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The aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.We reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.Over the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.Although this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.