Does Postoperative Gabapentin Reduce Pain, Opioid Consumption & Anxiety & Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?

Gabapentin Gabapentin is an anti-epileptic agent originally developed to treat spasticity (1), and eventually was found to be effective against chronic neuropathic pain (1,2). Gabapentin is available as an oral preparation and is primarily absorbed in the small intestine (1). Gabapentin is not metabolized in humans and is eliminated unchanged via the kidneys. It has no known drug-drug interactions, but it is reported that antacids can reduce the bioavailability of Gabapentin by about 20%, and Cimetidine can decrease the clearance of Gabapentin from the body by about 12% (1,2). Side effects of Gabapentin tend to be mild with somnolence (20%), dizziness (18%), ataxia (13%), and fatigue (11%) being the most common (1). The exact mechanism of Gabapentin in pain management is unknown, but it has demonstrated inhibition of mechanical hyperalgesia, and mechanical/thermal allodynia in those with neuropathic pain (1).

Over the past 5 years, there have been 20 studies examining the effect of Gabapentin on postoperative pain (1 & 3-22). All but one of these studies (16) has found that Gabapentin demonstrated a significant reduction in the amount of postoperative opioid required (16-67%) and a simultaneous reduction in pain scores. There was no difference in side effect profile between the Gabapentin and the control groups in 11 studies(3-5,7,8,10,14-16,18,20), while one(18) found a higher incidence of nausea and urinary retention in the control groups, and two studies(11,13) found a higher incidence of nausea/vomiting in the Gabapentin group. The most common side effect of increased sedation was found in only 4 studies when doses greater than 900 mg per day were given (9,11-13). The daily dose of postoperative Gabapentin in the current protocol is 200 mg TID (600 mg/day) which we currently use in our clinical population with minimal side effect issues.

There have been 8 studies looking at the administration of Gabapentin in the postoperative period (4,6-8,11,20,22,23). Fassoulaki and colleagues (6) examined pain scores and opioid consumption in postoperative breast cancer patients. Seventy-five patients undergoing surgery for breast cancer were randomized to receive Mexiletine 600 mg/day, Gabapentin 1200 mg/day or placebo for 10 days. Opioid consumption was reduced by 50% in the Gabapentin and Mexiletine groups vs. the placebo group on days 2-10. Only the Gabapentin group had decreased pain after movement from the 2nd to the 5th postoperative day. There were no adverse effects reported in the Gabapentin group. Dierking and his colleagues randomized 80 patients to receive either 1200 mg of Gabapentin or placebo 1 hr preoperatively, then either Gabapentin 600 mg or placebo at hours 8, 16, and 24 postoperatively following abdominal hysterectomies(4). Opioid consumption was reduced by 32% in this study and there was no significant difference between side effects in either group. Another study looking at postoperative outcomes and Gabapentin was published by Gilron and his colleagues who randomized 110 patients to 4 study groups: (A) placebo (B) Gabapentin 600 mg TID (C) Rofecoxib 50 mg/day (D) Gabapentin 600 mg TID & Rofecoxib 50 mg/day starting 1hr preoperatively and continuing for 72 hours postoperatively (9). This study was unique because it went further than simply looking at pain scores and morphine consumption data. Gilron and his colleagues demonstrated that the Gabapentin and the Gabapentin and Rofecoxib groups also significantly decreased movement associated pain evoked by sitting and coughing post abdominal hysterectomy. Adverse events were similar in all groups except sedation, which was more frequent with Gabapentin. Consistent with previous literature, the multimodal Gabapentin/Rofecoxib combination demonstrated opioid sparing, lower pain scores, but most importantly, decreased movement associated pain, which may be a significant factor in faster rehabilitation. In our study we have chosen to use Gabapentin 200 mg TID (bioequivalence of 600 mg/day) based on our extensive clinical experience with our patient population. This appears to be the dose at which most patients do not exhibit the Gabapentin related side effects described earlier. Only four studies have prescribed Gabapentin beyond 72 hours postoperatively (6-8,11). This is an area in which further research is needed to determine whether prolonged postoperative administration and its benefits translate into earlier hospital discharge, decreased chronic pain rates and increased functional recovery even beyond the acute post surgical time period. By following patients to 4 weeks post surgery, this study will aim to answer some of the questions regarding the perioperative use of gabapentin and its possible role ameliorating functional recovery beyond the acute hospitalization period.

The Sunnybrook Health Sciences Acute Pain Service (APS) does not know if 200 mg of Gabapentin is effective at reducing morphine consumption, and improving analgesia. Much higher doses (i.e. greater than 1800 mg/day) published in the literature were initially used at Sunnybrook, but many patients (anecdotally) became too sedated. We are currently using the dose suggested in our protocol 200 mg TID without any major problems. Therefore our goal is to assess if Gabapentin 200 mg does in fact have opioid reducing and analgesic benefits in the radical prostate population. Our pilot data from 15 patients indicates these benefits might exist. Furthermore, examining the role of gabapentin in regards to perioperative anxiety and following patients beyond the acute post surgical time period and following any changes related to their functional recovery and quality of life will help to close some of the gaps in the literature regarding the perioperative usefulness of gabapentin.

Gabapentin and Anxiety