Depression, anxiety, and psychosis in Parkinson's disease

Introduction

Parkinson's disease is commonly associated with psychiatric morbidity, which includes depression, anxiety, and dopaminergic psychosis. These compound the patient's predicament. Fortunately a variety of effective treatments is available. This article reviews the diagnosis and symptoms of depression, anxiety, and psychosis in Parkinson's disease, and offers strategies for effective management.

Depression

Depression in Parkinson's disease (PD) is common, and its impact can equal that of the motor symptoms. The prevalence rates vary significantly, reflecting study design and the lack of uniform criteria for diagnosing depression. Cummings[1] reviewed nine studies conducted between 1987 and 1990 and calculated a prevalence of 43% (25% to 70%); this figure agrees with the experience at the Vancouver Hospital Movement Disorder Clinic.

Depression, if undiagnosed or unacknowledged, can wreak havoc upon efforts to control motor symptoms, and may create major family and spousal tensions at a time when a patient most needs support.[2,3] Depression may precede the diagnosis of PD, sometimes by years, and may need treatment before treatment of the parkinsonian motor symptoms is necessary.[4] Patients with a prior history of depression are more vulnerable to developing depression with their PD.[5] Anxiety is frequently a major component of depression and is often disproportionate to parkinsonian disability.

 Symptoms and differential diagnosis

The symptoms of depression in PD vary slightly from the typical symptom profile of primary depression. Depressed parkinsonian patients experience less guilt and self-reproach and more irritability, sadness, and concern with health.[6] Depression associated with agitation creates additional functional incapacity and family stressors, problems to which young-onset parkinsonian patients appear particularly prone.[7] Motor fluctuations in response to treatment ("on-off") may also cause concomitant oscillations in mood. Depression increases in the "off" state and improves in the "on" state.[8]

Completed suicide appears to be rare in the Parkinson population even though verbalized suicidal ideation is not uncommon.[1] In the Vancouver Hospital Movement Disorder Clinic population, younger-onset patients appear to be more at risk for suicide and suicidal gestures than older patients. Among clinic patients believed to have committed suicide, two patients appear to have died from an overdose of antiparkinsonian medication leading to a cardiac arrhythmia.

The advent of severe depression in PD may anticipate the development of intellectual impairment.[5] Depression may also compromise intellectual functions, giving an erroneous impression of dementia, a presentation known as pseudodementia. Gratifyingly, pseudodementia resolves with effective treatment of the depression.

Depressive illness must be distinguished from demoralization. Demoralization is a sadness, often time limited and secondary to adverse psychosocial circumstances such as stress and loss or to disappointment in failing to live up to one's own expectations. Demoralization carries the formal DSM lV diagnostic label of an adjustment disorder with depressed mood. By contrast, depressive illness secondary to PD carries the formal DSM lV diagnosis of mood disorder due to PD.

Demoralization is primarily a negative cognitive state—whether real, imagined, or exaggerated—that makes the sufferer feel sad. Depressive illness is primarily a biological disruption of the mood-regulating neural tissues that, in addition to causing alterations in sleep, appetite, weight, sex drive, and energy, produces psychic pain and self-destructive impulses. Depression and demoralization can coexist and frequently do. As a rule, demoralization responds to psychotherapy, depression to pharmacology.

In the PD patient, demoralization at disability, loss of autonomy, the prospect of a chronic progressive neurological disorder, the need to take daily medication with no end in sight, and the truncation or abandonment of life goals and long-term plans may be the primary disturbance behind the patient's sadness. Factors that create demoralization may be identified using the Parkinson's Impact Scale, a validated rating scale measuring quality of life, including self-esteem, in patients with PD.[9] The scale allows patients to rate their quality of life both at their best and at their worst. Categories most relevant to demoralization are self-positive, self-negative, family relationships, leisure, financial security, and sexuality.

 Diagnosis

The diagnosis of depression in PD may be difficult since parkinsonian symptoms such as hypomimia, bradyphrenia, and bradykinesia can mimic the affective flattening and psychomotor slowing of depression. Nonetheless, it is possible to discriminate parkinsonian motor symptoms from the affective and cognitive symptoms of depression by utilizing the Beck Depression Inventory, which is a self-administered mood rating scale.[10] The Beck Depression Inventory consists of 21 items that take 10 minutes to complete. Scores greater than 15 indicate the presence of mild depression while scores over 20 indicate the presence of moderate to severe depression.

 Treatment

Treatment of depression may be challenging, as patients are often reluctant to admit that they are depressed. This denial of depression is often frustrating to the health professional since it occurs in the face of substantial suffering and functional incapacity. American author William Stryon has suggested that if depression were a physical illness, depressed patients would be in intensive-care units.[11] Few individuals would refuse treatment for a heart attack, but many refuse help for depression. To make matters worse, family members of older, more disabled patients, acting as advocates, often collude in the denial of depression. Without acceptance of the diagnosis of depression by patients, their family, and other caregivers, treatment is impossible.[2]

 Psychological support

All patients, but especially young-onset patients, benefit from psychological support.[3,7] In both a general practitioner's and a specialist's office, psychological support is delivered through good, old-fashioned, effective clinical care. Good clinical care has been identified by Andrews[12] as one of the essential psychotherapies and is an amalgam of four steps: establishing a relationship with the patient; understanding the undercurrents in the relationship; being professional and enthusiastic about specific therapies and treatment for treatable syndromes; and providing the broad-based support and care that are needed until the principal disorder remits.

Psychological support is the treatment of choice for demoralization. For depressive illness, biological therapies are added. A trial with biological therapies is also indicated if demoralization fails to lift in response to improved mobility and functioning.

 Pharmacotherapy

Pharmacotherapy of depression in PD is generally effective. Tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and newer antidepressants such as venlafaxine and bupropion all have a role in the treatment of PD depression. Patients who are already hypotensive may do better with venlafaxine 37.5 mg b.i.d. or venlafaxine XR 75 mg o.d. as it spares blood pressure. Venlafaxine may also have a more rapid onset of effect. Normotensive depressed patients who have difficulty sleeping and/or maintaining weight can be helped with a tricyclic antidepressant such as nortriptyline 50 mg q.h.s. Nortriptyline taken between 6 p.m. and 8 p.m., combined with a glass of juice upon awakening but before getting out of bed, will help overcome early-morning dry mouth, hypotension, and grogginess.[7]

SSRIs are useful but may be stimulating rather than sedating. Some patients, especially the elderly, may experience agitation (authors' observation). SSRIs can also cause anorexia, which may be undesirable in an underweight patient or in one who already has gastric side effects from antiparkinson drugs. SSRIs are not contraindicated because of occasional case reports of worsening of parkinsonism. Nonetheless, patients' mobility should be monitored for this possible adverse effect.[13,14]

 Electroconvulsive therapy

Some patients fail to respond to medication or develop intolerable medication side effects. Electroconvulsive therapy (ECT) should be considered for this group of patients. Contrary to popular belief, ECT is a widely used and safe treatment for depression when medication fails. ECT has been shown to be effective and safe in PD for treating both depression[15] and dopaminergic psychosis.[16] Several studies also report varying periods of motor improvement following ECT in PD. A study is currently underway at UBC to examine this phenomenon in a controlled setting. ECT improves depression, may permit a reduction in antidepressant medications, and has intrinsic antiparkinsonian properties. Public resistance to ECT due to misinformation needs to be overcome before its usage becomes more widespread.

Anxiety

Common in Parkinson's disease, anxiety manifests itself as constant or episodic feelings of fear, incessant, uncontrollable worrying, and a variety of physical symptoms including muscle tension, palpitations, sweating, and shortness of breath. Treatment depends upon correctly identifying the source of anxiety. Anxiety is frequently part of the presenting symptoms of a depressive illness, and at times may be the dominant symptom. The depressive illness may be overlooked in this setting. Careful analysis of the patient's mental state will identify the core depressive symptoms and lead to appropriate treatment.

Anxiety often accompanies the "off" state—the periods of parkinsonian immobility. The anxiety associated with the off state can be severe. At the Vancouver Hospital Movement Disorder Clinic, anxiety associated with prolonged off periods is one of the most common reasons for parkinsonian patients presenting to emergency. The anxiety and immobility feed off each other, making both worse over time.[17] Management depends upon correctly diagnosing the problem, followed by a review and adjustment of the anti-parkinsonian medication regimen to minimize the off state. Patients need to be educated about the link between anxiety and the off state and reassured that even a prolonged off state will eventually resolve. To keep anxiety manageable during a profound off state, patients may benefit from lorazepam 0.5 mg as needed sublingually.[18]

Parkinsonian patients, like everyone, are vulnerable to adjustment reactions with anxiety in response to psychosocial stress. An adjustment reaction with anxiety is managed by identifying the source of anxiety, providing psychological support, and educating the patient in appropriate coping strategies.

Psychosis

About 20% of patients with Parkinson's disease who receive long-term treatment with dopaminergic agents (e.g., levodopa, bromocriptine, pergolide ropinerole, and pramipexole) will develop psychosis identified by the presence of chronic hallucinations and delusions.[4] Psychosis most commonly occurs in patients who have associated cognitive impairment. Clinically this presents as a delirium—a confusional psychosis. Approximately 3% of patients will develop a psychosis in the absence of a dementia—a nonconfusional psychosis.[16] Patients may recognize mild hallucinations as a medication side effect. They may tolerate them rather than compromise mobility with a reduction in medication.

Patients presenting with psychosis need to be evaluated for the possibility of confounding factors such as overmedication, recent travel involving time change, constipation, dehydration, and infection. If these are excluded, medications that may contribute to psychosis need to be withdrawn beginning with the anticholinergics and followed in sequence by amantadine, selegiline, and dopamine agonists.[18] Only when all of these have been stopped should any attempt be made to reduce the dose of levodopa. Drug holidays, fashionable 20 years ago, are now known to be dangerous and occasionally fatal.[19] Stopping levodopa may also rarely result in a neuroleptic malignant syndrome. Any significant reduction of anti-parkinsonian medication should be carried out in hospital.[19] Although a reduction in dopaminergic medication may allow the psychosis to resolve, the patient may be left physically incapacitated by immobility because of insufficient dopamine replacement. This set of circumstances requires specific strategies. Patients with nonconfusional psychosis can be treated with atypical antipsychotics. The data are best for clozapine 12.5 mg at night increasing to 25 mg at night,[20] or olanzapine 2.5 mg at night increasing to 10 mg at night.[21] Quetiapine 25 mg to 50 mg at night may also be useful.[22] Higher doses of the atypical neuroleptics are not, however, free from adverse effects, and may exacerbate the underlying parkinsonian immobility. Patients given atypical neuroleptics require close monitoring for this effect. Alternatively, ECT can be used, which clears the psychosis for up to 6 months. ECT is only helpful in nonconfusional psychosis.[16] Confusional psychosis is managed with the atypical neuroleptics.[20,21,22]

 Conclusion

Parkinson's disease is frequently associated with psychiatric disturbances that may produce incapacity equal to or greater than the motor manifestations. The psychiatric disturbances have a multifactorial relationship to the underlying neuropathology. Pathogenetic factors include negative psychological reactions to the motor disability, the neuropathology acting alone or in concert with a personal or familial diathesis to psychiatric illness, and the adverse effects of the antiparkinsonian medication. Effective treatment is available and depends upon accurate diagnosis of the psychiatric disturbance and its relationship to these pathogenetic factors.

Table. Parkinson's disease medication, side effects, and management

T.A. Hurwitz, MBChB, MRCP, FRCPC, and Susan M. Calne, RN

Dr Hurwitz is a clinical professor in the Department of Psychiatry at the University of British Columbia, chief of service in Neuropsychiatric Unit WI at UBC Hospital, and medical director at the BC Provincial Neuropsychiatry Program. Ms Calne is the coordinator of the Neurodegenerative Disorders Centre at Vancouver Hospital and Health Sciences Centre.