The Movement Disorder Society Evidence‐Based Medicine Review Update: Treatments for the non‐motor symptoms of Parkinson's disease
Authors: Seppi Klaus , Weintraub Daniel , Coelho Miguel , Perez‐Lloret Santiago , Fox Susan H. , Katzenschlager Regina , Hametner Eva‐Maria , Poewe Werner , Rascol Olivier , Goetz Christopher G. , Sampaio Cristina 
Published: October 2011

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; quetiapine for the treatment of psychosis; fludrocortisone and domperidone for the treatment of orthostatic hypotension; sildenafil for the treatment of erectile dysfunction, ipratropium bromide spray for the treatment of sialorrhea; levodopa/carbidopa controlled release (CR), pergolide, eszopiclone, melatonin 3 to 5 mg and melatonin 50 mg for the treatment of insomnia and modafinil for the treatment of excessive daytime sleepiness. Due to safety issues the practice implication is that pergolide and nefazodone are not useful for the above‐mentioned indications. Due to safety issues, olanzapine remains not useful for the treatment of psychosis. As none of the studies exceeded a duration of 6 months, the recommendations given are for the short‐term management of the different non‐motor symptoms. There were no RCTs that met inclusion criteria for the treatment of anxiety disorders, apathy, medication‐related impulse control disorders and related behaviors other than pathological gambling, rapid eye movement (REM) sleep behavior disorder (RBD), sweating, or urinary dysfunction. Therefore, there is insufficient evidence for the treatment of these indications. This EBM review of interventions for the non‐motor symptoms of PD updates the field, but, because several RCTs are ongoing, a continual updating process is needed. Several interventions and indications still lack good quality evidence, and these gaps offer an opportunity for ongoing research. © 2011 Movement Disorder Society