NEW ORLEANS—Psychotic, not physical, symptoms might be the most distressing aspect of Parkinson’s disease for patients, families, and caregivers, according to an overview presented at the 2015 Annual Meeting of the American Association for Geriatric Psychiatry. Psychosis is common and persistent, especially as the disease progresses, and it can be devastating, said Laura Marsh, MD, Executive Director of Mental Health at Michael E. DeBakey Veterans Affairs Medical Center in Houston.

“What’s most disabling to families is not the on–off fluctuations, the falling, [or] the other motor symptoms,” said Dr. Marsh. “It’s the cognitive and psychiatric problems that occur with increasing frequency over the disease course. This [situation] is what makes it really tough to handle this disease ... These can be challenging patients with multiple comorbidities treated with medications that can exacerbate psychiatric symptoms. The trick is balancing the drugs needed to manage their physical problems with the sometimes-related exacerbations of psychiatric symptoms.”

Visual and Auditory Hallucinations Are Common
Despite the difficulties that Parkinson’s disease psychosis can cause, research has not clearly indicated the condition’s incidence, Dr. Marsh said. Most studies find an incidence of between 8% and 40%, but the rate varies depending on the presence of comorbid dementia; the rate can be as low as 5% to 17% in patients without it, and as high as 81% in patients with it.

Among individuals with psychoses, visual and auditory hallucinations are most common. Other phenomena, such as a vivid sense of the presence of a person, or brief visual hallucinations of a person, object, or animal passing in the peripheral visual field, are referred to as minor hallucinations, but can still be highly disturbing.

Delusions might be somewhat less common but no less problematic. They occur in approximately 60% of patients with psychosis. Feelings that a spouse has been unfaithful might be the most painful for couples, especially when the spouse is the primary caregiver, Dr. Marsh said. “We may classify some of these [symptoms], like presence, as minor or benign, but, in truth, none of them are really minor,” Dr. Marsh said.

Drugs Can Ease or Worsen Symptoms
Patients often have complicated medical regimens, including drugs for motor function, mood, and cognition. “When patients are not doing well, they are often taking low doses of just about everything, so nothing is really effective,” she said. “Their motor function isn’t better, their mood isn’t better, and now they end up psychotic, too.”

As with many other disorders, prevention is the most effective therapy. Seemingly small problems like constipation or a urinary tract infection can easily disconcert a patient with Parkinson’s disease, especially if he or she is elderly. Sleep problems can predispose a person to psychotic symptoms; sleep management can help moderate these symptoms.

Reviewing a patient’s medications is a crucial step. Psychosis is a well-known side effect of anticholinergic medications, and patients sometimes take several medications with these properties. Slowly discontinuing one drug at a time until psychiatric symptoms improve, but before motor symptoms decline, is necessary.

“I recommend starting with discontinuing the anticholinergic medications and going down the patient’s list, if needed, until you get to only the L-dopa remaining,” Dr. Marsh said. “You want to keep that person moving and engaged.”

Controlled-release dopaminergic medications can be the most unpredictable of these culprit medications. “I like to eliminate controlled-release medications and use the regular carbidopa/levodopa 25/100 mg every three hours and have patients track their symptoms.”

How to Choose an Antipsychotic Drug
Choosing an antipsychotic medication, should it be necessary, is a delicate process. The D2-receptor antagonists cause parkinsonism. Of the more appropriate atypical antipsychotics, the literature contains the most data about clozapine, which has the best clinical track record. Quetiapine, though not backed by as much evidence, is fairly well tolerated and can be useful. Risperidone and olanzapine are poorly tolerated and impose unnecessary risks, including falls, seizures, worsened parkinsonism, and death.

Unfortunately, Dr. Marsh said, a recent study suggests that clinicians aren’t incorporating these facts into clinical practice. She referred to a 2013 claims database study of patients with Parkinson’s disease in long-term care. Quetiapine was prescribed to 40% of patients, risperidone to 39%, olanzapine to 17%, and typical antipsychotics to the remainder. “This is simply inappropriate use of these medications,” said Dr. Marsh.

An investigational drug may have promise, however. Pimavanserin, a serotonin 5-HT2A inverse agonist, performed well in a 2013 placebo-controlled trial carried out in 199 patients. Pimavanserin was associated with an almost six-point decrease in Scale for the Assessment of Positive Symptoms for Parkinson’s disease score, compared with a nearly three-point decrease associated with placebo. Ten patients in the pimavanserin group discontinued treatment because of an adverse event (four because of psychotic disorder or hallucination within 10 days of start of the study drug), compared with two in the placebo group. Overall, though, pimavanserin was well tolerated, and the researchers observed no significant safety concerns or worsening of motor function. The drug also is being investigated for Alzheimer’s disease psychosis.

—Michele G. Sullivan

Treating Parkinson’s Psychosis Requires Careful Risk–Benefit Analysis