Effect of fentanyl buccal tablet on pain-related anxiety: A 4-week open-label study among opioid-tolerant patients with chronic and breakthrough pain


  • Lynn R. Webster, MD
  • John Messina, PharmD
  • Fang Xie, PhD
  • Srinivas Nalamachu, MD




anxiety, breakthrough pain, chronic pain, fentanyl buccal tablet


Objective: To evaluate the effect of fentanyl buccal tablet (FBT) on pain-related anxiety in opioid-tolerant patients with chronic pain and breakthrough pain (BTP).
Design: This study consisted of a screening visit, open-label titration period, and 4-week open-label treatment period.
Setting: Thirty-one US study centers.
Patients: Opioid-tolerant adults with chronic, persistent pain experiencing 1-4 BTP episodes per day at baseline. Two hundred eighteen patients were enrolled in this study; 180 completed the titration period; and 169 completed the treatment period.
Intervention: Patients were treated with FBT (100-800 g) for BTP episodes for 4 weeks while continuing their around-the-clock opioid regimens.
Main outcome measures: Change from baseline in the Pain Anxiety Symptoms Scale (PASS) total score at the final visit.
Results: Based on a mean baseline PASS total score of 82.6, study patients had a high level of anxiety; 92 patients (42 percent) had a history of anxiety disorders. The change from baseline in PASS total score was not statistically significant (mean change, −1.6; p = 0.322). Numerical improvements were reported in some secondary measures (eg, Beck Depression Inventory total score [mean change, −1.1; p = 0.038]) and categorical measures (eg, Pain Flare Treatment Satisfaction, Patient Assessment of Function, and Clinician Assessment of Patient Function ratings). FBT was generally well tolerated, with no serious adverse events related to study drug.
Conclusions: Four weeks of treatment with FBT did not reduce anxiety to a clinically meaningful extent, although improvement was reported in several secondary measures of functioning. Further research is needed to assess the impact of treatment for BTP on anxiety symptoms in opioid-tolerant patients with BTP.

Author Biographies

Lynn R. Webster, MD

Salt Lake Regional Medical Center, Salt Lake City, Utah.

John Messina, PharmD

Clinical Research, Cephalon, Inc., Frazer, Pennsylvania.

Fang Xie, PhD

Biostatistics, Cephalon, Inc., Frazer, Pennsylvania.

Srinivas Nalamachu, MD

Mid-America Physiatrists, PA, Overland Park, Kansas.


Chou R, Clark E, Helfand M: Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: A systematic review. J Pain Symptom Manage. 2003; 26(5): 1026-1048.

Manchikanti L, Singh V, Datta S, et al.: Comprehensive review of epidemiology, scope, and impact of spinal pain. Pain Physician. 2009; 12(4): E35-E70.

Chou R, Fanciullo GJ, Fine PG, et al.: Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009; 10(2): 113-130.

Portenoy RK, Bennett DS, Rauck R, et al.: Prevalence and characteristics of breakthrough pain in opioid-treated patients with chronic noncancer pain. J Pain. 2006; 7(8): 583-591.

Portenoy RK, Hagen NA: Breakthrough pain: Definition, prevalence and characteristics. Pain. 1990; 41(3): 273-281.

Portenoy RK, Payne D, Jacobsen P: Breakthrough pain: Characteristics and impact in patients with cancer pain. Pain. 1999; 81(1-2): 129-134.

Svendsen KB, Andersen S, Arnason S, et al.: Breakthrough pain in malignant and non-malignant diseases: A review of prevalence, characteristics and mechanisms. Eur J Pain. 2005; 9(2): 195-206.

Zeppetella G, O’Doherty CA, Collins S: Prevalence and characteristics of breakthrough pain in cancer patients admitted to a hospice. J Pain Symptom Manage. 2000; 20(2): 87-92.

Bennett DS, Simon S, Brennan M, et al.: Prevalence and characteristics of breakthrough pain in patients receiving opioids for chronic back pain in pain specialty clinics. J Opioid Manag. 2007; 3(2): 101-106.

Taylor DR, Webster LR, Chun SY, et al.: Impact of breakthrough pain on quality of life in patients with chronic, noncancer pain: Patient perceptions and effect of treatment with oral transmucosal fentanyl citrate (OTFC, ACTIQ). Pain Med. 2007; 8(3): 281-288.

Caraceni A, Martini C, Zecca E, et al.: Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey. Palliat Med. 2004; 18(3): 177-183.

McCracken LM, Zayfert C, Gross RT: The Pain Anxiety Symptoms Scale: Development and validation of a scale to measure fear of pain. Pain. 1992; 50(1): 67-73.

Burns JW, Mullen JT, Higdon LJ, et al.: Validity of the pain anxiety symptoms scale (PASS): Prediction of physical capacity variables. Pain. 2000; 84(2-3): 247-252.

Mercadante S, Radbruch L, Caraceni A, et al.: Episodic (breakthrough) pain: Consensus conference of an expert working group of the European Association for Palliative Care. Cancer. 2002; 94(3): 832-839.

Hwang SS, Chang VT, Kasimis B: Cancer breakthrough pain characteristics and responses to treatment at a VA medical center. Pain. 2003; 101(1-2): 55-64.

Bennett D, Burton AW, Fishman S, et al.: Consensus panel recommendations for the assessment and management of breakthrough pain, Part 2: Management. P&T. 2005; 30(6): 354-361.

Vissers D, Stam W, Nolte T, et al.: Efficacy of intranasal fentanyl spray versus other opioids for breakthrough pain in cancer. Curr Med Res Opin. 2010; 26(5): 1037-1045.

Darwish M, Kirby M, Robertson P Jr, et al.: Absolute and relative bioavailability of fentanyl buccal tablet and oral transmucosal fentanyl citrate. J Clin Pharmacol. 2007; 47(3): 343-350.

Darwish M, Kirby M, Robertson P Jr, et al.: Single-dose and steady-state pharmacokinetics of fentanyl buccal tablet in healthy volunteers. J Clin Pharmacol. 2007; 47(1): 56-63.

Durfee S, Messina J, Khankari R: Fentanyl effervescent buccal tablets: Enhanced buccal absorption. Am J Drug Deliv. 2006; 4(1): 1-5.

Simpson DM, Messina J, Xie F, et al.: Fentanyl buccal tablet for the relief of breakthrough pain in opioid-tolerant adult patients with chronic neuropathic pain: A multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2007; 29(4): 588-601.

Slatkin NE, Xie F, Messina J, et al.: Fentanyl buccal tablet for relief of breakthrough pain in opioid-tolerant patients with cancer-related chronic pain. J Support Oncol. 2007; 5(7): 327-334.

Portenoy RK, Taylor D, Messina J, et al.: A randomized, placebo-controlled study of fentanyl buccal tablet for breakthrough pain in opioid-treated patients with cancer. Clin J Pain. 2006; 22(9): 805-811.

Portenoy RK, Messina J, Xie F, et al.: Fentanyl buccal tablet (FBT) for relief of breakthrough pain in opioid-treated patients with chronic low back pain: A randomized, placebo-controlled study. Curr Med Res Opin. 2007; 23(1): 223-233.

International Conference on Harmonisation Working Group: ICH harmonised tripartite guideline: Guideline for good clinical practice E6 (R1). Paper presented at the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Washington, DC, June 10, 1996.

Beck AT, Ward CH, Mendelson M, et al.: An inventory for measuring depression. Arch Gen Psychiatry. 1961; 4: 561-571.

Kerns RD, Turk DC, Rudy TE: The West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Pain. 1985; 23(4): 345-356.

Crombez G, Vlaeyen JW, Heuts PH, et al.: Pain-related fear is more disabling than pain itself: Evidence on the role of painrelated fear in chronic back pain disability. Pain. 1999; 80(1-2): 329-339.

McCracken LM, Gross RT: The role of pain-related anxiety reduction in the outcome of multidisciplinary treatment for chronic low back pain: Preliminary results. J Occup Rehabil. 1998; 8(3): 179-189.

Spertus IL, Burns J, Glenn B, et al.: Gender differences in associations between trauma history and adjustment among chronic pain patients. Pain. 1999; 82(1): 97-102.

Wasan AD, Davar G, Jamison R: The association between negative affect and opioid analgesia in patients with discogenic low back pain. Pain. 2005; 117(3): 450-461.

Zvolensky MJ, Goodie JL, McNeil DW, et al.: Anxiety sensitivity in the prediction of pain-related fear and anxiety in a heterogeneous chronic pain population. Behav Res Ther. 2001; 39(6): 683-696.

Cleeland CS, Ryan KM: Pain assessment: Global use of the Brief Pain Inventory. Ann Acad Med Singapore. 1994; 23(2): 129-138.

Keller S, Bann CM, Dodd SL, et al.: Validity of the Brief Pain Inventory for use in documenting the outcomes of patients with noncancer pain. Clin J Pain. 2004; 20(5): 309-318.

Fine PG, Messina J, Xie F, et al.: Long-term safety and tolerability of fentanyl buccal tablet for the treatment of breakthrough pain in opioid-tolerant patients with chronic pain: An 18-month study. J Pain Symptom Manage. 2010; 40(5): 747-760.



How to Cite

Webster, MD, L. R., J. Messina, PharmD, F. Xie, PhD, and S. Nalamachu, MD. “Effect of Fentanyl Buccal Tablet on Pain-Related Anxiety: A 4-Week Open-Label Study Among Opioid-Tolerant Patients With Chronic and Breakthrough Pain”. Journal of Opioid Management, vol. 7, no. 4, Jan. 2018, pp. 297-08, doi:10.5055/10.5055/jom.2011.0071.