Bupropion as the treatment of choice in depression associated with parkinson’s disease and it’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.
doi: 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.
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