Alleviating Injection Site Pain With Cryotherapy and Ibuprofen Following Long-Acting Intramuscular/Subcutaneous Antipsychotic Administration

Background Injection-site pain during long-acting injectable antipsychotic (LAI) administration poses a barrier to treatment adherence, with up to 30% of patients reporting significant discomfort. Cryotherapy combined with NSAIDs may offer superior analgesia compared with topical anesthetic alone. Aim To compare the efficacy of cryotherapy plus ibuprofen (CIP) vs topical lidocaine-prilocaine cream (LAP) and no pre-treatment (Control) in reducing LAI injection-site pain across 3 consecutive doses. Methods In this retrospective chart review, 525 adults (318 male, 207 female) receiving ≥3 LAI doses from January 2023 to March 2025 at 3 New York metropolitan outpatient clinics were analyzed. Patients self-selected into Control (n = 70), LAP (n = 121), or CIP (n = 334) arms. Pain was measured via a 0-10 Visual Analog Scale immediately after each dose. One-way ANOVA (α = 0.05) and Tukey’s HSD post hoc tests assessed group differences at Doses 1-3. Results The mean pain score showed progressive pain reduction in all groups. Mean VAS scores decreased from Dose 1 to Dose 3 as follows: Control 4.87 ± 1.41 to 4.10 ± 1.08; LAP 4.35 ± 1.27 to 3.23 ± 1.04; CIP 3.01 ± 1.00 to 1.87 ± 0.79. ANOVA demonstrated significant intervention effects at all doses (Dose 1 F(2,522) = 115.99; Dose 2 F(2,522) = 132.28; Dose 3 F(2,522) = 234.70; all P < 0.001). Tukey’s HSD revealed CIP vs Control mean differences of −1.86 to −2.23 (all P < 0.001) and CIP vs LAP –1.34 to −1.36 (all P < 0.001). Conclusions CIP significantly outperforms LAP and control in mitigating LAI injection pain, achieving mean VAS scores below clinically meaningful thresholds by Dose 3. Implementing CIP may enhance patient comfort and adherence. Prospective randomized trials are recommended to validate these findings.