Objective: To evaluate efficacy of duloxetine on motor symptoms in Parkinson’s disease (PD) patients with wearing-off in an open label trial.

Background: Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is widely used as an antidepressant. We have demonstrated that both serotonin and norepinephrine transporters play roles in reuptake of L-dopa-derived dopamine in the rat striatum with dopaminergic denervation by 6-hydroxydopamine (Kannari et al, 2006; Arai et al., 2008). These findings suggest that inhibition of both serotonin and norepinephrine transporters enhances and prolongs antiParkinsonian effects of levodopa in patients with Parkinson’s disease. Furthermore, we have shown that duloxetine enhances L-DOPA-induced motor behaviors in the rat model of PD.

Methods: Permission for the study was given by Ethical Committee of our hospital. Written informed consent was obtained from 13 PD patients (eight women and five men) from our outpatient clinic. The subjects were required to be positive for two verbally asked questions for depression (Arroll et al., 2005), to complete ON/OFF diary training; to be receiving at least three doses of Levodopa per day with a daily dosage of at least 300 mg of L-dopa; not to have MAO inhibitors; to have been on a stable regimen of antiParkinsonian drugs for at least 4 weeks before the trial; to have an average of at least 2 hours of OFF-time per day. The subjects entered an open label trial for 8 weeks. Duloxetine 20mg/day was given during the first week, then the dosage was increased to 40 mg/day. They were assessed at 0, 2, 4 and 8 weeks after initiation of duloxetine.

Results: Two patients could not complete the study due to adverse effects, exacerbation of dyskinesia and facial flushing. Accordingly, data obtained from 11 patients were analyzed. When compared to 0 week, UPDRS part II score during ON (-0.64, P<0.05) and OFF (-2.8, P<0.05) and UPDRS part III score during ON (-4.43, P<0.01) significantly improved at 8 weeks. Daily OFF time became significantly shortened (-4.9 hours, P<0.01) at 8 weeks. However, 4 patients complained of aggravation of troublesome dyskinesia.

Conclusions: Duloxetine enhances the effects of levodopa and reduces daily OFF time in depressive patients with Parkinson’s disease, but may worsen levodopa-induced dyskinesia. PD patients with OFF but without dyskinesia could be good candidates for adjunctive duloxetine treatment.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/duloxetine-a-serotonin-and-norepinephrine-reuptake-inhibitor-reduces-daily-off-time-in-parkinsons-disease/