Treatment of Parkinson's Disease Psychosis

Andrew Schleisman, PharmD Candidate 2017; Mikayla Spangler, PharmD, BCPS; Emily Knezevich, PharmD, BCPS, CDE


US Pharmacist. 2016;41(11):HS-20-HS-26. 

In This Article

Overview of PDP Management

Physical Versus Emotional Control

The intertwining pathophysiology of psychosis and PD through dopaminergic pathways presents healthcare professionals and patients with the unfortunate choice between physical and emotional stability. Dopaminergic agents that treat the symptoms of PD and maintain physical control are predominately associated with the triggering of psychosis symptoms through D2-receptor activation.[9,11] This swing to emotional instability could be broadly treated in one of two ways. One option is to stop the anti-PD agent; however, this is not feasible for most patients because physical instability and motor symptoms would return. Alternatively, an antipsychotic could be added, but nearly all typical and atypical antipsychotics work via D2-receptor antagonism, potentially tipping the scale toward physical instability. Accordingly, methods used in practice involve dose reduction of offending agents, as tolerated, or the use of an atypical antipsychotic with low D2-receptor affinity.[9,11]

Complexities Surrounding Antipsychotic use

The use of currently available antipsychotics in this population is complex, in part because of the black box warning regarding the increased risk of death when these agents are used in elderly patients with dementia.[12] This is significant for patients with PD for a multitude of reasons. First, PD is highly associated with the development of dementia, so many patients who are treated for psychosis likely have comorbid dementia. Additionally, psychotic symptoms of PD are more prominent with age, indicating a higher need for therapy in older patients. Even without the codiagnosis of dementia, antipsychotic use has been associated with a higher incidence of death in the PD population (hazard ratio 2.35, P <.001).[13] Although these medications have an increased risk of all-cause mortality, the exact mechanism has not been determined. Given the lack of alternative options, the risk of mortality must be balanced against the high morbidity and mortality associated with psychosis itself,[14] and antipsychotics remain the standard of practice for PDP treatment.

Stepwise Approach

The initial step in the treatment of PDP is to rule out external or secondary causes, such as infection, metabolic abnormalities, or structural lesions of the brain.[9,15] The next step, which is crucial for pharmacists, is to review the patient's current medications and identify any agents that may exacerbate psychotic symptoms. This includes not only anti-PD agents, but also medications for comorbid conditions. Potentially offending agents that are deemed nonessential should be discontinued. These may include tricyclic antidepressants, bladder antispasmodics, anticholinergics, benzodiazepines, muscle relaxants, and opioids—all of which are associated with some level of psychosis.[9,16]

If psychotic symptoms persist, it is important to review the anti-PD agents being used. Guidelines have suggested the reduction or discontinuation of anti-PD medications, starting with those with the most potential for psychosis induction and the least anti-PD activity.[16] Which agent to reduce or discontinue may be determined according to the following order: anticholinergics, amantadine, selegiline, dopamine agonists, and levodopa/carbidopa. Once the decision has been made to alter the use of a dopaminergic agent, it is vital to ensure that this medication is tapered gradually to avoid withdrawal and prevent neuroleptic malignant syndrome.[16,17] When anti-PD agents are being reduced, levodopa doses may need to be increased accordingly to maintain motor control.[17] If the above options do not resolve psychotic symptoms while maintaining motor control, the addition of an antipsychotic should be considered. Table 1 reviews the treatment algorithm for medical management of PDP. Above all, the patient and his or her caregiver should be closely involved in the treatment decision, fostering a patient-centered, individualized approach that emphasizes the risks and benefits specific to the patient.