Restoring Calm: Maintenance Ketamine Therapy Offers Hope for Severe Anxiety Disorders

In the study Safety and efficacy of maintenance ketamine treatment in patients with treatment-refractory generalized anxiety and social anxiety disorders by Glue et al. (2018), researchers explored the long-term effects of ketamine as a maintenance therapy for individuals suffering from chronic and treatment-resistant anxiety. The findings offer new hope: weekly subcutaneous injections of ketamine significantly reduced anxiety symptoms, were well tolerated, and improved patients’ day-to-day functioning.

Generalized Anxiety Disorder (GAD) and Social Anxiety Disorder (SAD) are among the most persistent and disabling mental health conditions, particularly when resistant to conventional treatments like SSRIs or cognitive-behavioral therapy. The promise of ketamine—a medication traditionally used in anesthesia and now repurposed for psychiatric use—has begun to reshape treatment possibilities for patients with limited options.

Study Design and Patient Population

This open-label trial involved 20 adult patients who had previously responded to ketamine in an earlier ascending dose study. Participants met DSM-IV criteria for treatment-refractory GAD and/or SAD:

• 15 participants (75%) met criteria for GAD
• 18 participants (90%) met criteria for SAD

Each patient received weekly subcutaneous injections of 1 mg/kg ketamine for three months, with some receiving twice-weekly doses based on clinical need. The trial aimed to observe not only ketamine’s therapeutic effects but also safety, tolerability, and patient-reported outcomes over time.

Significant Improvements in Anxiety Symptoms

Ketamine produced rapid and sustained relief from anxiety symptoms:

• Within 1 hour post-dose, both Fear Questionnaire and Hamilton Anxiety Rating Scale scores fell by approximately 50%.
• These reductions were maintained throughout the 14-week treatment period.

Patients also reported marked enhancements in social engagement, work functionality, and overall life satisfaction, signaling ketamine’s broad psychosocial benefits.

Safety, Tolerability, and Side Effects

The therapy was generally well tolerated:

• Common side effects included nausea, dizziness, and blurred vision.
• Transient increases in blood pressure (~10 mmHg) were observed at 30 minutes post-injection but resolved without intervention.
• Dissociative symptoms, measured by the Clinician-Administered Dissociative States Scale, decreased steadily over time—from an average of 20 points in Week 1 to 8.8 points by Week 14.

Importantly, no serious adverse events were reported during the maintenance period.

Real-Life Functional Gains

Beyond clinical ratings, 18 of the 20 participants reported improved social and occupational functioning, highlighting ketamine’s tangible impact on real-life wellness. These changes often reflect the kinds of improvements patients value most but that are harder to quantify in traditional trials.

Conclusions and Clinical Takeaways

The study by Glue et al. represents a pivotal early exploration into maintenance ketamine therapy for anxiety. Key takeaways include:

• Fast-acting: Symptom relief began within an hour of dosing.
• Durable: Weekly dosing maintained improvements over 3 months.
• Safe: Side effects were manageable and dissociative symptoms declined over time.
• Functional benefits: Social and work-related improvements were widely reported.

While the study was open-label and uncontrolled, it lays essential groundwork for future randomized controlled trials. It also highlights the potential for ketamine to expand beyond depression and PTSD into chronic anxiety treatment, particularly for patients who have exhausted traditional options.

References

1. Glue P, Neehoff SM, Medlicott NJ, et al. Safety and efficacy of maintenance ketamine treatment in patients with treatment-refractory generalized anxiety and social anxiety disorders. J Psychopharmacol. 2018;32(6):663–667. https://doi.org/10.1177/0269881118760660
2. Feder A, Costi S, Rutter SB, et al. A randomized controlled trial of repeated ketamine administration for chronic PTSD. Am J Psychiatry. 2021;178(2):193–202. https://doi.org/10.1176/appi.ajp.2020.20050596
3. Liriano F, Hatten C, Schwartz TL. Ketamine as treatment for post-traumatic stress disorder: A review. Drugs Context. 2019;8:1–7. https://doi.org/10.7573/dic.212573
4. Krystal JH, Abdallah CG, Sanacora G. Ketamine: A paradigm shift for depression research and treatment. Neuron. 2019;101(5):774–778. https://doi.org/10.1016/j.neuron.2019.02.005

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