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

Phase 4
18 Years
75 Years
Not Enrolling
Prostate Cancer

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Trial Information

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 and Anxiety

The preoperative effectiveness of Gabapentin in decreasing anxiety scores and improving
early functional recovery after anterior cruciate ligament knee surgery (n=40) has recently
been demonstrated(10). Premedication with Gabapentin 1200 mg improved preoperative
anxiolysis, postoperative analgesia, and early knee mobilization. By including a physical
measure (active and passive knee flexion), Menigaux and colleagues also demonstrated that
adequate postoperative analgesia enhances mobilization of the knee joint, thus potentially
improving functional recovery. This French study examined patient's preoperative anxiety
levels by administering an anxiety Visual Analogue Score prior to induction of anesthesia in
the operating room. Since this method of anxiety testing has not been validated, we will
use four reliable and well-validated anxiety tools in our present study. These measures are
all one page questionnaires that are of little burden to patients. The anxiety measures
are: The Spielberger State-Trait Anxiety Inventory, The Pain Catastrophising Scale, The Pain
Anxiety Symptoms Scale and a 7 Item Modified Hospital Anxiety & Depression Scale.

The State-Trait Anxiety Inventory (STAI) consists of two self-report scales, one measuring
state anxiety and the other measuring trait anxiety (24). Each scale consists of 20
statements about how the respondent may feel, and they are asked to rate how strongly they
agree ("very much so") or disagree ("not at all") with the item. The S-Anxiety scale
evaluates how respondents feel "right now, at this moment", whereas the T-Anxiety scale
evaluates how they feel "generally". This scale has been used extensively in research and
clinical practice, and has been shown to be valid and reliable (24).

Catastrophising or catastrophic thinking refers to "an exaggerated negative 'mental set'
brought to bear during actual or anticipated pain experience" (25). The PCS is a 13 item
self-report inventory that measures catastrophic thinking in relation to pain (26).
Respondents are asked to reflect on past painful experiences and to indicate the degree to
which they experience each of 13 thoughts or feelings when experiencing pain. Each item is
rated on a 5-point rating scale with the end points 0 = not at all and 4 = all the time. The
PCS yields a total score and three subscale scores assessing rumination (i.e., excessive
focus on pain sensations), magnification (i.e., exaggerating the threat value of pain
sensations) and helplessness (i.e., perceiving oneself as unable to cope with pain
symptoms). The PCS has been shown to have high internal consistency {coefficient alphas:
total PCS = .87, rumination = .87, magnification = .66, and helplessness = .78 (26). The PCS
has been shown to predict pain intensity in patients with acute postoperative pain (27) and
pain related disability in chronic neuropathic pain patients even after controlling for pain
severity (28).

The Pain Anxiety Symptoms Scale (PASS) is a 40-item assessment tool that measures fear and
anxiety responses to pain, and the short form of the PASS is a condensed version of the full
PASS with only 20 items (29). The PASS-20 is a reliable and valid scale with adequate
psychometric properties.

Finally, The Hospital Anxiety and Depression Scale (HADS, 30) is a widely used scale for
measuring the symptoms of anxiety and depression among medical inpatients, outpatients and
in the general population (31). The HADS is a 14-item questionnaire that measures symptoms
of anxiety (7 items) and depression (7 items). For each item, the patient is asked to select
from among 4 possible choices (scored from 0 to 3) the one that best describes how they have
been feeling over the past week. The HADS yields an anxiety (HADS-A) and a depression
(HADS-D) subscale score. We have chosen to administer only the (HADS-D) component because we
feel that the other anxiety measure provide enough information in regards to anxiety. In
general, the psychometric properties of the HADS are excellent. It has been administered in
more than 700 studies to more than 35,000 individuals. Internal consistency for the anxiety
and depression subscales show Chronbach alphas of between 0.80-0.93 for the anxiety subscale
and between 0.81 and 0.90 for the depression subscale (31,32). Concurrent validity of the
HADS is very good as measured by correlation coefficients of between 0.62 and 0.73 for the
HADS-D with various well-validated depression scales (e.g., Beck Depression Inventory,
SCL-90 Depression subscale (31,32). The HADS has been demonstrated to be sensitive to
changes due to disease progression and in response to therapeutic interventions (32). The 7
item modified HADS will take less than 2 minutes to fill out (33).

The burden to patients will be minimal because all of the above measures can be completed in
15-20 minutes. Patients will be asked to complete these items at baseline (prior to
surgery), on the day of hospital discharge (likely POD 3) and at the 3 month follow up post

Health Related Quality of Life

Outcomes pertaining to health related quality of life (HRQOL) are gaining importance when
assessing the impact that interventions have on various disease states (34). Many tools are
available, however it has been recommended that both a general and disease specific HRQOL
tool be used to help ensure any changes in HRQOL status are captured (34,35). Regardless of
the instrument(s) chosen they should be valid & reliable, as well as sensitive and
responsive to change (35, 36). Other key considerations include utilizing a tool that
captures the key dimensions of HRQOL, specifically physical, psychological, & social/role
functioning (35, 37). A critical component to assessing HRQOL is that, given the subjective
nature of quality of life, the data should be assessed by the patient, not the health care
provider (37).

In order to meet all of these criteria, this study will utilize the SF-36 Health Outcomes
questionnaire (SF-36), the UCLA Prostate Cancer Index, (UCLA-PCI) and the Brief Pain
Inventory (BPI).

The SF-36 is a widely used general HRQOL tool, with extensive validity and reliability and
responsiveness across many populations (38, 39). The SF-36 is a 36 question survey used to
describe overall health status. It has 8 subscales (physical functioning, role limitations,
bodily pain, general health perception, vitality, social function, role limitation as a
result of emotional problems, and general mental health). It takes 5-10 minutes to complete
and can be used with persons 14 and older.

The UCLA Prostate Cancer Index (UCLA-PCI) is also a valid and reliable tool, measuring
health related outcomes specific to the prostate cancer population (40). It takes about 10
minutes to complete. In a recent review of HRQL in prostate cancer studies, the SF-36 and
UCLA-PCA were the most frequently used general and disease specific tools used (41)

In order to make the measurement of pain more robust, a valid and reliable tool should be
used. The Numeric Rating Scale (NRS) & Brief Pain Inventory will be used. The Brief Pain
Inventory (BPI) is a widely used tool that has been validated in a wide variety of clinical
and research populations, including the cancer population (42) and post operative population
(43). It takes about 5 minutes to complete. The BPI measures pain intensity and pain
interference on work, activity, mood, enjoyment sleep, walking, and relationships. It is
important to assess baseline pain when undertaking a trial to assess pain or analgesia
related outcomes.

Recently published articles have examined the effect of post operative pain on HRQOL after
discharge, and have found that pain contributes to lower scores on HRQOL indices (44-46), at
one week and one month post discharge.

1. Rose MA, Kam PC. Gabapentin: pharmacology and its use in pain management. Anaesthesia

2. Dahl JB, Mathiesen O, Moiniche S. 'Protective premedication': an option with gabapentin
and related drugs? A review of gabapentin and pregabalin in the treatment of
post-operative pain. Acta Anaesthesiol Scand 2004;48:1130-6.

3. Al-Mujadi H, AR, Katzarov MG et al. Preemptive gabapentin reduces postoperative pain
and opioid demand following thyroid surgery. Can J Anaesth 2006;53:268-73.

4. Dierking G, Duedahl TH, Rasmussen ML et al. Effects of gabapentin on postoperative
morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind
trial. Acta Anaesthesiol Scand 2004;48:322-7.

5. Dirks J, Fredensborg BB, Christensen D et al. A randomized study of the effects of
single-dose gabapentin versus placebo on postoperative pain and morphine consumption
after mastectomy. Anesthesiology 2002;97:560-4.

6. Fassoulaki A, Patris K, Sarantopoulos C, Hogan Q. The analgesic effect of gabapentin
and mexiletine after breast surgery for cancer. Anesth Analg 2002;95:985-91, table of

7. Fassoulaki A, Stamatakis E, Petropoulos G et al. Gabapentin attenuates late but not
acute pain after abdominal hysterectomy. Eur J Anaesthesiol 2006;23:136-41.

8. Fassoulaki A, Triga A, Melemeni A, Sarantopoulos C. Multimodal analgesia with
gabapentin and local anesthetics prevents acute and chronic pain after breast surgery
for cancer. Anesth Analg 2005;101:1427-32.

9. Gilron I, Orr E, Tu D et al. A placebo-controlled randomized clinical trial of
perioperative administration of gabapentin, rofecoxib and their combination for
spontaneous and movement-evoked pain after abdominal hysterectomy. Pain

10. Menigaux C, Adam F, Guignard B et al. Preoperative gabapentin decreases anxiety and
improves early functional recovery from knee surgery. Anesth Analg 2005;100:1394-9,
table of contents.

11. Mikkelsen S, Hilsted KL, Andersen PJ et al. The effect of gabapentin on post-operative
pain following tonsillectomy in adults. Acta Anaesthesiol Scand 2006;50:809-15.

12. Pandey CK, Navkar DV, Giri PJ et al. Evaluation of the optimal preemptive dose of
gabapentin for postoperative pain relief after lumbar diskectomy: a randomized,
double-blind, placebo-controlled study. J Neurosurg Anesthesiol 2005;17:65-8.

13. Pandey CK, Priye S, Singh S et al. Preemptive use of gabapentin significantly decreases
postoperative pain and rescue analgesic requirements in laparoscopic cholecystectomy.
Can J Anaesth 2004;51:358-63.

14. Pandey CK, Sahay S, Gupta D et al. Preemptive gabapentin decreases postoperative pain
after lumbar discoidectomy. Can J Anaesth 2004;51:986-9.

15. Pandey CK, Singhal V, Kumar M et al. Gabapentin provides effective postoperative
analgesia whether administered pre-emptively or post-incision. Can J Anaesth

16. Radhakrishnan M, Bithal PK, Chaturvedi A. Effect of preemptive gabapentin on
postoperative pain relief and morphine consumption following lumbar laminectomy and
discectomy: a randomized, double-blinded, placebo-controlled study. J Neurosurg
Anesthesiol 2005;17:125-8.

17. Rorarius MG, Mennander S, Suominen P et al. Gabapentin for the prevention of
postoperative pain after vaginal hysterectomy. Pain 2004;110:175-81.

18. Turan A, Karamanlioglu B, Memis D et al. Analgesic effects of gabapentin after spinal
surgery. Anesthesiology 2004;100:935-8.

19. Turan A, Karamanlioglu B, Memis D et al. The analgesic effects of gabapentin after
total abdominal hysterectomy. Anesth Analg 2004;98:1370-3, table of contents.

20. Turan A, Kaya G, Karamanlioglu B et al. Effect of oral gabapentin on postoperative
epidural analgesia. Br J Anaesth 2006;96:242-6.

21. Turan A, Memis D, Karamanlioglu B et al. The analgesic effects of gabapentin in
monitored anesthesia care for ear-nose-throat surgery. Anesth Analg 2004;99:375-8,
table of contents.

22. Turan A, White PF, Karamanlioglu B et al. Gabapentin: an alternative to the
cyclooxygenase-2 inhibitors for perioperative pain management. Anesth Analg

23. Gilron I. Review article: the role of anticonvulsant drugs in postoperative pain
management: a bench-to-bedside perspective. Can J Anaesth 2006;53:562-71.

24. Spielberger CD, Gorsuch RL, Lushene R et al. State-Trait Anxiety Inventory for Adults:
Manual. Palo Alto: Mind Garden, 1983.

25. Sullivan MJ, Thorn B, Haythornthwaite JA et al. Theoretical perspectives on the
relation between catastrophizing and pain. Clin J Pain 2001;17:52-64.

26. Sullivan MJ, Bishop SR, Pivik J. The Pain Catastrophizing Scale: Development and
Validation. Psychological Assessment 1995;7:524-32.

27. Pavlin DJ, Sullivan MJ, Freund PR, Roesen K. Catastrophizing: a risk factor for
postsurgical pain. Clin J Pain 2005;21:83-90.

28. Sullivan MJ, Lynch ME, Clark AJ. Dimensions of catastrophic thinking associated with
pain experience and disability in patients with neuropathic pain conditions. Pain

29. McCracken LM, Dhingra L. A short version of the Pain Anxiety Symptoms Scale (PASS-20):
Preliminary development and validity. Pain Research and Management 2002;7:45-50.

30. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand

31. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and
Depression Scale. An updated literature review. J Psychosom Res 2002;52:69-77.

32. Herrmann C. International experiences with the Hospital Anxiety and Depression Scale--a
review of validation data and clinical results. J Psychosom Res 1997;42:17-41.

33. Snaith RP. The Hospital Anxiety And Depression Scale. Health Qual Life Outcomes

34. Gotay CC. Assessing cancer-related quality of life across a spectrum of applications. J
Natl Cancer Inst Monogr 2004:126-33.

35. Fletcher A. Quality-of-life measurements in the evaluation of treatment: proposed
guidelines. Br J Clin Pharmacol 1995;39:217-22.

36. Herr HW. Quality of life in prostate cancer patients. CA Cancer J Clin 1997;47:207-17.

37. Fossa SD. Good quality of life in prostate cancer patients: how can it be obtained?
Scand J Urol Nephrol Suppl 1999;203:51-2.

38. Hopman WM, Towheed T, Anastassiades T et al. Canadian normative data for the SF-36
health survey. Canadian Multicentre Osteoporosis Study Research Group. Cmaj

39. Lofland JH. Measuring Patients' Health-Related Quality of LIfe: Practical
Considerations for Implementing an Outcomes Management Program. P & T 2002;27:209-11.

40. Litwin MS, Hays RD, Fink A et al. The UCLA Prostate Cancer Index: development,
reliability, and validity of a health-related quality of life measure. Med Care

41. McNaughton-Collins M, Walker-Corkery E, Barry MJ. Health-related quality of life,
satisfaction, and economic outcome measures in studies of prostate cancer screening and
treatment, 1990-2000. J Natl Cancer Inst Monogr 2004:78-101.

42. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad
Med Singapore 1994;23:129-38.

43. Tittle MB, McMillan SC, Hagan S. Validating the brief pain inventory for use with
surgical patients with cancer. Oncol Nurs Forum 2003;30:325-30.

44. Strassels SA, mcNicol E, Wagner AK et al. Persistent Postoperative Pain, Health-Related
Quality of LIfe, and Functioning 1 Month After Hospital Discharge. Acute Pain

45. Wu CL, Naqibuddin M, Rowlingson AJ et al. The effect of pain on health-related quality
of life in the immediate postoperative period. Anesth Analg 2003;97:1078-85, table of

46. VanDenKerkhof EG, Hopman WM, Towheed T et al. Pain, health-related quality of life and
health care utilization after inpatient surgery: a pilot study. Pain Res Manag

Inclusion Criteria:

- Undergoing radical prostatectomy

- Able to read and write english (assistance is allowed)

- Normal creatinine blood serum level

- No known allergies to study medications

Exclusion Criteria:

- Patients not providing informed consent

- Patients less than 18 years of age or greater than 75 years of age

- Known allergy to any of the medications being used

- History of drug or alcohol abuse

- Preoperative pain

- Patients unable or unwilling to use PCA

- Patients with impaired renal function (Creatinine >106)

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Will Gabapentin 200mg TID have pain and opioid sparing effects?

Outcome Time Frame:

3 days after surgery

Safety Issue:


Principal Investigator

Colin McCartney, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sunnybrook Health Sciences Center


Canada: Health Canada

Study ID:




Start Date:

June 2007

Completion Date:

January 2010

Related Keywords:

  • Prostate Cancer
  • gabapentin
  • opioid consumption
  • analgesic
  • anxiety
  • quality of life
  • Anxiety Disorders
  • Prostatic Neoplasms