Parkinson's Disease

Comorbidity

Behavioural and Psychiatric Disturbances

These problems can be at least as disabling as the motor symptoms of Parkinson’s disease (PD) and may arise either from treatment or secondary to PD or as a comorbid condition. Effective management of such associated problems depends upon proper identification of the underlying cause.

Depression

Depression is prevalent in PD, with 40–60% of people with PD suffering depression symptoms. Much of the depression is associated with ‘off’ periods and improves with more effective management of PD.

People with PD who have depression usually respond as well to conventional antidepressant therapy as people who do not have PD. The newer, non-sedating selective serotonin reuptake inhibitors (SSRIs) may be more suitable for patients with an anergic depression; some tricyclic antidepressants may be hazardous in overdose and their anticholinergic and cardiovascular effects may be particularly troublesome for elderly people with PD. Amoxapine should not be used in people with PD due to the risk of neuroleptic malignant syndrome secondary to blockade of dopamine receptors.

There are several effective SSRIs available for people with PD. Despite some reports of apparent exacerbation of PD symptoms, there is little compelling evidence that the SSRIs present any peculiar risk for PD patients. However, as with any co-prescribing, pharmacokinetic, pharmacodynamic and pharmacological activity of medications and their potential for drug–drug interactions must be carefully considered.

Dementia
Dementia associated with PD may affect as many as 2 in 5 people with PD, although dementia is rare in earlyonset PD (EOPD). Although both PD-associated dementia and Alzheimer’s disease (AD) involve memory loss, poor concentration, poor initiative and slow responses in PD-associated dementia are more prominent than the classical cognitive deficits of AD – aphasia, apraxia and agnosia.

In the differential diagnosis of the dementia syndromes, it is important to exclude reversible causes as well as pathologies other than PD and AD.

It is also important to distinguish symptoms of higher brain functions that are caused by lack of dopamine from those that can be reversed by appropriate anti-parkinsonian medication. Frontal lobe dysfunction that responds to levodopa is common and does not constitute dementia until permanent.

People with PD-associated dementia often have an adverse prognosis, decline more rapidly and respond less well to levodopa whilst suffering more adverse events. It is, therefore, important that the diagnosis is correct.

If PD-related dementia is considered probable, the person with PD should not be exposed to anticholinergics or drugs with anticholinergic side effects; he/she should be maintained on minimal doses of levodopa, whilst recognising at the same time that optimal control of PD symptoms is important. Cholinesterase inhibitors have proved effective for the treatment of dementia in some people with PD.

Hallucinations and psychosis
High, daily doses of levodopa and most other anti-PD drugs are associated with higher risk of hallucinations. Combinations of drugs increase the risk of psychosis. Elderly people with PD who also have dementia and people with PD who have a history of psychiatric problems are at particular risk of psychosis.

Hallucination and psychoses are associated with poor outcomes and – if possible – the underlying cause should be determined. Lowering the dose of levodopa and eliminating concurrent anticholinergics, selegiline, amantadine or dopamine agonists should be undertaken to see whether these might be responsible, despite the likely exacerbation of the motor symptoms of PD.

In refractory cases an atypical antipsychotic may prove effective, whereas the typical antipsychotics will exacerbate the motor symptoms of PD. Clozapine and quetiapine have both been tried with positive results, although the former requires careful monitoring for potentially fatal blood dyscrasias and cardiac reactions.

Sleep problems
Fragmented sleep is common and often occurs early in the course of PD. Other problems include nightmares or vivid dreams, changes in the sleep/wake cycle and sleepiness in the daytime. Whilst fragmented sleep appears to be related with PD, nightmares and vivid dreams appear to be related more with medications and may precede hallucinations.

Depending upon the particular problem, alterations of dose regimen or types of medication can help. For example, a short-acting sedative at night or a mild stimulant such as coffee may be beneficial. More potent stimulants should be avoided if at all possible.