JBJS - 2026-08-05 - Journal Article; Randomized Controlled Trial
Significant Anxiolytic Effect and Enhanced Recovery Benefits of Perioperative Low-Dose Olanzapine in Patients with Anxiety Undergoing THA: A Randomized Controlled Trial.
Jiang B, Fan J, Lai Y, Cai Y, Ding Z, Luo Z, Zhou Z
Topics
Key Takeaway
Perioperative low-dose olanzapine (2.5 mg nightly × 5 days) reduced STAI-S anxiety scores, resting VAS pain scores on PODs 1–3, and opioid consumption compared to both alprazolam and placebo in anxious THA patients.
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Summary
This single-center RCT enrolled primary THA patients with preoperative STAI-S ≥40 and randomized them to oral olanzapine 2.5 mg, alprazolam 0.4 mg, or placebo nightly for 5 perioperative days. Olanzapine produced lower STAI-S scores on PODs 1 and 3, lower resting VAS on PODs 1–3, reduced PONV incidence, and lower opioid consumption on PODs 1–3 versus both comparators. Both active treatment arms outperformed placebo on PSQI sleep quality at POD 3, and the olanzapine group demonstrated superior Harris Hip Scores and HOOS at follow-up with no significant difference in adverse events across groups.
Key Limitation
The absence of reported blinding methodology and single-institution enrollment limits generalizability and introduces risk of assessor bias in subjective outcomes including VAS and STAI-S.
Original Abstract
BACKGROUND
Major anxiety symptoms are commonly observed in patients undergoing total hip arthroplasty (THA); these symptoms exacerbate pain and compromise hip recovery. Olanzapine demonstrates clinically meaningful efficacy in reducing anxiety; thus, we investigated its anxiolytic effect and benefits for enhancing recovery in these high-risk patients.
METHODS
We prospectively enrolled 135 patients who were scheduled for primary THA at our institution between April 2024 and March 2025 and who scored at least 40 points on the State-Trait Anxiety Inventory-State (STAI-S) before surgery. Patients randomly received oral olanzapine (2.5 mg), alprazolam (0.4 mg), or a placebo once nightly for 5 days beginning on the day of admission. The 3 groups (45 patients in the olanzapine group, 45 in the alprazolam group, and 44 in the placebo group after 1 patient was lost to follow-up) were compared postoperatively in terms of the STAI-S score, Pittsburgh Sleep Quality Index (PSQI), visual analog scale (VAS) pain score, opioid consumption, and functional recovery of the hip. Adverse events related to drugs and surgery were recorded.
RESULTS
Compared with placebo and alprazolam, olanzapine was associated with significantly lower STAI-S scores on postoperative days (PODs) 1 and 3, significantly lower resting VAS pain scores on PODs 1 to 3, and significantly lower incidence of postoperative nausea and vomiting. The olanzapine group and the alprazolam group demonstrated significantly better sleep quality based on the PSQI on POD 3 compared with the placebo group. Moreover, the olanzapine group had lower opioid consumption on PODs 1 to 3 than the placebo group. Patients in the olanzapine group exhibited better Harris hip scores and Hip Disability and Osteoarthritis Outcome Scores. The 3 groups did not significantly differ in terms of adverse events.
CONCLUSIONS
Perioperative low-dose olanzapine may be an effective option for reducing anxiety levels, sleep disorders, and postoperative nausea and vomiting, mitigating postoperative pain and enhancing hip recovery among patients with anxiety symptoms undergoing THA.
LEVEL OF EVIDENCE
Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.