Verapamil in the treatment of reversible cerebral vasoconstriction syndrome: A systematic review

Introduction: Extrapolating from efficacy in subarachnoid haemorrhage (SAH), nimodipine has been used as a treatment for reversible cerebral vasoconstriction syndrome (RCVS). However, 4-hourly dosing is a practical limitation and verapamil has been proposed as an alternative. The potential efficacy, adverse effects, preferred dosing and formulation of verapamil for RCVS have not been systematically reviewed previously. 

Method: A systematic review was conducted of the databases PubMed, EMBASE, and the Cochrane Library from inception to July 2022 for peer-reviewed articles describing the use of verapamil for RCVS. This systematic review adheres to the PRISMA guidelines and was registered on PROSPERO. 

Results: There were 58 articles included in the review, which included 56 patients with RCVS treated with oral verapamil and 15 patients treated with intra-arterial verapamil. The most common oral verapamil dosing regimen was controlled release 120 mg once daily. There were 54/56 patients described to have improvement in headache following oral verapamil and one patient who died from worsening RCVS. Only 2/56 patients noted possible adverse effects with oral verapamil, with none requiring discontinuation. There was one case of hypotension from combined oral and intra-arterial verapamil. Vascular complications including ischaemic and haemorrhagic stroke were recorded in 33/56 patients. RCVS recurrence was described in 9 patients, with 2 cases upon weaning oral verapamil. 

Conclusions: While no randomised studies exist to support the use of verapamil in RCVS, observational data support a possible clinical benefit. Verapamil appears well tolerated in this setting and represents a reasonable treatment option. Randomised controlled trials including comparison with nimodipine are warranted.