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Current Treatment Options in Psychiatry

, Volume 6, Issue 2, pp 132–142 | Cite as

Augmenting Treatment for Posttraumatic Stress Disorder and Co-Occurring Conditions with Oxytocin

  • Julianne C. FlanaganEmail author
  • Jennifer M. Mitchell
PTSD (S Creech and L Sippel, Section Editors)
  • 17 Downloads
Part of the following topical collections:
  1. Topical Collection on PTSD

Abstract

Purpose of Review

The goal of this manuscript is to review the extant literature examining the neurobiological and behavioral mechanisms underlying the potential utility of intranasal oxytocin as a novel pharmacologic intervention for the treatment of posttraumatic stress disorder (PTSD) and for the treatment of comorbid PTSD and alcohol and substance use disorders.

Recent Findings

Research indicates that intranasal oxytocin is a low-cost and easily accessible medication with an excellent safety profile. Oxytocin holds promise for facilitating more effective PTSD treatment, particularly when used in combination with evidence-supported psychotherapy interventions. There is still a significant need to identify the mechanisms of action underlying oxytocin treatment of PTSD and to maximize methods of nasal spray delivery, examine dose-response outcomes, and clarify the characteristics of individuals and populations that are most likely to benefit from adjunctive oxytocin treatment.

Summary

Collectively, preclinical and human laboratory research suggest that oxytocin may be an effective mechanism by which treatment outcomes for PTSD and common comorbidities can be enhanced. Adequately powered randomized controlled trials are needed to address efficacy, identify predictors of treatment outcome, and to assess the use of intranasal oxytocin within appropriate PTSD populations.

Keywords

Oxytocin Posttraumatic stress Comorbidity Treatment Medication-enhanced psychotherapy 

Notes

Compliance with Ethical Standards

Conflict of Interest

Julianne C. Flanagan declares that she has no conflict of interest. Jennifer M. Mitchell declares that she has no conflict of interest

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012;21:169–84.Google Scholar
  2. 2.
    Tanielian T, Haycox LH, Schell TL, Marshall GN, Burnam MA, Eibner C, et al. Invisible wounds of war. Summary and recommendations for addressing psychological and cognitive injuries. DTIC Document; 2008.Google Scholar
  3. 3.
    Pietrzak RH, Goldstein RB, Southwick SM, Grant BF. Prevalence and axis I comorbidity of full and partial posttraumatic stress disorder in the United States: results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. J Anxiety Disord. 2011;25(3):456–65.Google Scholar
  4. 4.
    Petrakis IL, Rosenheck R, Desai R. Substance use comorbidity among veterans with posttraumatic stress disorder and other psychiatric illness. Am J Addict. 2011;20(3):185–9.Google Scholar
  5. 5.
    Kilmer B, Eibner C, Ringel JS, Pacula RL. Invisible wounds, visible savings? Using microsimulation to estimate the costs and savings associated with providing evidence-based treatment for PTSD and depression to veterans of Operation Enduring Freedom and Operation Iraqi Freedom. Psychol Trauma Theory Res Pract Policy. 2011;3(2):201–11.Google Scholar
  6. 6.
    Kehle-Forbes SM, Meis LA, Spoont MR, Polusny MA. Treatment initiation and dropout from prolonged exposure and cognitive processing therapy in a VA outpatient clinic. Psychol Trauma Theory Res Pract Policy. 2016;8(1):107–14.Google Scholar
  7. 7.
    Hembree EA, Foa EB, Dorfan NM, Street GP, Kowalski J, Tu X. Do patients drop out prematurely from exposure therapy for PTSD? J Trauma Stress. 2003;16(6):555–62.Google Scholar
  8. 8.
    Bradley R, Greene J, Russ E, Dutra L, Westen D. A multidimensional meta-analysis of psychotherapy for PTSD. Am J Psychiatr. 2005;162:214–27.Google Scholar
  9. 9.
    Bisson JI, Roberts NP, Andrew M, Cooper R, Lewis C. Psychological therapies for chronic post-traumatic stress disorder (PTSD) in adults. Cochrane Libr. 2013.Google Scholar
  10. 10.
    Schnurr PP, Lunney CA. Residual symptoms following prolonged exposure and present-centered therapy for PTSD in female veterans and soldiers. Depress Anxiety. 2019;36(2):162–9.Google Scholar
  11. 11.
    Larsen SE, Fleming CJ, Resick PA. Residual symptoms following empirically supported treatment for PTSD. Psychol Trauma Theory Res Pract Policy. 2019;11(2):207.Google Scholar
  12. 12.
    Krystal JH, Davis LL, Neylan TC, Raskind MA, Schnurr PP, Stein MB, et al. It is time to address the crisis in the pharmacotherapy of posttraumatic stress disorder: a consensus statement of the PTSD Psychopharmacology Working Group. Biol Psychiatry. 2017;82(7):e51–e9.Google Scholar
  13. 13.
    Olff M, Langeland W, Witteveen A, Denys D. A psychobiological rationale for oxytocin in the treatment of posttraumatic stress disorder. CNS Spectr. 2010;15(8):522–30.Google Scholar
  14. 14.
    Eskandarian S, Vafaei AA, Vaezi GH, Taherian F, Kashefi A, Rashidy-Pour A. Effects of systemic administration of oxytocin on contextual fear extinction in a rat model of post-traumatic stress disorder. Basic Clin Neurosci. 2013;4(4):315.Google Scholar
  15. 15.
    Missig G, Ayers LW, Schulkin J, Rosen JB. Oxytocin reduces background anxiety in a fear-potentiated startle paradigm. Neuropsychopharmacology. 2010;35(13):2607–16.Google Scholar
  16. 16.
    MacDonald K, MacDonald TM. The peptide that binds: a systematic review of oxytocin and its prosocial effects in humans. Harv Rev Psychiatry. 2010;18(1):1–21.Google Scholar
  17. 17.
    Acheson D, Feifel D, de Wilde S, Mckinney R, Lohr J, Risbrough V. The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample. Psychopharmacology. 2013;229(1):199–208.Google Scholar
  18. 18.
    Koch S, van Zuiden M, Nawijn L, Frijling JL, Veltman DJ, Olff M. Intranasal oxytocin as strategy for medication-enhanced psychotherapy of PTSD: salience processing and fear inhibition processes. Psychoneuroendocrinology. 2014;40:242–56.Google Scholar
  19. 19.
    Lancaster CL, Teeters JB, Gros DF, Back SE. Posttraumatic stress disorder: overview of evidence-based assessment and treatment. J Clin Med. 2016;5:11.Google Scholar
  20. 20.
    The Management of Posttraumatic Stress Disorder Work Group. VA/DoD clinical practice guideline for the management of posttraumatic stress disorder and acute stress disorder. Washington, D.C.; 2017.Google Scholar
  21. 21.
    Resick PA, Monson CM, Chard KM. Cognitive processing therapy for PTSD: a comprehensive manual: Guilford Publications; 2016.Google Scholar
  22. 22.
    Shapiro F. Eye movement desensitization and reprocessing: basic principles, protocols, and procedures. New York: Guilford Press; 1995.Google Scholar
  23. 23.
    Davidson JT, Rothbaum BO, van der Kolk BA, Sikes CR, Farfel GM. Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Arch Gen Psychiatry. 2001;58(5):485–92.Google Scholar
  24. 24.
    Stein DJ, Ipser J, McAnda N. Pharmacotherapy of posttraumatic stress disorder: a review of meta-analyses and treatment guidelines. CNS Spectr. 2009;14(1):25–31.Google Scholar
  25. 25.
    Friedman MJ, Marmar CR, Baker DG, Sikes CR, Farfel GM. Randomized, double-blind comparison of sertraline and placebo for posttraumatic stress disorder in a Department of Veterans Affairs setting. J Clin Psychiatry. 2007;68:711–20.Google Scholar
  26. 26.
    Hetrick SE, Purcell R, Garner B, Parslow R. Combined pharmacotherapy and psychological therapies for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev 2010;7(7).Google Scholar
  27. 27.
    Rauch SA, Kim HM, Powell C, Tuerk PW, Simon NM, Acierno R, et al. Efficacy of prolonged exposure therapy, sertraline hydrochloride, and their combination among combat veterans with posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry 2018.Google Scholar
  28. 28.
    Raskind MA, Peskind ER, Chow B, Harris C, Davis-Karim A, Holmes HA, et al. Trial of prazosin for post-traumatic stress disorder in military veterans. N Engl J Med. 2018;378(6):507–17.Google Scholar
  29. 29.
    Raskind MA, Peskind ER, Hoff DJ, Hart KL, Holmes HA, Warren D, et al. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry. 2007;61(8):928–34.Google Scholar
  30. 30.
    Simpson TL, Malte CA, Dietel B, Tell D, Pocock I, Lyons R, et al. A pilot trial of prazosin, an alpha-1 adrenergic antagonist, for comorbid alcohol dependence and posttraumatic stress disorder. Alcohol Clin Exp Res. 2015;39(5):808–17.Google Scholar
  31. 31.
    Germain A, Richardson R, Moul DE. Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US military veterans. J Psychosom Res. 2012;72:89–96.Google Scholar
  32. 32.
    Raskind MA, Peterson K, Williams T, Hoff DJ, Hart KL, Holmes HA, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatr. 2013;170(9):1003–10.Google Scholar
  33. 33.
    Kida S. Reconsolidation/destabilization, extinction and forgetting of fear memory as therapeutic targets for PTSD. Psychopharmacology. 2018;236(1):49–57.Google Scholar
  34. 34.
    Maples-Keller JL, Jovanovic T, Dunlop BW, Rauch SA, Yasinski C, Michopoulos V, et al. When translational neuroscience fails in the clinic: dexamethasone prior to virtual reality exposure therapy increases drop-out rates. J Anxiety Disord. 2019;61:89–97.Google Scholar
  35. 35.
    Bentz D, Michael T, Dominique J, Wilhelm FH. Enhancing exposure therapy for anxiety disorders with glucocorticoids: from basic mechanisms of emotional learning to clinical applications. J Anxiety Disord. 2010;24(2):223–30.Google Scholar
  36. 36.
    Otto MW, McHugh RK, Kantak KM. Combined pharmacotherapy and cognitive-behavioral therapy for anxiety disorders: medication effects, glucocorticoids, and attenuated treatment outcomes. Clin Psychol Sci Pract. 2010;17(2):91–103.Google Scholar
  37. 37.
    Yehuda R, Bierer LM, Pratchett LC, Lehrner A, Koch EC, Van Manen JA, et al. Cortisol augmentation of a psychological treatment for warfighters with posttraumatic stress disorder: randomized trial showing improved treatment retention and outcome. Psychoneuroendocrinology. 2015;51:589–97.Google Scholar
  38. 38.
    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(9):1184–90.Google Scholar
  39. 39.
    Mithoefer MC, Mithoefer AT, Feduccia AA, Jerome L, Wagner M, Wymer J, et al. 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry. 2018;5(6):486–97.Google Scholar
  40. 40.
    Mataix-Cols D, De La Cruz LF, Monzani B, Rosenfield D, Andersson E, Pérez-Vigil A, et al. D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data. JAMA Psychiatry. 2017;74(5):501–10.Google Scholar
  41. 41.
    Tuerk PW, Wangelin BC, Powers MB, Smits J, Acierno R, Myers US, et al. Augmenting treatment efficiency in exposure therapy for PTSD: a randomized double-blind placebo-controlled trial of yohimbine HCl. Cogn Behav Ther 2018:1–21.Google Scholar
  42. 42.
    Rauch SA, Koola C, Post L, Yasinski C, Norrholm SD, Black K, et al. In session extinction and outcome in virtual reality exposure therapy for PTSD. Behav Res Ther. 2018;109:1–9.Google Scholar
  43. 43.
    • Flanagan JC, Sippel LM, Wahlquist A, Moran-Santa Maria MM, Back SE. Augmenting prolonged exposure therapy for PTSD with intranasal oxytocin: a randomized, placebo-controlled pilot trial. J Psychiatr Res. 2017;98:64–9 The first randomized controlled study to examine oxytocin combined with behavioral PTSD treatment.Google Scholar
  44. 44.
    Frijling JL, Zuiden M, Nawijn L, Koch S, Neumann ID, Veltman DJ, et al. Salivary oxytocin and vasopressin levels in police officers with and without post-traumatic stress disorder. J Neuroendocrinol. 2015;27(10):743–51.Google Scholar
  45. 45.
    Reijnen A, Geuze E, Vermetten E. Individual variation in plasma oxytocin and vasopressin levels in relation to the development of combat-related PTSD in a large military cohort. J Psychiatr Res. 2017;94:88–95.Google Scholar
  46. 46.
    Sippel LM, Han S, Watkins LE, Harpaz-Rotem I, Southwick SM, Krystal JH, et al. Oxytocin receptor gene polymorphisms, attachment, and PTSD: results from the National Health and Resilience in Veterans Study. J Psychiatr Res. 2017;94:139–47.Google Scholar
  47. 47.
    Guastella AJ, Hickie IB, McGuinness MM, Otis M, Woods EA, Disinger HM, et al. Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research. Psychoneuroendocrinology. 2013;38(5):612–25.Google Scholar
  48. 48.
    Milewski M, Goodey A, Lee DJ, Rimmer E, Saklatvala R, Koyama S, et al. Rapid absorption of dry-powder intranasal oxytocin. Pharm Res. 2016;33(8):1936–44.Google Scholar
  49. 49.
    Quintana DS, Westlye LT, Hope S, Nærland T, Elvsåshagen T, Dørum E, et al. Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial. Transl Psychiatry. 2017;7(5):e1136.Google Scholar
  50. 50.
    Olff M, Frijling JL, Kubzansky LD, Bradley B, Ellenbogen MA, Cardoso C, et al. The role of oxytocin in social bonding, stress regulation and mental health: an update on the moderating effects of context and interindividual differences. Psychoneuroendocrinology. 2013;38(9):1883–94.Google Scholar
  51. 51.
    Bartz JA, Zaki J, Bolger N, Ochsner KN. Social effects of oxytocin in humans: context and person matter. Trends Cogn Sci. 2011;15(7):301–9.Google Scholar
  52. 52.
    Mitchell JM, Arcuni PA, Weinstein D, Woolley JD. Intranasal oxytocin selectively modulates social perception, craving, and approach behavior in subjects with alcohol use disorder. J Addict Med. 2016;10(3):182–9.Google Scholar
  53. 53.
    Ebner NC, Lin T, Muradoglu M, Weir DH, Plasencia GM, Lillard TS, et al. Associations between oxytocin receptor gene (OXTR) methylation, plasma oxytocin, and attachment across adulthood. Int J Psychophysiol. 2019;136:22–32.Google Scholar
  54. 54.
    •• Shamay-Tsoory SG, Abu-Akel A. The social salience hypothesis of oxytocin. Biol Psychiatry. 2016;79(3):194–202 Excellent review consolidating and explaining inconsistent findings in clinical oxytocin research.Google Scholar
  55. 55.
    MacDonald E, Dadds MR, Brennan JL, Williams K, Levy F, Cauchi AJ. A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research. Psychoneuroendocrinology. 2011;36(8):1114–26.Google Scholar
  56. 56.
    Lerman B, Harricharran T, Ogunwobi OO. Oxytocin and cancer: an emerging link. World J Clin Oncol. 2018;9(5):74–82.Google Scholar
  57. 57.
    Xu H, Fu S, Chen Q, Gu M, Zhou J, Liu C, et al. The function of oxytocin: a potential biomarker for prostate cancer diagnosis and promoter of prostate cancer. Oncotarget. 2017;8(19):312–5.Google Scholar
  58. 58.
    Weisman O, Zagoory-Sharon O, Schneiderman I, Gordon I, Feldman R. Plasma oxytocin distributions in a large cohort of women and men and their gender-specific associations with anxiety. Psychoneuroendocrinology. 2013;38(5):694–701.Google Scholar
  59. 59.
    Loth E, Poline JB, Thyreau B, Jia T, Tao C, Lourdusamy A, et al. Oxytocin receptor genotype modulates ventral striatal activity to social cues and response to stressful life events. Biol Psychiatry 2013.Google Scholar
  60. 60.
    Eckstein M, Becker B, Scheele D, Scholz C, Preckel K, Schlaepfer TE, et al. Oxytocin facilitates the extinction of conditioned fear in humans. Biol Psychiatry. 2014;78(3):194–202.Google Scholar
  61. 61.
    Ellenbogen MA, Linnen A, Cardoso C, Joober R. Intranasal oxytocin attenuates the human acoustic startle response independent of emotional modulation. Psychophysiology. 2014;51(11):1169–77.Google Scholar
  62. 62.
    Bertsch K, Gamer M, Schmidt B, Schmidinger I, Walther S, Kästel T, et al. Oxytocin and reduction of social threat hypersensitivity in women with borderline personality disorder. Am J Psychiatr. 2013;170(10):1169–77.Google Scholar
  63. 63.
    Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature. 2005;435(7042):673–6.Google Scholar
  64. 64.
    Gibbons CJ, Nich C, Steinberg K, Roffman RA, Corvino J, Babor TF, et al. Treatment process, alliance and outcome in brief versus extended treatments for marijuana dependence. Addiction. 2010;105(10):1799–808.Google Scholar
  65. 65.
    • van Zuiden M, Frijling JL, Nawijn L, Koch S, Goslings JC, Luitse JS, et al. Intranasal oxytocin to prevent PTSD symptoms: a randomized controlled trial in emergency department patients. Biol Psychiatry. 2016;81(12):1030–40 First study to examine a repeated dosing strategy to prevent PTSD onset.Google Scholar
  66. 66.
    Dunlop B, Mansson E, Gerardi M. Pharmacological innovations for posttraumatic stress disorder and medication-enhanced psychotherapy. Curr Pharm Des. 2012;18(35):5645–58.Google Scholar
  67. 67.
    Domes G, Heinrichs M, Glascher J, Buchel C, Braus DF, Herpertz SC. Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry. 2007;62:1187–90.Google Scholar
  68. 68.
    Sripada CS, Phan KL, Labuschagne I, Welsh RC, Nathan PJ, Wood AG. Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex. Int J Neuropsychopharmacol. 2013;16(2):255–60.Google Scholar
  69. 69.
    Driessen M, Schulte S, Luedecke C, Schaefer I, Sutmann F, Ohlmeier M, et al. Trauma and PTSD in patients with alcohol, drug, or dual dependence: a multi-center study. Alcohol Clin Exp Res. 2008;32(3):481–8.Google Scholar
  70. 70.
    Mills KL, Teesson M, Ross J, Peters L. Trauma, PTSD, and substance use disorders: findings from the Australian National Survey of Mental Health and Well-Being. Am J Psychiatr. 2006;163(4):652–8.Google Scholar
  71. 71.
    Hien DA, Campbell A, Ruglass LM, Hu M, Killeen TK. The role of alcohol misuse in PTSD outcomes for women in community treatment: a secondary analysis of NIDA's Women and Trauma Study. Drug Alcohol Depend. 2010;111(1):114–9.Google Scholar
  72. 72.
    Back SE. Toward an improved model of treating co-occurring PTSD and substance use disorders. Am J Psychiatr. 2010;167(1):11–3.Google Scholar
  73. 73.
    Cohen LR, Hien DA. Treatment outcomes for women with substance abuse and PTSD who have experienced complex trauma. Psychiatr Serv. 2014;57(1):100–6.Google Scholar
  74. 74.
    Hien DA, Jiang H, Campbell ANC, Hu MC, Miele GM, Cohen LR, et al. Do treatment improvements in PTSD severity affect substance use outcomes? A secondary analysis from a randomized clinical trial in NIDA’s Clinical Trials Network. Am J Psychiatr. 2010;167(1):95.Google Scholar
  75. 75.
    Back SE, Waldrop AE, Brady KT. Treatment challenges associated with comorbid substance use and posttraumatic stress disorder: clinicians' perspectives. Am J Addict. 2009;18(1):15–20.Google Scholar
  76. 76.
    Back SE, Brady KT, Sonne SC, Verduin ML. Symptom improvement in co-occurring PTSD and alcohol dependence. J Nerv Ment Dis. 2006;194(9):690–6.Google Scholar
  77. 77.
    Back SE, Waldrop AE, Brady KT, Hien D. Evidenced-based time-limited treatment of co-occurring substance-use disorders and civilian-related posttraumatic stress disorder. Brief Treat Crisis Interv. 2006;6(4):283.Google Scholar
  78. 78.
    Najavits LM, Weiss RD, Liese BS. Group cognitive-behavioral therapy for women with PTSD and substance use disorder. J Subst Abus Treat. 1996;13(1):13–22.Google Scholar
  79. 79.
    Koob GF, Buck CL, Cohen A, Edwards S, Park PE, Schlosburg JE, et al. Addiction as a stress surfeit disorder. Neuropharmacology. 2014;76:370–82.Google Scholar
  80. 80.
    Petrakis IL, Ralevski E, Desai N, Trevisan L, Gueorguieva R, Rounsaville B, et al. Noradrenergic vs serotonergic antidepressant with or without naltrexone for veterans with PTSD and comorbid alcohol dependence. Neuropsychopharmacology. 2012;37(4):996–1004.Google Scholar
  81. 81.
    Brady KT, Sinha R. Co-occurring mental and substance use disorders: the neurobiological effects of chronic stress. Am J Psychiatr. 2005;162(8):1483–93.Google Scholar
  82. 82.
    Hien DA, Levin FR, Ruglass LM, López-Castro T, Papini S, Hu M, et al. Combining seeking safety with sertraline for PTSD and alcohol use disorders: a randomized controlled trial. J Consult Clin Psychol. 2015;83(2):359.Google Scholar
  83. 83.
    Petrakis IL, Desai N, Gueorguieva R, Arias AJ, O'Brien E, Jane JS, et al. Prazosin for veterans with posttraumatic stress disorder and comorbid alcohol dependence: a clinical trial. Alcohol Clin Exp Res. 2016;40(1):178–86.Google Scholar
  84. 84.
    Back SE, Flanagan JC, Jones JL, Augur I, Peterson AL, Young-McCaughan S, et al. Doxazosin for the treatment of co-occurring PTSD and alcohol use disorder: design and methodology of a randomized controlled trial in military veterans. Contemp Clin Trials. 2018;73:8–15.Google Scholar
  85. 85.
    Blodgett JC, Del Re AC, Maisel NC, Finney JW. A meta-analysis of topiramate's effects for individuals with alcohol use disorders. Alcohol Clin Exp Res. 2014;38(6):1481–8.Google Scholar
  86. 86.
    Johnson BA, Ait-Daoud N, Wang X, Penberthy JK, Javors MA, Seneviratne C, et al. Topiramate for the treatment of cocaine addiction: a randomized clinical trial. JAMA Psychiatry. 2013;70(12):1338–46.Google Scholar
  87. 87.
    Watts BV, Schnurr PP, Mayo L, Young-Xu Y, Weeks WB, Friedman MJ. Meta-analysis of the efficacy of treatments for posttraumatic stress disorder. J Clin Psychiatry. 2013;74(6):1,478–550.Google Scholar
  88. 88.
    Back SE, McCauley JL, Korte KJ, Gros DF, Leavitt V, Gray KM, et al. A double-blind randomized controlled pilot trial of N-acetylcysteine in veterans with PTSD and substance use disorders. J Clin Psychiatry. 2016;77(11):e1439–e46.Google Scholar
  89. 89.
    Batki SL, Pennington DL, Lasher B, Neylan TC, Metzler T, Waldrop AE, et al. Topiramate treatment of alcohol use disorder in veterans with posttraumatic stress disorder: a randomized controlled pilot trial. Alcohol Clin Exp Res. 2014;38(8):2169–77.Google Scholar
  90. 90.
    McRae-Clark AL, Baker NL, Moran-Santa Maria M, Brady KT. Effect of oxytocin on craving and stress response in marijuana-dependent individuals: a pilot study. Psychopharmacology. 2013;228(4):1–9.Google Scholar
  91. 91.
    Carson DS, Hunt GE, Guastella AJ, Barber L, Cornish JL, Arnold JC, et al. Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus. Addict Biol. 2010;15(4):448–63.Google Scholar
  92. 92.
    Pedersen CA, Smedley KL, Leserman J, Jarskog LF, Rau SW, Kampov-Polevoi A, et al. Intranasal oxytocin blocks alcohol withdrawal in human subjects. Alcohol Clin Exp Res. 2013;37(3):484–9.Google Scholar
  93. 93.
    Peters S, Slattery DA, Flor PJ, Neumann ID, Reber SO. Differential effects of baclofen and oxytocin on the increased ethanol consumption following chronic psychosocial stress in mice. Addict Biol. 2013;18(1):66–77.Google Scholar
  94. 94.
    King CE, Griffin WC, Luderman LN, Kates MM, McGinty JF, Becker HC. Oxytocin reduces ethanol self-administration in mice. Alcohol Clin Exp Res. 2017;41(5):955–64.Google Scholar
  95. 95.
    King CE, McGinty JF, Becker HC. Effects of oxytocin on stress-induced reinstatement of alcohol-seeking in mice with and without a history of stress. Alcohol. 2017;60:231–2.Google Scholar
  96. 96.
    Flanagan JC, Hand A, Jarnecke AM, Moran-Santa Maria MM, Brady KT, Joseph J. Effects of oxytocin on working memory and executive control system connectivity in posttraumatic stress disorder. Exp Clin Psychopharmacol. 2018;26(4):391–402.Google Scholar
  97. 97.
    Sippel LM, Allington CE, Pietrzak RH, Harpaz-Rotem I, Mayes LC, Olff M. Oxytocin and stress-related disorders: neurobiological mechanisms and treatment opportunities. Chronic Stress. 2017;1:1–15.Google Scholar
  98. 98.
    • Leppanen J, Ng KW, Kim Y, Tchanturia K, Treasure J. Meta-analytic review of the effects of a single dose of intranasal oxytocin on threat processing in humans. J Affect Disord. 2018;225:167–79 Good review of methodological limitations of oxytocin literature.Google Scholar
  99. 99.
    Walum H, Waldman ID, Young LJ. Statistical and methodological considerations for the interpretation of intranasal oxytocin studies. Biol Psychiatry. 2016;79(3):251–7.Google Scholar
  100. 100.
    Leng G, Ludwig M. Intranasal oxytocin: myths and delusions. Biol Psychiatry. 2016;79(3):243–50.Google Scholar
  101. 101.
    • Kendrick KM, Guastella AJ, Becker B. Overview of human oxytocin research. Curr Top Behav Neurosci. 2017. Comprehensive review of clinical oxytocin literature in psychiatry.Google Scholar
  102. 102.
    Churchland PS, Winkielman P. Modulating social behavior with oxytocin: how does it work? What does it mean? Horm Behav. 2012;61:392–9.Google Scholar
  103. 103.
    Striepens N, Kendrick KM, Hanking V, Landgraf R, Wüllner U, Maier W, et al. Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans. Sci Rep. 2013;3:3440.Google Scholar
  104. 104.
    Quintana DS, Guastella AJ, Westlye LT, Andreassen OA. The promise and pitfalls of intranasally administering psychopharmacological agents for the treatment of psychiatric disorders. Mol Psychiatry. 2016;21(1):29.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PsychiatryMedical University of South CarolinaCharlestonUSA
  2. 2.Department of NeurologyUniversity of California San FranciscoSan FranciscoUSA
  3. 3.Department of PsychiatryUniversity of California San FranciscoSan FranciscoUSA

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