About Treatment Resistance and Refractory Depression

Published on 
October 2016

What is Treatment Resistance?

Contemporary psychiatric treatment has helped relieve the symptoms and suffering of many individuals struggling with 

The field offers a range of effective, evidence-based, biological, and psychotherapeutic treatments.

Despite these advances, many clinicians, patients, and their families struggle with the reality that even effective medications and short-term psychotherapeutic or inpatient treatments have not been enough to return a patient to full functioning. Being measurably less depressed is not the same as being free of depression. It may still leave a patient unable to work, attend school, or function adequately in a relationship.

Patients with “treatment resistant” or “treatment refractory” disorders are those who do not respond to the usual first- and even second- and third-line treatments. Many people whose lives have been adversely affected by psychiatric illness struggle with a range of difficulties that may include 

At Riggs, our patients, on average, are diagnosed with six different disorders. Most have “treatment resistant” mood disorders, like major depressive disorder or bipolar disorder that have not responded adequately to treatment, and at the same time meet diagnostic criteria for several other disorders. Some patients qualify for the designation of treatment resistance because they have failed many treatment efforts over time, while others have come to realize that they simply need more than outpatient treatment can provide.

Treatment Resistance and Comorbid Disorders

Among the factors that adversely affect the outcome of major depressive disorders and contribute to treatment resistance is the presence of comorbid personality disorders, such as:

  • Personality Disorders. These are quite common in patients treated at Riggs, and are enduring, persistent, and habitual, but maladaptive ways of responding to others or dealing with impulses or stressful situations that interfere with relationships or performance in roles. Borderline Personality Disorder is one of the best known of these, and is found in many Riggs patients. It is characterized by unstable and intense relationships, self-destructive behavior, uncertainty about one’s identity and a substantial risk of suicide. In Riggs patients, personality disorders appear to play a major role in treatment resistance, and much of our treatment program is designed to help patients deal with this aspect of the overall problem.
  • Mood Disorders. Treatment resistance in patients with mood disorders goes beyond personality disorder. A history of early trauma, abuse, neglect, or other deprivation is found frequently in patients with chronic major depressive disorders, and this group of chronically depressed patients responds better to psychotherapy than to medications, according to Dr. Charles Nemeroff and his colleagues (Nemeroff, et al. 2003). In the case of patients with bipolar disorder, intensive, longer-term psychosocial treatments are associated with better outcome than brief treatments. In the area of mood disorders, like bipolar disorder and major depressive disorder, then, evidence is growing that multiple simultaneous or so called co-morbid disorders, particularly the presence of a mood disorder plus a personality disorder plus a history of trauma, abuse or neglect, are associated with a high likelihood of treatment resistance.
  • Psychotic Spectrum Disorders. Among the psychotic spectrum disorders there is similar evidence that the genuine benefits of state-of-the-art psychopharmacologic treatments are mitigated by serious side effects, like weight gain, diabetes, and increased risk of cardiovascular illness. And, regardless of side effects, in the case of schizophrenia, fully a third of patients with the disorder fail to respond adequately to the best of the new medications, according to the American Psychiatric Association’s Practice Guideline.


Of course, no medication works unless a patient takes it. Poor adherence to prescribed medication is an additional confounding problem that makes people with psychotic spectrum and mood disorders “treatment resistant.” It is in error to assume that patients don’t take medications because they are unmotivated to get better. Patients with these disorders may rebel against diagnostic labels that pigeonhole them in ways that make it hard to hold on to their integrity, dignity, and identity as competent human beings. Riggs staff have led the way in developing the field of psychodynamic psychopharmacology, which attends not only to the importance of the use of medications with patients, but to the meaning of taking the medication. There is much to be gained by working with patients about the meaning of medications to maximize adherence through a mutually agreed upon medication regimen, while also attending to other aspects of treatment beyond medications.

Riggs – A National Referral Center for Treatment Resistance

Riggs is a national referral center for “treatment resistant” or “treatment refractory” patients. Most of our patients present with treatment refractory disorders – whether they have failed many or just a handful of treatment efforts. We know that among our patients

  • 80% have treatment refractory mood disorders;
  • 40% have had six or more self-destructive episodes;
  • 50% have made at least one serious suicide attempt; 
  • 60% have had three or more pre-Riggs hospitalizations;
  • 60% have also experienced early neglect, trauma, or abuse; and
  • About 35% meet criteria for post-traumatic stress disorder. 

Results from our 15-year follow along study of patients in treatment at Riggs suggest that a stay at Riggs often reverses the downward trajectory of previously “treatment resistant” patients’ lives and begins to help them move in a direction in which they can better utilize outpatient treatment, which most return to after treatment at Riggs.

If you are or know someone with a “treatment resistant” bipolar disorder or major depressive disorder, psychotic spectrum, anxiety, personality, or other disorder, or if you are a clinician who treats these patients, or if you are realizing that you simply need more than outpatient treatment to make the kind of gains that you are seeking, then Riggs may be a useful treatment option to consider.