. Other risk factors for seizures include a history
of seizures, use of alcohol, recent benzodiazepine withdrawal,
organic brain disease, head trauma, or pretreatment epilepti-
form discharges on EEG.
The use of bupropion by pregnant women is not associated
with specific risk of increased rate of birth defects. Bupropion
is secreted in breast milk, so the use of bupropion in nursing
women should be based on the clinical circumstances of the
patient and the judgment of the clinician.
Few deaths have been reported after overdoses of bupro-
pion. Poor outcomes are associated with cases of huge doses
and mixed-drug overdoses. Seizures occur in about one-third
of all overdoses and are dose dependent, with those having sei-
zures ingesting a significantly higher median dose. Fatalities can
involve uncontrollable seizures, sinus bradycardia, and cardiac
arrest. Symptoms of poisoning most often involve seizures,
sinus tachycardia, hypertension, GI symptoms, hallucinations,
and agitation. All seizures are typically brief and self-limited. In
general, however, bupropion is safer in overdose cases than are
other antidepressants except perhaps SSRIs.
Drug Interactions
Given the fact that bupropion is frequently combined with SSRIs
or venlafaxine, potential interactions are significant. Bupropion
has been found to have an effect on the pharmacokinetics of
venlafaxine. One study noted a significant increase in venla-
faxine levels and a consequent decrease in its main metabolite
O-desmethylvenlafaxine during combined treatment with sus-
tained-release bupropion. Bupropion hydroxylation is weakly
inhibited by venlafaxine. No significant changes in plasma levels
of the SSRIs paroxetine and fluoxetine have been reported. How-
ever, few case reports indicate that the combination of bupropion
and fluoxetine (Prozac) may be associated with panic, delirium,
or seizures. Bupropion in combination with lithium (Eskalith)
may rarely cause CNS toxicity, including seizures.
Because of possibility of inducing a hypertensive crisis,
bupropion should not be used concurrently with monoamine
oxidase inhibitors (MAOIs). At least 14 days should pass after
the discontinuation of an MAOI before initiating treatment with
bupropion. In some cases, the addition of bupropion may permit
persons taking antiparkinsonian medications to lower the doses
of their dopaminergic drugs. However, delirium, psychotic
symptoms, and dyskinetic movements may be associated with
the coadministration of bupropion and dopaminergic agents
such as levodopa (Larodopa), pergolide (Permax), ropinirole
(Requip), pramipexole (Mirapex), amantadine (Symmetrel),
and bromocriptine (Parlodel). Sinus bradycardia may occur
when bupropion is combined with metoprolol.
Carbamazepine (Tegretol) may decrease plasma concentra-
tions of bupropion, and bupropion may increase plasma concen-
trations of valproic acid (Depakene).
In vitro biotransformation studies of bupropion have found
that formation of a major active metabolite, hydroxybupropion,
is mediated by CYP2B6. Bupropion has a significant inhibitory
effect on CYP2D6.
Laboratory Interferences
A report has appeared indicating that bupropion may give
a false-positive result on urinary amphetamine screens. No
other reports have appeared of laboratory interferences clearly
associated with bupropion treatment. Clinically nonsignificant
changes in the electrocardiogram (premature beats and nonspe-
cific ST-T changes) and decreases in the white blood cell count
(by about 10 percent) have been reported in a small number of
persons.
Dosage and Clinical Guidelines
Immediate-release bupropion is available in 75-, 100-, and 150-
mg tablets. Sustained-release bupropion is available in 100-,
150-, 200-, and 300-mg tablets. Extended-release bupropion
comes in 150- and 300-mg strengths.
There have been problems associated with one of the
extended-release generic versions called Budeprion XL 300-mg
tablets, which was found not to be therapeutically equivalent to
Wellbutrin XL 300 mg and was removed from the market.
Initiation of immediate-release bupropion in the aver-
age adult person should be 75 mg orally twice a day. On the
fourth day of treatment, the dosage can be increased to 100 mg
three times a day. Because 300 mg is the recommended dose,
the person should be maintained on this dose for several weeks
before increasing it further. The maximum dosage, 450 mg a day,
should be given as 150 mg three times a day. Because of the risk
of seizures, increases in dose should never exceed 100 mg in
a 3-day period; a single dose of immediate-release bupropion
should never exceed 150 mg, and the total daily dosage should
not exceed 450 mg. The maximum of 400 mg of the sustained-
release version should be used as a twice-a-day regimen of either
200 mg twice daily or 300 mg in the morning and 100 mg in
the afternoon. A starting dosage of the sustained-release version,
100 mg once a day, can be increased to 100 mg twice a day after
4 days. Then 150 mg twice a day may be used. A single dose
of sustained-release bupropion should never exceed 300 mg.
The maximum dosage is 200 mg twice a day of the immediate-
release or extended-release formulations. An advantage of the
extended-release preparation is that after appropriate titration, a
total of 450 mg can be given all at once in the morning.
