PT Mobile Logo

Search form


6 Signs Your Patient Is at Risk for Treatment-Resistant Depression

6 Signs Your Patient Is at Risk for Treatment-Resistant Depression

  • Duration of the episode: the longer the episode of depression, the greater the atrophy in specific brain regions (eg, hippocampus); the cognitive and behavioral changes that take place during long episodes make a return to previous well-being difficult

  • Severity of the episode: both ends of the depression spectrum (most severe, mildest) are hypothesized to increase the risk of poor response—severe depression is associated with biological unbalances; mild depression, with lower drug versus placebo response

  • Melancholic features: TRD is more prevalent in bipolar depression than in MDD; the specific investigation of subthreshold manic symptoms is pivotal

  • Lack of symptomatic improvement within the first couple of weeks since the start of treatment

  • Comorbidity: anxious symptoms and full anxiety disorders (especially generalized anxiety disorder) were found to be predictors of lower rates of response and remission; personality disorders, especially avoidant and borderline, are negative prognostic factors

  • Old age, long duration of an episode, anxiety symptoms, and major life events can contribute to TRD.

  • For more information, see Factors That Predispose Patients to Treatment-Resistant Depression, on which this slideshow was based

Editor's note: This article was originally published on August 19, 2016 and has since been updated. PDF version.


This is very useful. Velandy Manohar, MD

Velandy @

are there gender predisposition

fathalalim @

This is a very-well written article but its premise, to me it is a fallacy. I have never encounter one case of so-called TRD that does not respond to a trial with a mood stabilizer.
If we believe that depression is associated with certain receptors in the brain, it should not be a matter of discussion that when you have targeted all of them the mood should improve. On the other hand, almost 100% of patients that have come to me with “depression and anxiety” have a mood disorder and agitation, which is worsened using SSRIs (check the “ARAD” syndrome described by Dr. Ronald Pies).
This paper’s case vignette reminded me of a study published by a group in Canada that reported (in 2000) improvement of Conduct Disorder and Oppositional-Defiant Disorder with risperidone. Like in this case, patients improved because risperidone can help to balance the mood in patients with sub-threshold cases of bipolar spectrum disorder.
If clinicians continue to believe that “bipolar” is just what Kraepelin described (hundreds of years ago) we will keep seeing “Treatment-Resistant Depression”. Also, responsible for the failure to capture mild cases of the bipolar spectrum is the unjustifiable neglect of entering the family history into the equation to formulate a diagnosis. In gathering family history, we must be a “detective” and decline to be satisfied with “nobody in family has mental illness”. Many people use alcohol and cannabis (or worst yet, opioids) to control a “racing mind”, impulsivity or explosive temper.
Finally, one major obstacle in making a proper diagnosis of a bipolar spectrum disorder is the fear of “giving a bad label”, that some clinicians have. And this is puzzling to me because I see doctors telling the mother of a young child “your son has a malignant brain cancer” or to the wife of a man in his 40s, “your husband has a Stage-4 pancreatic cancer” while doctors and others in the mental health field hesitate to talk about a treatable illness.

Dr. Manuel Mota-Castillo
Chief of Psychiatry and Training Director at
Burrell College of Osteopathic Medicine (BCOM) and
Director of Behavioral Health Services at
Memorial Medical Center, both in Las Cruces, NM

Manuel @

You are missing one or two. Lack of cognitive behavioural therapy and support counselling , or poor social support system and lack of education or engagement in supportive adjunctive therapies.

Brenda E @

Depression needs to be treated holistically from the sufferers perspective with reablement recovery concepts negotiated and introduced into his/her daily lives from his/her first interaction with the health practitioner.Early active participation of sufferers in management makes it easier to prevent development of acute crises,adaptation to living with some depressive symptoms associated with long term conditions and maintaining liveable health and wellbeing .

Tunde @

Did Julia ever receive interpersonal therapy? Cognitive behavioral therapy? Or were the medications the only interventions tried?

Mark @

Same: did Julia have someones to talk with her? Medicines alone cannot work miracles ... persons with sadness have unresolved trauma that needs address. The assumption that a person is treatment resistant is absurd if the pt doesn't receive treatment.

Robert @

Depression has a social and spiritual component that cannot be ignored. It has a contagion of its own , in our society . Highly immobilizing and crippling when ignored

Brenda E @

yes depression is usually treated as a medical or bhological disease while social, cognitive or spiritual aspects are not considered which if taken in cosideration disbling aspects could be avoided

Mamdouh @

1. Was the patient provided with CBT or other evidence based form of counseling? 2. Was this depression the result of PTSD earlier in her life? 3. Was she nutritionally deficient? 4. Was family therapy instituted to create a milieu that supports the patient? 5. Could mindfulness training have helped her earlier in her life to create a sense of patient awareness and control over symptoms and emotions? 6. Tricyclics are a problem in aging...could better dosing of lithium have helped? 7. How are family and relationship dynamics important in the epidemiology of TRD? 8. How did sleep hygiene interact in the development of TRD, what interventions might have been considered if the patient complained of sleep issues, common in PTSD and other psychiatric diagnoses. 9. Battlefield acupuncture is being used by the DOD for depression/mania, etc. It would be important to highlight meta analytic studies using those distinct auricular acupuncture points.

Donna @

This is another example of how important is to reason within the bipolar spectrum.

Jose Miguel @

I agree that bipolar depression is underdiagnosed. It enters my consideration any time that I meet a patient with a historic poor response to antidepressants or a seasonal aspect to the symptoms of their illness.

Peter @

From another perspective- is it really TRD? or is it poverty, chronic pain, substance abuse, etc?

Also, I spent a large part of my career in the prison system and rarely saw Major Depression in that population. How can that be? If anyone has a reason to be depressed, those people do. We came to the conclusion that ASPD provides a protective effect against depression.

Marilyn @

Could it be that people in prison express depression differently? For example: Perhaps because of the vulnerability that being in jail would create they express mor anger.

Kay T. @

The fact that depression is often more accepted to be expressed as hostility or anger could be a reason for not seeing it as prevalent in the prisons. Depression is still seen as a weakness in men, but anger is somehow okay for men to express.

W @

I have never encounter a case of the so-called TRD that didn't improve on mood stabilizers, after tapering off the antidepressants. The idea that a person on fluoxetine, mirtazapine and bupropion continues to be depressed contradicts the concept of a biological foundation for depression.
To make my response more controversial (because I love to irritate an establishment that is "treatment resistant" to the idea of changing old tricks, aka fallacies) I will join a very small number of psychiatrists that don't believe in Borderline Personality Disorder (BPD) as a real diagnosis. I do support the concept of a Borderline organization (thinking in black and white) but I have to be loyal to my experience: In the past 30 years, every patient with a label of BPD lost the Dx when the antidepressants were d/c and (in those with real Borderline organization) DBT was implemented.
Finally, if you wonder why my animosity toward the establishment (APA, AACAP) this is one of many reasons: DSM-5 now allows the diagnosis of ADHD in autistic children and also kept the unscientific idea of diagnosing a child with Oppositional-Defiant Disorder or Conduct Disorder when the reason for the behavior is due to Social Anxiety Disorder, bipolar disorder, PTSD or another real diagnosis.

Manuel @

Thanks, I love controversial thinking!

John @

Excellent comment. Thank you for your perspective.

Donna @

Odd is a diagnosis for people who are trying to manage a child's behavior. It leads us away from trying to understand the why of the child's behavior.
BPD may well be a Spectrum issue or if that is too dramatic then Executive Function Deficits cluster which results in social problems driving dysfunction in regulating self esteem and the emotions which we all struggle to manage in our lives.

James @

I'm with you and some others in seeing that there is no "Borderline Personality Disorder". I see these people as being on the Bipolar Spectrum, with the so-called "Borderline" traits and behaviors being maladaptive characteristics and reactive patterns ["phenotype"] to the internal mood-instability ["genotype"].
I remember reading psychoanalytic descriptions of the "cause" and symptoms of Schizophrenia that were written over 100 years ago, before the biological basis was better understood and more widely accepted. "Bad parenting", "internalization of conflicts", etc. The descriptions are strikingly similar to the "analyses" of "personality disorders" now, and thus, I think, mistaken. I believe that all "personality disorders", including Anti-Social, will eventually be identified with biological markers [and hopefully, treatments] as Schizophrenia, Bipolar, Depression/Anxiety, etc., are now. The term "personality disorder" will no longer be seen or used as a "diagnosis" of a "disease", but merely a construct to describe and recognize patterns of behavior [signs] suggestive of an underlying biological condition. Thus for example, "Borderline" traits suggest symptoms or signs of a patient's core Bipolar Spectrum disorder. "Personality disorder" may still be useful in recognizing an underlying disease or guiding psychotherapy, which is fine.

Perry @

perfect. My friend and colleague, Manuel Mota-Castillo, a child/adolescent psychiatrist has for many years been "preaching" the same about what is called ODD/CD; would that we could count you in in our discussion group (dnpistone@outlook.com)

Daniel N Pistone, MD Psychiatrist

Daniel @

I've been doing counseling for about 20 years with people considered SMD adults including quite a few with the diagnosis of BPD. I haven't encountered any without a history of complex trauma beginning as young kids. I use methods from STEPPS, DBT and Trauma Focused CBT that was developed for children. This combined with mood stabilizers other than gabapentin works pretty well in keeping them out of hospitals and jails, while increasing their overall quality of life.

Sue @

Add new comment

Loading comments...

By clicking Accept, you agree to become a member of the UBM Medica Community.