13 Nov 2025 Comparative Analysis of the Efficacy and Safety of Various Single Enantiomer and Racemic Mixture Pairs

This is a systematic review conducted by the Drug Assessment Working Group of the Therapeutics Initiative. You can read the Abstract below. To view the complete report click on the DOWNLOAD button.

Abstract

Introduction:

Chiral switching and single-isomer development have led to preferential prescribing of newer, pure isomer agents despite substantially higher costs. Dexlansoprazole, the R-(+)-enantiomer of lansoprazole, has recently surpassed its parent drug for acid-related gastrointestinal disorders. Escitalopram, the S-(+)-enantiomer of racemic citalopram, has similarly replaced citalopram in depression treatment. Esomeprazole, the S-(-)isomer of omeprazole, is widely promoted for claimed pharmacokinetic and therapeutic advantages. Although claims suggest these enantiomers are safer, more effective, faster acting, or provide superior clinical benefits, the clinical significance of these purported advantages remains uncertain.

Objective:

To examine utilization patterns in British Columbia (BC) and critically evaluate the comparative pharmacological profiles, clinical efficacy, safety, and cost-effectiveness of dexlansoprazole versus lansoprazole, escitalopram versus citalopram, and esomeprazole versus omeprazole, to determine whether claims supporting preferential prescribing are justified.

Methods:

Systematic and narrative reviews were conducted using MedLine, EMBASE, PubMed, Cochrane CENTRAL, Epistemonikos, regulatory sources, and product monographs. Searches were performed from inception through 2024/2025, depending on the drug class. Provincial prescribing data (2000–2024) were analyzed using PharmaNet and related administrative health databases to assess annual prevalence of use and trends. Head-to-head randomized controlled trials (RCTs) were included. Outcomes assessed included healing of erosive esophagitis (EE) and symptom resolution in gastroesophageal reflux disease (GERD) for dexlansoprazole-lansoprazole, antidepressant response and remission in major depressive disorder (MDD) for escitalopram-citalopram, bioavailability and acid suppression potency for esomeprazole-omeprazole, adverse drug reactions (ADRs), and economic considerations. Study robustness was evaluated using minimal clinically important differences, the Fragility Index, and the Cochrane Risk of Bias 2 Tool.

Results:

Across all three comparisons, newer enantiomers have become predominant in BC despite substantially higher costs. Dexlansoprazole prescriptions surpassed lansoprazole in 2024; escitalopram became the predominant antidepressant from 2013–2022 while citalopram use declined; and esomeprazole use exceeded omeprazole, influenced by formulary status and prescriber preference, and seen in the prescribing data year-over-year.

Twelve RCTs (N=2,552) compared escitalopram and citalopram in adults with MDD. All were at high risk of bias. No trial demonstrated a clinically meaningful advantage of escitalopram over citalopram. Reported differences favoring escitalopram did not exceed minimal clinically important differences, and claims of faster onset were inconsistent. ADRs were similar, with no evidence of differential QT prolongation or clinically meaningful safety advantages.
Four RCTs (N=4,584) compared dexlansoprazole and lansoprazole in adults with EE or GERD. Two reported the superiority of dexlansoprazole for specific outcomes; however, findings were fragile and overall study quality was low, with high risk of bias. Safety outcomes were comparable.

Multiple RCTs and pharmacodynamic studies compared esomeprazole and omeprazole. Esomeprazole demonstrated superior bioavailability and more consistent acid suppression, attributed to reduced interindividual variability. Clinical trials showed marginally higher healing rates in EE and modest improvements in GERD symptom control; however, differences were small, fragile, and often clinically insignificant. Omeprazole remained substantially less costly.
Across all comparisons, adverse events were similar between enantiomers and their parent drugs. Most included trials were at high risk of bias, and superiority findings were frequently fragile or methodologically limited.

Conclusion:

Preferential prescribing of dexlansoprazole, escitalopram, and esomeprazole in BC is not supported by robust head-to-head evidence demonstrating clinically meaningful superiority. Observed differences are modest, fragile, and methodologically limited, while cost differentials are substantial. Current utilization trends do not consistently align with the best available evidence and represent an opportunity for more cost-effective, evidence-based prescribing.

To view the complete report click on the DOWNLOAD button.