Treatment-resistant depression (TRD): signs, symptoms and treatment

Here are some of the options that are available to you if you have TRD.

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his page was clinically reviewed by Dr Donna Grant (MBBS, MCRPsych, BSc Hons), Consultant Psychiatrist at Priory Hospital Chelmsford, in April 2024.

What is treatment-resistant depression?

Even though there are lots of different treatment methods for depression, including talking therapies and antidepressant medications, unfortunately these don’t always work for everyone.

Treatment-resistant depression (TRD) can be diagnosed when your first line of depression treatment, usually involving two courses of antidepressants, hasn’t made you feel better or has only made you feel partially better. Evidence suggests TRD it can affect up to a third of people who have depression.

Ask yourself the following questions:

  • Do you feel as though your treatment so far hasn’t made you feel any better?
  • Do you feel as though your treatment has partially helped, but you’re still having some depression symptoms?
  • Have you had problems with side effects when taking medication for depression?

If you’ve answered ‘yes’ to any of these questions, it’s important that you speak to your doctor, as these might be a sign that your depression is treatment-resistant and you need to try other options.

If your depression treatment hasn’t resulted in the improvements you’d hoped for, this can be very discouraging and can make you feel hopeless about the future. Treating TRD can be a lengthy process as it often involves trying different combinations of techniques until you find the one that works for you. However, it’s really important that you don’t give up. While it can be difficult not to feel disheartened, many people with TRD eventually recover from their symptoms and learn to effectively manage their condition.

TRD symptoms

TRD symptoms are essentially the same as the symptoms of depression. The difference that might lead to a diagnosis of TRD is that these symptoms tend to persist for a long time and don’t respond to standard ways of treating the condition, such as counselling and antidepressants.

TRD involves five or more of the following depression symptoms, that either respond partially to initial treatment or not at all:

  • Feeling sad and hopeless for most of the day, nearly every day for a number of weeks
  • Less interest in hobbies and activities you once enjoyed
  • Decrease or increase in appetite
  • Sleeping too much (hypersomnia) or struggling to get to sleep and stay asleep (insomnia)
  • Excessive fatigue nearly every day, and feeling tired after even small tasks
  • Struggling to think or concentrate
  • Thoughts of death or suicide

common Signs of dysthymia

Treating TRD

A combination of medication and therapy is often the most effective way to treat TRD. While antidepressants can help to relieve many of the most problematic symptoms of depression, individual or group-based therapy allows you to work with your specialist therapist to understand specific issues or concerns that may be contributing to your illness.

At Priory, we can provide expert treatment for TRD, helping you to overcome your symptoms and start to make progress in your recovery. Depending on the severity of your symptoms, we offer a number of different treatment programmes for TRD. These include:

  • Inpatient treatment
  • Outpatient and day care
  • Online therapy via our dedicated platform


Therapy for TRD can help you to:

  • Learn new coping mechanisms to cope with stressful life events
  • Manage relationships more effectively
  • Work through past trauma which may be stopping you from recovering sufficiently
  • Discuss any patterns of substance abuse and understand how this may worsen or cause symptoms of depression
  • Replace or adjust negative emotions or beliefs with more positive thinking

A method known as cognitive behavioural therapy (CBT) has been found to be very effective in the treatment of TRD. The aim of CBT is to challenge any negative thinking or beliefs you have that may be contributing to your depression, and help you to learn methods of dealing with challenges in a more positive way. It will also help you to address any deep-rooted beliefs that may be holding you back and preventing you from getting better.

CBT sessions also aim to equip you with lifelong coping mechanisms, so there’s less chance of you becoming depressed again in the future.

Find out more about other therapy types that we can use to treat TRD.

Therapy formats

We also offer a number of therapy formats when it comes to treating TRD:

  • 1:1 therapy
  • Group therapy
  • Family therapy


Antidepressants are designed to influence chemicals in the brain that are linked to mood, helping to fight depression symptoms.

Making sure you have been taking your prescribed antidepressants at the right dose and length of time to be effective will be the next stage of treatment for TRD. If you have severe or long-term depression, it can take time to find medication that is effective. The challenge is to find a particular type of antidepressant that effectively improves your symptoms where other drugs haven’t.

Switching from one type of antidepressant to another that has different properties can help, while it’s also possible to add a second antidepressant or other medications that aren’t usually used for treating depression. This can be especially useful when you’re feeling some relief from depression symptoms but your condition isn’t completely under control yet.

It may also be that you were not able to take the prescribed medication because of adverse effects. A change of medication will allow us to treat you more effectively with medication that you're able to tolerate.

While you may find it frustrating when several medications to treat your depression don’t work as they should, our consultants will work with you to find the right medication or combination of medications for your individual circumstances.

Specialised treatment

We are also able to deliver a new and innovative treatment method that has been found to be particularly effective when treating TRD.

Repetitive transcranial magnetic stimulation (rTMS), is a painless, non-invasive and safe treatment method, which uses rapidly alternating magnetic fields to stimulate the areas of your brain that are involved in controlling mood.

If you’re living with TRD, rTMS can help relieve symptoms of depression when therapy and antidepressant medication haven’t been successful. We can offer rTMS at Priory Wellbeing Centre Harley Street, which is one of the few places in the country where this state-of-the-art treatment can be accessed.

How to manage TRD

There are also a number of things you can do yourself, to help manage your TRD and increase the chances of your treatment being a success. Many of these align with coping strategies people use to help to deal with depression:

  • Get into a healthy routine – try and do things at the same time each day, like getting up and going to bed, eating, and taking time out for yourself. A healthy and reliable routine gives you purpose and can really help in your recovery
  • Talk to family and friends – it’s important that you talk to close friends, family or loved ones about what you’re going through, instead of bottling it up. Remember, it’s often said that a problem shared is a problem halved. These people love you and want to give you emotional support when you need it
  • Stop drinking or taking drugs – alcohol and recreational drugs can interfere with your treatment, result in addictive and harmful behaviours, and can make your depression symptoms even worse
  • Look after yourself physically – exercise, eat well and try to get enough sleep at night
  • Try to reduce stress – stress can be a trigger for depression and can make your low mood worse. Try to avoid situations that you find stressful if you can, and consider learning techniques to help you cope with stress, such as meditation, yoga and mindfulness
  • Engage with treatment – make sure you attend all of your therapy sessions and take any medications that have been prescribed. We understand that it can be frustrating when treatment hasn’t worked previously – but persistence is key. You’ll get there if you keep at it, and we’re here to support you every step of the way

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