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Brain failure - Parkinson disease
Brain failure - Parkinson disease
Date Created: 04/01/2001 Last Modified: 20/01/2003 Last Checked: 20/01/2003
Parkinson disease: neuropsychiatric symptoms
Recent studies have found that mild cognitive impairment is very common, and dementia, depression, and psychotic symptoms develop in a large proportion of patients.
These neuropsychiatric symptoms are important determinants of mortality and disease progression, as well as quality of life, caregiver distress, and nursing home admission.
Quality of life
Recent studies strongly indicate that the factor most closely associated with poorer 'Quality of life' is the presence of depression.
Of other Parkinson disease symptoms, postural instability and cognitive impairment contribute rather less to poor Quality of life
Chronic pain is a common symptom
Pain occurs in about 40% of patients, and in a few becomes severe enough to overshadow the motor symptoms of the disorder. Pain may be of several types: musculoskeletal, neuritic, dystonia-associated, central, and akathitic discomfort.
Dopamine agonists
It now appears that early use of the new dopamine agonists such as ropinirole (as monotherapy) is able to effectively control the clinical symptoms for more than 3 years thereby offering the possibility of delaying the use of levodopa, and thus the likely occurrence of levodopa-induced dyskinesias and neuropsychiatric symptoms. These are frequently a prominent part of the overall picture especially in the later stages.
- Ergot derivatives:-- bromocryptine, lisuride, pergolide, and cabergoline
- Non-ergot drugs:-- pramipexole and ropinirole
They are all are powerful stimulators of the D2 dopamine receptor.
Motor fluctuations
Some are due to central pharmacodynamic mechanisms such as reduced striatal synthesis and storage of dopamine and sub sensitization of post synaptic dopaminergic receptors. Strategies to overcome these central pharmacodynamic mechanisms and to increase daily "on" hours are:-- dopamine agonists, controlled release preparations, MAO-B and COMT inhibitors.
Other fluctuations, especially the "delayed on" (time from dose intake to turning "on") and complete failure of "on" response, are caused by peripheral pharmacokinetic mechanisms. Those with response fluctuations may have gastric atony and, combined with the poor solubility of levodopa, this causes delayed and incomplete absorption of levodopa. Improvement of levodopa absorption may be achieved by crushing levodopa and drinking it as a suspension.
Treatment of neuropsychiatric symptoms
Few good treatment trials concerning neuropsychiatric symptoms have been published. The evidence suggests that depression and hallucinations may be treated using various antidepressants and atypical antipsychotic agents. Providing this is done with due attention to the receptor profiles of drugs and their interactions then it may be possible to get improvement with little or minimal worsening of Parkinson disease symptoms.
Risperidone is new and relatively expensive and seems popular in some circles. There is reason to doubt the validity of its tag as an 'atypical neuroleptic'. For instance, it does not appear to exhibit limbic selectivity. It is therefore not surprising that recent research confirms what one would predict from that data; that risperidone is poorly tolerated. It offers no significant advantages over appropriately selected 'older' neuroleptics (but see also information on receptors etc in 'Psychopharmacology Update Notes' for further details).
Olanzapine and Quetiapine are better than risperidone but may, in patients with Parkinson disease, worsen motor functions, at least to some extent. One hopes that Quetiapine, as is being suggested, may prove to be as effective as clozapine, but better tolerated.
Experience indicates that sparing and restrained use of L-DOPA is prudent. Patients benefit from help in coming to terms with an inexorably progressive condition and advice on modifying their lifestyle and lowering their expectations of their physical capabilities.
It seems to me that the availability of so many dopaminergic drugs, often used in combinations, is tempting doctors to try too hard to reduce Parkinson disease symptoms. The more advanced 'brain failure' is the more likely side effects are. Neuropsychiatric symptoms, such as depression and visual hallucinations are common, but may be underestimated and / or unrecognised in patients. These symptoms are of great importance to Quality of life for patients.
When dyskinesia or neuropsychiatric symptoms resulting from excess dopaminergic actions are present reduction of anti Parkinson disease drugs is required; consequent worsening of motor function is of secondary importance. A reasonable order for this appears to be:-- anti-cholinergics are stopped first, then selegiline, dopamine agonists, amantadine, and finally COMT inhibitors, which have no psychotomimetic action of their own.
Parkinson disease is accompanied by depression and memory problems with a frequency that probably justifies neuropsychiatric screening of a large proportion of suffers. The existence of such co-morbidity may serve as a warning to be extra careful in choice of treatment. Due consideration of the social, psychiatric and motor facets accompanying Parkinson disease will aid balanced management.
All text ©Dr Ken Gillman MRC Psych - PsychoTropical Research®
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