Depression

Thoughts on Difficult-to-Treat Depression

How this new terminology can help us.

Posted Sep 06, 2020

Sam Wordley/bigstock
Source: Sam Wordley/bigstock

There’s a new phrase in town: difficult-to-treat-depression.  It’s intended to replace the term treatment-resistant depression, used for many years to capture those who experience a chronic and recurrent illness and don’t achieve sustained remission (complete relief of symptoms) despite adequate therapy.  Here I will share with you my thoughts on this change and my desire that we use this categorization thoughtfully, without placing vulnerable people into diagnostic buckets too quickly.

One reason for the new terminology is that the word “resistant” may have negative connotations and suggest that the person is to blame for being resistant to treatment efforts – definitely not true.  A second concern is that persisting with a series of medication trials that are considered unlikely to achieve remission is wasted effort, puts an undue burden on the individual, and creates unpleasant side effects.

Resistance to treatment occurs for many reasons.  The current phrase, treatment-resistant depression (TRD), is complex and hard to define, with no universal agreement.  It is most often considered a failure to respond to at least two adequate courses of antidepressant medication.  However, this definition does not align with current clinical practice that includes psychotherapy as a fundamental treatment option, neurostimulation treatments (ECT, rTMS, Vagus Nerve Stimulation) or the newer use of ketamine and esketamine, all of which change treatment response rates.  TRD also does not consider a person’s degree of functional impairment, depression subtype, comorbidities, and psychosocial stressors which can make it more complex to treat.  Recent innovations, such as the use of clinical genomics to tailor optimal dose and type of antidepressant medication, the impact of modifiable lifestyle factors like sleep, diet, exercise, social isolation on depression, and our understanding of systemic inflammation as risk factors for depression, are also not reflected in the current TRD definition and statistics.

The alternative model, difficult-to-treat depression (DTD), is defined as “depression that continues to cause significant burden despite usual treatment efforts.”  What does that mean? “Significant burden” is subjective and will vary by person.  “Usual treatment efforts” depends on the local health care setting, treatment guidelines, and practice and thus will also vary.  DTD is based largely on expert consensus.  Its premise is that full resolution of depression symptoms might not be achievable in some people and thus it shifts the focus away from a goal of remission to one of optimal symptom control and functional improvement in which the inconvenience, side effects, and burden of repeated treatments on patients’ lives are minimized.  

There are many good provisions in the DTD model and I respect the leaders in psychiatry who support it.  Mental health experts have recognized the need for a balance between alleviating severity, reversing what is reversible, and being prepared to step back at times while maintaining hope and realistic goals.  It’s reassuring to know that before declaring “remission is not possible” and assigning this label to a person, the provider is expected to do a comprehensive evaluation of all treatable causes of the presenting symptoms and confirm correct diagnosis, adequate treatment (dose and duration) and prior adherence to treatment; consider the pharmacogenetics; and assess general medical and psychiatric comorbidities and psychological stressors (environmental factors) that may have been unrecognized.  

This process includes self-management strategies and collaborative shared decision making when considering treatment options as advocated by an international consensus statement on DTD.  The goal is then to use all available interventions to evaluate and manage the person’s symptoms.  Only then, when these steps are not effective, should the DTD designation be applied.  If a person is thought to have DTD, it is expected that he or she will receive a thorough re-evaluation of their symptoms annually and be offered new treatments in development as they are made available.

I have some questions regarding the implementation of the new DTD diagnosis and treatment guidelines and the challenges it presents:  How should remission from depression be defined?  Who decides what a clinically meaningful benefit is?  How, when, and for whom should a provider shift the focus from remission to “controlling symptoms and restoring function?”  Who determines how much treatment is “enough” for any one person?  Addressing these questions is a challenge that requires exceptional clinical skills and judgment.  

I suggest we modify our thinking to “the steps to remission are not yet identified for this person” with the view of depression as “treatable with challenges.”  I would expect that the person be involved in all discussions and decisions in a patient-centered shared decision-making collaborative model.  When given adequate information, the person is better able to determine what he is willing to do, and what is beneficial and important to him.  Then I would leave it to him to decide how far to go and when to stop treatment trials and “manage” his symptoms.  I would also require a periodic re-evaluation of the person’s symptoms and preserve his right to resume active treatment at a later date.

One thing I know for sure: I would not be here today if my treatment team regarded me as resistant and did not continue to tirelessly search for creative, out-of-the box, cutting edge treatments for my severe depression, which eventually worked!  I was fortunate, as this may not have happened outside of academic psychiatry or in settings where providers may not be as aware of off-label or newer treatments.  I have often been reminded that in life you never know what is coming around the corner, including new treatment possibilities.  All persons deserve to have this hope.

I need to remind you today that “better” is not good enough.  It is possible and realistic for those of us who have depression to expect wellness and well-being, and to have a treatment team that understands this.  My hope is that all mental health providers will apply the label difficult-to-treat depression judiciously.