Evaluating Strategies for Combining Pharmacotherapy with Cognitive Behavioral Therapy

Part of the Current Clinical Psychiatry book series (CCPSY)


This chapter provides an overview of the rationale for combining cognitive-behavioral therapies and pharmacologic treatments. Relevant research literature is presented across a range of disorders including anxiety and related disorders, mood disorders, eating disorders, schizophrenia, and substance use disorders. In addition, practical considerations are discussed related to how the combination approach may be utilized and applied in clinical practice including a case example to highlight how a combination approach may be completed successfully in a clinical setting. Finally, novel treatment approaches are discussed as a means of highlighting future directions for the use of combined treatments.


Cognitive-behavioral therapy Pharmacologic treatments Combined treatment approaches Novel treatment approaches d-cycloserine 


  1. 1.
    Forand NR, DeRubeis RJ, Amsterdam JD. Combining medication and psychotherapy in the treatment of major mental disorders. In: Lambert MJ, editor. Bergin and Garfield’s handbook of psychotherapy and behavior change. 6th ed. Hoboken, NJ: Wiley; 2013. p. 735–74.Google Scholar
  2. 2.
    Otto MW, Smits JAJ, Reese HE. Combined psychotherapy and pharmacotherapy for mood and anxiety disorders in adults: review and analysis. Clin Psychol Sci Pract. 2005;12(1):72–86.CrossRefGoogle Scholar
  3. 3.
    Canton J, Scott KM, Glue P. Optimal treatment of social phobia: systematic review and meta-analysis. Neuropsychiatr Dis Treat. 2012;8:203–15.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Davidson JRT, Foa EB, Huppert JD, Keefe F, Franklin M, Compton J, Zhao N, Connor K, Lynch TR, Kishore G. Fluoxetine, comprehensive cognitive behavioral therapy, and placebo in generalized social phobia. Arch Gen Psychiatry. 2004;61:1005–13.CrossRefPubMedGoogle Scholar
  5. 5.
    Haug TT, Blomhoff S, Hellstrøm K, Holme I, Humble M, Madsbu HP, Wold JE. Exposure therapy and sertraline in social phobia: 1-year follow-up of a randomised controlled trial. Br J Psychiatry. 2003;182:312–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Foa EB, Franklin ME, Moser J. Context in the clinic: how well do cognitive-behavioral therapies and medications work in combination? Biol Psychiatry. 2002;52(10):987–97.CrossRefPubMedGoogle Scholar
  7. 7.
    Furukawa TA, Watanabe N, Churchill R. Psychotherapy plus antidepressant for panic disorder with or without agoraphobia: systematic review. Br J Psychiatry. 2006;188:305–12.CrossRefPubMedGoogle Scholar
  8. 8.
    Otto MW, McHugh RK, Simon NM, Farach FJ, Worthington JJ, Pollack MH. Efficacy of CBT for benzodiazepine discontinuation in patients with panic disorder: further evaluation. Behav Res Ther. 2010;59:831–8.Google Scholar
  9. 9.
    Otto MW, Tolin DF, Simon NM, Pearlson GD, Basden S, Meunier SA, et al. The efficacy of d-cycloserine for enhancing response to cognitive behavior therapy for panic disorder. Biol Psychiatry. 2010;67:365–70.CrossRefPubMedGoogle Scholar
  10. 10.
    Simon NM, Otto MW, Worthington JJ, Hoge EA, Thompson EH, Lebeau RT, Moshier SJ, Zalta AK, Pollack MH. Next-step strategies for panic disorder refractory to initial pharmacotherapy: a 3-phase randomized clinical trial. J Clin Psychiatry. 2009;70:1563–70.PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Power KG, Simpson RJ, Swanson V, Wallace LA. A controlled comparison of cognitive-behaviour therapy, diazepam, and placebo, alone and in combination, for the treatment of generalised anxiety disorder. J Anxiety Disord. 1990;4(4):267–92.CrossRefGoogle Scholar
  12. 12.
    Crits-Christoph P, Newman MG, Rickels K, Gallop R, Gibbons MB, Hamilton JL, Ring-Kurtz S, Pastva AM. Combined medication and cognitive therapy for generalized anxiety disorder. J Anxiety Disord. 2011;25:1087–94.PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Schneier FR, Neria Y, Pavlicova M, Hembree E, Suh EJ, Amsel L, Marshall RD. Combined prolonged exposure therapy and paroxetine for PTSD related to the World Trade Center attack: a randomized controlled trial. Am J Psychiatry. 2012;169(1):80–8.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Rothbaum BO, Cahill SP, Foa EB, Davidson JR, Compton J, Connor KM, Astin MC, Hahn CG. Augmentation of sertraline with prolonged exposure in the treatment of posttraumatic stress disorder. J Traumatic Stress. 2006;19:625–38.Google Scholar
  15. 15.
    Simon NM, Connor KM, Lang AJ, Rauch S, Krulewicz S, LeBeau RT, Pollack MH. Paroxetine CR augmentation for posttraumatic stress disorder refractory to prolonged exposure therapy. J Clin Psychiatry. 2008;69(3):400–5.CrossRefPubMedGoogle Scholar
  16. 16.
    van Minnen A, Arntz A, Keijsers GP. Prolonged exposure in patients with chronic PTSD: predictors of treatment outcome and dropout. Behav Res Ther. 2002;40(4):439–57.CrossRefPubMedGoogle Scholar
  17. 17.
    Department of Veterans Affairs, Department of Defense. VA/DoD clinical practice guideline for management of post-traumatic stress disorder. 2010.Google Scholar
  18. 18.
    Rodrigues H, Figueira I, Gonçalves R, Mendlowicz M, Macedo T, Ventura P. CBT for pharmacotherapy non-remitters – a systematic review of a next-step strategy. J Affect Disord. 2011;129(1–3):219–28.CrossRefPubMedGoogle Scholar
  19. 19.
    Keller MB, McCullough JP, Klein DN, Arnow B, Dunner DL, Gelenberg AJ, Zajecka J. A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med. 2000;342(20):1462–70.CrossRefPubMedGoogle Scholar
  20. 20.
    Manber R, Kraemer HC, Arnow BA, Trivedi MH, Rush AJ, Thase ME, Keller MB. Faster remission of chronic depression with combined psychotherapy and medication than with each therapy alone. J Consult Clin Psychol. 2008;76(3):459–67.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Fava GA, Grandi S, Zielezny M, Canestrari R, Morphy MA. Cognitive behavioral treatment of residual symptoms in primary major depressive disorder. Am J Psychiatry. 1994;151(9):1295–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Thase ME, Friedman ES, Biggs MM, Wisniewski SR, Trivedi MH, Rush JA. Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. Am J Psychiatry. 2007;164(5):739–52.CrossRefPubMedGoogle Scholar
  23. 23.
    National Institute for Health and Care Excellence. The management of bipolar disorder in adults, children and adolescents, in primary and secondary care. Clinical guideline 38. London, UK: National Institute for Health and Care Excellence; 2006.
  24. 24.
    Miklowitz DJ, Otto MW. Psychosocial interventions for bipolar disorder: a review of literature and introduction of the systematic treatment enhancement program. Psychopharmacol Bull. 2007;40(4):116–31.PubMedGoogle Scholar
  25. 25.
    Scott J, Garland A, Moorhead S. A pilot study of cognitive therapy in bipolar disorders. Psychol Med. 2001;31(3):459–67.PubMedGoogle Scholar
  26. 26.
    Ball JR, Mitchell PB, Corry JC, Skillecorn A, Smith M, Malhi GS. A randomized controlled trial of cognitive therapy for bipolar disorder: focus on long-term change. J Clin Psychiatry. 2006;67(2):277–86.CrossRefPubMedGoogle Scholar
  27. 27.
    Scott J, Paykel E, Morriss R, Bentall R, Kinderman P, Johnson T, Hayhurst H. Cognitive-behavioural therapy for severe and recurrent bipolar disorders: randomised controlled trial. Br J Psychiatry. 2006;188:313–20.CrossRefPubMedGoogle Scholar
  28. 28.
    National Institute for Health and Care Excellence. Core interventions in the treatment and management of schizophrenia in primary and secondary care (update). Clinical guideline 82. London, UK: National Institute for Health and Care Excellence; 2009.
  29. 29.
    Schizophrenia Patient Outcomes Research Team. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophr Bull. 2010;36(1):94–103.CrossRefGoogle Scholar
  30. 30.
    Wykes T, Steel C, Everitt B, Tarrier N. Cognitive behavior therapy for schizophrenia: effect sizes, clinical models, and methodological rigor. Schizophr Bull. 2008;34(3):523–37.PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Tarrier N, Wittkowski A, Kinney C, McCarthy E, Morris J, Humphreys L. Durability of the effects of cognitive-behavioural therapy in the treatment of chronic schizophrenia: 12-month follow-up. Br J Psychiatry. 1999;174:500–4.CrossRefPubMedGoogle Scholar
  32. 32.
    Sensky T, Turkington D, Kingdon D, Scott JL, Scott J, Siddle R, Barnes TR. A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication. Arch Gen Psychiatry. 2000;57(2):165–72.CrossRefPubMedGoogle Scholar
  33. 33.
    Bacaltchuk J, Hay P, Trefiglio R. Antidepressants versus psychological treatments and their combination for bulimia nervosa. Cochrane Database Syst Rev. 2001;2001(4), CD003391.Google Scholar
  34. 34.
    Whittal ML, Agras WS, Gould RA. Bulimia nervosa: a meta-analysis of psychosocial and pharmacological treatments. Behav Ther. 1999;30:117–35.CrossRefGoogle Scholar
  35. 35.
    Agras WS, Rossiter EM, Arnow B, Schneider JA, Telch CF, Raeburn SD, Koran LM. Pharmacologic and cognitive-behavioral treatment for bulimia nervosa: a controlled comparison. Am J Psychiatry. 1992;149:82–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Vocks S, Tuschen-Caffier B, Pietrowsky R, Rustenbach SJ, Kerstig A, Herpertz S. Meta-analysis of the effectiveness of psychological and pharmacological treatments for binge eating disorder. Int J Eat Disord. 2010;43(3):205–17.PubMedGoogle Scholar
  37. 37.
    Grilo CM, Masheb RM, Wilson GT. Efficacy of cognitive behavioral therapy and fluoxetine for the treatment of binge eating disorder: a randomized double-blind placebo-controlled comparison. Biol Psychiatry. 2005;57:301–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Halmi KA, Agras WS, Crow S, Mitchell J, Wilson GT, Bryson SW, Kraemer HC. Predictors of treatment acceptance and completion in anorexia nervosa: implications for future study designs. Arch Gen Psychiatry. 2005;62(7):776–81.CrossRefPubMedGoogle Scholar
  39. 39.
    Magill M, Ray LA. Cognitive-behavioral treatment with adult alcohol and illicit drug users: a meta-analysis of randomized controlled trials. J Stud Alcohol Drugs. 2009;70(4):516–27.PubMedCentralCrossRefPubMedGoogle Scholar
  40. 40.
    Agosti V, Nunes EV, O’Shea D. Do manualized psychosocial interventions help reduce relapse among alcohol-dependent adults treated with naltrexone or placebo? A meta-analysis. Am J Addict. 2012;21(6):501–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Lam DH, Bright J, Jones S, Hayward P, Schuck N, Chisholm D, et al. Cognitive therapy for bipolar disorder: a pilot study of relapse prevention. Cognit Ther Res. 2000;24:503–20.CrossRefGoogle Scholar
  42. 42.
    Lam DH, Watkins ER, Hayward P, Bright J, Wright K, Kerr N, et al. A randomized controlled study of cognitive therapy for relapse prevention for bipolar affective disorder. Arch Gen Psychiatry. 2003;60:145–52.CrossRefPubMedGoogle Scholar
  43. 43.
    Barker MJ, Greenwood KM, Jackson M, Crowe SF. Cognitive effects of long-term benzodiazepine use: a meta-analysis. CNS Drugs. 2004;18:37–48.CrossRefPubMedGoogle Scholar
  44. 44.
    Ahmed M, Westra HA, Stewart SH. A self-help handout for benzodiazepine discontinuation using cognitive behavioral therapy. Cognit Behav Pract. 2008;15:317–24.CrossRefGoogle Scholar
  45. 45.
    Fava GA, Grandi S, Zielezny M, Rafanelli C, Canastrari R. Four year outcome for cognitive behavioral treatment of residual symptoms in major depression. Am J Psychiatry. 1996;153:945–7.CrossRefPubMedGoogle Scholar
  46. 46.
    Fava GA, Rafanelli C, Grandi S, Canastrari R, Morphy MA. Six year outcome for cognitive behavioral treatment of residual symptoms in major depression. Am J Psychiatry. 1998;155:1443–5.CrossRefPubMedGoogle Scholar
  47. 47.
    Otto MW, et al. Discontinuation of benzodiazepine treatment: efficacy of cognitive-behavior therapy for patients with panic disorder. Am J Psychiatry. 1993;150(10):1485–90.Google Scholar
  48. 48.
    Schmidt NB, Wollaway-Bickel K, Trakowski JH, Santiago HT, Vasey M. Antidepressant discontinuation in the context of cognitive behavioral treatment for panic disorder. Behav Res Ther. 2002;40:67–73.Google Scholar
  49. 49.
    Hofmann SG, Huweler R, MacKillop J, Kantak KM. Effects of d cycloserine on craving to alcohol cues in problem drinkers: preliminary findings. Am J Drug Alcohol Abuse. 2012;38:101–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Hofmann SG, Sawyer AT, Asnaani A. D-cycloserine as an augmentation strategy for cognitive behavioral therapy for anxiety disorders: an update. Curr Pharm Des. 2012;18:5659–62.CrossRefPubMedGoogle Scholar
  51. 51.
    Hofmann SG, Smits JA, Rosenfield D, Simon N, Otto MW, Meuret AE, Marques L, Fang A, Tart C, Pollack MH. d-Cycloserine as an augmentation strategy with cognitive-behavioral therapy for social anxiety disorder. Am J Psychiatry. 2013;170:751–8.PubMedCentralCrossRefPubMedGoogle Scholar
  52. 52.
    Hofmann SG, Fang A, Gutner CA. Cognitive enhancers for the treatment of anxiety disorders. Restor Neurol Neurosci. 2013.Google Scholar
  53. 53.
    Danysz W, Parsons CG. Glycine and N-methyl-d-aspartate receptors: physiological significance and possible therapeutic applications. Pharmacol Rev. 1998;50:597–664.PubMedGoogle Scholar
  54. 54.
    Ressler KJ, Rothbaum BO, Tannenbaum L, et al. Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch Gen Psychiatry. 2004;61:1136–44.CrossRefPubMedGoogle Scholar
  55. 55.
    Smits JA, Rosenfield D, Otto MW, Marques L, Davis ML, Meuret AE, Simon NM, Pollack MH, Hofmann SG. d-cycloserine enhancement of exposure therapy for social anxiety disorder depends on the success of exposure sessions. J Psychiatr Res. 2013;47:1455–61.PubMedCentralCrossRefPubMedGoogle Scholar
  56. 56.
    Nave AM, Tolin DF, Stevens MC. Exposure therapy, d-cycloserine, and functional magnetic resonance imaging in patients with snake phobia: a randomized pilot study. J Clin Psychiatry. 2012;73:1179–86.CrossRefPubMedGoogle Scholar
  57. 57.
    Wilhelm S, Buhlmann U, Tolin DF, Meunier SA, Pearlson GD, Reese HE, et al. Augmentation of behavior therapy with d-cycloserine for obsessive compulsive disorder. Am J Psychiatry. 2008;165:335–41.CrossRefPubMedGoogle Scholar
  58. 58.
    Litz BT, Salters-Pedneault K, Steenkamp MM, Hermos JA, Bryant RA, Otto MW, et al. A randomized placebo-controlled trial of D-cycloserine and exposure therapy for posttraumatic stress disorder. J Psychiatr Res. 2012;46:1184–90.CrossRefPubMedGoogle Scholar
  59. 59.
    Guastella AJ, Richardson R, Lovibond PF, Rapee RM, Gaston JE, Mitchell P, Dadds MR. A randomized controlled trial of d-cycloserine enhancement of exposure therapy for social anxiety disorder. Biol Psychiatry. 2008;63:544–9.CrossRefPubMedGoogle Scholar
  60. 60.
    Heresco-Levy U, Kremer I, Javitt DC, et al. Pilot-controlled trial of D cycloserine for the treatment of post-traumatic stress disorder. Int J Neuropsychopharmacol. 2002;5:301–7.Google Scholar
  61. 61.
    Gottlieb JD, Cather C, Shanahan M, Creedon T, Macklin EA, Goff DC. D-cycloserine facilitation of cognitive behavioral therapy for delusions in schizophrenia. Schizophr Res. 2011;131:69–74.Google Scholar
  62. 62.
    Kennedy AP, Gross RE, Whitfield N, Drexler KPG, Kilts CD. A controlled trial of the adjunct use of d-cycloserine to facilitate cognitive behavioral therapy outcomes in a cocaine-dependent population. Addict Behav. 2012;37:900–7.Google Scholar
  63. 63.
    Siegmund A, Golfels F, Finck C, Halisch A, Rath D, Plag J, et al. D closerine does not improve but might slightly speed up the outcome of in-vivo exposure therapy in patients with severe agoraphobia and panic disorder in a randomized double blind clinical trial. J Psychiatr Res. 2011;45:1042–7.CrossRefPubMedGoogle Scholar

Additional Resources

  1. 64.
    Anxiety and Depression Association of America. Treatment
  2. 65.
    Association for Behavioral and Cognitive Therapies. Treatment options, CBT or medication?
  3. 66.
    Otto MW, Simon NM, Olatunji BO, Sung SC, Pollack MH. 10-Minute CBT: integrating cognitive-behavioral strategies into your practice. Oxford: Oxford University Press; 2011.Google Scholar
  4. 67.
    National Institute of Mental Health Psychotherapies.
  5. 68.
    Sudak SM. Combining CBT and medication: an evidence-based approach. Hoboken, NJ: Wiley; 2011.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of PsychiatryMassachusetts General HospitalBostonUSA
  2. 2.Harvard Medical SchoolBostonUSA
  3. 3.Department of PsychiatryMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  4. 4.Harvard Medical School, Anxiety Disorders Center/Center for CBTInstitute of LivingHartfordUSA

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