Treatment-Resistant Depression
Treatment-Resistant Depression Treatment in London
Specialist care for adults whose depression hasn’t responded to two or more antidepressants. Consultant-led from day one, monitored at every session, and built around your treatment history rather than a template.
You've done everything you were told to do. It still isn't working.
If you’ve been through several antidepressants, talking therapy, maybe a specialist referral, and you still feel stuck, you may have treatment-resistant depression. It isn’t a sign that you’ve failed, or that nothing will help. It means the standard route hasn’t been the right one for you.
Save Minds is a private, consultant-led clinic in London for treatment-resistant depression. Every patient is assessed by a consultant psychiatrist, and treatment (where clinically appropriate) is delivered in a private clinical suite with continuous monitoring. You’ll see your own progress data throughout, and your consultant adjusts the programme based on what it shows.
You don’t need a GP referral. The first step is a free, confidential discovery call.
- The Basics
What is treatment-resistant depression?
Treatment-resistant depression (TRD) is depression that hasn’t improved enough after at least two different antidepressants, each taken at a proper dose for long enough to work. That is the definition used by the FDA, the European Medicines Agency and most UK psychiatrists. You may also hear it called medication-resistant, drug-resistant or refractory depression. They all mean the same thing.
It is not a separate illness. It’s a way of describing depression that hasn’t responded to the standard treatment pathway, and it’s used to decide what should happen next.
- Diagnosis
How is treatment-resistant depression diagnosed?
There isn’t a single test. A consultant psychiatrist will look at:
Which antidepressants you’ve tried, at what dose, and for how long (a trial usually needs to be 6–8 weeks at a therapeutic dose to count)
Whether the medication was taken consistently, and whether side effects meant you stopped early
Whether the original diagnosis is right (bipolar depression, ADHD, thyroid problems and chronic pain are all commonly missed)
Whether talking therapy has been tried alongside medication
This matters because a significant number of people labelled as treatment-resistant are what clinicians call pseudo-resistant: the medication was never given a fair trial. A proper treatment history review is the first thing we do at Save Minds.
- In the UK
How common is treatment-resistant depression?
More common than most people expect. A 2025 University of Birmingham study of NHS records found that 48% of patients with a depression diagnosis had tried at least two antidepressants, and 37% had tried four or more. International estimates put the figure at around a third of people with depression.
48% had tried at least two antidepressants · 37% had tried four or more · around 1 in 3 people with depression worldwide
- NICE & NHS
What do NICE and the NHS say?
NICE deliberately avoids the label “treatment-resistant depression”. Its guideline (NG222) instead talks about depression that has not responded adequately to treatment, and recommends a stepped approach: switching or combining antidepressants, adding an augmenting medication such as lithium or an antipsychotic, and combining medication with psychological therapy. On the NHS, these steps typically happen through a GP and then a community mental health team, and waits for specialist review can be long. Save Minds is a private clinic and is not an NHS service, but we’ll always work alongside your existing GP and care team where you want us to.
- Signs
Signs you may have treatment-resistant depression
The symptoms of treatment-resistant depression are the same as depression itself. What’s different is the pattern: they keep coming back, or never fully leave, no matter what you try. If several of these feel familiar, it’s worth talking to a specialist.
You’ve taken two or more antidepressants for at least six to eight weeks each with little or no improvement
You felt slightly better on medication, but never well. Low mood, exhaustion or a flat, numb feeling (anhedonia) stayed
Side effects stopped you continuing a medication before it had a fair chance
You’ve had multiple episodes of depression over several years, with shorter gaps between them
Talking therapy helped you cope, but didn’t shift the underlying depression
You’ve been told to “give it more time” or “try one more” for longer than you can remember
You’re holding down a job and a life, but only just. High-functioning doesn’t mean well
Anxiety, chronic pain, PTSD or OCD sit alongside the depression and make it harder to treat
You’ve had thoughts that life isn’t worth living
If you are having thoughts of ending your life right now, please contact your GP, call NHS 111 (option 2), or call Samaritans free on 116 123. If you are in immediate danger, call 999. Save Minds treats severe suicidal ideation, but alongside – never instead of – urgent NHS crisis care.
Treatment-resistant anxiety and depression
Anxiety and depression frequently occur together, and the combination is one of the strongest predictors that standard antidepressants won't be enough. If you've been treated for both and neither has resolved, this page applies to you. See also our pages on anxiety leading to depression and OCD leading to depression.
Treatment-resistant bipolar depression
Depression in bipolar disorder responds differently to antidepressants and can be made worse by them. If you have bipolar disorder, or have ever had a period of unusually high energy or reduced need for sleep, tell your consultant. It changes the treatment plan. Read more on our bipolar disorder page.
- Why antidepressants stop working
What causes treatment-resistant depression?
Nobody knows for certain why some depression responds to standard antidepressants and some doesn’t. But there are patterns, and most of them are things a thorough assessment can pick up.
The medication was never the right fit
SSRIs and SNRIs, the antidepressants most people are prescribed first, act on serotonin, noradrenaline and dopamine. These monoamine systems involve a relatively small share of the brain's neurons. If the biology driving your depression sits elsewhere, more of the same class of drug is unlikely to help. This is the reasoning behind rapid-acting treatments that act on the glutamate system instead, which we explain on our how treatment works page.
Something else is driving the depression
Undiagnosed bipolar disorder, ADHD, autism, PTSD, an underactive thyroid, chronic pain, sleep apnoea and heavy alcohol use can all keep depression going in the background. Treat the depression without treating these and it keeps coming back.
The trial wasn't long enough or the dose was too low
Antidepressants are often stopped or switched after three or four weeks, before they've had time to work, or left at a starting dose that was never increased. Pseudo-resistance is common, and it's fixable.
Long duration and repeated episodes
The longer depression has gone on and the more episodes you've had, the less likely each new antidepressant is to work. This is why waiting is rarely the safe option.
Ongoing stress, trauma or isolation. Medication can’t fix a situation. Persistent stress, unresolved trauma and loneliness all blunt the response to treatment. That’s why our programme includes therapeutic support and continuous review, not just a prescription.
- Treatment options
Treatment-resistant depression treatment options
When two antidepressants haven’t worked, the evidence doesn’t support simply trying a third. The options below are the ones most often considered in the UK once depression is treatment-resistant. Which is right for you depends on your history, your diagnosis and what you’re able to tolerate, which is why the assessment comes first.
| Option | What it involves | How you’d access it | Worth knowing |
|---|---|---|---|
| Augmentation with lithium or an antipsychotic | Adding lithium, aripiprazole or quetiapine to your existing antidepressant | GP or psychiatrist (NHS or private) | Recommended in NICE guidance; lithium needs regular blood tests |
| Switching or combining antidepressants | Moving to a different class (e.g. an SNRI, mirtazapine, vortioxetine or an MAOI) or combining two | GP or psychiatrist | Diminishing returns after the second failed trial |
| Psychological therapy | CBT, behavioural activation or schema therapy alongside medication | NHS Talking Therapies or private | Best used in combination, not as a replacement |
| Esketamine nasal spray (Spravato) | A licensed nasal spray taken under clinical supervision with an oral antidepressant | Specialist centres; limited NHS availability | NICE has only recommended it in narrow circumstances |
| Intravenous ketamine | Consultant-administered infusions in a monitored clinical setting, given as a course | Private specialist clinics such as Save Minds | Off-label in the UK; has recognised risks and is not suitable for everyone |
| rTMS (transcranial magnetic stimulation) | Daily magnetic stimulation of the prefrontal cortex over several weeks | Some NHS trusts; private clinics | Non-invasive; needs 20–30 sessions |
| ECT (electroconvulsive therapy) | Brief seizures induced under general anaesthetic | NHS secondary care | Reserved for severe or life-threatening depression |
| Psilocybin, VNS, deep brain stimulation | Experimental or highly specialist | Clinical trials only | Not available as routine treatment in the UK |
- Our Approach
How Save Minds treats treatment-resistant depression
Save Minds is a consultant-led clinic in St John’s Wood, London, founded in 2017 specifically for people who haven’t found relief through standard care. We’ve delivered over 7,500 treatment sessions to more than 750 patients, and we’re registered with and rated Good by the Care Quality Commission. Your programme is built in four parts:
Full psychiatric assessment
A consultant psychiatrist who specialises in treatment-resistant conditions reviews your diagnosis, your full treatment history and anything that may have been missed. This is a one-off £450 consultation and it determines whether you’re eligible.
Your personal treatment plan
Based on the assessment, your consultant recommends what’s clinically appropriate. That may include medication changes, therapeutic support, and, where suitable, our monitored intravenous treatment programme. No two plans are the same.
Supervised treatment in a private clinical suite
Every session is administered by a consultant with continuous monitoring of your vital signs and post-session observation. A typical programme is 15–20 sessions over 4–6 months, tapering as you improve.
Daily progress tracking
From day one, our app sends you a short daily check-in. Combined with nine validated clinical scales reviewed by your consultant, it gives both of you a real-time picture of what’s working, and the programme is adjusted on that data rather than on a ten-minute chat.
Our treatment has recognised risks and is not suitable for everyone. It is prescribed off-label, following individual medical and psychiatric assessment, and you’ll be given full information about expected effects and uncertainties before you consent. Individual outcomes vary. Read more about benefits and risks, what a session is like and full pricing.
- Real Patient Case Study
10+ Years of Previous Treatment.
A 9-Week Programme at Save Minds.
10+ Years
living with depression
5 Treatments
tried without success
9 Weeks
Save Minds programme
A 42-year-old London professional who tried everything — and finally found what worked.
Photo is an anonymised representation to protect patient privacy.
“I spent years just getting through each day. This is the first time I’ve felt like myself again.”
- Why Save Minds
Why people with treatment-resistant depression choose Save Minds
At Save Minds, each consultant has a clearly defined role.
Consultant psychiatrist. Assesses your psychiatric history, determines your eligibility for IV ketamine treatment and conducts your subsequent psychiatric reviews.
Consultant anaesthetist. Responsible for your IV ketamine treatment: assessing you for treatment, administering each infusion, monitoring you throughout and adjusting your treatment programme according to your clinical response.
No rotating treatment teams. You are treated by the same dedicated consultant anaesthetist throughout your course, providing genuine clinical continuity from your first infusion onwards.
Specialists in cases that haven’t responded. Treatment-resistant depression, anxiety, PTSD, OCD and suicidal ideation are what we do, not a side service. Most of our patients arrive after five or more failed treatments and, often, more than a decade of illness.
Regulated, monitored and accountable. As a Care Quality Commission (CQC)-registered clinic rated Good, Save Minds operates under strict clinical protocols. Our medical board is chaired by Dr Stephen Shaw, whose distinguished leadership includes roles as former Medical Director of NHS London, former Chief Executive Officer of Barnet Hospital, and former Lead Consultant in Intensive Care Medicine at the Royal Free London.
Experienced clinical leadership. The clinic is led by our Founder, CEO, and Lead Clinician, Dr Rajalingam Yadhunanthanan, a dual consultant in anaesthesia and intensive care medicine at the Royal Free London NHS Foundation Trust with over 20+ years of clinical experience. Our expert team also includes Dr Paul Morrison, an NHS consultant psychiatrist and Honorary Clinical Senior Lecturer at King’s College London.
You see your own data. Mood, sleep and wellbeing scores are tracked daily and visible to you. Progress isn’t a feeling you have to argue for at your next appointment. It’s on the screen.
A calm, private setting in central London. We’re based at The Aura Centre on Charlbert Street in St John’s Wood, NW8, a short walk from St John’s Wood Underground station on the Jubilee line and easy to reach from across London and the Home Counties. Open Monday to Friday 9am–8pm and Saturday 9am–6pm.
No referral, no waiting list. You don’t need a GP referral and there’s no waiting list for a discovery call. Fees are paid as you go, session by session, with no large upfront payment.
- Questions
Treatment-resistant depression: your questions answered
What is treatment-resistant depression?
Treatment-resistant depression is depression that has not improved enough after at least two different antidepressants, each taken at an adequate dose for at least six to eight weeks. It’s sometimes shortened to TRD, or called medication-resistant or drug-resistant depression.
Is treatment-resistant depression a diagnosis?
Not a formal one. It doesn’t have its own ICD-10 or DSM-5 code; the underlying diagnosis is still major depressive disorder. “Treatment-resistant” describes how the depression has responded to treatment so far, and it’s used by clinicians to decide the next step.
Can treatment-resistant depression be cured?
Many people with treatment-resistant depression do reach remission, meaning their symptoms lift to the point where depression no longer defines daily life. What it usually takes is a different approach rather than another version of the same one. Depression can return, so a good programme also plans for maintaining recovery. We can’t promise a cure, and anyone who does should be treated with caution.
Does treatment-resistant depression go away on its own?
It’s unlikely. The longer depression goes untreated, or under-treated, the more entrenched it tends to become and the harder it is to shift. Waiting is rarely the safe choice.
Is treatment for treatment-resistant depression available on the NHS?
Yes, in stages. Your GP can adjust or augment medication and refer you to NHS Talking Therapies. More specialist options, such as lithium augmentation, rTMS or ECT, are usually accessed through a community mental health team, and waiting times vary widely by area. Save Minds is a private clinic and does not offer NHS-funded treatment.
What do the NICE guidelines say about treatment-resistant depression?
NICE guideline NG222 covers depression that hasn’t responded to treatment. It recommends checking that previous treatments were adequate, combining medication with psychological therapy, and considering augmentation with lithium or an antipsychotic. NICE does not use the term “treatment-resistant depression” itself.
Do I need a GP referral?
No. You can book a free discovery call directly. If treatment goes ahead, we’re happy to keep your GP informed with your consent.
How much does treatment-resistant depression treatment cost?
The discovery call is free. The consultant psychiatrist assessment is a one-off £450. Treatment sessions are £990 for the first and £595 for each subsequent session, paid as you go. A typical programme is 15–20 sessions over 4–6 months. See full pricing.
What is the best antidepressant for treatment-resistant depression?
There isn’t one. Once two antidepressants have failed, the evidence favours changing strategy (augmentation, a different mechanism of action, or combining medication with therapy) over hunting for a better antidepressant. A consultant psychiatrist can tell you which of those makes sense for your history.
Is treatment-resistant depression treatable with therapy alone?
Talking therapy such as CBT is a valuable part of treatment and NICE recommends it in combination with medication. For most people with genuinely treatment-resistant depression, therapy on its own hasn’t been enough, which is usually why they’re reading this page.
Do you treat treatment-resistant depression alongside anxiety, PTSD or chronic pain?
Yes. Most of our patients have more than one condition, and the programme is built around all of them, not just the depression.
Where is your treatment-resistant depression clinic?
St John’s Wood, London NW8, a short walk from St John’s Wood station on the Jubilee line. Patients travel to us from across London, the South East and further afield.
Who is not suitable for treatment at Save Minds?
Our programme has recognised risks and isn’t right for everyone. Certain heart conditions, uncontrolled high blood pressure, a history of psychosis, current substance misuse and some other conditions may rule it out. Eligibility is decided at the psychiatric assessment. Start with our Am I Suitable page.
Find out if you're eligible
If you’ve tried two or more antidepressants and you’re still not well, you don’t have to keep waiting for the next one to work. A free, confidential discovery call takes about 20 minutes. We’ll listen to what you’ve been through, answer your questions honestly, and tell you whether a consultant assessment is the right next step. No pressure, no GP referral, no commitment.