Prolonged oro-facial dystonia in a 58 year old female following therapy with bupropion and St John's Wort.
- SourceAvailable from: Edzard Ernst[show abstract] [hide abstract]
ABSTRACT: The aim of this systematic review was to assess the published clinical evidence on interactions between herbal and conventional drugs. Four electronic databases were searched for case reports, case series or clinical trials of such interactions. The data were extracted and validated using a scoring system for interaction probability. One hundred and eight cases of suspected interactions were found. 68.5% were classified as 'unable to be evaluated', 13% as 'well-documented' and 18.5% as 'possible' interactions. Warfarin was the most common drug (18 cases) and St John's wort the most common herb (54 cases) involved. Herb-drug interactions undoubtedly do occur and may put individuals at risk. However our present knowledge is incomplete and more research is urgently needed.British Journal of Clinical Pharmacology 12/2001; 52(5):587-95. · 3.58 Impact Factor
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ABSTRACT: A total of 17 years after its introduction, bupropion remains a safe and effective antidepressant, suitable for first-line use. Bupropion undergoes metabolic transformation to an active metabolite, 4-hydroxybupropion, through hepatic cytochrome P450-2B6 (CYP2B6) and has inhibitory effects on cytochrome P450-2D6 (CYP2D6), thus raising concern for clinically-relevant drug interactions. Common side effects are nervousness and insomnia. Nausea appears slightly less common than with the SSRI drugs and sexual dysfunction is probably the least of any antidepressant. Bupropion is relatively safe in overdose with seizures being the predominant concern. The mechanism of action of bupropion is still uncertain but may be related to inhibition of presynaptic dopamine and norepinephrine reuptake transporters. The activity of vesicular monoamine transporter-2, the transporter pumping dopamine, norepinephrine and serotonin from the cytosol into presynaptic vesicles, is increased by bupropion and may be a component of its mechanism of action. Bupropion is approved for use in major depression and seasonal affective disorder and has demonstrated comparable efficacy to other antidepressants in clinical trials. Bupropion is also useful in augmenting a partial response to selective serotonin reuptake inhibitor antidepressants, although bupropion should not be combined with monoamine oxidase inhibitors. It may be less likely to provoke mania than antidepressants with prominent serotonergic effects. Bupropion is effective in helping people quit tobacco smoking. Anecdotal reports indicate bupropion may lower inflammatory mediators such as tumor necrosis factor-alpha, may lower fatigue in cancer and may help reduce concentration problems.Expert Review of Neurotherapeutics 10/2006; 6(9):1249-65. · 2.96 Impact Factor
- BMJ (Clinical research ed.). 03/2004; 328(7438):509-11.
Letter to the Editors
Prolonged oro-facial dystonia in a 58 year old
female following therapy with bupropion and St
James C. Milton & Aza Abdulla
Department of Geriatric Medicine, Princess Royal University
Hospital, Farnborough Common, Kent, England
Bupropion is widely used as an adjunct to stop smoking.
The exact mode of action is unknown but it inhibits
reuptake of dopamine, serotonin and norepinephrine in
the central nervous system, as well as being a noncom-
petitive nicotine receptor antagonist . Dystonia is
reported as a rare side-effect, occurring in less than 1 in
report of a dose-dependent, short-lived oro-facial dysto-
reports of interactions between bupropion and St John’s
Wort (Hypericum perforatum) . We report the case of
a patient who developed a persistant dystonia following
bupropion, used in association with St John’s Wort.
A 58 year old Caucasian female presented with a 2 h
history of dystonic movements affecting the right side of
her face, neck and right arm. She had been taking bupro-
pion for the preceding 4 days at a dose of 150 mg day-1.
Her only other medications were St John’s Wort at a
dose of 300 mg once a day, which she had been taking
for several years, and hormone replacement therapy in
the form of Tridestra®(oestradiol and medroxyprogest-
erone). Her past medical history consisted of a com-
pletely resolved left Bells’ Palsy 37 years previously.
She smoked 15–20 cigarettes a day and drank alcohol
occasionally. There was no family history of movement
Examination revealed episodic spasms of the right
side of the face and right hand. During these attacks her
eyes would roll back into her head and she was unable to
communicate. These episodes occurred every 3 to 4 min
and lasted approximately 45 s. In between attacks, neu-
rological examination was unremarkable.
A diagnosis of acute facial dystonia secondary to
bupropion was made. She was initially treated with
parenteral chlorpheniramine, procyclidine and diaz-
epam. This did not alter the duration of the dystonic
movements but lengthened the spasm-free intervals.
CT scan of the brain was unremarkable. Her blood
results showed she had subclinical hypothyroidism, with
a raised TSH of 31.66 and a normal free T4 of 14.2. She
was commenced on thyroxine. Her other bloods results,
including biochemistry and screening for Wilson’s
disease, were unremarkable.
One week later she was discharged on oral chlorphe-
niramine, procyclidine and diazepam. On follow-up
2 weeks later she had persistant orofacial dystonia,
although the periods between attacks had increased.
Sodium valproate 800 mg twice daily was added with
little effect. This was subsequently changed to carbam-
azepine 400 mg twice daily, with some response. The
action of carbamazepine in dystonia is not clearly under-
stood, whereas valproate has been shown to enhance
GABA function in the brain, causing inhibition of the
dopaminergic pathways that are involved in dystonia .
The oro-facial dystonia became less frequent over
a 5 month period and eventually completely resolved.
All medications were gradually withdrawn, with no
recurrence of dystonia.
Bupropion was introduced as an antidepressant but
Its exact mode of action is unknown. It noncompetitively
dopamine and norepinephrine reuptake, as well as inhib-
iting monoamine uptake. It seems likely that its effect in
smoking is related to more than one receptor or trans-
porter. It is also a weak serotonin reuptake inhibitor .
Dystonia is a syndrome of sustained muscle contrac-
tions that produces twisting and repetitive movements
and postures. It is thought that this is due to serotonin-
induced stimulation of dopaminergic pathways within
the central nervous system . It is a well recognised
side-effect of several medications that affect dopamine
concentrations, including antipsychotics and the selec-
tive serotonin re-uptake inhibitors (SSRIs) . However,
we could only find one case report of a dose-dependent,
short-lived oro-facial dystonia in a patient receiving high
dose bupropion .
British Journal of Clinical Pharmacology
© 2007 The Authors
Journal compilation © 2007 Blackwell Publishing Ltd
Br J Clin Pharmacol
64:5 717–718 717
St John’s Wort is a herbal medication known to be a
weak inhibitor of serotonin, norepinephrine and dopam-
ine reuptake. There are several reports of St John’s Wort
interacting with SSRIs, resulting in various side-effects,
including the serotonin syndrome. It is thought that these
side-effects are due to an additive effect of the two
agents, as they have a similar mode of action .
Dystonia is a rare side-effect of bupropion, possibly
due to its weak serotonin reuptake inhibition, although
the exact mechanism is unknown. We hypothesize that
when it is used in combination with St John’sWort there
is an additive effect on serotonin reuptake inhibition,
making dopaminergic side-effects, such as dystonia,
more likely to occur.
To our knowledge there are no reports of such a pro-
longed dystonia following bupropion, nor any cases of
interactions between St John’s Wort and bupropion.
John’s Wort in combination with bupropion .
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19 September 2006
30 March 2007
19 June 2007
Dr J. C. Milton, Department of Geriatric Medicine, Princess Royal University
Hospital, Farnborough Common, Kent, England. E-mail: jim_milton@
Letter to the Editors
Br J Clin Pharmacol