Drug treatment in postural hypotension/vasovagal syncope

Management of postural hypotension is imperfect since it is impossible to normalize standing BP without generating excessive supine hypertension

• practical goal is to improve standing BP so as to minimize symptoms and to improve standing time in order to be able to undertake orthostatic activities of daily living, without excessive supine hypertension.
• possible to achieve these goals with a combination of
  • drug treatments options e.g. fludrocortisone, midodrine or droxidopa
  • supplemented with procedures to improve orthostatic defenses during periods of increased orthostatic stress. Such procedures include water bolus treatment and physical countermaneuvers

Drug treatment may be started (usually by a specialist centre) e.g. fludrocortisone (100 - 200 mcg at night). This drug causes a retention of salt and water and may also result in an increased adrenoreceptor sensitivity. Main complications are hypokalemia and supine hypertension. (4)

• a systematic review (13 studies; n=513) concludes evidence about effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in those with orthostatic hypotension and diabetes or Parkinson's is very uncertain, with lack of data on long-term treatment in other diseases (5)

Other possible drug treatments include:

• Midodrine is a directly acting alpha1-adrenoceptor agonist
  • it and its active metabolite, desglymidodrine, have a duration of action of 2-4 hours
  • main side-effects are supine hypertension, paresthesias (including troublesome scalp-tingling), and goose-bumps. Rarely patients develop bladder pain or an inability to void, problems that preclude use of midodrine in those patients
  • Fludrocortisone and midodrine may be used as combination therapy but this may increase risk of glaucoma and increased intraocular pressure, so requires careful monitoring (6)
    
    
• Droxidopa, an oral norepinephrine precursor
  • generally well tolerated. It seems to have a duration of action of about 6-8 hours
  • patients with dopamine beta-hydroxylase deficiency seem to have better BP control with droxidopa than midodrine (4)
    
    
• Pyridostigmine has been shown to be effective in the treatment of neurogenic orthostatic hypotension (1,2):
  • there was a significant improvement in standing BP in patients with without worsening supine hypertension
  • greatest effect is on diastolic BP, suggesting that the improvement is due to increased total peripheral resistance

There is evidence that paroxetine, a selective serotonin-reuptake inhibitor, reduces the rate of spontaneous syncope in patients with vasovagal syncope resistant to or intolerant of conventional therapy (3).

Reference:

1. Low PA, Tomalia VA. Orthostatic Hypotension: Mechanisms, Causes, Management. J Clin Neurol. 2015 Jul;11(3):220-6.
2. Singer W et al. Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol 2006;63:513-8.
3. Evidence Based Medicine(1999); 4 (6): 170.
4. Low VA, Tomalia TA. Orthostatic Hypotension: Mechanisms, Causes, Management.J Clin Neurol. 2015 Jul; 11(3): 220-226.
5. Veazie S, Peterson K, Ansari Y, Chung KA, Gibbons CH., Raj SR, Helfand M. Fludrocortisone for orthostatic hypotension. Cochrane Database of Systematic Reviews 2021, Issue 5. Art. No.: CD012868. DOI: 10.1002/14651858.CD012868.pub2. Accessed 09 December 2021.
6. Gilani A et al. Postural Hypotension. BMJ 2021;373:n922 http://dx.doi.org/10.1136/bmj.n922