Neurally mediated reflex syncope is the most common cause of transient loss of consciousness. In patients not responding to non-pharmacological treatment, pharmacological or pacemaker treatment might be considered.
To examine the effects of pharmacological therapy and pacemaker implantation in patients with vasovagal syncope, carotid sinus syncope and situational syncope.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 1, 2008), PubMed (1950 until February 2008), EMBASE on OVID (1980 until February 2008) and CINAHL on EBSCOhost (1937 until February 2008). No language restrictions were applied.
We included parallel randomized controlled trials and randomized cross-over trials of pharmacological treatment (beta-blockers, fludrocortisone, alpha-adrenergic agonists, selective serotonine reuptake inhibitors, ACE inhibitors, disopyramide, anticholinergic agents or salt tablets) or dual chamber pacemaker treatment. Studies were included if pharmacological or pacemaker treatment was compared with any form of standardised control treatment (standard treatment), placebo treatment, or (other) pharmacological or pacemaker treatment. We did not include non-randomized studies.
Data collection and analysis
Two reviewers independently assessed the risk of bias. Using a standardised data extraction form, they extracted characteristics and results of the various studies. In a consensus meeting they discussed any disagreements that had occurred during data extraction. If no agreement could be reached, a third reviewer was asked to make a decision. Summary estimates with 95% confidence intervals of treatment effect were calculated using relative risks, rate ratios or weighted means differences depending on the type of outcome reported.
We included 46 randomized studies, 40 on vasovagal syncope and six on carotid sinus syncope. No studies on situational syncope matched the criteria for inclusion in our review. Studies in general were small with a median sample size of 42. A wide range of control treatments were used with 22 studies using a placebo arm. Blinding of patients and treating physicians was applied in eight studies. Results varied considerably between studies and between types of outcomes.
For vasovagal syncope, the occurrence of syncope upon provocational head-up tilt testing was lower upon treatment with beta-blockers, ACE-inhibitors and anticholinergic agents compared to standard treatment. For carotid sinus syncope, the occurrence of syncope upon carotid sinus massage was lower on midodrine treatment compared to placebo treatment in one study.
There is insufficient evidence to support the use of any of the pharmacological or pacemaker treatments for vasovagal syncope and carotid sinus syncope. Larger studies using patient relevant outcomes are needed.
Plain language summary
Drugs and pacemakers for transient loss of consciousness
Neurally mediated reflex syncope (including fainting) is the most common cause of transient loss of consciousness. It is caused by a sudden decrease in blood pressure and/or lowering of heart rate. The main treatment goal therefore is to increase blood pressure and heart rate. In most patients, this can be achieved by non-pharmacological treatment measures (e.g. adequate fluid and salt intake, physical counterpressure manoeuvres). In patients not responding to this treatment, pharmacological or pacemaker treatment might be considered. We investigated the effectiveness of these treatments for different subtypes of neurally mediated reflex syncope, namely vasovagal syncope (fainting), carotid sinus syncope (fainting due to pressure on the neck) and situational syncope (fainting when passing urine of faeces or swallowing). Where data were available, we determined the treatment effectiveness for different outcome measures including occurrence of syncope, amount of (pre-)syncopes per year during follow-up and quality of life.
We included 46 randomized studies, 40 on vasovagal syncope and six on carotid sinus syncope. No studies on situational syncope matched the criteria for inclusion in our review. Studies in general were small with a median size of 42 patients. A wide range of control treatments were used with 22 studies using placebo control treatment. Blinding of patients and treating physicians was applied in eight studies. The type of outcomes reported by studies varied considerably with only 16 studies reporting on non-provoked recurrences during follow-up. As a consequence of all these differences, results varied considerably between studies and between types of outcomes. In some studies significant results were reported for one type of outcome, but not for other outcomes.
We conclude that there is insufficient evidence either to support or to refute the use of any of the pharmacological or pacemaker treatments for vasovagal syncope and carotid sinus syncope.