The Movement Disorder Society Evidence‐Based Medicine Review Update: Treatments for the non‐motor symptoms of Parkinson's disease

Abstract

The Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for Parkinson's Disease (PD) was first published in 2002 and was updated in 2005 to cover clinical trial data up to January 2004 with the focus on motor symptoms of PD. In this revised version the MDS task force decided it was necessary to extend the review to non-motor symptoms. The objective of this work was to update previous EBM reviews on treatments for PD with a focus on non-motor symptoms. Level-I (randomized controlled trial, RCT) reports of pharmacological and nonpharmacological interventions for the non-motor symptoms of PD, published as full articles in English between January 2002 and December 2010 were reviewed. Criteria for inclusion and ranking followed the original program outline and adhered to EBM methodology. For efficacy conclusions, treatments were designated: efficacious, likely efficacious, unlikely efficacious, non-efficacious, or insufficient evidence. Safety data were catalogued and reviewed. Based on the combined efficacy and safety assessment, Implications for clinical practice were determined using the following designations: clinically useful, possibly useful, investigational, unlikely useful, and not useful. Fifty-four new studies qualified for efficacy review while several other studies covered safety issues. Updated and new efficacy conclusions were made for all indications. The treatments that are efficacious for the management of the different non-motor symptoms are as follows: pramipexole for the treatment of depressive symptoms, clozapine for the treatment of psychosis, rivastigmine for the treatment of dementia, and botulinum toxin A (BTX-A) and BTX-B as well as glycopyrrolate for the treatment of sialorrhea. The practical implications for these treatments, except for glycopyrrolate, are that they are clinically useful. Since there is insufficient evidence of glycopyrrolate for the treatment of sialorrhea exceeding 1 week, the practice implication is that it is possibly useful. The treatments that are likely efficacious for the management of the different non-motor symptoms are as follows: the tricyclic antidepressants nortriptyline and desipramine for the treatment of depression or depressive symptoms and macrogol for the treatment of constipation. The practice implications for these treatments are possibly useful. For most of the other interventions there is insufficient evidence to make adequate conclusions on their efficacy. This includes the tricyclic antidepressant amitriptyline, all selective serotonin reuptake inhibitors (SSRIs) reviewed (paroxetine, citalopram, sertraline, and fluoxetine), the newer antidepressants atomoxetine and nefazodone, pergolide, Ω-3 fatty acids as well as repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression or depressive symptoms; methylphenidate and modafinil for the treatment of fatigue; amantadine for the treatment of pathological gambling; donepezil, galantamine, and memantine for the treatment of dementia; ...

Parkinsonian Syndromes

“…Cognitive impairment, autonomic dysfunction, and falls are all features of severe PD that substantially affect function and quality of life and incompletely respond to medication manipulation. 19 …”

Beneficial Effects of Ramelteon on Rapid Eye Movement Sleep Behavior Disorder Associated with Parkinson's Disease - Results of a Multicenter Open Trial

“…Indeed, it has been reported that a good night's sleep can improve motor symptoms in the morning in some patients with PD (32). It should be noted that the International Parkinson and Movement Disorder Society Task Force has reported that the evidence for the efficacy of melatonin is insufficient (33). However, the present study suggests that ramelteon may improve RBD as well as other sleep disturbances in patients with PD.…”

Progression of Parkinson’s Disease and Unmet Needs in Mid- to Late-stage Patients

“…13 Some evidence supports the efficacy of certain treatments for depression, dementia, psychosis, constipation and sialorrhoea; however, there is insufficient evidence for efficacious treatments for other important non-motor symptoms that certainly contribute to poor quality of life, such as orthostatic hypotension, neurogenic bladder disturbance, erectile dysfunction, fatigue, insomnia and excessive daytime sleepiness. 14 Pain, the most frequent non-motor symptom of PD, may be due to central and/or peripheral mechanisms. 15,16 Manifesting as arthralgic Safinamide is a unique molecule with a novel mechanism of action.…”