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 changes in the levels of levodopa, thus providing a relatively constant amount of dopamine. As the disease progresses, this honeymoon gradually diminishes, and a majority of patients begin to develop motor complications after five or more years. At this stage, adjustment of medications becomes 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 (wearing off), dyskinesias, off-period dystonia, freezing, and 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 (usually seen in very advanced PD)
• Dose failure (failure to turn on from a dose)

dyskinesias are unwanted involuntary movements that typically occur during the peak effect of a dose of levodopa.

Off-period dystonia may also occur as a motor complication, especially in the morning before the first dose of medication. Medication adjustments may be used to try to minimize each of these complications.

Freezing is a type of motor block or hesitation that may appear at the beginning of a movement, when passing through doorways, or while turning. This type of motor block does not always respond to medication. Sensory cues, such as auditory, visual, or proprioceptive (touch) triggers, are employed to overcome the block.

Frequent falling, usually seen in advanced PD only, may require an evaluation for physical therapy as well as use of a cane, scooter, or wheelchair.

Nonmotor complications

While PD is classified as a movement disorder, there are many nonmotor aspects of the disease. These may be as disabling as or more disabling than the motor symptoms, and treating them can improve the quality of life for both patient and family/caregiver. Recognizing that a symptom is part of the disease is an important step toward effective treatment.

• Depression is reported to affect up to 50% or even more of PD patients. Treatments are usually very effective, although complete resolution is rare. Treatments include certain antidepressant medications, usually a class of drugs known as selective serotonin reuptake inhibitors (SSRIs) including Prozac, Paxil, Luvox, Zoloft, or others. Another class of drugs, known as tricyclic antidepressants, may be used including Elavil, Endep, and others. With modern techniques and anesthesia, electroconvulsive therapy (also called electroshock therapy or ECT) may 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. When severe, these symptoms may be treated with benzodiazepines; however, the potential for addiction should be factored into the decision to use them. Since symptoms are often worse during periods of low levodopa levels, some adjustment in dosing frequency may be effective as well.

 

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

 

• Mild orthostatic hypotension is frequently seen in patients with PD. Strategies for treatment include reducing antihypertension medications, 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, with anticholinergics the first to go. 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 serious blood disorder (agranulocytosis). Quetiapine (Seroquel) and olanzapine (Zyprexa) may also be useful.