Controversies on Dosing of Prophylactic Nimodipine in Subarachnoid Haemorrhage, a Narrative Review

Nimodipine has been used for over four decades to prevent neurological complications related to angiographic vasospasm following subarachnoid haemorrhage (SAH). While clinical use remains widespread, few trials have demonstrated significant outcome benefits-typically defined as reductions in mortality or persistent vegetative states. According to contemporary standards, these benefits may be considered marginal. Controversies surrounding nimodipine relate to its poorly understood mechanism of action, the individual patient variability in response, and the reliance on a standardized dosing regimen. Additionally, the complex and multifactorial nature of delayed cerebral ischemia (DCI) obscures clinical endpoints and complicates the establishment of a therapeutic plasma concentration, thereby limiting opportunities for individualized dosing strategies.

We conducted a comprehensive literature search across Medline, Embase, the Cochrane Library, Web of Science, and PubMed. The search was limited to experimental and clinical studies focusing on nimodipine's dosing regimens and pharmacokinetics, excluding studies that reported only clinical outcomes.

A total of 16 experimental studies, 23 clinical studies, and 8 dose-response trials were reviewed. Identified limitations included variability in administration routes, bioavailability, drug clearance, and lack of standardized clinical endpoints.

This review consolidates the current evidence on nimodipine's dosing and its pharmacokinetic profile. It highlights the knowledge gaps that may contribute to inform the design of future studies focused on individualized therapy.

Significant variability in nimodipine's pharmacokinetics may contribute to suboptimal dosing in SAH patients. Reassessment of the current standardized dosing approach is warranted, along with consideration of individualised dosing strategies to enhance therapeutic outcomes. Studies defining nimodipine's optimal dosing are warranted.