Are Rates of Treatment Resistant Depression Increasing?

Summary: Yes, a new, long-range study conducted in the U.K. shows rates of treatment resistant depression increasing over a 25-year period between 1996 and 2021. This finding may cause providers to reassess assumptions about the prevalence of TRD.

Key Points:

• Data shows rates of TRD are significantly higher than previous estimates
• TRD is associated with increased risk of physical comorbidities
• TRD is associated with increased prevalence of co-occurring mental health disorders
• Data shows people with TRD use more resources on treatment than people with MDD, yet are less economically active than people with MDD

What is Treatment-Resistant Depression?

While people generally understand the basic facts about mental health disorders such as mood disorders, anxiety, and others, many people have never heard of treatment resistant depression or know that rates of treatment resistant depression may be increasing in the U.S. and around the world.

The most recent research exploring treatment-resistant depression (TRD) among people diagnosed with major depressive disorder (MDD) appears in the peer-reviewed journal article “Examining the Needs, Outcomes and Current Treatment Pathways of 2461 People With Treatment-Resistant Depression: Mixed-Methods Study.”

In this publication, a group of researchers in the United Kingdom (UK) tested how various clinical treatment approaches impacted patients with TRD, and collected important new data on the current prevalence of TRD in adult populations.

Before we go any further, here’s how we define treatment resistant depression:

“Treatment-resistant depression (TRD) is a subtype of major-depressive disorder (MDD) that shows unsatisfactory response after at least two attempts at treatment with at least two types of antidepressant medications.”

For details on TRD and how we treat TRD at Crownview Psychiatric, please read our treatment page here:

Inpatient Depression Treatment Center

In this article, we’ll review the study we introduce above on treatment resistant depression, discuss the negative consequences of TRD, and close with a list of recommendations from the study authors on how to best improve support and treatment for patients with treatment-resistant depression.

First, let’s identify the scope of the problem.

How Many People Have Treatment Resistant Depression (TRD)?

Here are the statistics on depression in the U.S. and the world, and published by the U.S. Department of Health and Human Services (HHS) and the World Health Organization (WHO):

• 280 million adults have clinical depression, worldwide
• 23 million adults in the U.S. have clinical depression

Now let’s look closer at the depression data. Here’s the most recent information, as published in the 2023 National Survey on Drug Use and Health (2023 NSDUH):

Major Depressive Episode: 2023

• Adults 18+ total: 8.5% (21.9 million)
• Adults 18-25: 17.5% (5.9 million)
• Adults 26-49: 10.2% (10.5 million)
• Adults 50+: 4.5% (5.3 million)

Now let’s look at the number of people with MDD with severe impairment, or symptoms that create significant disruption in daily life.

Major Depressive Episode, Severe Impairment: 2023

• Adults 18+ total: 5.9% (15.2 million)
• Adults 18-25: 11.8% (4.3 million)
• Adults 26-49: 7.4% (7.6 million)
• Adults 50+: 2.7% (3.2 million)

We’ll end this statistics section with information on the prevalence of treatment for TRD:

• Among people with MDE estimated to have TRD, 66.7% received evidence-based treatment:
  • That’s 4.4 million out of a total of 22 million people with MDE, or around 20%
• Among people with MDE with severe impairment, 70.1% received evidence-based treatment:
  • That’s 3.1 million out of a total of 15.2 million people with MDE with severe impairment, which is also around 20%

Those treatment rates are far too low. However, we understand how people with TRD may often feel about treatment. When it doesn’t work, they may decide to discontinue treatment. If that happens, they may contribute to the treatment gap, which is the difference between the number of people who need treatment for TRD and the number of people who get treatment for TRD.

Consequences of Chronic Major Depressive Disorder (MDD), Chronic Treatment Resistant Depression (TD)

If studies show rates of resistant depression increasing, then the treatment gap we identify above will also increase, and more people will experience the negative consequences of TRD. The long-term consequences of treatment-resistant depression (TRD) can lead to severe disruption across multiple life domains.

When MDD or TRD goes untreated and unresolved, consequences include:

• Difficulty with family, peer, and romantic relationships
• Impaired work performance
• Decreased/impaired academic attainment
• Decreased, impaired, or total loss of ability to engage in typical activities of daily life, including maintaining personal hygiene and basic healthy habits
• Increased rates of co-occurring mental health disorders, such as:
  • Anxiety
  • Insomnia
  • Obsessive-compulsive disorder (OCD)
• Alcohol/substance misuse
• Increased rates of chronic physical comorbidities
• Greater incidence of self-harm
• Increased premature mortality rate

In a large-scale study on the long-term consequences of TRD, Dr. Jonas Lundberg offers this assessment of the dangers of chronic, unresolved TRD:

“We found that the treatment-resistant group used outpatient resources twice as much, had twice the amount of sick leave, spent three times the number of days in hospital and had a 23 percent higher mortality rate than patients without treatment-responsive depression.”

Those serious and severe consequences are the reason it’s important to understand whether rates of treatment resistant depression are increasing. Let’s take a look at this new study from the U.K. and see what they found.

Treatment Resistant Depression Among Adults: Is It Increasing?

The research team collected data from the U.K. National Health Service (NHS) Electronic Health Record (EHR) system. Criteria for eligibility in the study included patients:

• Age 18+
• Diagnosed with major depressive disorder (MDD) between 1996 and 2021
• Currently receiving ongoing treatment and care for MDD

Next, the team selected patients with TRD by identifying the following characteristics:

• Third antidepressant added to treatment plan
• Augmenting agent/medication added to treatment plan after inadequate response to two trials of standard antidepressant medication

Here’s what they found.

TRD Among Adults in the U.K.: Stable or Increasing?

Total MDD Patients with TRD:

• 48%

Depressive symptoms:

• 31% of TRD patients reported recurring depressive symptoms
• 26% of MDD patients reported recurring depressive symptoms

Economic factors:

• 41% of TRD patients were economically inactive
• 32% of MDD patients were economically inactive

Mortality:

• On average, people with TRD died five years earlier than people with MDD

Co-occurring Disorders

• Substance use: 20% TRD v. 18% MDD
• Anxiety disorders: 31% TRD v. 24% MDD
• Personality disorders: 16% TRD v. 11% MDD
• Self-harm: 3% TRD v. 1% MDD
• Psychosis: 15% TRD v. 8% MDD

Physical Comorbidities:

• Cardiovascular: 6% TRD v. 3% MDD
• Respiratory: 4% TRD v. 3% MDD
• Gastrointestinal: 5% TRD v. 2% MDD
• Type 2 diabetes: 6% TRD v. 4% MDD

Medication Trials:

• Two failed trials with standard antidepressants: 36%
• Three failed trials with standard antidepressants: 20%
• Four or more failed trials with standard antidepressants: 37%

Based on previous estimates of 30 percent to 35 percent prevalence of TRD among people with MDD, these results show that close to half of people with MDD develop TRD.

These results show treatment resistant depression increasing among adults in the U.K.

That’s a major finding: rather than thinking of this population as about a third of people with MDD, this data indicates it may be time to think of this population as about half of people with MDD.

That’s a big difference.

TRD in the UK: Additional Findings, Recommendations

In addition to collecting quantitative data on TRD, i.e. data involving numbers, the research team collected qualitative data on TRD, i.e. data on the subjective experience of having TRD and/or the subjective experience of treating people with TRD.

Qualitative Data on TRD: Prevailing Themes for Patients and Providers

1. Understanding TRD diagnosis.

Many patients reported not understanding that failure on two antidepressant trials meant they had TRD. They also reported hearing inconsistent language around the diagnosis, which had a negative impact of their overall understanding of their diagnosis, their disorder, and their symptoms.

2. TRD typically involve difficult treatment experiences.

Overall, both patients and providers reported that the TRD experience involves confusion and feelings of helplessness. Patients report years of lost time due to misdiagnosis and inadequate treatment, as well as significant impairment in daily functioning and interpersonal relationships. Both patients and providers also noted the need for “a holistic, patient-centered treatment approach, as the one size fits all approach…was recognized as inadequate.”

3. New approaches needed.

Patients emphasized the need for new and novel approaches to treatment, specifically the manner in which providers deliver psychotherapy. Patients suggested compassion-focused therapy to support cognitive-behavioral approaches, and consistently returned to the need for individualized, patient-centered care, with treatment plans created only after receiving patient input on what they’d like and what type of care they think might help.

4. Barriers to care.

The primary barrier to care identified by patients was that their therapists didn’t know what to do with them after failed trials of standard antidepressants. Neither patients nor clinicians showed adequate awareness about new and novel treatments for TRD, such as transcranial magnetic stimulation (TMS) or Ketamine/Spravato.

5. Awareness, please.

Patients reported they consistently needed to remind providers of their history, and that they spent a significant amount of time rehashing past treatment experiences, which was frustrating. Patients and providers indicated streamlining and ensuring accuracy of notes in patient records could improve outcomes for people with TRD, overall.

Next, we’ll share a list of recommendations from the research team for improving outcomes for patients with treatment resistant depression. Based on the quantitative and qualitative data collected, which we share above, the researchers created a list of seven priorities for the future.

Treatment Resistant Depression Increasing: 7 Steps to Improve Patient Outcomes

1. Inform any patient with TRD about what TRD is and a full and comprehensive list of evidence-based treatment options.
2. Create standardized systems that identify people with TRD early on, and get them on the appropriate treatment pathway.
3. Improve access to psychotherapeutic supports, with a focus on compassion-based cognitive behavioral therapies
4. Improve clinician training, awareness, and access to new treatment approaches
5. Include “low intensity, high-frequency” support such as peer groups, community groups, and occupational therapy.
6. Emphasize whole-person, holistic, comprehensive care with consistent support and input from qualified clinicians
7. Expand clinical research opportunities for patients with TRD

Those are all common-sense recommendations we’re behind, on hundred percent. As a reminder, before this research, the prevailing default position among mental health professionals was that TRD occurs in about a third of patients with MDD. This study changes that.

This research answers the question we pose at the beginning of the article “Is Treatment Resistant Depression Increasing?” with a provisional “Yes, according to new data from the U.K.”

We’ll close with the views of two researchers on the study, Dr. Kiranpreet Gill and Dr. Steven Marwaha of the University of Birmingham, as expressed in an interview here:

First, Dr. Gill:

“This paper highlights how widespread treatment-resistant depression is among those who are diagnosed with depression. With nearly half of all patients not responding to multiple drug options, we need better treatment options to be able to support patients for whom first line antidepressant medications don’t make a difference.”

Next, Dr. Marwaha:

“This study demonstrates people with TRD are at a higher risk of a range of poorer outcomes, and that we need better defined care pathways for helping this population, and are in urgent need of developing and testing new treatments for this group.”

Again, we agree: new and novel treatments for people with treatment resistant depression are needed, and at Crownview Psychiatric Institute, we provided the latest, most innovative treatments available. If you or someone you love has treatment resistant depression, or has depression and not yet experienced successful treatment, please call us today: we can help.

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