Can Doctors Accurately Predict Long-Term Recovery in Treatment-Resistant Depression?

What you need to know

• There is no single agreed-upon definition of treatment-resistant depression (TRD), with over 150 existing definitions focused mainly on medication response.

• Limited long-term studies show that a majority of patients with TRD significantly improve over time, even after years of chronic illness.

• Current evidence does not support that doctors can accurately predict long-term recovery chances in individual TRD patients.

Defining Treatment-Resistant Depression

Depression that does not respond well to treatment is a major challenge in psychiatry. But what exactly do we mean by “treatment-resistant depression” or TRD? This study found there is no single agreed-upon definition. In fact, researchers identified over 150 different definitions of TRD in use.

Most of these definitions focus on how well a person responds to antidepressant medications. For example, a common definition is failing to respond to at least two different antidepressant trials. However, the researchers point out that these definitions have important limitations:

• They mainly look at medication response, not other treatments like psychotherapy
• They don’t consider factors like quality of life or ability to function
• The definitions keep changing as new depression treatments become available

This lack of a standard definition makes it difficult to compare research studies on TRD. It also means that when doctors use the term “treatment-resistant depression,” they may mean different things.

The researchers argue that the term “treatment-resistant” can be misleading. It may suggest that no treatments will work, when in reality there may still be effective options to try. They propose that terms like “difficult-to-treat depression” may be more accurate.

Long-Term Outcomes in Treatment-Resistant Depression

A key question is: what happens to people with TRD in the long run? Do they tend to stay depressed, or can they recover over time? The researchers found only a handful of studies that followed TRD patients for several years or more. While limited, these studies showed some encouraging results.

One study followed TRD patients for an average of 3 years after they received intensive hospital treatment. At the start, these patients had very severe, chronic depression that had not responded to multiple treatments. But by the end of the study:

• 60% had reached full remission (meaning their depression symptoms had gone away)
• 70% had either fully or partially recovered

Another study tracked TRD patients for 3-7 years and found:

• 60% were either free of depression symptoms or had only mild symptoms
• 40% continued to have significant depression

While a substantial minority did remain chronically depressed, the majority of patients showed major improvements over time. This was true even though they had been ill for an average of 16-22 years before the studies began.

These findings challenge the assumption that TRD is a permanently unchanging condition. Even after many years of severe, unresponsive depression, a majority of patients were able to achieve significant recovery over time.

Can Doctors Predict Individual Outcomes?

If most TRD patients improve over time, but some remain chronically ill, can doctors predict which category a particular patient will fall into? The researchers examined studies on predicting treatment response and long-term outcomes in depression.

They found a growing body of research using advanced techniques like machine learning to try to predict treatment outcomes. However, these prediction models had significant limitations:

• Most only tried to predict response to one specific treatment, not long-term outcomes
• Many studies had small sample sizes and lacked validation in separate patient groups
• Predictive accuracy varied widely across studies

The largest, most well-designed studies tended to show lower predictive abilities. For example, one study followed over 800 patients receiving various depression treatments for 2 years. Their prediction model could only correctly identify 47% of patients who would develop chronic depression - essentially no better than chance.

Overall, the evidence did not support that doctors can reliably predict long-term outcomes for individual TRD patients using current methods. While certain factors may indicate better or worse odds statistically, there is still too much individual variation to make accurate predictions.

The Role of Social Factors

Interestingly, some studies found that non-medical factors played an important role in long-term TRD outcomes. For example, one study found that higher education levels and strong social support predicted better chances of remission.

This highlights that recovery from depression depends on more than just biological factors that medications target. A person’s social circumstances, relationships, and psychological resources also shape their path to recovery.

The researchers note this is especially relevant because studies have found that many people seeking assisted dying for psychiatric reasons report social isolation as a factor. This suggests improving social support could potentially change outcomes for some patients, even if they have not responded to medications.

Implications for Assisted Dying Policies

Some countries allow assisted dying (also called euthanasia or physician-assisted suicide) for psychiatric disorders in certain cases. A key eligibility requirement is usually that the person’s condition is considered “irremediable” - meaning it cannot be improved.

The authors argue their findings have important implications for these policies:

1. There is no clear scientific definition of when depression becomes truly irremediable. The term “treatment-resistant” does not necessarily mean no improvements are possible.

2. Long-term studies show that even after decades of severe, unresponsive depression, a majority of patients can achieve significant improvements over time.

3. Current prediction models cannot reliably distinguish which individuals will or will not recover in the long run.

4. Social factors play an important role in outcomes, suggesting some cases may not be purely biological/medical issues.

They conclude that based on available evidence, doctors cannot accurately determine that a particular patient’s depression is irremediable and will never improve. This challenges a core assumption of many assisted dying policies for psychiatric disorders.

The authors argue this issue needs more attention as countries consider expanding assisted dying to include mental illnesses. They suggest more research is needed on long-term outcomes and better prediction models before assuming any psychiatric condition is truly irremediable.

Conclusions

• There is no single agreed-upon definition of treatment-resistant depression, making the concept somewhat ambiguous.

• Limited long-term studies show a majority of even very severe, chronic TRD patients significantly improve over time.

• Current evidence does not support that doctors can accurately predict long-term recovery chances for individual TRD patients.

• These findings raise important questions about determining “irremediability” in the context of assisted dying policies for psychiatric disorders.

This research sheds light on the long-term nature of severe depression and challenges some common assumptions. While treatment-resistant depression is very serious, the evidence suggests maintaining hope for eventual recovery is often warranted. The authors argue this calls for caution in labeling any psychiatric condition as truly irremediable.