Tuesday, March 4, 2014

Treatment Resistant Depression and Borderline Personality Disorder

On October 18, 2013, John Gunderson, perhaps the most internationally recognized expert on borderline personality disorder (BPD), wrote a piece in the American Psychiatric Association’s newspaper, Psychiatric News. He opined that many if not the majority of cases of treatment resistant depression (TRD - depression that does not respond to antidepressant drugs) may in fact be undiagnosed cases of patients with BPD.  This opinion is totally consistent with my own clinical experience.

John Gunderson, M.D.

Of course, the psychiatric-industrial-Pharma complex immediately went on the offensive. On his Medscape blog, Nassir Ghaemi - a fan of  bipolar m.a. - wrote a two part rebuttal. He expressed the opinion, asserted and not backed by any particular review of the literature, that the DSM criteria for BPD are invalid. In the past, he has also expressed the belief that the DSM duration criteria for manic and hypomanic episodes in bipolar disorder are far too restrictive, and seems to liberally substitute his own personal criteria for these disorders in his arguments

He goes on to assert that the “…bland, broad DSM definition allows Dr Gunderson and other borderline experts to diagnose the condition in a large chunk of persons with mood illness, not just bipolar illness but also simple depression, since depression entails relationship problems, is often associated with irritability and paranoia, frequently involves mood reactivity, often involves suicidal attempts, and can also entail nihilistic thoughts of feeling abandoned or empty.
Nassir Ghaemi, M.D.

As I shall discuss a little later, these symptoms, when all taken together as a group, are not typical for your average run-of-the-mill case of Major Depressive Disorder (MDD), but are extremely typical of depression in BPD.
Dr. Ghaemi's statement here is misleading, because, while any given patient with major depression and no BPD may indeed have any one or two of these characteristics, they usually do not have almost all of them together. Omitting mention of this pertinent fact is a tactic frequently employed in arguments from the everyone-who-is-moody-is-bipolar crowd.

As a reference for his assertion, Ghaemi cites a study by Angst, who is another bipolar disease monger whose circular pseudo-logic I dissected in a previous post.  

Ghaemi then goes on to focus on one of Gunderson’s statements in his article: Gunderson cited a study that showed that the presence of BPD was a major predictor of persistence of depression over time in a sample of persons who met MDD criteria.
I agree with Dr. Ghaemi that such a study does not prove, in isolation and by itself, that BPD is the most common cause of TRD, as there could very well be very many other even more common causes.
His impeccable logic: “It does not follow that if x makes y worse, then most cases of treatment resistant y are examples of x. Substance abuse makes the course of MDD worse; but it does not follow - it is scientifically incorrect and illogical - to then conclude that most cases of TRD are cases of substance abuse, end of story."
Of course, the fact that Gunderson cited this one particular study did not mean that he thought he was providing a complete literature review, but Ghaemi seems to be implying that Gunderson is saying that this one study is the only evidence he is relying upon - which he didn’t say. There are a host of studies, btw, that show that severe personality disorders are often predictive of a poor response to all sorts of psychiatric medications for all sorts of psychiatric disorders.
Ghaemi himself, on the basis of some highly questionable studies, opines that the most common cause of TRD is “unrecognized bipolarity.” He of course cites references produced by his fellow bipolar m.a. disease mongers in Hagop Akiskal’s incredibly biased Journal of Affective Disorders.
Their logic has always been a one or another version of the following:
Treatment resistant depression is often accompanied by symptoms such as racing thoughts or  hyperactivity
Racing thoughts, hyperactivity, and other such symptoms can look vaguely similar to symptoms of mania
Therefore, such patients must be bipolar
This is every bit as invalid as the logic that Ghaemi is attributing to Gunderson. In fact, anxiety disorders can and do produce, superficially, all of the symptoms that Ghaemi and his buddies attribute to an underlying “bipolarity.” When looked with a more discerning eye, of course, the symptoms of anxiety disorders and mania look very, very different.
A certain type of anxiety mixed with depression, is, as I shall discuss in a bit, one of the major qualitative factors that distinguish depression in BPD from other types of depression. I think the articles that Ghaemi is quoting are not only consistent with what Gunderson is arguing, but could have been used by him as clear evidence for his main thesis!
I have met Professor Gunderson. I think he is more than capable of telling the difference between BPD and bipolar disorder

It’s not subtle.

Dr. Ghaemi shows such limited understanding of BPD that I suspect that, in all likelihood, he has never or rarely sat down with such patients in long-term psychotherapy and painstakingly dissected the environmental and interpersonal context in which their depressive symptoms come and go.
Another person who, like myself, has done this with patients is my colleague, academic psychiatrist Ken Silk. He did a far more complete literature search [“The Quality of Depression in BPD and the Diagnostic Process.” Silk, K. Journal of Personality Disorders 24 (1), 2/2010] than was presented in the discussions by either Dr. Ghaemi or Dr. Gunderson.

Kenneth Silk, M.D.

He points out that, rather than restricting the diagnosis of MDD to those who clearly display a biologic depression - the cases that used to respond to tricyclic antidepressants back when they were the dominant drugs - the diagnosis has spread along with the assumption that most presentations of depression are some form of major depression and, even if not MDD, should respond to antidepressants. The term depression is now used in academic discussions to refer to a mood rather than an actual diagnostic construct.

He lists the qualitative difference between the symptoms of MDD and those of depressed BPD’s. Besides the fact that the BPD patients meet criteria for BPD, not to mention that they also exhibit the family dynamics typical of those with the disorder, the quality of their depression is characterized by the following [My comments in italics]:

1.      A“mad-bad” depression closely tied to anger and hostile behavior.

2.      Mood symptoms that are very sensitive to interpersonal situations in which the patient feels abandoned, lonely, or empty in the absense [or in the presence for that matter] of a longed-for important other.

3.      Depressed moods can come on quickly and disappear quickly [the opposite of true MDD] depending on the reactions of an attachment figure.

4.      The depression is at times more closely related to chronic self-criticism and a feeling of intrinsic “badness” than in MDD without BPD.

5.      It is associated with chronic self destructive behavior [including self-injurious behavior like cutting].

6.      It is associated with a loss of gratification and frustration.
7.      Recovery from BPD facilitates recovery from MDD when it is co-occurring, rather than the other way around.
8.      The depression often comes from exhaustion and demoralization from repeated unsuccessful battles with chronic and overwhelming anxiety. [BPD often is accompanied by panic disorder].

9.      Patients with BPD often exhibit impulsive aggression (a hair trigger leading to rage). [Patients with true major depression, especially of the melancholic variety, tend not to show this characteristic at all. They are usually extremely passive because they do not have the energy to strike out].

Important questions glossed over by Dr. Ghaemi include: in what context do symptoms appear? How attached is the low mood to specific interpersonal events? Is affective dysregulation (high reactivity to interpersonal problems) prominent? 

An important additional point is that these qualitative differences in depression  that Dr. Silk lists are not measured clearly by any of the standard symptom rating scales used in the vast majority of psychiatric studies. Therefore, citing any studies which employ these instruments in this debate is sort of irrelevant to the basic question. 

A few final caveats.  People with BPD can still have depression that does respond to an antidepressant. And even when the depression in BPD does not improve with SSRI antidepressants directly, other symptoms such as panic attacks can improve dramatically with these drugs (especially if the SSRI is combined with certain benzodiazepines).  SSRI’s can also decrease reactivity by raising the bar, so to speak, so that it takes somewhat more extreme behavior by an attachment figure to create a severe emotional reaction. 

In patients in which either or both of these two things happen, their depression may improve indirectly because of the effects of the drug on the other symptoms, as opposed to in MDD, in which the decrease in low mood is a direct effect of the drugs.

Finally, patients can also have both BPD and true bipolar disorder. In fact, patients with bipolar disorder, when not in the midst of a manic or a depressive episode (when they are euthymic), can have just about any psychological or psychiatric reaction or personality issue in addition to bipolar disorder.  That is because, when they are euthymic, they are basically just like anyone else! 

Writers in the Journal of Affective Disorders just love to merely assume that any emotional reaction a patient with bipolar disorder has simply must be due to the underlying bipolar disorder.  What hogwash.


  1. I've run into several 15-minute (actually, it was more like 5 minutes)psychiatrists who diagnosed me with depression, but in the light of your post, perhaps that isn't the whole picture. I have a sister who appears to be severely cursed with BPD--and, the real clincher as for my "diagnosis"--I seem to have been married to someone as beset with BPD as I. The last person I would seek out for help in this matter is a psychiatrist, because with few exceptions, they all seem captured by Pharma. Of course, finding a psychologist who can do justice to treating this disorder is no easy feat either. It's really a tragedy that patients, most of all, are the ones caught in the pinch of this whole dilemma.

    Are there any diagnostic tests my current therapist could administer to help narrow down the possibility of BPD or is it more contextual and talk-oriented?

    1. Hi Roger,

      There are really no valid "tests" for almost any psychiatric disorders. The only way to learn about a patient is to take an extensive history complete with probing follow up questions. That should take at least 45 minutes just to cover the very basics.

      To help you find what you're looking for, let me refer you to two posts on my Psychology Today blog:


  2. It appears subtle qualitative differences may be important to detect early schizophrenia in cases of depression in adolescence or early adulthood. Take the symptom, "impaired concentration," for example. Someone that is just going down a checklist, when they see that the patient has "impaired concentration," they would just mark it down for depression. However, for those with early schizophrenia, impaired concentration tends to be associated with specific qualitative changes in the patient's subjective experience:

    1.) The patient has become less able to comprehend what they hear or read, resulting in apparent impaired concetration (disturbance of receptive language) and

    2.) when the patient tries to think about something, unrelated, trivial thoughts pop up and interfere with the main line of thought (thought interference), which may escalate to

    3.) the popping up of random, unrelated thoughts simultaneously or in rapid succession that prevent the patient from thinking about anything at all (thought pressure).

    In at-risk patients, each of these "basic symptoms," each of which either seem to or do impair concentration, are considered to be highly predictive of transition to psychosis, apparently especially to schizophrenia, as shown in this table in this study:

    So, yes, looking at the important qualitative differences in signs and symptoms is a must in psychiatry.

  3. What a great post! Should be required reading for all psychiatric trainees. It's always struck me as sad and somewhat comical that the academic "mood disorder experts" seem to know a lot about brain circuits but very little about people circuits.

  4. The 10 Commandments of good psychiatry:

  5. The whole concept of TRD has always seemed to me like a shift of the responsibility for poor outcome to the patient, as in the patient is responsible for the drugs being ineffective. When, in fact, it is often an incorrect diagnosis or treatment that is responsible.

  6. Dr. Allen, I couldn't agree more with you and Gunderson and less with Dr. Ghaemi. I routinely see patients for initial evaluations who have been medicated for years with numerous trials of antidepressants, mood stabilizers, antipsychotics, benzodiazepines, etc, with associated diagnoses of treatment resistant depression and/or bipolar spectrum disorders. Not surprisingly, most have never had psychological testing nor any psychotherapeutic interventions beyond brief supportive counseling.
    In our clinic, we routinely screen such patients firsthand with a computer self-administered and interpreted MCMI-III through Pearson...very user friendly and cost-effective, and including validity scales. If an underlying personality disorder is suspected, patients are then referred to one of our therapists as well as a DBT group, prior to seeing me, the psychiatrist, unless there is a significant risk issue. Not putting the cart before the horse has made all of the difference.

  7. Dr Ghaemi is a hack, who is very happy to give drugs to children for alleged bipolar disorder. A truly horrible man.

  8. Some degree of "treatment-resistant depression" is iatrogenic -- adverse reactions to drugs and prolonged post-discontinuation syndrome.

    Med Hypotheses. 2011 Jun;76(6):769-73. Epub 2011 Apr 2.
    Tardive dysphoria: The role of long term antidepressant use in inducing chronic depression.
    El-Mallakh RS, Gao Y, Jeannie Roberts R.

    Many people with this condition show up on my site. The cause is traced back to going on and off psychiatric drugs, usually with identifiable withdrawal syndrome.

    PS Here is a review article summarizing 7 models of the relationship between antidepressant treatment and “emergence” of mania (and therefore, a bipolar diagnosis):

    Psychiatry still cannot distinguish adverse effects of drugs from "unmasking" of psychiatric illness, thus casting doubt on the "unmasking" theories.