Among the atypical antipsychotics, clozapine has been most extensively studied in PD and has been shown in open and double-blind trials to be effective and well tolerated at low dosages (6.25 to 50 mg/d). A limited number of open studies of some of the newer atypicals have been performed. While extreme caution must be used in comparing data from these studies due to highly variable dosing and other study design issues, clozapine and quetiapine appear to be the agents best tolerated by PD patients.12,18,22 Initial antipsychotic dosing should be low and escalation cautious—regardless of the agent chosen—because of the dose-related potential for worsening of parkinsonian symptoms, sedation, and orthostatic hypotension.
A team approach to treatment
Because psychiatric and PD symptoms and treatments are closely interrelated, the psychiatrist, neurologist, patient, and caregiver must collaborate for the best therapeutic result. A simplistic approach to treatment can result in a catastrophic downward spiral in patient functioning.
Often, compromises must be made between optimal control of parkinsonian and psychiatric symptoms to achieve the best overall patient function. Patients and caregivers must be counseled about possible psychiatric symptoms associated with PD and antiparkinsonian therapy, as well as the potential for adverse effects from psychiatric medications. With this knowledge, patients and caregivers can help assess the severity of symptoms and set treatment priorities, depending on how symptoms may be affecting the patient’s level of functioning. For example, if an effective antiparkinsonian regimen has triggered infrequent, nondistressing hallucinations with preserved insight, intervention may not be required beyond patient and caregiver education (Box 2).
Patient workup. When intervention is required for psychiatric symptoms, it should begin with careful neurologic evaluation. Triggering factors such as infections (commonly urinary tract infections and pneumonia), metabolic disorders (hyperglycemia, hypothyroidism), subdural hematomas (if the patient is falling), and drug interactions should be ruled out or appropriately addressed.
Next, try to sequentially eliminate antiparkinsonian medications until the psychosis resolves or motor function worsens.23 Because of considerable overlap between PD symptoms and depression (psychomotor retardation, fatigue, and anergia), optimizing PD therapy sometimes can result in substantial psychiatric improvement. Some evidence also suggests that the dopamine agonist pramipexole may be effective in treating both PD and depression.5
When psychiatric medications are necessary for depression, anxiety, or psychosis, carefully review target symptoms, treatment expectations, and possible adverse effects with the patient and caregiver. Keep in mind the progressive nature of PD and, in addition to frequent monitoring, educate and encourage caregivers to immediately report any suspected adverse effects.
Any motor function deterioration should trigger a re-evaluation of psychotropic medications before you presume that the patient’s PD is progressing. Because antiparkinsonian drug regimens change over time, review the patient’s medications at each appointment, and alert patients and caregivers to potential psychiatric complications of any new medication.
Caregiver treatment In addition to treating the patient, it is important to monitor the impact of psychiatric symptoms and PD on the patient’s caregiver. Frequently assess whether the caregiver and patient have adequate social supports, and address any emerging needs. Useful interventions include caregiver counseling, referrals to support groups, and respite care.24
CASE REPORT: Panic attacks or hallucinations?
Mrs. K had a 4-year history of rapidly progressing PD treated with entacapone, carbidopa-levodopa, and a deep brain stimulator. Increasing periods of motor freezing, which were often accompanied by panic attacks, led her to become increasingly depressed and demanding of her caregiver husband. Eventually, she was admitted to an inpatient psychiatry unit because of suicidal ideation.
After a neurologic evaluation, the dosing times of her carbidopa-levodopa and entacapone were changed, but she continued to have panic attacks and remained depressed. Alprazolam promptly reduced her panic symptoms, and paroxetine was initiated for depression. A discussion with the patient and her husband revealed that they had some longstanding issues in their marriage that were exacerbated by Mrs K’s increasing dependency. The couple was referred for marital therapy, and Mrs. K agreed to begin attending a senior center.
Following discharge, the panic remained controlled and depression improved. Entacapone was replaced with tolcapone to see if motor freezing would decrease. Mrs. K’s movements improved, but her husband reported she had awakened on several nights with visual hallucinations. The hallucinations were infrequent, unaccompanied by agitation, and not distressing to the patient. Following a discussion of therapeutic options with Mrs. K and her husband, antipsychotic therapy was not instituted. The patient continues to live at home and attends the senior center regularly.
Related resources
- Parkinson’s Disease Foundation: http://www.pdf.org
- American Parkinson Disease Association: http://apdaparkinson.com
- National Parkinson Foundation: http://www.parkinson.org
- Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease 2001: treatment guidelines. Neurology 2001;56:5(suppl):S1-S88.