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European Journal of Neurology 2008, 15: 885–886 Unraveling depression in ParkinsonÕs disease Depression is a common psychiatric non-motor symp- SSRIs sertraline is characterized by a low selectivity tom occurring in ParkinsonÕs disease (PD) and nega- for serotonin relative to dopamine reuptake, suggesting tively affecting patientsÕ quality of life and disability [1].
a favorable efficacy profile. One recent randomized There is large variability in depression prevalence rates study showed that sertraline treatment in PD is safe and this is related to overlap with motor features, dif- and unlike the tricyclic antidepressant amitriptyline ficulties in the evaluation of cognitively impaired pa- improves quality of life, particularly activities of daily tients and lack of scales specifically designed and validated for PD. In a prospective study, Hughes et al.
In the current issue of the journal, Kulisevsky [2] reported that presence of depression and dementia et al.[12] report the results of 6-month prospective were important predictors of mortality in PD subjects evaluation of serterline therapy in a large cohort of 310 followed for over 11 years. In a cohort of 114 PD depressed PD patients at various disease stages and patients, Weintraub et al. [3] found that depression and recruited from over 50 Spanish movement disorder cognitive impairment were associated with altered centers. Interestingly, the authors found that sertraline functional ability, in addition to psychosis, age, PD treatment not only improved depression but also duration, apathy, sleepiness, and motor impairment.
resulted in motor benefit as expressed by changes in Nuti et al. [4] reported in a population of 90 PD sub- both total Unified Parkinson’s disease Rating Scale (UPDRS) and sub-scores including motor. Only a few according to DSM-IV criteria) were present in 40% of patients noticed increase of tremor amplitude. The cases with associated generalized anxiety (11%) and study is important given the large number of included panic disorder (30%). Finally, Chaudhuri et al. [5] used subjects. However, patients were not randomized and a specific questionnaire (NMS Quest) to assess non- neurologists were allowed changes in dopaminergic motor symptoms and reported that sadness was present therapy during the observation period making inter- pretation of the results somehow controversial.
Despite the relevance of depression in PD, there is Nonetheless, these findings are complementary to little evidence for efficacy and safety of antidepressant those of a randomized study showing that pramipexole, therapies and trials assessing effectiveness of individual a dopamine agonist with high affinity for D3 receptors, drugs are mostly open-label, non-randomized, and improved both mood and mobility in a cohort of PD limited to small patient cohorts [6]. A Cochrane review patients on stable levodopa monotherapy [13].
published in 2003 on the treatment of depression in PD Some considerations should now be drawn: first, found only three randomized controlled trials on anti- depression has gained clinical relevance in PD and depressant medications for a total of 106 patients [7].
application of a revised version of UPDRS along with The authors concluded that available data on the specific questionnaires and scales will help recognition effectiveness of antidepressant therapies in PD were of affected patients. Secondly, depression affects quality insufficient and no recommendation was possible for of life and patient self-perception of motor function and this further emphasizes the need for treatment. Thirdly, This may explain why depression in PD is under- SSRIs and in particular sertraline have now demon- treated, at least according to some recent large surveys.
strated good safety and tolerability for clinical use and The Parkinson Study Group collected data on 23 000 they may be considered first line in treating PD PD patients in the USA and found that 26% was on depression. Dopamine agonists are also likely to be treatment with antidepressant drugs [8]. A recent reg- beneficial and pramipexole is currently evaluated in a ister-based study in Denmark showed that among double-blind multicentre study. Finally, effectiveness 22 827 patients on anti-Parkinson medications, 19.9% and safety should be confirmed in placebo-controlled were taking antidepressants [9]. Similarly, a cross-sec- trials. Placebo effect is large in depression and partic- tional epidemiologic study on non-motor symptoms ularly in PD. A recent study of rotigotine patch in ad- conducted in selected movement disorder centers in vanced PD reported a 35% responder rate to placebo Italy (PRIAMO) revealed that only 169 of 1072 PD (vs. 67% to pramipexole and 59.7% to rotigotine) [14].
patients (15.8%) were treated for depression [10].
Therefore, further studies are warranted to fill this Moreover, serotonin reuptake inhibitors (SSRIs) important gap, ensure best medical therapy to patients that are frequently used to treat depression have been and provide class I evidence of efficacy for anti- reported to occasionally worsen parkinsonism. Among Ó 2008 The Author(s)Journal compilation Ó 2008 EFNS ease. Cochrane database of Systematic Reviews 2003; (3): Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy 8. Richard IH, Kurlan R and the Parkinson Study Group. A survey of antidepressant drug use in ParkinsonÕs disease.
Neurology 1997; 49: 1168–1170.
9. Brandt-Christensen M, Kvist K, Nilsson FM, Andersen PK, Kessing LV. Treatment with antiparkinson and 1. Global ParkinsonÕs Disease Survey Steering Committee.
Factors impacting on quality of life in ParkinsonÕs disease: epidemiological study. Movement Disorders 2007; 31: 22.
results from an international study. Movement Disorders 10. Antonini A, Colosimo C, Marconi R, Morgante L, Barone P. The PRIAMO study: background, methods 2. Hughes TA, Ross HF, Mindham RH, Spokes EG. Mor- and recruitment. Neurological Sciences 2008; 29: 61– tality in ParkinsonÕs disease and its association with dementia and depression. Acta Neurologica Scandinavica 11. Antonini A, Tesei S, Zecchinelli A, et al. Randomized study of sertraline and low-dose amitriptyline in patients 3. Weintraub D, Moberg PJ, Duda JE, et al. Effect of psy- with ParkinsonÕs disease and depression: effect on quality chiatric and other nonmotor symptoms on disability in of life. Movement Disorders 2006; 21: 1119–1122.
ParkinsonÕs disease. Journal of the American Geriatrics 12. Kulisevsky J, Pagonabarraga J, Pascual-Sedano B, Gironell A, Garcı´a-Sa´nchez C, Martı´nez-Corral M.
4. Nuti A, Ceravolo R, Piccinni A, et al. Psychiatric com- Motor changes during sertraline treatment indepressed orbidity in a population of ParkinsonÕs disease patients.
patients with ParkinsonÕs disease. European Journal of European Journal of Neurology 2004; 11: 315–320.
5. Chaudhuri KR, Martinez-Martin P, Schapira AH, et al.
13. Barone P, Scarzella L, Marconi R, et al. Pramipexole International multicenter pilot study of the first compre- versus sertraline in the treatment of depression in hensive self-completed nonmotor symptoms questionnaire ParkinsonÕs disease: a national multicenter parallel-group for ParkinsonÕs disease: the NMSQuest study. Movement randomized study. Journal of Neurology 2006; 253: 601– 6. Horstink M, Tolosa E, Bouccelli U, et al. Review of the 14. Poewe W, Rascol O, Quinn N, et al. Efficacy of pramip- therapeutic management of ParkinsonÕs disease. European exole and transdermal rotigotine in advanced ParkinsonÕs Journal of Neurology 2006; 13: 1186–1202.
disease: a double-blind, double-dummy, randomised 7. Ghazi-Noori S, Chung TH, Deane KHO, Rickards H, controlled trial. Lancet Neurology 2007; 6: 513–20.
Clarke CE. Therapies for depression in ParkinsonÕs dis- Journal compilation Ó 2008 EFNS European Journal of Neurology 15, 885–886



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