Alansary AM, Elbeialy MAK Impact of Preoperative Aripiprazole on Postoperative Analgesia in Laparoscopic Hysterectomy: A Randomized Double-blind Placebo-controlled Trial. Clin J Pain. 2024 Jun 1;40(6):341-348. doi: 10.1097/AJP.0000000000001210. (Original study)

OBJECTIVES: Aripiprazole is a second-generation atypical antipsychotic with worldwide clinical approval. Nevertheless, its perioperative antinociceptive application has not been studied. As a result, the purpose of this study was to investigate the analgesic effects of perioperative aripiprazole on reducing postoperative pain, as well as the possible adverse effects.

PATIENTS AND METHODS: This randomized controlled study enrolled 80 female patients scheduled for laparoscopic hysterectomy who were assigned randomly into 2 equal groups in 1:1; aripiprazole group (n = 40), patients received an aripiprazole 30 mg tablet orally 3 hours before surgery and placebo group (n = 40), patients received a placebo tablet 3 hours before surgery. The 24-hour morphine consumption postoperatively was the primary outcome, and the time to the first analgesic request, sedation scores, and the incidence of perioperative adverse events were the secondary outcomes.

RESULTS: The mean 24-hour morphine consumption was significantly lower with aripiprazole (2.5 ± 0.5 mg) than with placebo (23.7 ± 1.6 mg; mean ± SE -21.2 ± 0.3, 95% CI: -21.7 to -20.6, P < 0.001). In addition, the mean time to the first analgesic request was significantly longer with aripiprazole (212.2 ± 14.7 min) than with placebo (27.0 ± 2.0 min; mean ± SE 185.2 ± 2.3, 95% CI: 180.5 to 189.8, P < 0.001). Furthermore, the aripiprazole group reported higher sedation scores ( P < 0.001). Bradycardia and hypotension were reported more frequently among patients in the aripiprazole group ( P < 0.05).

CONCLUSION: Aripiprazole was effective in reducing pain after laparoscopic hysterectomy. Although self-limited, side effects should be taken into consideration when using the medication perioperatively.

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Comments from MORE raters

Physician rater

This article is useful for gynecologists. The main finding of the study is that aripiprazole (a second-generation atypical antipsychotic) was effective in reducing pain after laparoscopic hysterectomy. The results of this study suggest that preoperative administration of a single oral dose of 30mg of aripiprazole may be an effective adjunct to conventional analgetics for postoperative pain management. However, caution must be taken with its administration and monitoring of potential side effects may be mandatory. Although the side effects were self-limited such as hypotension, bradycardia, and sedation, they needed to be taken into consideration when using this medication. Also, the research focused on only laparoscopic surgeries. In addition, a limitation of the research was that the study was confined to the first 24 hours postoperatively. Further research is needed to determine the optimal dosage of aripiprazole for different groups of patients during the perioperative period.

Physician rater

Nice study that does not allow, despite the benefit on the main outcome, to propose aripiprazole in practice given its side effects incompatible with an outpatient surgical procedure. Moreover, the absence of multimodal analgesia in both groups probably increases the impact in the active group.

Physician rater

Aripiprazole for post-operative pain management was investigated in this study. A single preoperative dose decreased postoperative morphine requirements from 23 mg to 2 mg and delayed the request for pain medication. Of note, this medication is used for the treatment of agitation accompanying schizophrenia or bipolar disorder. The authors only reported sedation. I remain concerned about other side effects that persist for a long time in the postoperative period since the drugs half-life is 75 hours. It does decrease the need for pain management postoperatively. The question remains: "At what cost?"
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