Sublingual Ketamine for Depression and Anxiety: A Retrospective Study of Real-World Clinical Outcomes

Objective

To evaluate the effectiveness of repeated at-home ketamine treatments for depression, generalized anxiety, and social anxiety and assess safety in terms of adverse effects and tendency towards long-term use.

Methods

This retrospective analysis included patients with depression, generalized anxiety, and/or social anxiety who received ketamine treatment (delivered at-home via low-dose, sublingual lozenges) through a private telehealth provider. Data was collected between May 2022 and April 2023. The primary outcome was change in depression, generalized anxiety, and social anxiety symptoms from baseline to three follow-up time points, measured via Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Assessment (GAD-7), and Social Anxiety Disorder Severity Scale (SAD-D-10), with analysis subgroups established based on baseline diagnosis. Secondary outcomes included side effects, adverse events, long-term use, well-being improvements, and comparison of outcomes between treatment-resistant and non-resistant depression cases.

Results

Of 431 patients (mean [SD] age, 43.6 [10.9] years; 49.2% women), 81 (18.8%) reported minor side effects resolving within 24 hours, and 397 concluded treatment in ≤ 6 months. Statistically significant improvement on the primary outcome was observed at all follow-ups in all three subgroups (p < 0.001). No significant differences were found between treatment-resistant and non-resistant depression outcomes.

Conclusions

Repeated sublingual ketamine significantly reduced depression, generalized anxiety, and social anxiety with no major adverse events and minimal tendency towards long-term use observed. These findings prompt further exploration of ketamine as an alternative or adjunct to medications such as SSRIs and benzodiazepines to minimize response delays and dependence risk.