Recognition and treatment of neuropsychiatric disturbances in Parkinson’s disease

Abstract

The non-motor symptoms of Parkinson’s disease (PD) have been attracting increasing attention due to their ubiquitous nature and their often devastating effects on the quality of life. Behavioral problems in PD include dementia, depression, apathy, fatigue, anxiety, psychosis, akathisia, personality change, sleep disorders and impulse control disorders. Some of these are intrinsic to the neuropathology while others occur as an interplay between pathology, psychology and pharmacology. While few data exist for guiding therapy, enough is known to guide therapy in a rational manner.

Keywords:

• akathisia
• anxiety
• apathy
• cognition
• dementia
• depression
• fatigue
• neuropsychiatric symptoms
• non-motor symptoms
• Parkinson’s disease
• personality
• sleep

Financial & competing interests disclosure

JH Friedman has worked for Teva, Lundbeck, Auspex, Theravance, Osmotica, Avid, Pfizer and Demos Press. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Behavioral problems in Parkinson’s disease (PD) must be considered at each office visit as they are important determinants of quality of life for both patient and caregivers.

• Few data exist on treating most of these problems so that one must extrapolate from data that exists on the general geriatric population for PD, which may not be accurate.

• Decision to treat should be based on disability and effect on quality of life.

• About 80% of PD patients will have dementia 20 years after diagnosis. Memory retrieval problem, as opposed to registration, is encountered in PD dementia. Cholinesterase inhibitors and memantine can be helpful.

• Visual hallucinations, delusions and illusions can occur in PD, with or without insight. Excluding contributing factors, such as a concomitant infection, psychoactive medications (anticholinergic), sedatives and benzodiazepines, is the first step of management. Clozapine and pimavanserin are the current best treatment options for psychosis in PD.

• About half of PD patients report fatigue as one of their three most bothersome symptoms and about one third rate it as the single worst symptom, including motor dysfunction. Management begins by excluding confounders like depression, anxiety, apathy and other medical conditions which may cause fatigue. Methylphenidate or modafinil have been used with varying results.

• Depression affects about 30–50% of people with PD. selective-serotonin reuptake inhibitor, serotonin norepinephrine reuptake inhibitor and tricyclic antidepressants all have some efficacy, and selection can be based on comorbid problems, and electroconvulsive therapy can be considered for refractory cases. Transcranial magnetic stimulation in PD is insufficiently studied.

• Anxiety in PD often predates the motor symptoms, develops more commonly in older people, is frequently associated with depression and affects up to 50% of PD patients. selective-serotonin reuptake inhibitors are often helpful. Other options include buspirone, benzodiazepine and mirtazapine and electroconvulsive therapy in refractory cases.

• Sleep problems in PD include rapid-eye movement-behavior disorder, restless legs and insomnia. The treatment falls into three categories: improving PD symptoms that interfere with sleep; providing a medication to help fall asleep or stay asleep and providing medication to improve daytime wakefulness.

• Impulse control disorders like pounding, hypersexuality, and excessive gambling, eating and shopping can occur in PD. These problems occur more commonly with dopamine agonists, thus tapering the agonist is recommended and switching to another agonist is usually futile.

• Akathisia is an inner restlessness accompanied by an inability to remain still. Association with levodopa timing, time of day and other motor symptoms of PD is seen to varying degree. Open-label use of clozapine showed benefit in a small cohort.

• Apathy and personality changes can be seen in PD, but no effective treatment is available.