The two studies noted above have led to an increased focus on the role of norepinephrine(Drug information on norepinephrine) for depression in patients who have PD. However, there are significant interindividual differences in response to medications and frequently tolerability is the most important factor to consider. The many tolerability issues include the anticholinergic effects of tricyclics and the risk of a slight worsening of the motor signs of PD with selective serotonin reuptake inhibitors.11 In addition, there is a potentially serious interaction between selegiline(Drug information on selegiline) and rasagiline—monoamine oxidase type B inhibitors that are widely used (at low doses) for their mild therapeutic and potential disease-slowing effects—and antidepressants.
In case reports, electroconvulsive therapy (ECT) has been shown to be an effective treatment of depression in patients with PD. In most cases, both the mood and the motor symptoms improve, although the motor improvement is short-lived.12 Despite the negative image of ECT, patients with severe depression who have PD should consider it when pharmacological agents have failed.
Dobkin and colleagues13 have begun investigation of the feasibility and effectiveness of cognitive-behavioral therapy (CBT) for depression. Results are thus far promising, and it appears that when CBT is modified appropriately, it is effective for depression associated with PD.
There are a number of other relevant treatment issues. Optimal control of the physical aspects of PD is a prerequisite to adequate treatment of depression. Numerous studies have demonstrated a tight correlation between “off” periods and depression, and unless there is good control of the fluctuations, antidepressant therapy will be suboptimal.14
The study of depression in PD has stimulated some interesting treatment approaches, such as deep brain stimulation (DBS). This procedure is widely used to treat the motor complications of PD and has led to progress in mapping the circuits involved in depression. This, in turn, has led investigators to begin treatment trials of DBS in refractory depression.15 Although these treatments are still experimental, they are promising.
Drug Reactions: Psychosis and Impulse Control Disorders
Great strides have been made in the treatment of PD, and there is a wide array of medications with which to relieve parkinsonian symptoms. While these drugs have effects on a variety of CNS neurotransmitter systems, they primarily affect dopamine(Drug information on dopamine) transmission. Therefore, it is not surprising that they often produce dramatic behavioral changes that cause significant difficulties for patients and their families and caregivers.
Psychosis is very rare in untreated patients with PD; however, antiparkinsonian medications can cause hallucinations, delusions, agitation, and mania—all of which can greatly complicate care. While psychosis does occur with the older levodopa-based drugs, it appears to be more frequently associated with the newer direct postsynaptic dopamine agonists, pramipexole(Drug information on pramipexole) and ropinirole(Drug information on ropinirole). The anticholinergic agents can cause a worsening of cognitive deficits and can precipitate delirium, which may include a variety of psychotic symptoms.
In patients with PD, visual hallucinations are the most common drug effect, although auditory and tactile hallucinations also occur. Often, these take the form of nonthreatening visual illusions that do not require active intervention. However, overtly threatening hallucinations can develop—human or animal figures that are stereotyped for each patient and are most common at night.16