Journal of Pain & Palliative Care Pharmacotherapy. 2013;27:402–405. Copyright © 2013 Informa Healthcare USA, Inc. ISSN: 1536-0288 print / 1536-0539 online DOI: 10.3109/15360288.2013.847522
PATIENT EDUCATION AND SELF ADVOCACY: QUESTIONS AND RESPONSES ON PAIN MANAGEMENT Edited by Yvette Col´on
J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by National University of Singapore on 06/12/14 For personal use only.
Buprenorphine for Chronic Pain Raul Calderon and David Copenhaver AB STRACT Questions from patients about pain conditions, analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The use of transdermal buprenorphine for chronic pain management is discussed. A brief history of the medication is provided. The use of the medication in opioid maintenance, and withdrawal and other concerns are discussed. Possible side effects are described. KEYWORDS buprenorphine, transdermal, analgesia, withdrawal, side effects
spinal cord and digestive tract similar to other opioids such as morphine, oxycodone and fentanyl. There are properties of buprenorphine that make it appealing for use in patients that are opioid dependent, addicted and more recently for those with chronic pain. Patients with addiction may use drug in a different way than prescribed and continue to use the drug despite clear evidence of overly harmful consequences. Patients with opioid dependence develop tolerance to the drug in which higher doses of medication is needed to get same level of pain relief and patients may feel withdrawal from stopping the medication abruptly. While it appears that your doctor has suggested buprenorphine for your chronic pain, it is worth briefly discussing the history of buprenorphine’s use for opioid dependence. In 2002, the United States Food and Drug Administration approved Suboxone and Subutex, buprenorphine sublingual preparations, for purpose of detoxification and long-term replacement therapy of opioid dependence. Some of the benefits of using buprenorphine include long halflife (medication effect last longer) preventing withdrawal for 24 hours or longer, it has a ceiling effect on slowing down breathing with increased dose and it is easier to withdraw from buprenorphine compared to methadone. We will discuss some of these advantages of buprenorphine in the following paragraphs, as these are also important to consider when
QUESTION FROM A PATIENT My doctor suggested I try buprenorphine patch to help control my chronic pain. How is this different than morphine, what are some of the things I should know about it and what are some of the benefits it may offer compared to morphine?
ANSWER Prior to beginning any chronic opioid therapy, it is important to determine whether you are a good candidate. This is evaluated by assessing pain relief, improvement of function, side effects and evidence of abuse or abnormal behaviors. Buprenorphine is a semi-synthetic opioid (produced by chemical manipulation of natural occurring substances) that has been available since 1981 in intravenous form for the treatment of pain. While buprenorphine binds to opioid receptors in the brain, Raul Calderon, MD, is a Fellow and David Copenhaver, MD, MPH, is an Assistant Professor of Anesthesiology and Attending Physician in the University of California Davis Division of Pain Medicine, Sacramento, California, USA. Address correspondence to: Raul Calderon, MD, Division of Pain Medicine, UC Davis Medical Center, Lawrence J. Ellison Ambulatory Care Center, 4860 Y St., Suite 3020, Sacramento CA 95817. (E-mail: painfellowship@ ucdmc.ucdavis.edu).
402
J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by National University of Singapore on 06/12/14 For personal use only.
R. Calderon and D. Copenhaver
selecting this medication for the treatment of chronic pain. In the setting of taking buprenorphine, patients will require higher than usual doses of short acting medications to treat acute pain. The launch of transdermal formulation (drug delivery through the skin) of buprenorphine in 2001 created a new interest for its use in patients with chronic moderate to severe pain. Currently, Butrans transdermal patch is available as 5, 10 and 20 mcg/hour strengths. Before starting a patient on buprenorphine therapy, one must make sure patient is a good candidate which includes patients with chronic pain that are expected to require around the clock pain medication for an extended period of time. Butrans is not intended to be used as a PRN (as needed) medication for pain that is thought to be mild and short duration only, for acute pain or for postoperative pain unless patient was already receiving opioids prior to surgery or is expected to have moderate to severe pain that will last for months to years. As with other opioids, adverse effects to buprenorphine may include headache, generalized pain, nausea, insomnia, constipation and abdominal pain.1
Buprenorphine for Pain Multiple randomized, placebo controlled, double blind studies (studies of highest quality) have showed that buprenorphine can be effective for control of pain.2,3 When two such trials were evaluated which included both cancer and noncancer patients over half of patients used 35 mcg/hour patch. A total of 42.7% of patients reported good to complete pain relief and 47.7% reported pain relief as adequate. The studies also found that the tolerability was good to buprenorphine.
Buprenorphine Use in Elders and Kidney Dysfunction Elder patients may have multiple morbidities (medical diseases) and may be taking multiple medications that may interact with additional medications prescribed. In addition, renal impairment may be present but undetected. Thus, elders may have a smaller window of medication dose before significant side effects can occur with many opioid medications. Several studies have shown that buprenorphine was equally effective in those aged 65 and younger, between 65 and 75 and older than 75 years of age.4 There was no increased toxicity in elders and no dose adjustment was needed.5,6 Since buprenorphine is largely excreted though the gastrointestinal tract, the elimination is not influenced by the renal function. Studies have shown no C
2013 Informa Healthcare USA, Inc.
403
change in pain ratings or blood levels of buprenorphine or its metabolite (breakdown byproduct) before or after hemodialysis.7 It is also relatively safe in mild to moderate liver disease.
Effects on Respiratory Depression (Slowing Down Breathing) One of the major areas of concern with opioid use today is that it may lead to respiratory depression and accidental death. Potent opioids such as fentanyl, morphine, oxycodone and methadone all cause respiratory depression that is increased by larger doses. This respiratory depression is most significant in patients that do not take opioids on a regular basis and thus have not developed some tolerance to this side effect. In the event patients take multiple medications that can cause respiratory depression such as benzodiazepines (such as valium), muscle relaxants (such as soma) and the use alcohol, these substances can increase the respiratory depressant effect of opioids. In contrast to other potent opioids, buprenorphine has a ceiling effect when it comes the side effect of respiratory depression. Increasing doses of buprenorphine will continue to give analgesia without significantly slowing down breathing. Thus, it may be considered safer than other opioids in this regard. This assumes that it is the only medication used that can affect breathing. Care must be taken as respiratory depression can occur with buprenorphine if combined with other medications such as benzodiazepines, muscle relaxants and alcohol. If buprenorphine does cause respiratory depression this can be reversed with naloxone (opioid reversal agent) but higher doses would be needed given the higher receptor affinity (the natural attraction of drug to receptor) and longer half-life.8
Tolerance and Opioid Induced Hyperalgesia Buprenorphine appears to produce less analgesic tolerance (chronic exposure to a drug leads to decreased pain relief and will require higher doses to maintain prior benefit) compared to fentanyl as shown in a retrospective study of 900 cancer and noncancer patients.9 Opioid induced hyperalgesia or opioid induced abnormal pain sensitivity is thought to be caused by the chronic use of most opioids. Buprenorphine on the other hand appears to prevent hyperalgesia and it has been proposed that it is possibly through the opioid receptor like 1 receptor (ORL1).10
404
Journal of Pain & Palliative Care Pharmacotherapy
J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by National University of Singapore on 06/12/14 For personal use only.
Calculation for Starting Dose
Once the determination that a patient is a good candidate for buprenorphine therapy, one must calculate how much opioid pain medication the patient is currently consuming. Next, a mathematical conversion to an equivalent dose of oral morphine must take place. This conversion will help estimate the equivalent dose of buprenorphine patch required. Purdue Pharma LP recommends in their package insert that in a patient with less than 30 mg of oral morphine equivalent, Butrans patch of 5 mcg/hour would be the recommended starting point.1 In patients with an oral morphine equivalent of 30–60 mg, a Butrans patch of 10 mcg/hour would be recommended.1 For those with greater than 80 mg oral morphine equivalent, a 20 mcg/hour Butrans patch may be used but it may not provide adequate analgesia so an alternative analgesic may be considered.1
Preventing Withdrawal Prior to starting therapy with buprenorphine, patients that have been taking full agonist opioids such as morphine, fentanyl, oxycodone and methadone must stop them long enough that there is evidence of mild opioid withdrawal. Since buprenorphine is a partial opioid antagonist (although it activates a receptor it also partially blocks its activation), if the patient on opioids takes buprenorphine when not in withdrawal, it can precipitate a severe withdrawal. For patients using short acting opioids (such as oxycodone, dilaudid or morphine) the induction of buprenorphine should begin about 12–24 hours after last use of those medications.11 For those using longer acting medications (such as Oxycontin or Morphine Sustained Relief) induction of buprenorphine should be done after about 24–48 hours.11,12 For patients on methadone, physicians will sometime transition patients to short acting pain medications before changing to buprenorphine.13
CONCLUSION Transdermal buprenorphine may be useful to help treat moderate to severe pain that is expected to be chronic or of long duration and in those patients that require continuous pain medication. Some of its benefits include a patch that will deliver a constant dose for seven days to help provide continuous pain relief thus simplifying dosing regimen. It has been shown not to have a ceiling effect on slowing-down respirations, which makes it safer as long as it is not combined with other medications that can slow down
breathing. It addition, it has been shown to require no dosage changes for elders or in people with kidney dysfunction. One must keep in mind that if patients are on buprenorphine and there is an increase of pain such as with surgery or trauma, patients will need higher than normal doses of short acting opioids to help with pain control secondary to the partial activity of opioid receptors by buprenorphine. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES [1] Butrans [package insert]. Stamford, CT: Purdue Pharma L.P.; 2012. [2] Bohme K, Likar R. Efficacy and tolerability of a new opioid analgesic formulation, buprenorphine transdermal therapeutic system in the treatment of patients with chronic pain. A randomized, double blind, placebo-controlled study. Pain Clin. 2003;15:193–202. [3] Sittl R, Giessinger N, Likar R. Analgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer pain and other disorders: a multicenter, randomized, double-blind placebo controlled trial. Clin Ther. 2003;25:150–168. ´ Garrote JM, S´anchez Ma[4] Muriel Villoria C, P´erez-Castejon gro I, Neira Alvarez M. Effectiveness and safety of transdermal buprenorphine for chronic pain treatment in the elderly: a prospective observational study. Med Clin (Barc). 2007;128(6):204–210. [5] Likar R, Kayser H, Sittl R. Long-term management of chronic pain with transdermal buprenorphine: a multicenter, openlabel, follow-up study in patients from three short- term clinical trials. Clin Ther. 2006;28(6):943–52. [6] Kress HG. Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. Eur J Pain. 2009;13(3):219–230. [7] Filitz J, Griessinger N, Sittl R, Likar R, Schttler J, Koppert W. Effects of intermittent hemodialysis on buprenorphine and norbuprenorphine plasma concentrations in chronic pain patients treated with transdermal buprenorphine. Eur J Pain. 2006;10(8):743–748. [8] Davis MP. Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain. J Support Oncol. 2012;10;209–219. [9] Sittl R, Nuijten M, Nautrup BP. Changes in the prescribed daily doses of transdermal fentanyl and transdermal buprenorphine during treatment of patients with cancer and noncancer pain in Germany: results of a retrospective cohort study. Clin Ther. 2005;27(7):1022–1031. ¨ [10] Koppert W, Ihmsen H, Korber N, Wehrfritz A, Sittl R, Schmelz ¨ M, Schuttler J. Different profiles of buprenorphine-induced analgesia and antihyperalgesia in a human pain model. Pain. 2005;118(1–2):15–22. [11] Saxon AJ, Robinson James P, Sullivan MD. Assessment and treatment of chemical dependency. In Fishman SM, Ballantyne JC, Rathmell JP, editors, Bonica’s Management of Pain, 4th edition, Philadelphia, Wolters Kluwer/Lippincott Williams & Wilkins, 2010.
Journal of Pain & Palliative Care Pharmacotherapy
R. Calderon and D. Copenhaver
J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by National University of Singapore on 06/12/14 For personal use only.
[12] Pergolizzi J, Aloisi AM, Dahan A, Filitz J, Langford R, Likar R, Mercadante S, Morlion B, Raffa RB, Sabatowski R, Sacerdote P, Torres LM, Weinbroum AA. Current knowledge of buprenorphine and its unique pharmacological profile, Pain Pract. 2010;10(1–23):428–450. [13] Daitch J, Frey ME, Silver D, Mitnick C, Daitch D, Pergolizzi J. Conversion of chronic pain patients from full-
C
2013 Informa Healthcare USA, Inc.
405
opioid agonists to sublingual buprenorphine, Pain Physician. 2012;15:ES59–ES66.
RECEIVED: 18 September 2013 REVISED: 9 November 2013 ACCEPTED: 18 September 2013
PATIENT EDUCATION AND SELF ADVOCACY: QUESTIONS AND RESPONSES ON PAIN MANAGEMENT Edited by Yvette Col´on
J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by National University of Singapore on 06/12/14 For personal use only.
Buprenorphine for Chronic Pain Raul Calderon and David Copenhaver AB STRACT Questions from patients about pain conditions, analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The use of transdermal buprenorphine for chronic pain management is discussed. A brief history of the medication is provided. The use of the medication in opioid maintenance, and withdrawal and other concerns are discussed. Possible side effects are described. KEYWORDS buprenorphine, transdermal, analgesia, withdrawal, side effects
spinal cord and digestive tract similar to other opioids such as morphine, oxycodone and fentanyl. There are properties of buprenorphine that make it appealing for use in patients that are opioid dependent, addicted and more recently for those with chronic pain. Patients with addiction may use drug in a different way than prescribed and continue to use the drug despite clear evidence of overly harmful consequences. Patients with opioid dependence develop tolerance to the drug in which higher doses of medication is needed to get same level of pain relief and patients may feel withdrawal from stopping the medication abruptly. While it appears that your doctor has suggested buprenorphine for your chronic pain, it is worth briefly discussing the history of buprenorphine’s use for opioid dependence. In 2002, the United States Food and Drug Administration approved Suboxone and Subutex, buprenorphine sublingual preparations, for purpose of detoxification and long-term replacement therapy of opioid dependence. Some of the benefits of using buprenorphine include long halflife (medication effect last longer) preventing withdrawal for 24 hours or longer, it has a ceiling effect on slowing down breathing with increased dose and it is easier to withdraw from buprenorphine compared to methadone. We will discuss some of these advantages of buprenorphine in the following paragraphs, as these are also important to consider when
QUESTION FROM A PATIENT My doctor suggested I try buprenorphine patch to help control my chronic pain. How is this different than morphine, what are some of the things I should know about it and what are some of the benefits it may offer compared to morphine?
ANSWER Prior to beginning any chronic opioid therapy, it is important to determine whether you are a good candidate. This is evaluated by assessing pain relief, improvement of function, side effects and evidence of abuse or abnormal behaviors. Buprenorphine is a semi-synthetic opioid (produced by chemical manipulation of natural occurring substances) that has been available since 1981 in intravenous form for the treatment of pain. While buprenorphine binds to opioid receptors in the brain, Raul Calderon, MD, is a Fellow and David Copenhaver, MD, MPH, is an Assistant Professor of Anesthesiology and Attending Physician in the University of California Davis Division of Pain Medicine, Sacramento, California, USA. Address correspondence to: Raul Calderon, MD, Division of Pain Medicine, UC Davis Medical Center, Lawrence J. Ellison Ambulatory Care Center, 4860 Y St., Suite 3020, Sacramento CA 95817. (E-mail: painfellowship@ ucdmc.ucdavis.edu).
402
J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by National University of Singapore on 06/12/14 For personal use only.
R. Calderon and D. Copenhaver
selecting this medication for the treatment of chronic pain. In the setting of taking buprenorphine, patients will require higher than usual doses of short acting medications to treat acute pain. The launch of transdermal formulation (drug delivery through the skin) of buprenorphine in 2001 created a new interest for its use in patients with chronic moderate to severe pain. Currently, Butrans transdermal patch is available as 5, 10 and 20 mcg/hour strengths. Before starting a patient on buprenorphine therapy, one must make sure patient is a good candidate which includes patients with chronic pain that are expected to require around the clock pain medication for an extended period of time. Butrans is not intended to be used as a PRN (as needed) medication for pain that is thought to be mild and short duration only, for acute pain or for postoperative pain unless patient was already receiving opioids prior to surgery or is expected to have moderate to severe pain that will last for months to years. As with other opioids, adverse effects to buprenorphine may include headache, generalized pain, nausea, insomnia, constipation and abdominal pain.1
Buprenorphine for Pain Multiple randomized, placebo controlled, double blind studies (studies of highest quality) have showed that buprenorphine can be effective for control of pain.2,3 When two such trials were evaluated which included both cancer and noncancer patients over half of patients used 35 mcg/hour patch. A total of 42.7% of patients reported good to complete pain relief and 47.7% reported pain relief as adequate. The studies also found that the tolerability was good to buprenorphine.
Buprenorphine Use in Elders and Kidney Dysfunction Elder patients may have multiple morbidities (medical diseases) and may be taking multiple medications that may interact with additional medications prescribed. In addition, renal impairment may be present but undetected. Thus, elders may have a smaller window of medication dose before significant side effects can occur with many opioid medications. Several studies have shown that buprenorphine was equally effective in those aged 65 and younger, between 65 and 75 and older than 75 years of age.4 There was no increased toxicity in elders and no dose adjustment was needed.5,6 Since buprenorphine is largely excreted though the gastrointestinal tract, the elimination is not influenced by the renal function. Studies have shown no C
2013 Informa Healthcare USA, Inc.
403
change in pain ratings or blood levels of buprenorphine or its metabolite (breakdown byproduct) before or after hemodialysis.7 It is also relatively safe in mild to moderate liver disease.
Effects on Respiratory Depression (Slowing Down Breathing) One of the major areas of concern with opioid use today is that it may lead to respiratory depression and accidental death. Potent opioids such as fentanyl, morphine, oxycodone and methadone all cause respiratory depression that is increased by larger doses. This respiratory depression is most significant in patients that do not take opioids on a regular basis and thus have not developed some tolerance to this side effect. In the event patients take multiple medications that can cause respiratory depression such as benzodiazepines (such as valium), muscle relaxants (such as soma) and the use alcohol, these substances can increase the respiratory depressant effect of opioids. In contrast to other potent opioids, buprenorphine has a ceiling effect when it comes the side effect of respiratory depression. Increasing doses of buprenorphine will continue to give analgesia without significantly slowing down breathing. Thus, it may be considered safer than other opioids in this regard. This assumes that it is the only medication used that can affect breathing. Care must be taken as respiratory depression can occur with buprenorphine if combined with other medications such as benzodiazepines, muscle relaxants and alcohol. If buprenorphine does cause respiratory depression this can be reversed with naloxone (opioid reversal agent) but higher doses would be needed given the higher receptor affinity (the natural attraction of drug to receptor) and longer half-life.8
Tolerance and Opioid Induced Hyperalgesia Buprenorphine appears to produce less analgesic tolerance (chronic exposure to a drug leads to decreased pain relief and will require higher doses to maintain prior benefit) compared to fentanyl as shown in a retrospective study of 900 cancer and noncancer patients.9 Opioid induced hyperalgesia or opioid induced abnormal pain sensitivity is thought to be caused by the chronic use of most opioids. Buprenorphine on the other hand appears to prevent hyperalgesia and it has been proposed that it is possibly through the opioid receptor like 1 receptor (ORL1).10
404
Journal of Pain & Palliative Care Pharmacotherapy
J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by National University of Singapore on 06/12/14 For personal use only.
Calculation for Starting Dose
Once the determination that a patient is a good candidate for buprenorphine therapy, one must calculate how much opioid pain medication the patient is currently consuming. Next, a mathematical conversion to an equivalent dose of oral morphine must take place. This conversion will help estimate the equivalent dose of buprenorphine patch required. Purdue Pharma LP recommends in their package insert that in a patient with less than 30 mg of oral morphine equivalent, Butrans patch of 5 mcg/hour would be the recommended starting point.1 In patients with an oral morphine equivalent of 30–60 mg, a Butrans patch of 10 mcg/hour would be recommended.1 For those with greater than 80 mg oral morphine equivalent, a 20 mcg/hour Butrans patch may be used but it may not provide adequate analgesia so an alternative analgesic may be considered.1
Preventing Withdrawal Prior to starting therapy with buprenorphine, patients that have been taking full agonist opioids such as morphine, fentanyl, oxycodone and methadone must stop them long enough that there is evidence of mild opioid withdrawal. Since buprenorphine is a partial opioid antagonist (although it activates a receptor it also partially blocks its activation), if the patient on opioids takes buprenorphine when not in withdrawal, it can precipitate a severe withdrawal. For patients using short acting opioids (such as oxycodone, dilaudid or morphine) the induction of buprenorphine should begin about 12–24 hours after last use of those medications.11 For those using longer acting medications (such as Oxycontin or Morphine Sustained Relief) induction of buprenorphine should be done after about 24–48 hours.11,12 For patients on methadone, physicians will sometime transition patients to short acting pain medications before changing to buprenorphine.13
CONCLUSION Transdermal buprenorphine may be useful to help treat moderate to severe pain that is expected to be chronic or of long duration and in those patients that require continuous pain medication. Some of its benefits include a patch that will deliver a constant dose for seven days to help provide continuous pain relief thus simplifying dosing regimen. It has been shown not to have a ceiling effect on slowing-down respirations, which makes it safer as long as it is not combined with other medications that can slow down
breathing. It addition, it has been shown to require no dosage changes for elders or in people with kidney dysfunction. One must keep in mind that if patients are on buprenorphine and there is an increase of pain such as with surgery or trauma, patients will need higher than normal doses of short acting opioids to help with pain control secondary to the partial activity of opioid receptors by buprenorphine. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES [1] Butrans [package insert]. Stamford, CT: Purdue Pharma L.P.; 2012. [2] Bohme K, Likar R. Efficacy and tolerability of a new opioid analgesic formulation, buprenorphine transdermal therapeutic system in the treatment of patients with chronic pain. A randomized, double blind, placebo-controlled study. Pain Clin. 2003;15:193–202. [3] Sittl R, Giessinger N, Likar R. Analgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer pain and other disorders: a multicenter, randomized, double-blind placebo controlled trial. Clin Ther. 2003;25:150–168. ´ Garrote JM, S´anchez Ma[4] Muriel Villoria C, P´erez-Castejon gro I, Neira Alvarez M. Effectiveness and safety of transdermal buprenorphine for chronic pain treatment in the elderly: a prospective observational study. Med Clin (Barc). 2007;128(6):204–210. [5] Likar R, Kayser H, Sittl R. Long-term management of chronic pain with transdermal buprenorphine: a multicenter, openlabel, follow-up study in patients from three short- term clinical trials. Clin Ther. 2006;28(6):943–52. [6] Kress HG. Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. Eur J Pain. 2009;13(3):219–230. [7] Filitz J, Griessinger N, Sittl R, Likar R, Schttler J, Koppert W. Effects of intermittent hemodialysis on buprenorphine and norbuprenorphine plasma concentrations in chronic pain patients treated with transdermal buprenorphine. Eur J Pain. 2006;10(8):743–748. [8] Davis MP. Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain. J Support Oncol. 2012;10;209–219. [9] Sittl R, Nuijten M, Nautrup BP. Changes in the prescribed daily doses of transdermal fentanyl and transdermal buprenorphine during treatment of patients with cancer and noncancer pain in Germany: results of a retrospective cohort study. Clin Ther. 2005;27(7):1022–1031. ¨ [10] Koppert W, Ihmsen H, Korber N, Wehrfritz A, Sittl R, Schmelz ¨ M, Schuttler J. Different profiles of buprenorphine-induced analgesia and antihyperalgesia in a human pain model. Pain. 2005;118(1–2):15–22. [11] Saxon AJ, Robinson James P, Sullivan MD. Assessment and treatment of chemical dependency. In Fishman SM, Ballantyne JC, Rathmell JP, editors, Bonica’s Management of Pain, 4th edition, Philadelphia, Wolters Kluwer/Lippincott Williams & Wilkins, 2010.
Journal of Pain & Palliative Care Pharmacotherapy
R. Calderon and D. Copenhaver
J Pain Palliat Care Pharmacother Downloaded from informahealthcare.com by National University of Singapore on 06/12/14 For personal use only.
[12] Pergolizzi J, Aloisi AM, Dahan A, Filitz J, Langford R, Likar R, Mercadante S, Morlion B, Raffa RB, Sabatowski R, Sacerdote P, Torres LM, Weinbroum AA. Current knowledge of buprenorphine and its unique pharmacological profile, Pain Pract. 2010;10(1–23):428–450. [13] Daitch J, Frey ME, Silver D, Mitnick C, Daitch D, Pergolizzi J. Conversion of chronic pain patients from full-
C
2013 Informa Healthcare USA, Inc.
405
opioid agonists to sublingual buprenorphine, Pain Physician. 2012;15:ES59–ES66.
RECEIVED: 18 September 2013 REVISED: 9 November 2013 ACCEPTED: 18 September 2013
