PORTLAND, OR—Nonmotor symptoms are common in patients with Parkinson’s disease and they can substantially impact quality of life, according to an overview presented at the Fourth World Parkinson Congress.

“Nonmotor symptoms in Parkinson’s disease have become increasingly recognized, and the number of clinical trials that are now out there is also on the increase,” said Susan H. Fox, MD, PhD, Associate Professor of Neurology at the University of Toronto.

Over the course of the illness, nonmotor symptoms become increasingly prevalent and are major determinants of the progression of overall disability. Conflicting evidence can make it difficult to choose appropriate treatments for some nonmotor symptoms such as depression and psychosis. Additionally, neurologists lack validated scales that accurately measure nonmotor symptoms, which further complicates treatment. Nevertheless, the literature does provide guidance for neurologists.

Managing Depression

Depression can affect as much as 60% of patients with Parkinson’s disease, according to the Parkinson’s Disease Foundation. Most interventions for depression have not been assessed extensively in patients with Parkinson’s disease, said Dr. Fox. Tricyclic antidepressants such as amitriptyline were evaluated in Parkinson’s disease, but study populations have been small, and the evidence has been conflicting. Other interventions for depression include selective serotonin reuptake inhibitors (SSRIs) such as citalopram, sertraline, paroxetine, and fluoxetine. Evidence for these drugs is considered insufficient.

A study of nortriptyline and paroxetine versus placebo found that nortriptyline significantly reduced depression, but that paroxetine did not. A follow-up study, however, comparing paroxetine to venlafaxine showed that paroxetine was effective in patients with Parkinson’s disease and depression.

Pramipexole, a dopamine agonist, may be an effective intervention for depression in Parkinson’s disease, according to Barone et al. Additionally, rasagiline, a monoamine oxidase-B inhibitor, has been tested in patients with Parkinson’s disease. Evidence suggests that rasagiline has a nonsignificant clinical effect on depression in these patients. Richard et al concluded that venlafaxine may be effective in this population. Their study did not identify any safety concerns. According to Dobkin et al, cognitive behavioral therapy may be an effective nonpharmacologic treatment for depression in Parkinson’s disease.

Cognitive Problems

Clinical trials so far have provided insufficient evidence about the efficacy of the acetylcholinesterase inhibitors donepezil and galantamine for treating cognitive impairment such as dementia in Parkinson’s disease. Studies do suggest, however, that rivastigmine promotes positive outcomes among patients with cognitive problems, but adverse events are common. Researchers compared oral and patch preparations of rivastigmine in a long-term open-label study that included a large number of patients. Fewer patients experienced tremor with the patch, compared with the oral formulation.

The data for memantine as an intervention for cognitive impairment in Parkinson’s disease are mixed. The drug is considered to have insufficient evidence. Exercise and cognitive behavioral therapy have also been studied for cognitive impairment, but experts have not developed evidence-based recommendations about these interventions.

Measuring Psychosis

Psychosis can cause significant morbidity in patients with Parkinson’s disease. Treating psychosis can be complicated because symptoms such as hallucinations, delusions, and paranoia may not persist. It may be difficult to determine whether the intervention reduced these psychotic symptoms or whether they resolved themselves, said Dr. Fox.

In addition, a lack of widely used validated scales makes measuring psychosis in Parkinson’s disease more difficult. Trials often have used rating scales borrowed from Alzheimer’s disease research. The difference between Alzheimer’s disease and Parkinson’s disease may bias the study results or cause researchers to overlook a drug that may provide benefit, said Dr. Fox.

Still, the literature does provide guidance. Overall, clozapine is considered effective in controlling psychosis in Parkinson’s disease. The associated risk of agranulocytosis makes this treatment less popular, however. As a result, some physicians avoid prescribing clozapine because it requires patients to undergo specialized blood monitoring.

Quetiapine may help to manage psychosis in Parkinson’s disease; most physicians would consider it a first-line agent for treating psychosis because of its ease of use, said Dr. Fox. However, insufficient evidence supports the drug’s use. Pimavanserin, a 5-HT_2A inverse agonist, was recently approved for treatment of psychosis in Parkinson’s disease.

Other Nonmotor Symptoms

Autonomic dysfunctions such as overactive bladder syndrome, sialorrhoea, and constipation are also common nonmotor symptoms of Parkinson’s disease. Studies show that botulinum toxins are efficacious for treating sialorrhoea in Parkinson’s disease. Side effects such as dry mouth, transient swallowing difficulties, and severe dysphagia have been reported, although the latter is rare.

Lubiprostrone is considered likely efficacious for treating constipation in Parkinson’s disease. Researchers concluded that there is insufficient evidence for the drug’s safety in patients with Parkinson’s disease, however. Typical adverse events include nausea, diarrhea, and dyspnea.

When it comes to treating sleep disorders associated with Parkinson’s disease (eg, insomnia, excessive daytime somnolence, and sudden onset of sleep), there is insufficient evidence. Drugs such as melatonin and eszopiclone are not well studied in this population.

“I don’t think we fully understand the pathology or the cause of many nonmotor symptoms. Certainly we have a better understanding than we did a few years ago, but we still have a long way to go,” said Dr. Fox.

—Erica Tricarico

Suggested Reading

Seppi K, Weintraub D, Coelho M, et al. The Movement Disorder Society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord. 2011;26 Suppl 3:S42-S80.

What Are the Best Treatments for Nonmotor Symptoms in Parkinson’s Disease?

Suggested Reading