Are Common Depression Rating Scales Missing Important Treatment Effects?

What you need to know

• Common depression rating scales like the Hamilton Depression Rating Scale (HAM-D) and Montgomery–Åsberg Depression Rating Scale (MADRS) may not fully capture meaningful improvements in patients undergoing neurosurgical treatments for major depression.

• These scales focus primarily on symptom reduction but do not adequately measure improvements in quality of life and daily functioning, which patients often consider more important.

• Relying solely on symptom-based scales to determine treatment response may miss clinically significant benefits experienced by some patients.

• Including measures of functional capacity and quality of life as primary outcomes in clinical trials could better capture meaningful treatment effects.

The limitations of standard depression rating scales

Major depressive disorder (MDD) is a common and debilitating mental health condition. While many patients benefit from standard treatments like medication and psychotherapy, a significant number continue to struggle with persistent symptoms that severely impact their lives. For these individuals with treatment-resistant depression, neurosurgical approaches like deep brain stimulation or targeted brain lesions may be considered as a last resort.

However, evaluating the effectiveness of these experimental neurosurgical treatments has proven challenging. Clinical trials typically rely on standardized rating scales to measure changes in depression symptoms and classify patients as “responders” or “non-responders” to the intervention. The two most commonly used scales are the Hamilton Depression Rating Scale (HAM-D) and the Montgomery–Åsberg Depression Rating Scale (MADRS).

While these scales are well-established and widely used, they have significant limitations. Importantly, they focus primarily on measuring the presence and severity of depressive symptoms. However, they do not adequately capture improvements in quality of life, daily functioning, and other outcomes that patients often consider more meaningful than symptom reduction alone.

This case report highlights how relying solely on symptom-based scales like the HAM-D and MADRS may cause researchers to miss clinically significant benefits experienced by some patients undergoing neurosurgical treatments for depression. The authors present the case of a 28-year-old woman who underwent an experimental neurosurgical procedure for severe, treatment-resistant depression, with surprising results.

A case study in treatment effects

The patient was a 28-year-old woman with a long history of severe, debilitating depression that had not responded adequately to multiple medication trials, psychotherapy, transcranial magnetic stimulation, or electroconvulsive therapy. Her depression left her mostly homebound, unable to work, and experiencing chronic suicidal thoughts.

Given the severity and treatment-resistance of her condition, she was enrolled in a pilot clinical trial of MRI-guided focused ultrasound (MRgFUS) capsulotomy - an experimental neurosurgical procedure that uses focused sound waves to create a small lesion in a brain area called the anterior limb of the internal capsule. This brain circuit has been implicated in depression and is sometimes targeted in neurosurgical treatments.

Before the procedure, the patient scored in the severe range on both the HAM-D and MADRS depression rating scales. At 12 months after treatment, her scores on both scales had improved somewhat but still fell in the moderate depression range. Based on standard criteria used in clinical trials, which typically define treatment response as a 50% or greater reduction in depression scale scores, she would be classified as a “non-responder” to the treatment.

However, when interviewed 14 months after the procedure, the patient reported significant improvements in her quality of life and daily functioning that were not fully captured by the depression rating scales:

• She described her overall mood as “brighter” and said she no longer experienced suicidal thoughts or urges to self-harm.

• She had resumed some of her hobbies and taken on part-time work.

• Her ability to concentrate and focus on tasks had markedly improved, allowing her to apply to and be accepted into a PhD program - fulfilling a long-standing goal.

• Her relationship with her partner had improved as he was no longer in a primary caregiving role.

• She was in more frequent contact with friends (though in-person visits were limited by COVID-19 restrictions).

While the patient continued to experience some depressive symptoms like sadness and feelings of worthlessness, she considered the treatment a success overall. She stated that she would not hesitate to make the same decision to undergo the procedure again.

The mismatch between scales and patient experience

This case illustrates a concerning mismatch between how depression treatments are typically evaluated in clinical trials and the outcomes that matter most to patients. The patient experienced meaningful improvements in her quality of life, daily functioning, and future outlook. However, because her scores on symptom-based rating scales did not improve dramatically, she would likely be classified as a “non-responder” in a clinical trial.

The authors note that similar cases have been reported in studies of deep brain stimulation for depression, suggesting this may be a widespread issue in evaluating neurosurgical treatments for psychiatric conditions. They argue that sole reliance on scales like the HAM-D and MADRS to determine treatment efficacy may lead researchers to dismiss potentially beneficial treatments for patients who have exhausted all other options.

Why standard scales fall short

There are several reasons why commonly used depression rating scales may fail to capture clinically meaningful treatment effects:

1. Focus on symptoms rather than functioning: Scales like the HAM-D and MADRS primarily measure the presence and severity of depressive symptoms. However, they do not adequately assess changes in social, academic, occupational, or daily functioning - areas that patients often consider more important than symptom reduction alone.

2. Emphasis on full remission: The common practice of defining treatment response as a 50% or greater reduction in scale scores sets a high bar that may not reflect meaningful partial improvements.

3. Failure to capture individual priorities: Standardized scales cannot account for the specific goals and priorities of individual patients, which may vary widely.

4. Insensitivity to qualitative changes: Numerical rating scales may miss subtle but important qualitative shifts in a patient’s outlook, sense of hope, or quality of life.

5. Potential ceiling effects: For patients with very severe, treatment-resistant depression, even substantial improvements may not register as a large percentage change on rating scales with upper limits.

Implications for future research

The authors argue that to better capture clinically meaningful treatment effects in trials of neurosurgical interventions for depression, researchers should:

1. Include measures of functional capacity and quality of life as primary outcomes, rather than relying solely on symptom-based scales.

2. Develop and validate new outcome measures specifically designed to assess the effects of neurosurgical treatments on depression.

3. Incorporate qualitative interviews and patient-reported outcomes to capture individual experiences and priorities.

4. Consider using more nuanced definitions of treatment response that account for partial but meaningful improvements.

5. Explore the use of personalized outcome measures that allow patients to identify and track progress towards individual goals.

While the paper focuses on trials of neurosurgical treatments for depression, the authors suggest that similar issues likely apply to studies of neurosurgical interventions for other psychiatric conditions. They emphasize the need for further research to determine the most appropriate and clinically relevant outcome measures for these types of trials.

Conclusions

• Commonly used depression rating scales like the HAM-D and MADRS may fail to capture clinically meaningful improvements in some patients undergoing neurosurgical treatments for severe, treatment-resistant depression.

• Relying solely on these scales to determine treatment efficacy risks dismissing potentially beneficial interventions for patients who have exhausted all other options.

• Future clinical trials should incorporate measures of functional capacity, quality of life, and patient-reported outcomes to better assess the full impact of neurosurgical treatments for depression.

• There is a need to develop more nuanced and patient-centered approaches to evaluating outcomes in trials of novel treatments for severe psychiatric disorders.