Anxiety symptoms have been correlated, although not consistently, with the on-off motor phenomenon often found in advanced PD.13 They can also be an adverse effect of many of the antiparkinsonian medications, including anticholinergics, dopamine agonists, catechol-O-methyltransferase inhibitors, and selegiline. Both anxiety and depression have been associated with an increased risk for falls.14
Psychotic symptoms. Up to 25% of PD patients experience delusions or hallucinations.15 Risk factors include dementia, sleep disturbance, and—most commonly—the use of dopaminergic agents. Up to one-fifth of patients using dopaminergic drugs experience psychotic symptoms.16
Psychotic symptoms can occur with or without the clouded sensorium characteristic of delirium. Psychotic symptoms with an associated confusional state can be associated with use of anticholinergic agents and drugs such as selegiline and amantadine.17 Catechol-O-methyltransferase inhibitors cause more sustained dopaminergic activity of levodopa, which can result in psychotic symptoms. Therefore, the use of all known classes of antiparkinsonian medications has been associated with drug-induced psychosis.
In advanced PD, paranoid delusions, delusions of spousal infidelity, and visual hallucinations are common, whereas negative symptoms and thought disturbances are not.18 Psychosis may be a more important contributor to caregiver distress than the motor symptoms of PD and may be more likely than any other factor to lead to nursing home placement of the PD patient (Box 1).15
Psychiatric interventions
Goals for psychiatric treatment of depression, anxiety, and psychosis associated with PD seem relatively straightforward:
- improvement or remission of psychiatric symptoms
- restoration of optimal patient functioning.
Ideally, these goals would be achieved without causing sedation, orthostatic hypotension, or exacerbating motor symptoms. The older age of patients and the progressive nature of this neurodegenerative disorder predispose patients to cognitive side effects. Unfortunately, despite the high prevalence of psychiatric disturbances in PD, evidence with which to evaluate treatment efficacy and safety and to guide treatment selection is extremely limited.
For depression associated with PD, extensive clinical experience supports the efficacy of tricyclic antidepressants. Even so, selective serotonin reuptake inhibitors (SSRIs) are the preferred treatment, although only open-label trials and case reports support their efficacy.5,12 Compared with tricyclics, SSRIs exhibit a relative lack of problems with sedation, orthostatic hypotension, and memory-impairing anticholinergic side effects. While case reports have cited worsening of motor symptoms with SSRIs, a recent prospective study found no significant worsening of PD symptoms during treatment with citalopram, fluoxetine, fluvoxamine, or sertraline.19 Co-administration of an SSRI with selegiline is not absolutely contraindicated, but the combination does carry a very small risk of development of serotonin syndrome.1,5
CASE REPORT: A downward spiral
Mr. J had a 6-year history of PD with pronounced bradykinesia and gait disturbance treated with amantadine and carbidopa-levodopa. His rigidity began to worsen, so the dosage of carbidopa-levodopa was increased. His wife then reported that he had increased confusion and balance problems. On evaluation, he was found to have a urinary tract infection. Following antibiotic treatment, mental status and gait returned to usual baseline.
One year later, Mr. J began having trouble getting out of bed, with unpredictable motor freezing episodes. Pramipexole was added to his regimen, and he began having prominent visual hallucinations. Low-dose trifluoperazine was added, and hallucinations improved. The patient became increasingly depressed, and sertraline was started.
Over the next year, his function progressively worsened, with increased motor freezing and unpredictable dyskinesias. Hallucinations complicated attempts to change his medications. Amantadine was stopped without improvement. He was referred for surgical evaluation, but because of his cognitive status and depression was deemed not to be a candidate.
He began to fall repeatedly and developed orthostatic hypotension. His clinical course continued to be complicated by hallucinations and delusions that his wife was being unfaithful. Ongoing psychosis and severe gait instability led to his admission to a nursing home.
Data are even more scant on the safe use of other antidepressants in PD. Electroconvulsive therapy has been proven helpful in refractory cases and sometimes results in transient motor symptom improvement.1,5,12 While clinical experience suggests that psychotherapy frequently helps, no extensive controlled studies exist. One small study suggests the efficacy of structured cognitive psychotherapy.20
Anxiety. No studies have examined the treatment of anxiety in PD patients. Given the extremely high comorbidity of anxiety with depression, antidepressants should probably be considered as a first-line pharmacotherapy. Benzodiazepines should be used cautiously, as they increase the risk of falls, sedation, and confusion in older patients. One small controlled study found that buspirone was well tolerated in PD patients at low dosages (10 to 40 mg/d), but anxiety did not improve. At high dosages (100 mg/d), anxiety worsened.21
Psychosis. Data on use of antipsychotic agents in PD are also limited, but some evidence supports their use in treating PD-related psychotic symptoms. While conventional antipsychotics can help control psychosis, the potential is high for worsening of parkinsonian symptoms due to D2 receptor blockade.