Rationale <p>Ketamine-assisted therapy is emerging as a fast-acting intervention for treatment-resistant depression and anxiety. However, individual response to treatment varies, and little is known about how personality traits and trauma history influence outcomes.</p> Objectives <p>This study investigated whether distinct personality profiles emerge in a real-world sample of patients undergoing ketamine therapy and examined how these profiles, along with trauma history, relate to baseline symptoms and short-term treatment outcomes.</p> Methods <p>A total of 184 patients seeking ketamine-assisted therapy at a Canadian clinic completed baseline assessments, including the Mini-IPIP (personality), PHQ-9 (depression), GAD-7 (anxiety), and WHOQOL-BREF (quality of life). Latent profile analysis (LPA) was used to identify personality-based subgroups. Paired-sample t-tests and ANOVAs were conducted to examine differences in symptom severity and change scores after treatment.</p> Results <p>Three personality profiles were identified: Easygoing Extraverts, Average, and Reserved Introverts. Reserved Introverts reported significantly higher baseline depression and anxiety than other profiles. While all profiles showed improvements in depression and anxiety one-week post-treatment, the personality profiles did not predict differential symptom change. However, participants with a trauma history showed greater reductions in depression and improvements in physical quality of life than those without.</p> Conclusions <p>Personality traits relate to baseline mental health severity but not short-term response to ketamine. Trauma history may predict greater benefit from treatment. These findings support further integration of personality and trauma assessments into personalized care approaches.</p>