Clinical Review

Recognizing and Treating Neuropsychiatric Symptoms in Parkinson's Disease

Journal of Clinical Outcomes Management. 2015 July;22(7)

 

References

Other neuroleptic medications have not resulted in widespread use, because trials have been open label, or outcomes demonstrated motor worsening. Cholinesterase inhibitors have been the subject of a few positive case series, however results appear to be sporadic, the effect size is relatively small, and side effects of this medication class are common [77–79]. It is clear that there is an unmet need for a medication for psychotic symptoms. Clozapine is effective but onerous in its monitoring requirements. Practically speaking, there are relatively few PD patients who take advantage of it because of its feasibility challenges. Yet the problem of psychotic symptoms is a significant one that imposes important challenges to the patient and caregiver, and may limit the number of medications that the patient needs in order to optimize quality of life.

Pimavanserin, a novel medication which acts as a selective serotonin inverse agonist, is in the early application stages for FDA approval for treatment of psychotic symptoms in PD [80]. In its pivotal phase III controlled trial, the drug reduced not only positive symptoms (hallucinations/delusions) without causing motoric worsening, but also reduced caregiver burden. Pimavanserin improved certain sleep features without causing daytime sedation. If this drug meets final approval, it may present an exciting option for many patients for whom treatment was previously limited.

Depression

A study of early PD suggested that depression is often unrecognized and frequently untreated [1]. Indeed it is not unusual for depression to predate the diagnosis of PD by an average of 4 to 6 years [81]. Expanding to the larger PD population, it is generally accepted that about 30% to 50% of PD patients experience clinically significant depression, and once diagnosed may have a long term course, or may recur [82,83]. This is important as untreated depression is an important cause of poor quality of life in early PD. In addition depression can exacerbate motor disability, lead to earlier motor treatment with medication, and increase caregiver stress [83–85].

Diagnosis

Diagnosing depression in PD is more challenging as somatic, cognitive, and vegetative symptoms of altered mood can be imitated features in PD, such as facial masking, fatigue, sleep changes, weight loss, and working memory dysfunction ( Table). Therefore, nonsomatic features tend to be more valuable to the clinician to query, such as the hedonic state (does the patient seek pleasurable activity?), mood, pessimism, state of hope, sense of capability[86,87]. Diagnosis of major and minor depression as well as dysthymia in PD using DSM-IV criteria has been validated [88]. To avoid underdiagnosis of this important commonly coexisting comorbidity, being inclusive with somatic overlapping features is still more important than trying to distinguish which disease state it belongs to.

A number of clinimetric rating scales for depression have been used and their advantages have been largely related to their objective nature (quantifiable); thus, they tend to be most useful in epidemiologic research studies or for larger scale screening purposes. Examples include the the Beck Depression Inventory, the Geriatric Depression Scale, and the Hamilton Depression Scale, all of which have been shown to be valid tools in PD (with the exception of the UPDRS Depression). It is important to note that they do not substitute for a diagnostic clinical interview [89].

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