In an increasingly fast-paced world, anxiety disorders are becoming more common and have a significant impact on our quality of life, social relationships, and personal and professional development. Treatment usually combines psychological and pharmacological intervention, and learning stress management techniques as an essential part of the process.
New evidence is emerging for the use of ketamine assisted psychotherapy to treat anxiety. Standard pharmacological treatments such as SSRIs and benzodiazepines, show limited efficacy, and can produce adverse effects such as sedation and dependence (Kolovos et al., 2017). New approaches are needed to treat anxiety and anxiety related disorders, usually characterized by incessant and uncontrolled worrying. Ketamine, a medicine traditionally used as an anesthetic, is one of a range of psychedelics recently studied for easing anxiety and anxiety related disorders.
A quick review of its mechanisms
Chronic or treatment-resistant anxiety can damage glutamate receptors in the hippocampus and cause neurons in the prefrontal cortex to shrink, leading to mood and thinking problems. Drugs that block NMDA receptors can help restore hippocampal function by reducing their activity, as shown in animal studies. Ketamine, which blocks NMDA receptors on inhibitory GABA neurons, increases the release of glutamate (Trullas and Skolnick, 1990). This extra glutamate activates AMPA receptors, which boost the activity of BDNF and mTORC1—key molecules that support brain cell growth and flexibility. Recent studies have also explored how ketamine’s metabolites contribute to its antidepressant effects (Highland et al., 2021).
Ketamine for Social Anxiety
A 2018 study (Taylor et al., 2018) tested ketamine on 18 adults with social anxiety disorder (SAD). They received a low dose of ketamine through an IV (0.5 mg/kg over 40 minutes) or a placebo. The results? Ketamine lowered anxiety significantly more than placebo, based on a clinical scale (LSAS), with effects lasting up to two weeks. About 1 in 3 people saw major improvement, compared to none with placebo. Although the study is small, it shows promising results for the use of ketamine to treat SAD. It should be noted that ketamine was administered without therapeutic support, and the results would likely be better with this combination, as it would allow the profound changes in self and perception that ketamine can bring to be used to solidify and anchor possible behavioral changes that mitigate anxiety.
Helping Hard-to-Treat Anxiety
A 2022 review (Tully et al., 2022) looked at 18 studies with over 500 people who had stubborn anxiety, including generalized anxiety disorder (GAD) and SAD, often alongside depression. Ketamine, given through IV, injections, or pills, reduced anxiety within hours, with benefits lasting up to a week. For example, one study found weekly injections lowered anxiety scores for days. Ketamine works by calming overactive brain signals, but effects fade, so repeated doses are needed at first, and a psychotherapeutic integration process may help solidify the changes.
Real-World Results
A 2023 study (Tuuli et al., 2023) tracked over 2,700 patients in US clinics getting ketamine IV therapy (KIT). Of those, over 800 participants were evaluated during ongoing sessions. KIT cut anxiety and depression symptoms significantly, with many feeling better for up to a year. Impressively, 80% of patients with suicidal thoughts saw improvement, and around 50% had the suicidal thoughts completely disappear. Compared to people on standard antidepressants, KIT patients experienced a faster recovery from both depression and anxiety symptomatology.
What This Means for You
Ketamine offers fast relief for tough anxiety cases, especially when other treatments fail. It’s not a cure-all – at Clinica Synaptica we believe a good psychotherapeutic accompaniment is an essential part of this process, to help dive into the causes and consequences of the anxiety in a day to day life, and to enhance and boost change. As research keeps growing, we strive to set a golden standard of care for anyone who needs it.
Bibliography
Highland JN, Zanos P, Riggs LM, et al. Hydroxynorketamines: pharmacology and potential therapeutic applications. Pharmacol Rev. 2021;73(2):763-791.
Kolovos, S., van Tulder, M.W., Cuijpers, P., Prigent, A., Chevreul, K., Riper, H., Bosmans, J.E., 2017. The effect of treatment as usual on major depressive disorder: A meta-analysis. J. Affect. Disord. 210, 72–81. doi:10.1016/j.jad.2016.12.013
Taylor JH, Landeros-Weisenberger A, Coughlin C, Mulqueen J, Johnson JA, Gabriel D, Reed MO, Jakubovski E, Bloch MH. Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial. Neuropsychopharmacology. 2018 Jan;43(2):325-333. doi: 10.1038/npp.2017.194. Epub 2017 Aug 29. PMID: 28849779; PMCID: PMC5729569.
Trullas R, Skolnick P. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol. 1990;185(1): 1-10. doi:10.1016/0014-2999(90)90204-J
Tully JL, Dahlén AD, Haggarty CJ, Schiöth HB, Brooks S. Ketamine treatment for refractory anxiety: A systematic review. Br J Clin Pharmacol. 2022 Oct;88(10):4412-4426. doi: 10.1111/bcp.15374. Epub 2022 May 20. PMID: 35510346; PMCID: PMC9540337.
Tuuli M. Hietamies, L. Alison McInnes, Andrew J. Klise, Matthew J. Worley, Jimmy J. Qian, Leanne M. Williams, Boris D. Heifets, Steven P. Levine (2023). The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis, Journal of Affective Disorders, 335, pg 484-492, https://doi.org/10.1016/j.jad.2023.04.141.
