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plasticity and promoting rapid antidepressant effects. 5. Effects on Brain Connectivity: Ketamine’s actions on the glutamate system and synaptic remodelling have been linked to changes in brain connectivity. Resting-state fMRI studies have shown that ketamine can restore the connectivity between brain regions involved in mood regulation. The precise contributions of these mechanisms to the antidepressant effects of ketamine are still under investigation. Ketamine’s unique mechanism of action sets it apart from traditional antidepressant medications. The rapid and robust antidepressant effects associated with ketamine have sparked considerable interest in its potential as a novel treatment for various mood disorders, including TRD. Efficacy of Ketamine for Adolescent Treatment Resistant Depression • Several studies have investigated the use of ketamine in the management of treatment-resistant depression (TRD) specifically in adolescents. • The research in this area is still limited; there are key findings that provide important insights into the efficacy of ketamine in this population. The key insights are as follows: 1. Rapid and Sustained Antidepressant Effects: Research has consistently shown that ketamine administration leads to rapid and significant reductions in depressive symptoms in adolescents with TRD. Studies have reported improvements within hours to days after a single ketamine infusion. The antidepressant effects have been observed to be sustained for several days to weeks following treatment. 2. Higher Response Rates Compared to Placebo: Multiple studies have demonstrated that ketamine has consistently superior antidepressant effects compared to placebo in adolescents with TRD. 3. Treatment-Resistant Subgroups: Studies have suggested that individuals with a history of more severe and chronic depression, as well as those with a history of suicidal ideation, may have a greater likelihood of responding positively to ketamine therapy. 4. Safety and Tolerability: Ketamine has been found to be safe and well-tolerated in the adolescent populations when administered under proper medical supervision. Adverse effects are typically mild and transient, including dissociative symptoms, transient changes in perception, dizziness, and increases in blood pressure and heart rate. Serious adverse effects are rare, including respiratory depression or dependence, which appear to be minimal when sub-anaesthetic doses are used. 5. Long-Term Efficacy and Maintenance: Limited evidence suggests that repeated or maintenance ketamine infusions may be effective in sustaining the antidepressant effects in some adolescents with TRD. More research is needed to determine optimal dosing, frequency, and long-term outcomes of maintenance in this population. 6. Integration with Psychotherapy: Studies have highlighted the potential benefits of integrating ketamine treatment with psychotherapy, such as CBT or family therapy. Combining ketamine with psychotherapy may enhance treatment response and provide a comprehensive approach to address the underlying psychological factors contributing to depression in adolescents. The current limitations with the available evidence and future directions • Research in adolescents is limited and there is a lack of randomised controlled trials, which is the gold standard. • The route, scheduling, dosing, and administration of ketamine is not consistent between studies. • Co-morbidity is a rule rather than an exception in child and adolescent psychiatric conditions, and across the various studies, there is a range of co-morbidities and concurrent treatment. • The current studies that have been conducted have small sample sizes and are of short duration. • All available studies in adolescents have utilised IVI formulation of ketamine (FDA approved ketamine for adult TRD is intranasal) Conclusion: Where to from here? While research is ongoing, and it is still currently limited. Ketamine shows potential to be well tolerated in the adolescent population with minimal side effects and shows potential to be effective in reducing the symptom burden in adolescents with TRD, however further research is needed before its use in clinical practice becomes standard. • More research is needed to: - To establish safety data Determine efficacy. - Comparison with placebo and other standard treatments for depression - Method of delivery (a study showed parents’ strong preference for intranasal/oral or sublingual routes) - Explore the role of psychotherapy during ketamine treatment for depression. References available on request. MHM | 2024 | Volume 11 | Issue 2 | The Use of Ketamine in Adolescents with Treatment Resistant Depression: Where are we and what does the current evidence say? MHM 12 | MENTAL HEALTH MATTERS | 2024 | I sue 2 H