SAN FRANCISCO – Depression and psychosis were strongly correlated in Parkinson’s disease, while the presence of clinical anxiety upped the odds of psychosis by a statistically significant 8%, in a cross-sectional study presented at the 2016 congress of the International Psychogeriatric Association.
Felicia C. Goldstein, PhD, professor of neurology at Emory University, Atlanta, compared 48 patients with Parkinson’s disease and psychosis with 96 nonpsychotic controls who also had Parkinson’s disease. The groups were similar in terms of age, age of disease onset, educational level, Montreal Cognitive Assessment score (MoCA), and Unified Parkinson’s Disease Rating Scale (UPDRS) score, although patients with psychosis had about a 1.5-year longer mean duration of Parkinson’s disease than did controls (8.8 years vs. 7.3 years; P = .06).
Patients with psychosis were significantly more likely than controls to meet DSM-5 and Beck Depression Inventory II criteria for depression, with odds ratios of 8.0 (95% confidence interval, 2.5-25.6; P = .001) and 1.1 (1.02-1.1; P = .01), respectively. Patients with psychosis also were significantly more likely to have a positive result on the Beck Anxiety Inventory (OR, 1.1; 95% CI, 1.01-1.15; P = .01), and met DSM-5 criteria for anxiety more often than did controls (OR, 3.0; 95% CI, 0.9-9.5), although the latter correlation did not reach statistical significance (P = .07).
“The association between psychosis and anxiety has not been previously reported,” Dr. Goldstein noted. The findings underscore the link between psychosis and mood disorders in Parkinson’s disease and the need to treat these comorbidities, she said.
Neuropsychiatric symptoms in Parkinson’s disease also merit close monitoring and treatment, because they correlate with greater disability, faster progression of motor symptoms, and increased mortality, Adriana P. Hermida, MD, said in a separate oral presentation at the congress. In particular, depression is “the elephant in the room when it comes to Parkinson’s disease,” she said. “It is there, it is underrecognized, and it is undertreated.” Suicidal ideation is common, and patients should be treated even if they do not meet all criteria for a depressive disorder, added Dr. Hermida of the department of psychiatry and behavioral sciences at Emory.
For depression in Parkinson’s disease, Dr. Hermida said she typically starts with a selective serotonin reuptake inhibitor, most often escitalopram or sertraline. If the patient has a partial response, she adds another antidepressant, but if there is no response, she switches antidepressants. Second-line options for add-ons and switches include mirtazapine, which improves sleep and appetite and may improve tremor; venlafaxine extended release, which can raise blood pressure and may benefit hypotensive patients; and bupropion extended release, which is best for patients who need more activation, do not have substantial concerns with anxiety, and have REM sleep behavior disorder, she said. She said she also will consider dopamine agonists such as pramipexole, but they can increase the risk of psychosis, impulse control disorders, and dopamine dysregulation syndrome. She also noted that electroconvulsive therapy can rapidly improve both depression and motor symptoms, and should not be reserved for last-resort cases. Parkinson’s medications should be held the day of ECT, and cognition should be monitored afterward, she said.
Approximately 30% of Parkinson’s patients meet DSM-5 criteria for an anxiety disorder, and more than half have significant symptoms of anxiety, Dr. Hermida continued. Anxiety, like other signs and symptoms of Parkinson’s disease, can fluctuate throughout the day and tends to occur most frequently during “off” periods. No randomized controlled trials have examined anxiolytics in Parkinson’s disease patients, but studies of mindfulness-based cognitive therapy have yielded good results, she noted. Benzodiazepines “should be used sparingly, if at all,” as they increase the risk of confusion, gait abnormalities, and falls.
Psychosis should be treated if symptoms are ego-dystonic, she said. She said she uses first-line clozapine, which is more effective for delusions than quetiapine and has fewer adverse motor effects. She said she has not yet used pimavanserin (Nuplazid), a selective 5-HT2A inverse agonist that in April 2016 became the first drug approved by the Food and Drug Administration for treating hallucinations and delusions in Parkinson’s disease. The pivotal trial lasted 6 weeks and included 199 patients; those who received pimavanserin had a median 5.8-point drop on the Scale to Access Psychosis in Parkinson’s Disease (SAPS-PD), compared with 2.7 for placebo (P = .001), Dr. Hermida noted. Patients did not experience sedation or motor impairment, which are common adverse effects of other antipsychotics in this population.
Dr. Goldstein and Dr. Hermida reported no funding sources or conflicts of interest.