Effects of combined MAO-B inhibitors and levodopa vs. monotherapy in Parkinson’s disease

Abstract

Background: Prior studies report that monoamine oxidases inhibitors (MAO-I) when used as an adjunct to levodopa ameliorate motor symptoms in Parkinson’s disease (PD), but this was not tested in relation to cognitive or psychiatric measures.Objective: Here, we tested the effects of MAO-I as an adjunct to levodopa, in comparison to levodopa or dopamine (DA) agonists alone, on various cognitive, affective and quality of life measures.Methods: We studied three groups of subjects: healthy controls, PD patients on combined levodopa and MAO-I, and PD patients on levodopa or DA agonists only.Results: We found that compared to monotherapy, combined MAO-I and levodopa seemed to improve cognition, including probabilistic learning, working memory and executive functions. There were no differences between the different medication regimes on deterministic learning, attention or memory recall. It was also found that MAO-I as an adjunct to levodopa improves affective measures such as depression, apathy, anxiety and quality of life. Interestingly, this enhancing effect of combined levodopa and MAO-I was more pronounced in PD patients with severe akinesia, compared to patients with severe tremor.Conclusion: Our data are in agreement with (a) the Continuous Dopaminergic Stimulation (CDS) theory which states that continuous stimulation of the basal ganglia enhances motor, psychiatric and cognitive functions in PD patients; and/or (b) findings that MAO-I increase the bioavailability of monoamines that have beneficial effects on motor and behavioral dysfunction in PD.

Pharmacological treatment of apathy in Parkinson’s disease, review of the literature

“…Krishna et al (27) performed a comparison cohort study. A group of 37 patients used a mono-amine oxidase B inhibitor (MAO-B inhibitor) (rasagiline or selegiline) combined with levodopa.…”

“…Based on the ndings in this review, one could say with caution that rivastigmine (26), pramipexole (24), istradefylline (20), and selegiline combined with levodopa (27) are better in the treatment of apathy in PD than monotherapy with levodopa, DA or placebo (Table 3). These studies show signi cant outcomes in favor of the intervention treatment.…”

“…These studies show signi cant outcomes in favor of the intervention treatment. Other treatment like apomorphine (21,22), rasagiline (25,27), and levodopa (7,28) have contradictive results and therefore inconclusive. By using the Cochrane Collaboration's Risk of Bias evaluation tool, we found that most studies had a high risk of bias because of selection bias based on the type of study, like cohort studies and observational studies.…”

Dysphoria, dopaminergic medication and spatial memory in Parkinsons disease

“…However, the role of MAO-B inhibitors as add-on to DA agonist treatment for cognitive and affective functions in PD has not yet been addressed. A study by Krishna and Moustafa [62] suggests that MAO-B inhibitors as an adjunct to levodopa therapy provide a better effect on cognitive function (including working memory, cognitive flexibility and probabilistic learning) and depression compared to monotherapy with levodopa or DA agonists. The authors assume that the beneficial effects of combined levodopa and MAO-B therapy on cognitive and affective measures may be the continuous dopaminergic stimulation of the basal ganglia and/or increase of the availability of monoamines.…”

Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson’s Disease

“…A meta-analysis of a combination of selegiline and levodopa showed an improvement in the clinical symptoms of PD patients, owing to enhanced drug effect, compared to monotherapy of selegiline. Combination therapy was demonstrated to prolong the effectiveness of levodopa, reduce the amount of levodopa, reduce fluctuations in motor or nonmotor functions, and improve the effectiveness and quality of life [88,89]. Moreover, selegiline treatment was shown to induce the expression of oxidative stress-related proteins such as HO-1, PrxI, TrxI, TrxRxI, γGCS, and p62/A170.…”