Effectiveness of midodrine treatment in patients with recurrent vasovagal syncope not responding to non-pharmacological treatment (STAND-trial)

Europace. 2011 Nov;13(11):1639-47. doi: 10.1093/europace/eur200. Epub 2011 Jul 13.


Aims: Initial treatment of vasovagal syncope (VVS) consists of advising adequate fluid and salt intake, regular exercise, and physical counterpressure manoeuvres. Despite this treatment, up to 30% of patients continue to experience regular episodes of VVS. We investigated whether additional Midodrine treatment is effective in these patients.

Methods and results: In our study, patients with at least three syncopal and/or severe pre-syncopal recurrences during non-pharmacological treatment were eligible to receive double-blind cross-over treatment starting either with Midodrine or placebo. Treatment periods lasted for 3 months with a wash-out period of 1 week in-between. At baseline and after each treatment period, we collected data about the recurrence of syncope and pre-syncope, side effects, and quality of life (QoL). Twenty-three patients (17% male, mean age 32) included in the cross-over trial received both Midodrine and placebo treatment. The proportion of patients who experienced syncopal and pre-syncopal recurrences did not differ significantly between Midodrine and placebo treatment (syncope: 48 vs. 65%, P= 0.22; pre-syncope: 74 vs. 78%, P> 0.99). The median number of syncopes and pre-syncopes per 3 months were also not significantly different during Midodrine and placebo treatment (0 vs. 1; P= 0.57; and 6 vs. 8; P= 0.90). The occurrence of side effects was similar during Midodrine and placebo treatment (48 vs. 57%; P= 0.75). Also, QoL did not differ significantly.

Conclusion: Our findings indicate that additional Midodrine treatment is less effective in patients with VVS not responding to non-pharmacological treatment than reported as first-line treatment.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists / adverse effects
  • Adrenergic alpha-1 Receptor Agonists / therapeutic use*
  • Adult
  • Cross-Over Studies
  • Double-Blind Method
  • Exercise*
  • Female
  • Fluid Therapy*
  • Humans
  • Male
  • Middle Aged
  • Midodrine / adverse effects
  • Midodrine / therapeutic use*
  • Outcome Assessment, Health Care
  • Quality of Life
  • Recurrence
  • Syncope, Vasovagal / drug therapy*
  • Syncope, Vasovagal / epidemiology
  • Treatment Outcome


  • Adrenergic alpha-1 Receptor Agonists
  • Midodrine