12 PSYCHIATRIC ISSUES IN PARKINSON’S DISEASE Table 12.1 Symptom Associated Phenomena Low mood, anhedonia, hopelessness Depression Lack of motivation and initiative Apathy, abulia Impairment in planning/attention, poor orientation, memory, behavioral disturbances Executive dysfunction/dementia of Parkinson’s disease Early or prominent visual hallucinosis Lewy body dementia Frank psychosis Dementia, medication-induced effect Hypersexuality, poor impulse control, disinhibition Dopaimne dysregulation syndrome, frontal lobe dysfunction
INTRODUCTION
Psychiatric complications associated with Parkinson’s disease (PD) are common. They represent a special challenge to the practitioner because many of the psychiatric syndromes do not merely co-occur with PD but often are predictable consequences of responsible treatment of the underlying neurological condition.1
Cavalier treatment of the psychiatric complications may result in poor control of motor symptoms, increased dysfunction, and decreased quality of life, particularly in late or burdensome disease.
Some psychiatric syndromes in PD are associated with the disease itself:
Depression and anxiety
Cognitive impairment
Apathy
Other psychiatric symptoms may be associated with the treatment of PD:
Impulse control disorders
Psychosis
Irritability/agitation/dysphoria (eg, “off” periods, treatment withdrawal)
Dopaminergic circuits in the mesolimbic and mesocortical areas play important roles in reward, affective control, and impulsivity. Disruption of these circuits by cell loss or therapy may therefore have tremendous effects on behavior, affect, personality, and thought content.2
EXAMINATION OF THE PATIENT
An evaluation of the patient with PD starts with a careful examination of the patient’s reported psychiatric symptoms and a complete mental status examination (see Chapter 11).
Careful elucidation of the patient’s psychiatric symptoms and performance on the mental status examination will guide the diagnosis (Table 12.1).
A dramatic or unexpected worsening of motor control after the addition of a neuroleptic medication should prompt adjustment of the dose, consideration of an alternative, or optimization of antiparkinsonian medications.
DEPRESSION AND ANXIETY
The incidence of depression and anxiety is greater in patients with PD than in age-matched controls. Depression and anxiety are the result of complex psychological and neurobiological factors.4
The psychiatric burden is not thought to stem solely from the functional decline associated with progressive motor dysfunction or the diagnosis of PD itself.
Depression in PD follows a bimodal distribution, with the psychiatric burden peaking around the time of symptom onset/diagnosis and with the loss of independence in late disease.
Fortunately, the depression in PD is often mild.
However, several core and associated symptoms of depression (eg, fatigue, apathy, sleep disruption, psychomotor retardation, weight loss) are intrinsic to PD, so that the diagnosis can be tricky at times.
There have been isolated reports of increased suicidality among patients who underwent deep brain stimulation surgery of the subthalamic nucleus, although a direct correlation remains unclear.
The noradrenergic, dopaminergic, and serotoninergic pathways are thought to be implicated in depression in PD.2
Important Aspects of Psychiatric Phenomena
Generalized anxiety disorder, panic disorder, social phobia, phobic disorder, agoraphobia, and obsessive–compulsive disorder (OCD) have all been described in PD.
Just like depression, anxiety can be part of the “premotor” manifestations of PD, and it can be another nonmotor manifestation of wearing off.
Treatment of Depression and Anxiety
Depression in patients with PD should be a target of focused therapy because studies have shown that depression in this population is a major determinant of quality of life. The modality of treatment should be tailored to the severity of the depressive symptoms.
For mild depression associated with PD, nonpharmacologic approaches may be most indicated. These include the following:
Supportive psychotherapy
Cognitive behavioral therapy
In moderate to more advanced depression, pharmacotherapy is often indicated.
Certain phenomena of the “off period,” such as paroxysmal anxiety and panic, may not respond well to antidepressant and anxiolytic therapy but can respond to dopaminergic adjustments that minimize wearing-off periods.
Selective serotonin reuptake inhibitors (SSRIs) may mitigate symptoms of depression and anxiety in patients with PD, with minimal worsening of movement symptoms.
In a recent study examining venlafaxine XR and paroxetine in depression in PD, equal efficacy was found between the two classes.6 This was the largest randomized, placebo-controlled clinical trial of commonly used antidepressant medications for the treatment of depression in PD, had the longest observation period, and was the first to evaluate a serotonin–norepinephrine reuptake inhibitor (SNRI).
When pharmacotherapy has been ineffective or poorly tolerated, or when depression in PD is severe, electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) may be helpful, although the evidence of efficacy for TMS in PD is still being investigated.
It is important to mention that certain PD medications, such as dopamine agonists and monoamine oxidase (MAO) inhibitors, have demonstrated partial antidepressant effects in patients with PD, even when they are not being used for their prokinetic properties. However, they are not typically used as the sole treatment for depression in PD.
There is a remarkable paucity of randomized clinical trials examining the pharmacologic management of anxiety in PD.
However, based on clinical experience, the agents that are effective in the treatment of primary anxiety disorders (eg, SSRIs and benzodiazepines) also appear to be effective in PD-related anxiety.
APATHY
Just as the symptoms of depression are sometimes hard to distinguish from those of PD itself (ie, masked facies, psychomotor slowing, poor appetite), differentiating among depression, the symptoms of PD, and apathy may be challenging.
Apathy is associated with symptoms of poor motivation and initiative, without depressed mood, anhedonia, or hopelessness.
Apathy can be part of a depressive syndrome or occur on its own.
Apathy appears to correlate well with more severe depression and greater functional impairment in patients with PD, and it may be a predictor of dementia in the absence of depression.7
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