Ketamine in Clinical Practice:
Treatment resistant Depression
Ketamine, originally developed as an anAesthetic, has gained significant attention in psychiatry, particularly for its potential in treating treatment-resistant depression (TRD).
It is distinguished from traditional antidepressants by its rapid onset of action and novel mechanism, making it a crucial alternative for individuals who do not respond to conventional treatments.
Mechanism of Action
Unlike conventional antidepressants that primarily target serotonin and norepinephrine systems, ketamine acts on the glutamate system, specifically as an N-methyl-D-aspartate (NMDA) receptor antagonist. This leads to an increase in glutamate release, which enhances synaptic plasticity, neural connectivity, and neurogenesis. These changes are believed to underlie ketamine’s rapid antidepressant effects.
Ketamine’s influence on brain-derived neurotrophic factor (BDNF) also plays a key role in its efficacy. BDNF supports neuroplasticity and may help reverse stress-related damage in the brain, particularly in the prefrontal cortex and hippocampus, regions crucial for mood regulation.
Clinical Use of Ketamine for Depression
Administration and Treatment Protocols
Intravenous (IV) Infusion: The most widely used method in clinical settings. Patients receive a low-dose IV infusion (typically 0.5 mg/kg over 40 minutes). The effects are often felt within hours, with peak efficacy occurring around 24 hours post-infusion.
Intramuscular (IM) Injection: Some clinics offer IM administration, which is more convenient but may have slightly less predictable absorption.
Nasal Spray (Esketamine - Spravato®): A derivative of ketamine, esketamine, is available as a nasal spray approved for TRD in some countries, including the US and Europe, but it is not currently approved for routine NHS use in the UK due to cost-effectiveness concerns.
Ketamine-Assisted Psychotherapy (KAP): Some clinics combine ketamine treatment with guided psychotherapy sessions to enhance and prolong its antidepressant effects. Ketamine’s dissociative properties may allow patients to engage in deeper psychological exploration.
Efficacy in Treatment-Resistant Depression
Ketamine is particularly effective in cases of severe depression with suicidality and treatment-resistant depression (TRD). Clinical trials have shown:
A significant reduction in depressive symptoms within hours, compared to the weeks or months required for SSRIs/SNRIs.
Around 60-70% of TRD patients experience noticeable improvements after a single infusion.
Repeated administration prolongs the antidepressant effect, though the duration of benefits varies. Booster infusions may be needed for sustained relief.
However, ketamine is not a cure and often needs to be part of a broader treatment plan, including therapy and lifestyle modifications.
- Access to Ketamine Treatment in the UK -
NHS Access
Ketamine for Depression: The use of ketamine for TRD is not routinely funded by the NHS. However, some specialist centers offer it on a self-pay basis.
Oxford Health NHS Foundation Trust provides an NHS-affiliated ketamine treatment service for depression at Warneford Hospital, Oxford. It is one of the few NHS centers offering ketamine treatment, but patients must pay privately for the service.
Esketamine (Spravato®) is approved by the European Medicines Agency (EMA) but is not currently available through NHS prescribing due to cost concerns.
Private Ketamine Clinics in the UK
Several private clinics in the UK offer ketamine therapy for TRD and other conditions:
Save Minds Ketamine Clinic (London) – Provides IV ketamine infusions for severe depression.
OneWelbeck (London) – Specializes in ketamine infusions for depression and PTSD.
Awakn Clinics – Offers ketamine-assisted psychotherapy (KAP) for depression, PTSD, and addiction.
Private treatment costs vary but typically range from £300-£800 per infusion, with multiple sessions required for sustained benefits.
Other Clinical Uses of Ketamine
Beyond depression, ketamine is used for:
Anesthesia & Pain Management – Especially in emergency settings or for patients with opioid resistance.
PTSD & Anxiety Disorders – Some studies suggest benefits for trauma-related conditions.
Chronic Pain & Fibromyalgia – Low-dose ketamine infusions may provide relief in refractory cases.
Risks and Considerations
While ketamine’s rapid effects are promising, it is not without risks:
Dissociation & Hallucinations – Some patients experience out-of-body sensations or perceptual distortions during treatment.
Increased Blood Pressure & Heart Rate – Ketamine can temporarily raise cardiovascular parameters, requiring monitoring in high-risk patients.
Potential for Dependence – Though rare in therapeutic settings, prolonged or unsupervised use carries a risk of misuse.
Long-Term Effects Unclear – More research is needed on sustained ketamine therapy and its impact on brain function.