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A randomized, controlled, double-blinded clinical trial of gabapentin 300 versus 900 mg versus placebo for anxiety symptoms in breast cancer survivors

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Abstract

Gabapentin is used for the treatment of hot flashes and neuropathic pain in breast cancer survivors, and is commonly used off-label for the treatment of anxiety. Yet, clinical trial evidence to support the use of gabapentin for anxiety symptoms is lacking. In a randomized, double-blinded controlled trial we compared 300 mg gabapentin versus 900 mg gabapentin versus placebo. Subjects were 420 breast cancer patients who had completed all chemotherapy cycles. Anxiety traits and current (state) anxiety were measured using the Speilberger Strait-Trait Anxiety Inventory at baseline, 4 and 8 weeks. Pain was measured at baseline using a 10-point scale. Analyses included analysis of covariance and ordinary least squares regression. At 4 weeks, state anxiety change scores were significantly better for gabapentin 300 and 900 mg (p = 0.005) compared to placebo. The magnitude of improvement was proportional to baseline state anxiety. At 8 weeks, the anxiolytic effects of gabapentin compared to placebo persisted (p < 0.005). We found no significant interactions. The lower dose (300 mg) was associated with the best treatment outcomes for all patients except those with the highest baseline anxiety. Given its similar pharmacology, efficacy in the treatment of hot flashes, and low cost, gabapentin may provide a low cost and parsimonious alternative treatment choice for breast cancer survivors presenting in primary care practices with anxiety symptoms. Gabapentin is effective for hot flashes, and, therefore, may provide therapeutic benefit for both anxiety and hot flashes at a generic drug price. For patients reluctant to take a controlled substance, such as a benzodiazepine, gabapentin may offer an alternative therapy. Similarly, patients with a history of substance use may benefit from gabapentin without risk of addiction or abuse. For cancer survivors experiencing both hot flashes and anxiety, gabapentin may provide a single effective treatment for both and is an alternative therapy for anxiety for patients unwilling to take a benzodiazepine or those with a history of substance use.

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References

  1. Chalasani P, Downey L, Stopeck AT (2010) Caring for the breast cancer survivor: a guide for primary care physicians. Am J Med 123(6):489–495

    Article  PubMed  Google Scholar 

  2. Khatcheressian J, Wolff A, Smith T et al (2006) American Society of Clinical Oncology 2006 update of breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol 24(31):5091–5097

    Article  PubMed  Google Scholar 

  3. Lavigne JE, Griggs JJ, Tu XM, Lerner DJ. Hot flashes, fatigue, treatment exposures and work productivity in breast cancer survivors. J Cancer Surviv. 2008 Dec;2(4):296–302

  4. Hartl K, Schennach R, Muller M, Engel J, Reinecker H, Sommer H, Friese K (2010) Quality of life, anxiety, and oncological factors: a follow-up study of breast cancer patients. Psychosomatics 51:112–123

    PubMed  Google Scholar 

  5. Vahdaninia M, Omidvari S, Montazeri A (2010) What do predict anxiety and depression in breast cancer patients? A follow-up study. Soc Psychiatry Psychiatr Epidemiol 45(3):355–361

    Article  PubMed  Google Scholar 

  6. Armes J, Crowe M, Colbourne L et al (2009) Patients’ supportive care needs beyond the end of cancer treatment: a prospective, longitudinal survey. J Clin Oncol 27(36):6172–6179

    Article  PubMed  Google Scholar 

  7. Kroenke K, Spitzer RL, Williams JBW, Monahan PO, Lowe B (2007) Anxiety disorders in primary care: prevalence, impairment, comorbidity and detection. Ann Intern Med 146:317–325

    PubMed  Google Scholar 

  8. Ravindran LN, Stein MB (2010) The pharmacologic treatment of anxiety disorders: a review of progress. J Clin Psychiatry 71:7

    Article  Google Scholar 

  9. Pande AC, Feltner DE, Jefferson JW et al (2004) Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: a placebo-controlled multi-center study. J Clin Psychopharmacol 24:141–149

    Article  PubMed  CAS  Google Scholar 

  10. Montgomery SA, Tobias K, Zornberg GL et al (2006) Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine. J Clin Psychiatry 67:771–782

    Article  PubMed  CAS  Google Scholar 

  11. Scheiner FR (2006) Clinical practice: social anxiety disorder. N Engl J Med 355:1029–1036

    Article  Google Scholar 

  12. Landmark CJ (2008) Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of action and clinical efficacy. CNS Drugs 22(1):27–47

    Article  CAS  Google Scholar 

  13. Jacox A, Carr DB, Payne R, et al. (1994) Management of cancer pain. Clinical practice guideline no. 9. AHCPR publication no. 94-0592. Agency for Health Care Policy and Research, U.S. Department of Health and Human Services, Public Health Service, Rockville

  14. Keskinbora K, Pekel EF, Aydinli I (2007) Gabapentin and an opioid combination versus opioid alone for the management of neuropathic cancer pain: a randomized open trial. J Pain Symptom Manage 34:183–189

    Article  PubMed  CAS  Google Scholar 

  15. Caraceni A, Zecca E, Bonezzi C et al (2004) Gabapentin for neuropathic cancer pain: a randomized, controlled trial from the gabapentin cancer pain study group. J Clin Oncol 22:2909–2917

    Article  PubMed  CAS  Google Scholar 

  16. Caraceni A, Brunelli C, Martini C et al (2005) Cancer pain assessment in clinical trials. A review of the literature. J Pain Symptom Manage 29:507–519

    Article  PubMed  Google Scholar 

  17. Fassoulaki A, Triga A, Melemeni A et al (2005) Multimodal analgesia with gabapentin and local anesthetics prevents acute and chronic pain after breast surgery for cancer. Anesth Analg 101:1427–1432

    Article  PubMed  CAS  Google Scholar 

  18. Menigaux C, Adam F, Guignard B, Sessler DI, Chauvin M (2005) Preoperative gabapentin decreases anxiety and improves early functional recovery from knee surgery. Anesth Analg 100:1394–1399

    Article  PubMed  CAS  Google Scholar 

  19. Caraceni A, Portenoy RK (1999) A working group of the IASP task force on cancer pain. An international survey of cancer pain characteristics and syndromes. Pain 82:263–274

    Article  PubMed  CAS  Google Scholar 

  20. Pandya KJ, Morrow GR, Roscoe JA et al (2005) Gabapentin for hot flashes in 420 women with breast cancer: a randomized double-blind placebo-controlled trial. Lancet 366:818–824

    Article  PubMed  CAS  Google Scholar 

  21. Speilberger CD, Gorsuch RL, Luschene R (1970) STAI manual for the state-trait anxiety inventory. Consulting Psychologists, Palo Alto

    Google Scholar 

  22. Beaver K, Tysver-Robinson D, Campbell M, Twomey M, Williamson S, Hindley A et al (2009) Comparing hospital and telephone follow-up after treatment for breast cancer: randomized equivalence trial. BMJ 338:s3147

    Article  Google Scholar 

  23. Van den Bergh R, Essink-Bot ML, Roobol MJ et al (2009) Anxiety and distress during active surveillance for early prostate cancer. Cancer 115(17):386–3878

    Google Scholar 

  24. Den Oudsten BL, Van Heck GL, Van der Steeg AFW, Roukema JA, DeVries J (2009) The WHOQOL-100 has good psychometric properties in breast cancer patients. J Clin Epidemiol 62(2):195–205

    Article  Google Scholar 

  25. Fenlon DR, Corner JL, Haviland J (2009) Menopausal hot flushes after breast cancer. Eur J Cancer Care 18(2):14–148

    Article  Google Scholar 

  26. Cundy K, Annamalai T, Bu L, De Vera J, Estrela J, Luo W, Shirsat P, Torneros A, Yao F, Zou J, Barrett RW, Gallop MA (2004) XP13512: a novel gabapentin prodrug: II. Improved oral availability, dose proportionality, and colonic absorption compared with gabapentin in rats and monkeys. J Pharmacol Exp Ther 311:324–333

    Article  PubMed  CAS  Google Scholar 

  27. Laird B, Colvin L, Fallon M (2008) Management of cancer pain: basic principles and neuropathic cancer pain. Eur J Cancer 48:1078–1082

    Article  Google Scholar 

  28. Gabapentin. DRUGDEX® System. Thomson Healthcare. http://www.thomsonhc.com. Accessed 7 Aug 2012

  29. Vaidya R, Sood R, Karlin N, Jatoi A (2011) Benzodiazepine use in breast cancer survivors: findings from a consecutive series of 1000 patients. Oncology 81:9–11

    Article  PubMed  CAS  Google Scholar 

  30. Orriols L, Phillip P, Moore N et al (2011) Benzodiazepine-like hypnotics and the associated risk of road traffic accidents. Clin Pharmacol Ther 89(4):595–601

    Article  PubMed  CAS  Google Scholar 

  31. Cole J, Kando J (1993) Adverse behavioral events reported in patients taking alprazolam and other benzodiazepines. J Clin Psychiatry 54:49–63

    PubMed  Google Scholar 

  32. Lader M (1999) Limitations on the use of benzodiazepines in anxiety and insomnia: are they justified? Eur Neuropsychopharmacol 9:s399–s940

    Article  PubMed  CAS  Google Scholar 

  33. Baldwin D, Woods R, Lawson R (2011) Efficacy of drug treatments for generalized anxiety disorder: systemic review and meta-analysis. BMJ 342:d1199

    Article  PubMed  Google Scholar 

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Acknowledgments

The clinical trial was supported by the National Cancer Insitute. Gabpentin and placebo were provided by Pfizer. This secondary analysis was not supported by external funding.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Wegmans School of Pharmacy, St. John Fisher College, 3690 East Avenue, Rochester, NY, 14618, USA

    Jill E. Lavigne, Jennifer L. Mathews & Eric Amos

  2. Department of Radiation Oncology, James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA

    Charles Heckler, Gary R. Morrow & Karen Mustian

  3. Department of Psychiatry, Stanford University Medical School, Palo Alto, CA, USA

    Oxana Palesh

  4. Community Clinical Oncology Base, James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA

    Jeffrey J. Kirshner, Raymond Lord & Andrew Jacobs

Authors
  1. Jill E. Lavigne
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  2. Charles Heckler
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  3. Jennifer L. Mathews
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  4. Oxana Palesh
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  5. Jeffrey J. Kirshner
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  7. Andrew Jacobs
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  8. Eric Amos
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  9. Gary R. Morrow
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  10. Karen Mustian
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Correspondence to Jill E. Lavigne.

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Lavigne, J.E., Heckler, C., Mathews, J.L. et al. A randomized, controlled, double-blinded clinical trial of gabapentin 300 versus 900 mg versus placebo for anxiety symptoms in breast cancer survivors. Breast Cancer Res Treat 136, 479–486 (2012). https://doi.org/10.1007/s10549-012-2251-x

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  • DOI: https://doi.org/10.1007/s10549-012-2251-x

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