Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease

doi:10.1016/j.jns.2006.05.024

Journal of the Neurological Sciences

Volume 248, Issues 1–2, 25 October 2006, Pages 266-270

https://doi.org/10.1016/j.jns.2006.05.024 Get rights and content

Abstract

Depression affects approximately 45% of all patients with Parkinson's disease, reduces quality of live independent of motor symptoms and seems to be underrated and undertreated. Pramipexole shows D₃− versus D₂-receptor preference at cortico-frontal dopamine receptors and neurotrophic effects which seem to relate to its antidepressant and anti-anhedonic properties in Parkinson's disease and bipolar depression found in controlled studies. In the present study, effects of pramipexole were investigated under routine clinical conditions. Anhedonia was measured in patients with Parkinson's disease (n = 657) using the self-rated Snaith-Hamilton-Pleasure-Scale (SHAPS-D), depression was assessed by the observer-rated Short-Parkinson's-Evaluation Scale (SPES). Anhedonia was present in 45.7% of all patients and in 79.7% of the depressed patients with Parkinson's disease. Mild depression was present in 47%, moderate to severe depression in 22% of the patients. At the end of the study period of 9 weeks on an average, the mean dosage of pramipexole was 1.0 ± 0.6 mg/d (range 0.3 to 4.2). Frequency of depression (moderate to severe: 6.8%, mild: 37.6%) and anhedonia (25.5%) as well as motor deficits were significantly reduced during treatment with pramipexole. Drop-outs due to adverse events occurred in 3.5%. Future studies should investigate specificity of anti-anhedonic and antidepressive properties of pramipexole.

Introduction

Depression occurs in about 45% of patients with Parkinson's disease (PD) and reduces subjective and objective quality of life independent of motor deficits [1]. Anhedonia, the reduced capacity to experience pleasure, appears to be a key symptom of depression in PD [2], [3].

In PD, degeneration of dopaminergic neurons involves motor structures including basal ganglia, but also structures of the limbic system [4]. It has been postulated that experiencing joy and pleasure depends on dopaminergic reward mechanisms in the limbic system which are thought to be the basis of motivation, drive, and activation [5]. Degenerative processes in PD may effect dopaminergic reward mechanisms and lead to anhedonia, loss of motivation, avolition and apathy [6]. The novel D₂/D₃ receptor agonist pramipexole has a preference for D₃ versus D₂ receptors in regions of the brain which plays a key role in the etiology of depression [7]. These mechanisms could explain effects of pramipexole on anhedonia and depression found in animal experiments [8], [9] and patients with major depressive disorder [10], [11].

In two recently published studies from independent study sites, patients with refractory bipolar depression were treated with the dopamine agonist pramipexole as add-on therapy to various mood stabilizers [12], [13]. Both studies tested in a randomized, double-blind design the antidepressant effects of pramipexole against placebo. In both studies, pramipexole was well tolerated significantly more effective in reducing severity of depression and increasing numbers of responders. These effects may relate to pramipexole's preference for D₃ versus D₂ receptors and neurotrophic properties.

In controlled clinical trials, pramipexole has demonstrated efficacy as monotherapy in patients with early Parkinson's disease [14] and as adjunctive therapy in patients with more advanced disease [15]. The present observational data were collected in order to investigate whether the beneficial effects noted in controlled phase III trials of pramipexole in patients with Parkinson's disease are replicated during routine clinical practice. The study also aimed to demonstrate the practicability of the German version of the Snaith-Hamilton Pleasure Scale (SHAPS-D) for measurements of anhedonia in patients with PD under conditions of routine clinical practice.

Section snippets

Patients and methods

In this prospective, observational, open study, we included patients (n = 657) with clinical diagnosis of PD (presence of 2 of 3 cardinal features [tremor, bradykinesia, rigidity) and levodopa responsiveness) at 298 study sites (in- and outpatients) if pramipexole as an add-on to levodopa was clinically indicated (T1). Dosage of pramipexole was adjusted depending on efficacy and tolerability in weekly intervals allowing a maximal dose of 3 × 1.5 mg/d. Dosage of levodopa was adjusted as clinically

Results

Each study site recruited 2.2 patients (SD 3.2, range 1–40) on average. Patients with PD (n = 657) were 67.7 ± 9.2 (means ± SD) years old; 44.4% were female. 78% of the patients were in Hoehn and Yahr stages 2 or 3. At T2, the average dose of pramipexole was 1.0 ± 0.6 mg/d (range 0.3 to 4.2). During the study period, the average dosage of levodopa changed from 372.3 ± 125 mg/d at T1 to 344.3 ± 105 mg/d at T2. Most patients (86%) received comedication in addition to antiparkinson therapy. In addition,

Discussion

In the present study, frequency and severity of depression, anhedonia and motor functioning was studied during treatment with the dopamine agonist pramipexole under conditions of routine clinical practice. Frequency and severity of depression, anhedonia and motor deficits were significantly reduced during treatment with pramipexole.

Conclusion

In conclusion, anhedonia is a frequent symptom in patients with PD which can be reliably assessed by the self rated SHAPS. Because of the high frequency and clinical relevance of anhedonia and the antidepressant and anti-anhedonic properties of pramipexole, further studies of efficacy and effectiveness of this dopamine agonist in Parkinson's disease, anhedonia and depression are warranted.

Acknowledgement

This study was supported by Boehringer Ingelheim, Germany.

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Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Conclusion

Acknowledgement

Eur J Pharmacol

Biol Psychiatry

Parkinsonism Relat Disord

Biol Psychiatry

The quality of life in Parkinson's disease

Mov Disord

Depression and Parkinson's disease

J Neurol

Pramipexole in routine clinical practice: a prospective observational trial in Parkinson's disease

CNS Drugs

Pathoanatomy of Parkinson's disease

J Neurol

Anhedonia in schizophrenic, depressed, or alcohol-dependent patients — neurobiological correlates

Pharmacopsychiatry

Psychopathological and behavioral correlates of dopaminergic sensitivity in alcohol-dependent patients