Treatment Resistant Depression: Everything You Need to Know

Depression is a complex condition to live with. Taking antidepressants and going for psychotherapy helps most people, but if you have had it for a while and treatment doesn’t seem to be working, then you might have something called treatment-resistant depression (TRD). 

What exactly is treatment-resistant depression?

Some researchers define it as a case of depression that doesn't respond to two different antidepressants from different types - like SSRIs, SNRIs and TCAs. Other experts say that a person must try at least four types of therapy before depression can truly be considered treatment-resistant. However, if you suspect you have treatment-resistant depression, ask yourself the following questions: 

• Has your treatment failed to make you feel better?

• Has your treatment helped a bit, but you still don’t feel like your old self?

• Do you feel a bit better only to feel worse again?

• Have the side effects of your medication been hard to handle?

Treatment-resistant depression symptoms can range from mild to severe and may require trying a number of approaches to identify what helps.

You may be at risk of developing TRD if: 

• The onset of your depression began at an earlier age, before adulthood

• You have frequent and recurring episodes of depression

• You have a severe case of depression as per your diagnosis

What should you do if you have treatment-resistant depression? 

• Confirm your diagnosis

Only a trained mental health professional such as a therapist or a psychiatrist can tell you if you have treatment-resistant depression. They will rule out any other conditions, such as bipolar disorder, hypothyroidism or other hormonal disorders. Sometimes, switching medication or treating an underlying condition can improve your depressive symptoms.  When Major Depressive Disorder (MDD) is accompanied by other medical or psychiatric disorders such as anxiety or eating disorders, depression often can be harder to treat.

• Make sure you take the medication in the correct way

Many people who get prescriptions for depression don’t take them as recommended. Make sure you take your medication without missing doses and take them at the same time. Sometimes, giving up medication too soon can also be detrimental. It can take up to 4-12 weeks for your medication to take effect. Your psychiatrist may also recommend the following: 

• Consider switching antidepressants. For a number of people, the first antidepressant they tried isn't effective. You may need to try a few after talking to your psychiatrist before you find the one that works for you.

• Add another type of antidepressant. Your psychiatrist may prescribe two different classes of antidepressants at the same time. That way they'll affect a wider range of brain chemicals linked to your mood. These chemicals are neurotransmitters that include dopamine, serotonin and norepinephrine.

• Add a medication generally used for another condition. You may be prescribed a medication that's generally used for another mental or physical health problem, along with an antidepressant. This approach, known as augmentation, may include antipsychotics, mood stabilisers, anti-anxiety medications, thyroid hormones among other drugs.

• Consider pharmacogenetic testing. These tests check for specific genes that indicate how well your body can process a medication or how your depression might respond to a particular medication based on additional factors. There is no sure way to predict whether a medication will work for you, but pharmacogenetic tests can provide important clues for treatment, especially for people who have had poor results with certain medications. 

  Try psychotherapy 

Psychotherapy by a psychiatrist or a  therapist can be very effective. For most, psychotherapy combined with medication works well to treat their depression. It can help identify underlying concerns that may be adding to your depression. Additionally, your therapist can teach you some strategies and behaviours for overcoming depression. For example, psychotherapy can help you:

• Find better ways to cope with life's challenges

• Deal with past trauma

• Manage relationships better

• Learn to manage stress effectively 

• Address substance use issues

If therapy doesn't seem helpful, talk to your therapist about trying a different approach. Some of the approaches can be:

Cognitive Behavioural Therapy (CBT)

In this type of therapy, thoughts, feelings, and behaviours related to mood are addressed. It helps you identify and change distorted or negative thinking patterns and teaches you skills to respond to life's challenges in a positive way.

Acceptance and Commitment Therapy (ACT)

As a form of Cognitive Behavioural Therapy, Acceptance and Commitment therapy promotes positive behaviour, even when negative feelings or thoughts arise. It's designed for treatment-resistant conditions.

Interpersonal Psychotherapy (IPT)

Interpersonal Psychotherapy focuses on resolving relationship issues that may contribute to your depression. This also works in maintaining healthy interpersonal relationships which may become difficult to handle as a result of TRD.

Dialectical Behavioural Therapy (DBT)

The goal of this kind of therapy is to develop acceptance strategies and problem-solving skills. This is useful for chronic suicidal thoughts, which sometimes accompany treatment-resistant depression.

Group Therapy

This therapy involves a group of people who struggle with depression working together with a psychotherapist.

Mindfulness

This involves paying attention and accepting one's thoughts and feelings without judging them as "right" or "wrong". It encourages you to live in the present rather than worrying about the future.

Behavioural Activation

This type of treatment works to gradually decrease avoidance and isolation and increase your engagement in activities that you once enjoyed or activities that have shown to improve mood.

Procedures for TRD 

If medications and psychotherapy aren't working, you may want to talk to a psychiatrist about additional treatment options, such as 

• Repetitive Transcranial Magnetic Stimulation (rTMS)

This type of treatment uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression. An electromagnetic coil is placed against your scalp near your forehead. The electromagnet coil creates electric currents that stimulate nerve cells in the region of your brain involved with moods and depression. Typically, this treatment is delivered over 30-minute sessions in rapid bursts. 

• Ketamine

This is a medication that's delivered through an IV in low doses. It's used for rapid relief of hard-to-treat depressive symptoms and its effects can last from days to weeks.  An anaesthetic agent, it has been shown in preliminary studies to produce a rapid (within hours) improvement in depression for some patients. Usually, it's given in decreasing frequencies over several weeks. The FDA approved an intranasal form called esketamine that's given in a clinic under the supervision of a psychiatrist. Esketamine is for people who have tried at least two other antidepressant medicines that did not work for them. Ketamine and Esketamine work in a different way than antidepressants and they are typically used alongside an oral antidepressant.

• Electroconvulsive Therapy (ECT)

While you're asleep, a carefully measured dose of electricity is passed through your brain, intentionally triggering a small, brief seizure. ECT has been known to cause changes in brain chemistry that can reverse symptoms of major depression. Although there are potential side effects, such as temporary confusion or temporary memory loss, a series of ECT treatments may provide significant relief from severe depression.

• Vagus Nerve Stimulation (VNS)

This is an invasive procedure. Generally, VNS is only tried after other brain stimulation therapies such as ECT and rTMS have been unsuccessful in improving symptoms of depression. VNS stimulates the vagus nerve with electrical impulses. This treatment uses a device implanted in your chest that's connected by a wire to a nerve in your neck (vagus nerve). Electrical signals from the implant travel along the vagus nerve to the brain, which may improve depression symptoms.

Other steps you can take

To make the most of depression treatment:

• Stick to your treatment plan

Don't skip appointments with your therapist or psychiatrist. It'll take some time to get better, so even if you feel well, don't skip your medication. If you stop, depression symptoms may relapse, and you could experience withdrawal-like symptoms. 

• Stop drinking or using recreational drugs

Many people with depression drink or use recreational drugs as coping mechanisms. In the long run, alcohol and drugs worsen depression and make it harder to treat. If you are not able to stop drinking alcohol or using drugs on your own, talk to your psychiatrist or therapist.

• Manage stress

Stress has been known to worsen depression. Learn coping skills to manage stress for a faster recovery.

• Sleep well

Both the amount of time and how well you sleep can affect your mood, energy level, ability to concentrate and resilience to stress. If you have trouble sleeping, find ways to improve your sleep habits or ask your psychiatrist or therapist for advice.

• Get regular exercise

Exercise has a direct effect on mood, as feel-good hormones called endorphins are released, Physical activity such as gardening or walking can reduce stress, improve sleep and ease depression symptoms.

Getting better is possible. Work with your psychiatrist and therapist to find a treatment plan that works for you.