Parkinson's Disease

Complications of Treatment

Many PD patients have several years of trouble-free treatment following diagnosis. The remaining neurons of the substantia nigra are believed to be sufficiently active to smooth out fluctuations in concentration of levodopa to provide a relatively steady, physiological, level of dopamine. As the disease progresses, this "honeymoon" wanes, and a majority of patients begin to develop motor complications after five or more years. At this stage, adjustment of medications can become a frequent and increasingly complex task for physician and patient. Nonmotor complications of disease can also be debilitating, and are important objects of treatment.

Motor complications
Motor complications include:

• Motor fluctuations
• Dyskinesias
• Off-period dystonia
• Freezing
• Falls

Motor fluctuations refer to:

• Wearing off or premature loss of benefit from a given dose of levodopa
• On-off, or sudden and unpredictable switch to off (typically seen only in the most advanced patients)
• Dose failure

Motor fluctuations may be treated by increasing the frequency of levodopa dosing, increasing the dose of the decarboxylase inhibitor (carbidopa), adding a dopamine agonist or COMT inhibitor, or instituting apomorphine therapy.

Dyskinesias are uncontrolled movements that typically occur during the peak effect of a dose of levodopa. Dyskinesias may be reduced by reducing the levodopa dose, usually combined with increased frequency of dosing, or addition of a COMT inhibitor, dopamine agonist, or an MAO-B inhibitor. Amantadine may be effective in many patients.

Off-period dystonia may also occur as a motor complication, especially in the morning before the first dose of medication. Increasing the frequency of dosing or use of apomorphine upon rising are possible management strategies.

Freezing is a type of motor block or hesitation that may appear at movement initiation, when passing through doorways, or while turning. Episodes of freezing do not always respond to medication. Sensory cues, such as auditory, visual, or proprioceptive triggers, are employed by some patients to overcome the block.

Frequent falling, usually seen in advanced stages only, may require physical therapy evaluation and use of a cane, scooter, or wheelchair.

Nonmotor complications
Depression is reported to affect up to 50% or even more of PD patients. It is not yet clear whether most PD depression is reactive depression or is an intrinsic part of the disease process. Treatments are generally very effective, although complete resolution is rare. Treatments may include selective serotonin reuptake inhibitors (SSRIs) or tricyclics antidepressants. With modern techniques and anesthesia, electroconvulsive therapy (also called electroshock therapy) can be effective for relieving depression in PD. It may also improve motor symptoms of the disease, although it is not prescribed for this reason alone.

Anxiety and restlessness are common. They may be treated with benzodiazepines. Since symptoms are often worse during periods of low levodopa levels, some adjustment in dosing frequency may also be effective.

Sleep disorders are very common in PD, ranging from insomnia to excessive sleepiness to vivid dreaming. A careful history and reduction of unnecessary or medications that might cause insomnia or restlessness may be helpful. Treatment of depression may improve sleep.

Mild orthostatic hypotension is frequently seen in patients with PD. Strategies for treatment may include tapering antihypertensive agents, increasing salt intake, and use of compressive stockings. Fludrocortisone or midodrine may be indicated as well.

Psychosis may be a side effect of antiparkinsonian medications, as well as a feature of disease progression. Initial features may include vivid dreaming and nightmares, which may progress to delusions, paranoia, disorientation, and hallucinations. Reducing unnecessary medications is the first line of treatment; typically, anticholinergics are the first to be eliminated. Atypical neuroleptics are valuable for patients with continued symptoms. Clozapine (Clozaril®) is the most effective, but requires frequent blood monitoring for the rare occurrence of agranulocytosis. Quetiapine and olanzapine may also be useful.