Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) on Treatment Resistant Depression
Thank you for the opportunity to speak today. My name is Dr. Stephanie Fox-Rawlings. I was previously a neuroscientist at Children’s National Medical Center and now am a Senior Fellow at the National Center for Health Research. Our research center analyzes scientific and medical data to provide objective health information to patients, providers and policy makers. We do not accept funding from the drug or medical device industry. I have no conflicts of interest.
A standard definition for TRD [treatment resistant depression] would be beneficial to patients, prescribers, researchers, and insurance companies. A Medicare definition of TRD could have a widespread impact.
Unfortunately, definitions for TRD in clinical trials are diverse and some do not make sense. For example, the definition often used in studies of TMS and some other devices is a failure of just one prior treatment. One treatment failure is not uncommon and should not be considered treatment-resistant.
A definition that balances the need for identifying most patients without being overly broad could improve our knowledge of which treatments tend to work for whom. Providing a better definition for TRD would reduce the number of patients incorrectly given the diagnosis. A recent review by Mrazek et al found that most patients diagnosed with TRD may not be. [1] This can be due to inaccurate or incomplete diagnosis or to insufficient treatment duration or dosage. It can also be caused by limited access to affordable or effective mental health services.
About a third of misdiagnoses are due to nonadherence to treatment. This could be caused by cost, social or environmental conditions, or side effects. Stricter guidelines for TRD would help control for these confounding variables, helping to identify whether a treatment works or not.
It is important to reduce barriers to compliance, because after multiple treatment failures patients are less likely to achieve remission and more likely to try treatments with more severe side effects or less clear efficacy.
The definition of TRD would also need to address the issue of how to define remission and to describe what constitutes a sufficient and adequate treatment trial. It would further need to include the number of treatment trials and their types.
Inclusion of specific types of therapy in the definition may increase the likelihood that they are attempted. Many patients defined as having TRD have never tried cognitive behavior therapy, although it is often very effective. Patients may not know where to find a therapist, or have not heard of it, or prefer medication. If Medicare defines TRD as a condition for people who have tried and failed several types of therapies, including cognitive behavior therapy, that could influence patients to try it.
A recent review of TRD studies found that only about 15% of patients reported suicidal ideation and 17% had a previous suicide attempt. Either TRD was not appropriately defined in those studies, or a definition requiring either suicide ideation or attempt would inappropriately exclude many TRD patients.
To be useful for clinical trials, a definition for TRD needs to take into account the fact that depression waxes and wanes for most patients. Randomized studies with placebo and sham treatments are essential for differentiating between treatment efficacy, depression’s cyclic nature, and the strong placebo effect. Medicare analysis of a particular treatment need to include randomized, blinded, and placebo/ sham controlled studies.
Clinical trials should include men and women as well as sufficient numbers racial minorities and patients over 65. Many treatments have not been analyzed to insure that they are both safe and effective for patients 65 and older. Metabolism, eating habits, and activity levels change with age and can affect the way a treatment works. Similarly some treatments do not work as well for certain minority groups or for both men and women due to cultural and biological reasons.
Clinical trials should focus on clinically meaningful improvements in patients’ lives. This should include improvement in ability to function and in quality of life. For those that have suicide ideation or suicide attempts, a decrease would be beneficial, but this is not relevant to the population as a whole.
In conclusion, a clear, well-constructed TRD definition for Medicare would benefit patients. Treatments should be evaluated in terms of improving daily functioning and quality of life. Decisions concerning appropriate treatments for TRD should include well controlled randomized trials including men and women, minorities, and patients over 65.
Thank you for your time and consideration of our views.
- Mrazek DA, Hornberger JC, Altar CA, Degtiar I.(2014) A Review of the Clinical, Economic, and Societal Burden of Treatment-Resistant Depression: 1996–2013. Psychiatr Serv 65(8):977-87.