EXPERT ANALYSIS FROM THE AAGP ANNUAL MEETING

NEW ORLEANS (FRONTLINE MEDICAL NEWS)Psychotic, not physical, symptoms, might be the most distressing aspect of Parkinson’s disease for patients, families, and caregivers.

Psychosis is common and persistent, especially as the disease progresses, and it can be devastating, Dr. Laura Marsh said at the annual meeting of the American Association for Geriatric Psychiatry.

“What’s most disabling to families is not the on-off fluctuations, the falling, the other motor symptoms,” said Dr. Marsh, executive director of mental health at Michael E. DeBakey Veterans Affairs Medical Center, Houston. “It’s the cognitive and psychiatric problems that occur with increasing frequency over the disease course. This is what makes it really tough to handle this disease … These can be very 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.”

Despite the difficulties PD psychosis can cause, research doesn’t really have a firm grasp on its extent, Dr. Marsh said. Most studies find an incidence of 8%-40%, but the rate varies depending on the presence of comorbid dementia – as low as 5%-17% in those without it, and as high as 81% in those with it.

Among those with psychoses, visual and auditory hallucinations are most common. But other systems also can be affected, with olfactory, tactile, and visceral hallucinations. Visceral hallucinations frequently manifest as a sense of an unseen presence or passage near the patient, which can be highly disturbing.

Delusions might be somewhat less common but no less problematic, occurring in about 60% of those 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 – like presence – as ‘minor’ or benign, but in truth none of them are really minor,” Dr. Marsh said.

Patients’ often-complicated medical regimens, including drugs for motor function, mood, and cognition, complicate the picture. “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 is often the case, prevention is the most effective therapy. Seemingly small things, like constipation or a urinary tract infection, can easily throw a Parkinson’s patient off kilter, especially an older patient. Sleep problems can predispose to psychotic symptoms; sleep management can help moderate them.

A medication review is crucial. Psychosis is a well-known side effect of anticholinergic medications, and it’s not unusual for patients to be taking several of these. Slowly peeling off one at a time, until psychiatric symptoms improve but before motor symptoms decline, is a must.

“I recommend starting with the monoamine oxidase inhibitors and going down the list until you get to the L-dopa,” Dr. Marsh said. “You want to keep that person moving and engaged.”

Controlled-release anticholinergics are the most unpredictable of these culprit medications. “I like to get rid of that and use the regular 25-100 mg every 3 hours and have them track their symptoms.”

Choosing an antipsychotic medication, should it be necessary, is a delicate process. The D2-receptor agonists can actually cause Parkinsonism. Of the more appropriate atypical antipsychotics, clozapine possesses the most data and 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 even 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 Parkinson’s patients in long-term care. Quetiapine was being prescribed to 40%, risperidone to 39%, olanzapine to 17%, and typical antipsychotics to the remainder.

“This is simply inappropriate use of these medications,” she said.

Some promise may lie ahead, however. Pimavanserin, a serotonin 5-HT2A inverse agonist, performed well in a 2013 placebo-controlled trial carried out in 200 patients (Drugs Aging 2013;30:19-22). Pimavanserin was associated with an almost 6-point decrease in Scale to Assess Psychosis in PD (SAPS-PD), compared with a 3-point decrease associated with placebo. Ten patients in the pimavanserin group discontinued 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 there were no significant safety concerns or worsening of motor function.

The drug also is being investigated for Alzheimer’s disease psychosis.

Dr. Marsh disclosed that she had received honoraria from Roche Pharmaceuticals in 2013, and has received royalties from Taylor & Francis/Informa.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

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