Olivier Rascol

Orthostatic Hypotension in Patients with Parkinson's Disease Pathophysiology and Management

Orthostatic hypotension is common in elderly patients, and is now considered to be an important prognostic factor for cognitive decline and mortality. In patients with Parkinson’s disease, the prevalence of symptomatic orthostatic hypotension may be as high as 20%. Two factors could explain this high prevalence. First, dopaminergic drugs may induce or worsen orthostatic hypotension. Secondly, Parkinson’s disease is a cause of primary autonomic failure with an involvement of the peripheral autonomic system as shown by the ubiquitous distribution of Lewy bodies and reduced iobenguane [metaiodobenzylguanidine (MIBG)] cardiac uptake. These pathological and pharmacological characteristics clearly differentiate autonomic failure of Parkinson’s disease from multiple system atrophy. If autonomic abnormalities appear to be present from the first stage of the disease, early onset (within the first year) of symptomatic orthostatic hypotension in the course of parkinsonism can be considered as an exclusion criteria for idiopathic Parkinson’s disease.No specific clinical trials have evaluated the effects of antihypotensive drugs in patients with Parkinson’s disease and thus no specific therapeutic strategy can be recommended. The management of orthostatic hypotension in patients with Parkinson’s disease should always start with patient education and nonpharmacological treatment. Drug therapy should be reserved for symptomatic patients who do not get benefit from nonpharmacological management. Among the available drugs, α1-adrenergic agonists (mainly midodrine) or plasma volume expanders (mainly fludrocortisone) are the most frequently used. There are also some drugs that are currently investigational such as yohimbine and droxidopa. Other drugs such as desmopressin or octreotide may be of interest in some situations. Domperidone is widely used in patients with parkinsonism with no proven effect on orthostatic hypotension.

Diagnosis and Treatment of Orthostatic Hypotension in Parkinson's Disease

Orthostatic hypotension (OH) is a frequent comorbidity affecting between 23 and 38% of Parkinsons disease (PD) patients. Several pieces of evidence suggest that OH is related to faster cognitive decline and more frequent falls, and has been also connected to increased mortality. OH can be arbitrarily defined as a drop of systolic and/or diastolic blood pressure of 20 or 10 mmHg or more in the first three minutes after passing from decubitus to an upright position. Till test appears to be the most reliable tool for assessing the orthostatic response. On the other hand, the standing test and evaluation of orthostatic symptoms should be regarded as screening tests. The key physiopathological aspect of OH is an altered baroreflex function resulting from cardiac and vascular sympathetic denervation. Nonetheless, OH can be aggravated by heat, alcohol consumption or by drug treatments, such as antihypertensives, dopamine agonists or amantadine. Treatment should begin with re-considering drug treatments. After treatment is optimized, non- pharmacological measures may be employed. Drugs treatment should be reserved for patients in whom other strategies have failed. Midodrine and fludrocortisone are the most frequently used treatments, even though evidence about their efficacy and safety is weak. Midodrine has a shorter duration of action and thus avoidance of evening dosing may help keep nocturnal blood pressure dipping intact. Promising alternatives may include droxidopa and fipamezole.