The dissociative offers hope for treatment resistant depression, but it’s not the whole story.
In the past decade, we haven’t seen many new antidepressant medications come to market, so emerging therapies – including psychedelic-assisted treatments like ketamine – are offering new hope to those who haven’t had success with traditional options.
With the recent announcement that esketamine (sold as Spravato)[i] – a ketamine-derived nasal spray – will be added to the PBS specifically for treatment resistant depression (TRD), the importance of psychosocial interventions should not be forgotten. Ketamine treatment is rarely a standalone solution. Most patients still benefit from ongoing psychosocial support to help them process their experiences, understand their thoughts and build healthier coping strategies.
When treating any mental illness, including depression, it’s important that GPs and clinical teams work closely with each individual to uncover the underlying factors contributing to their symptoms. The right treatment plan depends on a range of things – including how long the person has been unwell, the type of symptoms and severity, and whether there are co-occurring conditions like ADHD or addiction.
However, the emergence of alternative therapies to bridge the treatment gap will continue to exist; so it’s important we educate ourselves so that we can provide informed support for patients.
When should treatments like ketamine be considered?
No single treatment should be seen as an overnight fix; however, I’ve worked with individuals for whom traditional antidepressants have failed to provide relief. While neurostimulation therapies like Transcranial Magnetic Stimulation (TMS) can be effective for some people, they don’t work for everyone.
For patients with TRD – where they haven’t responded to two separate courses of antidepressants from different drug classes – ketamine offers a promising alternative. It has shown rapid symptom reduction in both severe major depressive disorder (MDD) and bipolar depression, even in cases involving suicidal ideation[ii].
However, the use of ketamine must be approached with care. Ideal candidates are those who have access to structured follow-ups and can commit to supervised administration – typically via intravenous infusion or intranasal delivery.
High-risk patients and those to approach with caution
Despite its therapeutic potential, ketamine is not appropriate for all patients. Individuals with psychotic disorders are generally poor candidates, as ketamine may exacerbate psychosis. Those with unstable cardiovascular conditions are also at risk, given ketamine’s potential to transiently raise blood pressure and heart rate.
Caution is warranted in patients with recent or active substance use disorders due to the drug’s dissociative and habit-forming properties. Additionally, ketamine is not recommended during pregnancy or breastfeeding due to insufficient safety data.
Patients with poor social support or unstable housing may also be unsuitable, as close monitoring and reliable follow-ups are critical components of safe ketamine therapy.
Holistic care must complement ketamine therapy
One of the most important messages for clinicians and patients alike is that ketamine should not be viewed as a replacement for comprehensive mental health care. Rather, it is most effective when integrated into a broader treatment plan.
Patients should generally continue or optimise existing antidepressants, particularly SSRIs or SNRIs, unless contraindicated, and those with bipolar depression must remain on mood stabilisers like lithium or lamotrigine to prevent manic episodes.
Psychotherapy remains a cornerstone of treatment. Structured approaches, particularly cognitive-behavioural therapy (CBT) or trauma-informed therapies, can extend the benefits of ketamine. Without such supports, the antidepressant effects of ketamine are often short-lived.
Regular psychiatric follow-up is also essential to ensure safe administration, monitor response and coordinate ongoing treatment adjustments.
Key steps before and after prescribing ketamine
The decision to initiate ketamine treatment should follow a comprehensive clinical assessment, including:
- Diagnostic confirmation (typically MDD or bipolar depression)
- Documentation of treatment resistance
- Suicide risk assessment
- Substance use screening
- Cardiovascular review, including ECG if clinically indicated
Patients must be fully informed about the nature of the treatment, expected outcomes, side effects and the need for structured follow-up.
After administration, close monitoring is essential. Current protocols recommend that healthcare professionals supervise patients for at least two hours post-administration to monitor blood pressure, heart rate and mental state[iii].
Patients often need multiple sessions (typically four to six) to determine efficacy. Monitoring for common side effects – including dissociation, nausea, anxiety or transient cognitive changes – is also vital.
Because ketamine’s antidepressant effects can be short-term, a maintenance plan is crucial. This includes relapse prevention through ongoing pharmacotherapy, psychotherapy and lifestyle interventions to support long-term wellbeing.
Psychosocial interventions enhance treatment effectiveness
Psychosocial interventions play a crucial role in enhancing and sustaining the benefits of ketamine treatment. In my experience, Cognitive Behavioural Therapy (CBT) can be particularly effective in addressing residual depressive symptoms. Mindfulness-based CBT and Acceptance and Commitment Therapy (ACT) can help patients process dissociative experiences or distress that may arise post-ketamine. For individuals with PTSD or a history of trauma, trauma-focused therapy can be especially valuable, as ketamine may temporarily increase emotional openness, creating a therapeutic window[iv].
Additionally, psychoeducation for both patients and their families or support networks is essential to set realistic expectations – framing ketamine not as a cure, but as a tool that facilitates a deeper engagement in recovery.
Conclusion: the role of general practitioners
Even with limited time and resources, GPs play a critical role in the care of patients with TRD – including those exploring ketamine-based therapies. While GPs are not authorised to prescribe PBS-subsidised esketamine, they are pivotal in:
- Early screening for inadequate treatment response
- Educating patients about ketamine’s role in a multidisciplinary care plan
- Referring to psychiatric services or specialised clinics for structured treatment
GPs are also uniquely positioned to monitor physical health, assess mood and safety, and offer ongoing psychosocial support through regular check-ins.
Importantly, GPs can advocate for collaborative care models, ensuring communication across primary care, psychiatry and psychological services. This coordination is essential for providing patients with consistent, high-quality support throughout their treatment journey.
Dr Sampath Arvapalli is a consultant psychiatrist and is the medical director at The Banyans Healthcare. Dr Arvapalli brings a wealth of knowledge with special interests in general adult psychiatry, the treatment of addiction disorders, adult ADHD, personality disorders and psychotherapy.
References:
[i] https://budget.gov.au/content/bp2/download/bp2_2025-26.pdf
[ii] https://www.sciencedirect.com/science/article/abs/pii/S0165178120333060
[iii] https://www.tga.gov.au/sites/default/files/auspar-esketamine-hydrochloride-210507-pi.pdf
[iv] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5212809
[i] https://budget.gov.au/content/bp2/download/bp2_2025-26.pdf
[ii] https://www.sciencedirect.com/science/article/abs/pii/S0165178120333060
[iii] https://www.tga.gov.au/sites/default/files/auspar-esketamine-hydrochloride-210507-pi.pdf
[iv] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5212809
[1] https://budget.gov.au/content/bp2/download/bp2_2025-26.pdf
[1] https://www.sciencedirect.com/science/article/abs/pii/S0165178120333060
[1] https://www.tga.gov.au/sites/default/files/auspar-esketamine-hydrochloride-210507-pi.pdf [1] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5212809
