Bupropion as the treatment of choice in depression associated with parkinsonâ€™s disease and itâ€™s various treatments
Bupropion as the treatment of choice in depression associatedwith Parkinson’s disease and it’s various treatments
The Jerusalem Mental Health Center, Kfar Shaul Hospital, Hebrew University – Hadassah Medical School, Jerusalem, Israel
Parkinson disease (PD) is a chronic progressive degenerative disorder that affects over 6 million people
worldwide. It is manifested by motor and psychiatric signs. The latter inﬂicts up to 88% of PD patients.
With the prolongation of life expectancy, it is presumed that the prevalence of PD will further rise,together with comorbid depression. As a result, the need for an adequate therapeutic answer for com-pounded PD with depression is called for urgently.
Several theories try to explain the trigger of depression in PD patients by impaired activity in dopa-
mine, norepinephrine and serotonin systems.
Various treatment to combat depressive symptoms in PD patients were proposed and are in use, with
ambiguous results and disturbing side effects. These anti-depressive modalities include SSRI’s, SNRI, TCA,NRI and ECT.
Dopamine agonists showed some anti-depressant activity in several studies in depressive PD, but may
cause side effects such as dizziness, somnolence, confusion and even hallucinations. The role of dopamineagonists in the treatment of depression is still being explored because of no sufﬁcient number of con-trolled studies in this area.
Our hypothesis is to suggest NDRI – Bupropion – as the ﬁrst line of treatment in PD patients with
depression, in PD induced depression and/or in depression triggered by one of the treatments givenfor PD. Dual norepinephrine and dopamine reuptake inhibition is associated with unique clinical proﬁlethat compounds together anti-depressant efﬁcacy without serotonin associated side effects such asweight gain, sedation, sexual dysfunction.
Bupropion, as mainly dopaminergic and noradrenergic anti-depressant can alleviate therapeutically
depressive symptoms associated with PD. Clinical controlled studies on Bupropion use in PD depressedpatients are required to support this hypothesis.
40–60% of PD patients, more common in men than in women ,in contrast to major depression unrelated to PD that is twice more
Parkinson disease (PD) is a progressive neurodegenerative dis-
order connected with loss of pigmented (dopaminergic) neurons
There are several theories that try to explain the trigger of
in the zona compacta of the substantia nigra as well as in other
depression in PD patients by dopamine degeneration decrease
brain regions . Its prevalence is 133/100.000 of the elderly pop-
in the number and activity of norepinephrine neurons in locus
ulation, the average age at onset is 63 The disease is character-
ceruleus, and by decrease in the number and activity of serotonin
ized by motor signs as tremor, rigidity, bradykinesia, postural
instability as well as psychiatric signs and symptoms such as
According to the different theories of the pathophysiology of
depression, dementia, and impairment in cognitive abilities . It
depression in PD patients, the medication therapy for depression
is now appreciated that the non-motor symptoms affecting neuro-
includes: tricyclic anti-depressants (TCA), selective serotonin reup-
psychiatric, sleep, autonomic, and sensory domains occur in up to
take inhibitors (SSRIs), serotonin norepinephrin reuptake inhibitor
(SNRI), norepinephrine reuptake inhibitor (NRI), electro-convulsive
PD is a debilitating disorder that intervenes with and worsens
therapy (ECT) and other different dopaminergic medications
quality of life. Its comorbidity with depression is high and reaches
TCA may be useful for the treatment of depressive states in Par-
kinson patients, and according to a recent report nortryptiline wasfound to be more efﬁcient than the SSRI paroxetine in alleviating
* Corresponding author. Address: Kfar Shaul Mental Health Center, Jerusalem,
depressive symptoms in PD patients However, TCA is associ-
Israel. Tel.: +972 2 6551559/550; fax: +972 2 6541281.
ated with numerous side effects – anticholinergic effects, slow
0306-9877/$ - see front matter Ó 2010 Published by Elsevier Ltd.
S. Raskin, R. Durst / Medical Hypotheses 75 (2010) 544–546
cardiac conduction, sedation, orthostatic hypotension that embar-
other hand, it should and does react to anti-depressant with dopa-
rass their use for this sensitive population.
minergic activity, such as Bupropion.
SSRI anti-depressants represent the most common used medi-
cations in the treatment of depression in general as well as in PD
patients. Despite this fact, there are no adequately controlled clin-ical studies of their efﬁcacy for the depressive symptoms in Parkin-
Our proposition is to suggest NDRI – Bupropion – as the ﬁrst
son patients . Adverse reaction commonly bound with SSRI’s
line of treatment in PD patients with depression, in PD induced
use are gastrointestinal complaints, weight gain, and sexual dys-
depression and/or in depression triggered by one of the treatments
function. There are a few reports of cases where SSRI’s worsened
parkinsonian motor problems , others report the risk of caus-
Bupropion (Wellbutrin) was ﬁrst synthesized in 1966. It was
ing a potential serious serotonin syndrome, using SSRI’s with
aimed to address and overcome the anticholinergic and cardiac ef-
Selegiline (deprenyl), a selective, irreversible inhibitor of mono-
fects of the tricyclic anti-depressants Bupropion acts via dual
amine oxidase type B (MAO-B) that is widely used in the treatment
inhibition of norepinephrin and dopamine reuptake and is devoid
of clinically signiﬁcant serotonergic effects or direct effect of post
Some studies report the efﬁcacy of the SNRI Milnacipran
synaptic receptors. Dual norepinephrin and dopamine reuptake
and the NRI Reboxetine for depression in PD patients.
inhibition is associated with unique clinical proﬁle that com-
Although the meta analysis of anti-depressant studies in Parkinson
pounds together anti-depressant efﬁcacy without serotonin associ-
disease conclude that there is little empiric evidence to support the
ated side effects such as weight gain, sedation, sexual dysfunction
use of anti-depressants in PD, available data has not been analyzed
Bupropion was reintroduced into the American market in
to determine the effectiveness of anti-depressant treatment in PD
1989 as an anti-depressant with a unique mechanism of action,
depression. In addition PD patients may beneﬁt less from SSRIs
and without the risk of elevated drug induced seizures that was
treatment than elderly patients without PD .
formerly proclaimed, as compared with other anti-depressant
Depression associated with PD is not well alleviated or well
medications. Later, it was shown that Bupropion is effective for
tolerated by regular anti-depressant treatment such as TCA,
smoking cessation and in 1996 it was approved by the FDA for this
SSRI’s, and SNRI Probably the mechanism of depression
in some of PD patients is different to other clinical forms of
The idea of prescribing Bupropion for PD depressed patient was
depression associated with serotonin and norepinephrin neuro-
formerly suggested in 1984 and was only noted in a few more
transmitters. It is presumed that, in these patients, depression
studies later on but this mode of treatment did not receive
associated with PD is a result of reduced dopamine activity in
the appropriate attention nor the right clinical position it should.
the brain, thus, it should react to medications that increase the
Since, 6–7 million people worldwide suffer from PD and its preva-
activity of brain dopaminergic system. Depression is not only a
lence rises sharply at age 50 and continue to increase thereafter
psychological reaction to PD, but probably a part of PD, related
to degeneration of dopamine neurons of the ventral mesenceph-alon The role of dopamine agonists in the treatment ofdepression is still being explored because of no sufﬁcient number
of controlled studies in this area. Some studies has demonstratedimprovement in depressive symptoms in PD after L-dopa treat-
With the prolongation of life expectancy, it is presumed that the
ment other failed to conﬁrm this ﬁnding There is evi-
prevalence of PD will further rise, together with comorbid depres-
dence from open studies for the ergotalkaloids bromcriptine and
sion and depression as side effect to PD treatments. As a result, the
pergolide to have anti-depressive effect. Some studies demon-
need for an adequate therapeutic answer for compounded PD with
strated the efﬁcacy of selegine in depressed Parkinson patients
but it has dose dependent fatal effect when combined
A possible answer for these suffering patients that might be
with SSRIs . More controlled research is needed to determine
resistant to regular anti-depressant medications, and can progress
and conﬁrm the effectiveness of selegine alone as treatment for
to life threatening condition from the affective viewpoint, is an
anti-depressant with a different proﬁle mechanism such as dopa-
The second generation dopamine agonist pramipexole showed
minergic rather than serotonergic or serotonergic/noradrenergic
the anti-depressant activity in several studies in depressive PD
activity. Bupropion, as mainly dopaminergic and noradrenergic
and non-PD patients . Some controlled studies for selective
anti-depressant can alleviate therapeutically depressive symptoms
dopamine D2 D3 agonists pramipexole and ropinerole are existing
associated with PD. This suggestion proved itself in several cases of
and show anti-depressive effect Side effects such as dizzi-
depression that occurred concomitantly with PD in its initial clin-
ness, somnolence, confusion, hallucinations due to pramipexole
ical manifestations. Clinical controlled studies on Bupropion use in
treatment can be problematic for PD patients.
PD depressed patients are required to support this hypothesis.
Moreover, the various current treatments of PD such as dopami-
nergic medications can cause long term side effects, namely, chore-
atic dyskinesias, unpredictable motor ﬂuctuations
Bilateral subthalamic deep brain stimulation (STN DBS) DBS is
now in growing use in the treatment of Parkinson’s disease follow-ing failure of pharmacological agents administered in therapeuticdosages for sufﬁcient length of time . Accumulating data con-
cerning this procedure conﬁrms its efﬁcacy in the treatment of se-vere parkinsonian patients , yet, and parallel there are
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