Memantine for Post-Operative Pain Control

• Change in numerical ratings on pain diaries as outpatients (pre and post surgery) [ Time Frame: For 1 week pre-surgery, through 2 weeks post-surgery ] [ Designated as safety issue: No ]
• Daily pain numerical ratings at rest and with movement as inpatients. [ Time Frame: Immediately post-surgery until discharge (2-3 days) ] [ Designated as safety issue: No ]
• Total opiate dose via patient controlled IV hydromorphone [ Time Frame: Post-surgery day 1 ] [ Designated as safety issue: No ]
• Oxycodone dose taken prn [ Time Frame: Post-surgery day 2 through 3 months. ] [ Designated as safety issue: No ]

• Treatment group differences in side effects (nausea, itching, sedation, urinary retention following foley catheter discontinuation) [ Time Frame: One week pre-surgery through 3 months post-surgery ] [ Designated as safety issue: Yes ]
• Changes in cognitive function, assessed with Digit-Symbol Substitution Test and Trail Making Test B [ Time Frame: One week pre-surgery, immediately pre-surgery, and post-surgery days 1, 2, 3 ] [ Designated as safety issue: No ]
• Changes in pain and quality of life questionnaire responses (SF-McGill-2, Brief Pain Questionnaire, SF-36 v2) [ Time Frame: One week pre-surgery through 3 months post-surgery, particularly as outpatient ] [ Designated as safety issue: No ]

Pain is a common element of surgery. Opiates (morphine, oxycodone, hydrocodone, methadone, fentanyl) are very helpful in decreasing pain after surgery. Unfortunately, with repeated use opiates lose their effectiveness, such that patients need to utilize more opiates to achieve adequate pain relief - a phenomenon called tolerance. Sometimes tolerance to a pain reliever's effects can develop in just a few hours. It is thought that activation of the N-methyl d-aspartate (NMDA) receptor, a "switch" found on the surface of nerves, is partially responsible for opiate tolerance. Memantine is a medication that limits the activity of NMDA receptors in the brain and spinal cord. It has been used for years to help patients with Alzheimer's Disease. In this study, we will study the effects of memantine when combined with opiate medications to see whether it can increase the effectiveness of opiates for pain after surgery and reduce the side effects caused by opiates (e.g., sedation, nausea, itching).

• Drug: Memantine
  7 days prior to surgery, start taking 5mg memantine daily; 4 days prior to surgery, increase dose to 5mg twice daily; 2 days prior to surgery, increase dose to 10mg in the morning, and 5 mg in the evening; on the day of surgery, increase dose to 10mg twice daily, and continue on this dose until 14 days after surgery.
  Other Name: Namenda
• Drug: Placebo
  7 days prior to surgery, start taking one placebo tablet daily; 4 days prior to surgery, increase dose to one placebo tablet twice daily; 2 days prior to surgery, increase dose to 2 placebo tablets in the morning, and one placebo tablet in the evening; on the day of surgery, increase dose to 2 placebo tablets in the morning and 1 placebo tablet in the evening. On the first day after surgery through 14 days after surgery, take 1 placebo tablet twice daily.

• Active Comparator: Opiate Naive
  Subjects who have not taken opiate medication in previous 6 weeks before surgery
  Interventions:

  • Drug: Memantine
  • Drug: Placebo
• Active Comparator: Opiate tolerant
  Subjects who have taken opiate medications for the 6 weeks before surgery
  Interventions:

  • Drug: Memantine
  • Drug: Placebo

Inclusion Criteria:

• Surgery for total hip replacement, knee replacement OR lumbar spinal fusion
• Taking no opiate medication OR taking opiate medication for at least 6 weeks

Exclusion Criteria:

• History of alcohol or drug abuse
• Clinical diagnosis of Alzheimer's Disease
• Prior adverse reaction to memantine
• Severe renal impairment (creatinine clearance <30 ml/min)
• Inability to give informed consent