If you’re exploring treatments for depression, you’ve likely heard of both ketamine and esketamine. For those who haven’t found relief through traditional antidepressants, these innovative therapies offer new hope.
But how do they differ, and which might be right for you? Understanding their distinctions helps you make an informed decision about your mental health journey.
What Is Ketamine?
Ketamine has been used as an anaesthetic since the 1970s, primarily in surgical settings and emergency medicine. In recent years, psychiatrists have discovered its remarkable ability to rapidly reduce depression symptoms, particularly in cases where other treatments have failed. When used for depression, ketamine is typically administered intravenously (IV) in specialised clinic settings.
This “off-label” use means ketamine hasn’t received specific regulatory approval for treating depression, though substantial research supports its effectiveness. Studies show that approximately 55% of patients with treatment-resistant depression experience significant improvement after ketamine infusion therapy. The treatment involves carefully monitored IV sessions lasting 40 to 60 minutes, with patients often reporting mood improvements within hours to days.
What Is Esketamine?
Esketamine represents a breakthrough in treatment resistant depression therapy as the first ketamine-derived medication specifically approved for mental health use. Marketed under the brand name Spravato, this nasal spray received FDA approval in 2019 and TGA approval in Australia in 2021 for treating treatment-resistant depression.
Chemically, esketamine is the “S” enantiomer of ketamine – essentially one half of the ketamine molecule. This refined formulation allows for nasal administration while maintaining therapeutic benefits. The convenience of nasal spray delivery, combined with regulatory approval, makes esketamine more accessible to patients seeking advanced depression therapies.
How Are Esketamine and Ketamine Similar?
Both treatments share fundamental similarities that explain their effectiveness in treating depression. They belong to the same drug family and work through similar mechanisms in the brain, offering rapid relief compared to traditional antidepressants that can take weeks to show effects.
Key similarities include:
- Rapid onset of action (often within hours to days)
- Effectiveness in treatment-resistant cases
- NMDA receptor antagonism in the brain
- Ability to promote neuroplasticity
- Requirement for medical supervision during administration
Both options represent significant advances in psychiatric care, particularly for patients who haven’t responded to conventional treatments.
Key Differences Between the Two Treatments
While related, several important distinctions set these treatments apart. Understanding these differences helps patients and clinicians determine the most appropriate option for individual circumstances.
Administration method
Ketamine requires IV infusion through a cannula, while esketamine comes as a convenient nasal spray. This difference significantly impacts the treatment experience and accessibility.
Regulatory status
Esketamine has official approval for depression treatment, while ketamine remains off-label. This affects insurance coverage, with many providers covering approved esketamine treatment but not ketamine infusions.
Treatment setting
Both require medical supervision, but esketamine administration typically takes less clinical resources than IV ketamine setups.
Dosing precision
IV ketamine allows for precise dose adjustments during infusion, while esketamine uses predetermined spray doses.
Cost consideration
The esketamine cost can be partially offset by insurance coverage in many cases, while ketamine infusions often require out-of-pocket payment.
How Do They Work in the Brain?
Both medications target the brain’s NMDA receptors, but their action goes beyond simple receptor blocking. They trigger a cascade of changes that promote healing and recovery from depression.
When administered, these treatments:
- Block NMDA receptors, leading to increased glutamate release
- Stimulate BDNF (brain-derived neurotrophic factor) production
- Enhance synaptic connections between neurons
- Promote neuroplasticity – the brain’s ability to form new neural pathways
Both treatments appear to “reset” dysfunctional brain circuits associated with depression, offering relief when other medications haven’t worked.
Administration Methods and Protocols
The practical aspects of receiving these treatments differ significantly, affecting patient experience and accessibility.
Ketamine IV infusion:
- Requires IV line placement
- Sessions last 40 to 60 minutes
- Administered in specialised clinics
- Dose adjusted based on weight and response
- Typically given twice weekly initially
Esketamine nasal spray:
- Self-administered under supervision
- Takes 5-10 minutes to complete
- Given in certified treatment centres
- Fixed doses based on treatment phase
- Usually twice weekly for the first month, then weekly
Effectiveness in Treating Depression
Clinical evidence supports both treatments for managing treatment-resistant depression, though research approaches differ due to their regulatory statuses.
Esketamine benefits from extensive clinical trials required for approval. Studies show that approximately 50 to 70% of patients with treatment-resistant depression respond to esketamine when combined with an oral antidepressant. Response typically occurs within the first four weeks of treatment.
Ketamine research, while less standardised, demonstrates similar or potentially higher response rates. Some studies report up to 80% of patients experiencing significant improvement. However, optimal dosing and treatment schedules remain under investigation.
Both treatments show particular promise for:
- Rapid reduction of suicidal thoughts
- Breaking through medication resistance
- Providing relief when multiple antidepressants have failed
- Offering hope for severe, chronic depression
Safety, Side Effects, and Regulation
Understanding the safety profile of each treatment helps patients prepare for their experience and make informed decisions.
Common side effects for both include:
- Dissociation (feeling detached from reality)
- Dizziness
- Nausea
- Increased blood pressure
- Sedation
The Spravato side effects are generally well-documented due to extensive clinical trials. Most effects are mild to moderate and resolve within two hours of administration. Esketamine’s regulatory approval includes strict safety protocols, including blood pressure monitoring and a two-hour observation period.
Ketamine infusions may produce similar effects, though some patients report more intense dissociative experiences at higher doses. The lack of standardised protocols for depression treatment means safety measures can vary between providers.
Both treatments require:
- Medical supervision during administration
- Transportation arrangements (no driving after treatment)
- Regular monitoring of symptoms and side effects
- Careful screening for contraindications
Which Treatment Is Right for You?
Both treatments offer hope for those struggling with treatment-resistant depression, but individual circumstances guide the choice.
Consider esketamine if you:
- Prefer a treatment with regulatory approval
- Have insurance coverage for mental health treatments
- Want the convenience of nasal administration
- Value standardised treatment protocols
- Seek treatment at a certified esketamine treatment centre
Ketamine infusion might suit you if:
- You need flexible dosing options
- Previous esketamine treatment wasn’t effective
- You’re comfortable with off-label treatments
- Cost considerations favour ketamine in your situation
If you’re considering esketamine and want to understand the process in more detail, explore our guide on what to expect during and after your esketamine treatment. It covers each stage of treatment, recovery insights, and practical tips for maintaining progress.
What Makes Mind Oasis Different?
At Mind Oasis, we bring extensive experience in advanced depression treatments in Sydney to every patient interaction. Our team of specialist psychiatrists understands the complexities of treatment-resistant depression and the hope these innovative therapies can provide.
We prioritise patient safety while maximising treatment effectiveness. Our clinicians stay current with the latest research and guidelines, ensuring you receive evidence-based care tailored to your unique situation.
Beyond medication administration, we focus on your overall wellbeing. This includes addressing lifestyle factors, providing psychological support, and helping you build resilience for long-term recovery.
Taking the Next Step in Your Mental Health Journey
Both esketamine and ketamine represent significant advances in treating depression that haven’t responded to conventional approaches. While they share core mechanisms and effectiveness, important differences in administration, regulation, and accessibility may influence your choice.
Ready to explore whether esketamine or ketamine treatment could help you?
Contact Mind Oasis today to schedule a comprehensive assessment with our experienced team. We’ll help you understand your options and develop a personalised treatment plan for your journey toward better mental health.
Book your consultation online or call us at 1300 680 000 to take the first step toward recovery.