We need more studies on treatment-resistant depression

Key points to remember

  • Up to 30% of adults diagnosed with major depressive disorder do not feel better when taking the drugs that are commonly used to treat it; this is called treatment-resistant depression (TRD).
  • There has been no standard definition or way to diagnose DRT, which has made it difficult for doctors to spot – let alone treat – in their patients.
  • To solve the problem, an international team of researchers have come together to define the depressive spectrum, from major depressive disorder to partially resistant depression and to treatment resistant depression.

In a new report published in the journal Molecular Psychiatry, researchers around the world have come up with a more comprehensive and clearer definition of treatment-resistant depression (TRD).

The group also called for more research into how the disease can be better identified and treated and hopes to encourage more people to talk about depression.

Why define TRD?

Having a definition that can be widely used and understood is important on several levels. On the one hand, this matters to scientists designing clinical trials for new drugs and other potentially effective treatments for TRD.

A clear definition of TRD also helps clinicians who work with people who may have the disease and gives them a framework for diagnosing the disease, a crucial first step in making sure people receive treatment.

“My sweet take on what will happen in 50 years – and I hope 20 years, maybe even in my professional life – is to have a way to personalize treatment for each patient just as we do. let’s do cancer, ”Carmine Pariante, professor at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London and lead author of the recent study, said Verywell.

Personalized care can include biomarkers (which are measured in a patient’s blood sample), brain scans, and genetic data, which can help doctors and mental health professionals determine which patients are likely to respond well to the drug. treatment for depression and which might not.

Once providers have an idea of ​​patients at risk for depression who are unlikely to respond to usual treatments, they can begin to think of different ways to help them.

“Maybe two antidepressants together or an anti-inflammatory and an antidepressant, a psychedelic; whatever medication is appropriate for that person, ”Pariante said. “I think it would really make a big difference between what we do now and what we will do in the future.”

What is TRD?

Major depression, a mood disorder that leads to debilitating and persistent feelings of sadness and lack of interest in their daily lives, is one of the leading causes of disability around the world. However, up to 30% of adults with the disease do not respond to medications that are usually prescribed to treat it.

Carmine Parante

There is not a single validated biomarker that says “you are resistant to treatment, you are not resistant to treatment” because that is not a yes and a no.

– Carmine Parante

There are many reasons why some people are helped by standard treatments for depression and others are not. We all have different bodies, brains, and experiences, which means that no two people react the same to the many ways we deal with depression.

Another reason has less to do with people who suffer from depression and more with how the diagnosis is spoken and understood; for example, the criteria for defining and treating the disease.

“There is a big problem with patients who do not respond to currently available drugs,” Pariante said. “About one in two patients, or only 50%, responds to the first antidepressant prescribed, and maybe two in three respond to the second or third antidepressant. [that is tried]. ”

There is still “a core of 25% of patients who do not respond to available drugs, there is a real need to develop drugs for this target population,” according to Pariante, who explained that ideally such research would take the form of a trial in which several drugs are tested collaboratively at the same time until they work (a “platform trial”).

Gaps in TRD research

In the recent report, more than 60 scientists gathered to discuss and review the current description of TRD and draft new criteria for the condition.

As the experts collected data, they found that:

  • Only about a third of studies on TRD actually recruited people who were resistant to at least two approaches to antidepressant.
  • Only one in five studies recruited people who took the right amount (dosage) of medicine and for the right amount of time (duration).

Without agreement on the nature of the disease, how can providers determine which patients are considered resistant to treatment?

“These people exist from a clinical point of view, and they also exist from a biological point of view,” said Pariante. “There is something about the way their body, or their brain, reacts to depression.”


It is also possible that people may be helped somewhat by treatment for depression, in which case they are not totally resistant to treatment. Instead, they are said to have partially resistant depression (PRD).

Experts concluded that the diagnostic criteria for PRD versus TRD should be:

  • To classify a person as having PRD, a person should have more than 25%, but less than 50%, of a reduction in symptoms after using some type of antidepressant.
  • To classify a person as having TRD, they should have less than 25% reduction in symptoms after trying at least two different types of antidepressants. TRD is also a matter of timing. For example, if a person does not respond to treatment in a single episode of depression or chronic depression.

Not just drugs

TRD includes the word “treatment” because there are many ways to help people with depression, such as medication and psychotherapy. Experts said all options should be considered, not just drugs.

Carmine Parante

There is something about the way their body, or their brain, responds to depression.

– Carmine Parante

“I think the concept of resistance – or response, which is sort of the reverse concept – is kind of a continuum,” Pariante said. “So what’s always happened in medicine is that you kind of create an arbitrary cutoff on a continuous spectrum of people who, you know, range from people who are improving really well and pretty quickly, all the way up. ‘to people who don’t improve at everything. ”

Pariante said the continuum cutoff has changed slightly in different studies, “because at this time there isn’t a single validated biomarker that says ‘you are resistant to treatment, you are not resistant to treatment’. , because it is not a yes and no condition.

Precision leads to progress

Armed with a clear definition of TRD, the next step is to standardize and innovate the way vendors can diagnose it. Experts advocate a more holistic, data-driven approach (which combines biological information such as blood samples and brain scans) to search for biomarkers of depression.

Pariante added that TRD patients have real changes in their inflammatory biomarkers, and “if you measure biomarkers of inflammation – for example, c-reactive protein or other biomarkers that are activated in metabolic dysfunction or of infection – treatment-resistant depression is very similar to a diabetic or coronary patient, even if he does not actually have diabetes or coronary artery disease. ”

While potential new treatments for depression like psychedelics, anti-inflammatory drugs, and brain stimulation techniques show promise, Pariante said more research is needed to better understand which options will work in a specific group of people with depression.

For the past 20 or 30 years, Pariante has said that antidepressant research relies on the same kind of data. For example, drug research often builds on a previous drug and improves it and its side effects, but always seeks to address the same issues.

“Antidepressants were only copies of previous drugs, still around the same idea of ​​inhibition serotonin or stimulating noradrenaline functions, “Pariante said.” So a kind of stimulation of the function of the neurotransmitters that regulate mood. But ecologically, there has been very little change. ”

The future could look different, however. Pariante said that now, “scientists sort of start with biological abnormalities and this research can only be improved by having a more cohesive, homogeneous group of people with whom to study and test drugs.”

What this means for you

If you or someone you know has depression and is unsure of where to go for help, call the SAMHSA National Helpline, 1-800-662-HELP (4357). It is confidential, free and operates 24 hours a day, 365 days a year. It is available in English and Spanish.

If you call this helpline, they can direct you to local treatment centers, support groups, and other organizations.

About Antoine L. Cassell

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