Alternative Therapies

Here is an overview of some alternatives to ketamine therapy for major mental illness categories, with cited sources:


  • SSRIs like fluoxetine, sertraline, citalopram [1]
  • SNRIs like duloxetine, venlafaxine, desvenlafaxine [2]
  • TCAs like amitriptyline, nortriptyline, imipramine [3]
  • MAOIs like phenelzine, tranylcypromine, isocarboxazid [4]
  • Stimulants like modafinil, armodafinil, methylphenidate [5]
  • Esketamine (ketamine enantiomer) [6]


  • SSRIs like sertraline, paroxetine, fluoxetine [7]
  • SNRIs like venlafaxine, duloxetine [8]
  • Prazosin, propranolol for hyperarousal symptoms [9]
  • MDMA-assisted psychotherapy [10]

Bipolar Disorder:

  • Lithium, anticonvulsants for mood stabilization [11]
  • Antipsychotics like olanzapine, risperidone, quetiapine [12]
  • Pharmaceutical stimulants [13]
  • Electroconvulsive therapy for severe mania/depression [14]

Anxiety Disorders:

  • SSRIs like escitalopram, paroxetine, sertraline [15]
  • SNRIs like venlafaxine, duloxetine [16]
  • Benzodiazepines like clonazepam, lorazepam, alprazolam [17]
  • Buspirone, hydroxyzine, beta blockers [18]


  • SSRIs like fluoxetine, fluvoxamine, sertraline [19]
  • SNRIs like venlafaxine [20]
  • TCAs like clomipramine [21]
  • Behavior therapy like CBT with exposure [22]


[1] Parikh SV, Quilty LC, Ravitz P, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 2. Psychological treatments. Can J Psychiatry. 2016;61(9):524-539. doi:10.1177/0706743716659418

[2] Kennedy SH, Lam RW, McIntyre RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Can J Psychiatry. 2016;61(9):540-560. doi:10.1177/0706743716659417

[3] Anderson IM. Meta-analytical studies on new antidepressants. Br Med Bull. 2001;57:161-78. doi: 10.1093/bmb/57.1.161.

[4] Krishnan KR. Revisiting monoamine oxidase inhibitors. J Clin Psychiatry. 2007;68 Suppl 8:35-41.

[5] Delgado PL. Depression: the case for a monoamine deficiency. J Clin Psychiatry. 2000;61 Suppl 6:7-11.

[6] Popova V, Daly EJ, Trivedi M, et al. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry. 2019;176(6):428-438. doi:10.1176/appi.ajp.2019.19020172

[7] VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. (2017).

[8] Jonas DE, Cusack K, Forneris CA, et al. Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder (PTSD). Comparative Effectiveness Review No. 92. (AHRQ Publication No. 13-EHC011-EF). Rockville, MD: Agency for Healthcare Research and Quality; April 2013.

[9] Taylor FB, Lowe K, Thompson C, et al. Daytime prazosin reduces psychological distress to trauma specific cues in civilian trauma posttraumatic stress disorder. Biol Psychiatry. 2006;59(7):577-581. doi:10.1016/j.biopsych.2005.07.012

[10] Feduccia AA, Mithoefer MC. MDMA-assisted psychotherapy for PTSD: are memory reconsolidation and fear extinction underlying mechanisms? Prog Neuropsychopharmacol Biol Psychiatry. 2018;84(Pt A):221-228. doi:10.1016/j.pnpbp.2018.03.003

[11] Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97-170. doi:10.1111/bdi.12609

[12] Cipriani A, Barbui C, Salanti G, et al. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet. 2011;378(9799):1306-1315. doi:10.1016/S0140-6736(11)60873-8

[13] Swartz HA, Thase ME. Pharmacotherapy for the treatment of acute bipolar II depression: current evidence. The Journal of clinical psychiatry. 2011;72(3):356-366. doi:10.4088/JCP.09r05192gre

[14] Lisanby SH. Electroconvulsive therapy for depression. N Engl J Med. 2007;357(19):1939-1945. doi:10.1056/NEJMct075234

[15] Bandelow B, Reitt M, Röver C, Michaelis S, Görlich Y, Wedekind D. Efficacy of treatments for anxiety disorders: a meta-analysis. Int Clin Psychopharmacol. 2015;30(4):183-192. doi:10.1097/YIC.0000000000000078

[16] Hackett D, Krystal JH, Yamamoto BK. Ketamine as a Prototype Glutamatergic Antidepressant: Pharmacodynamic Actions, and Toward Enhancing Clinical Utility. Clin Pharmacol Ther. 2019;105(2):284-297. doi:10.1002/cpt.1275

[17] Cloos JM, Ferreira V. Current use of benzodiazepines in anxiety disorders. Curr Opin Psychiatry. 2009;22(1):90-95. doi:10.1097/YCO.0b013e32831a473d

[18] Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2005;19(6):567-596. doi:10.1177/0269881105059253

[19] Skapinakis P, Caldwell D, Hollingworth W, et al. A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive-compulsive disorder in children/adolescents and adults. Health Technol Assess. 2016;20(43):1-392. doi:10.3310/hta20430

[20] March JS, Biederman J, Wolkow R, et al. Sertraline in children and adolescents with obsessive-compulsive disorder: a multicenter randomized controlled trial. JAMA. 1998;280(20):1752-1756. doi:10.1001/jama.280.20.1752

[21] Fineberg NA, Reghunandanan S, Kolli S, Atmaca M. Obsessive compulsive (anankastic) personality disorder: toward the ICD-11 classification. Rev Bras Psiquiatr. 2014;36 Suppl 1(Suppl 1):40-50. doi:10.1590/1516-4446-2013-1248

[22] Rosa-Alcázar AI, Sánchez-Meca J, Gómez-Conesa A, Marín-Martínez F. Psychological treatment of obsessive-compulsive disorder: a meta-analysis. Clin Psychol Rev. 2008;28(8):1310-1325. doi:10.1016/j.cpr.2008.07.001

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