Tuesday, March 6, 2012

Re-labeling Depressive Symptoms as Manic Symptoms by Fiat

They look alike.  Madonna must really be a goat.

Another cartoonishly mischaracterized study described in a journal article was recently published in the Journal of Affective Disorders.  One of the editors of this journal is Hagop Akiskal  (I have discussed my opinion of Dr. Hagop Akiskal’s work in a previous blog post).  The article's title is Prevalence and clinical significance of subsyndromal manic symptoms, including irritability and psychomotor agitation, during bipolar major depressive episodes.  

The authors are Lewis L. Judd, Pamela J. Schettler, Hagop Akiskal [the very same], William Coryell, Jan Fawcett, Jess G. Fiedorowicz , David A. Solomon, and Martin B. Keller.

These authors suggest that the presence of something that they label as subsyndromal manic symptoms (that is, symptoms that they believe are the same as those that are usually seen in mania episodes but which are “below the threshold for mania" - whatever that means) are seen in the major depressive episodes (MDE’s) that are also characteristic of bipolar disorder.  

For those unfamiliar, patients with true bipolar disorder have both manic and major depressive episodes, obviously at different times, that are separated by relatively long periods of normal moods called euthymia.

They discuss how some other authors reported that “the most common manic symptom during bipolar MDEs was irritability (present in 73.1% of the sample), followed by distractibility (37.2%), psychomotor agitation (31.2%), flight of ideas or racing thoughts, (20.6%), and increased speech (11.0%). 

Now, of course, they do not mention that these very same symptoms are also seen in the major depressive episodes of people who never have had or will have a manic episode. And who respond to antidepressant medication and have no response at all to lithium (which is highly effective in bipolar disorder). Back in ancient history (the 70’s and 80’s) we labeled depressed patients who show such symptoms as having an agitated depression.  

Other patients with depression who are not agitated but are in fact extremely slowed down - as if on heavy sedatives - were said to have a retarded depression.  We stopped making this distinction between agitated and retarded major depressive episodes because we found that both types of depression usually respond to the same medications, (although agitated depressions seemed to have, on average, a somewhat worse prognosis for medication response).

This authors of this article state that irritable and agitated qualities of MDEs, defined in various ways, are prominent in the clinical and research literature on bipolar patients with yet another clinical entity called a mixed depressive state. In the opinion of a lot of psychiatrists like myself, a mixed state is something better characterized by the name dysphoric mania. The patient has all the symptoms of mania but, instead of the highly elevated, euphoric mood as most people in a manic state have, they feel awful.

I find I cannot use the definition of a "mixed state" that is used in the official diagnostic manual, the DSM, because it is actually impossible.  To have a mixed state according to DSM criteria, “The criteria are met both for a Manic Episode and for a Major Depressive Episode (except for duration) nearly every day.”  This is impossible since many of the symptoms of mania and depression are polar opposites of one another, so that one cannot have both at the same time!

Anyway, the authors of the article under discussion described their study population thusly:

 “Subjects entered the NIMH CDS at five academic medical centers from 1978 to 1981, while seeking treatment for a major affective episode. Intake research diagnoses were made using Research Diagnostic Criteria (RDC) based on the Schedule for Affective Disorders and Schizophrenia (SADS) interviews ... as well as available medical and research records. Patients with bipolar disorder (type I or II) entering the CDS in a major depressive episode (MDE) were selected for these analyses. We excluded from the analysis all patients who were manic at intake (N=60), along with a small group of patients (N=5) who met DSM-IV-TR criteria for a mixed episode at intake (i.e., had full concurrent MDE plus mania).” 

Notice that they "found" and then excluded anyone that might possibly meet the contradictory DSM criteria for a “mixed state,” which is what they were talking about earlier as if it were the population of patients who were about to be described in their study, which in fact it was not.

52  of their patients were diagnosed as bipolar I and 90 were bipolar II.  As most of my readers know, I think bipolar II is a phony diagnosis in the first place. 

They go on: “Irritability and psychomotor agitation are included in the SADS interview not only as manic/hypomanic symptoms, but also in the depression section of the interview, as qualifiers for the MDE (i.e., specifically for periods of the intake MDE when the subject did not have evidence of a manic syndrome).”

“We have included these two characteristics of intake MDEs as subsyndromal manic symptoms because we believe they are clinically indistinguishable from criteria A-2 and B-6 for mania and may, therefore, represent a subtle and little recognized form of mixed bipolar MDE.”

The authors are subtly defining by fiat any depressed person with irritability as having a “subthreshold” manic symptom!  Sez who??  This is especially interesting considering that they used what is essentially a symptom checklist to make their diagnosis in the first place, and were not really using clinical judgment to tease out differences in the presentation, pervasiveness, and persistence of symptoms that may just look alike during evaluations done at one point in time.

The similar symptoms are, in fact, clinically distinguishable, precisely because the symptoms occur in different clinical states – that is, manic episodes and depressive episodes.  The authors use the word “may” in the sentence about the symptoms being a little recognized form of mixed bipolar, and then proceed entirely from the assumption that they are just that. 

To really sort this out, maybe they should have compared a sample of patients with bipolar depressive episodes to patients with unipolar depressive episodes (patients who get depressive episodes but not manic episodes).  But of course, if these authors found these symptoms in unipolar depressives, they could easily redefine the unipolars as bipolars because of the symptoms.  

Voila! Almost anyone who has a depressive episode is immediately re-categorized as bipolar!  Because they define it that way.

Actually, retarded depression is more common in bipolar patients than agitated depression.  

About the only valid conclusion one can draw from the data presented in the article is that bipolar patients who have an agitated depressive episode may have a somewhat worse prognosis, and may be more likely to experience a quick shift into a manic state, than bipolar patients who have retarded depressive episodes.

Of course, we knew that decades ago.


  1. Ah, yes, "irritability" and "agitation," those old chestnuts.

    Herein lies one of the biggest problems in modern psychiatry: terminology. Let's assume that, in this study, "irritability" and "agitation" were well-defined and that there IS such a thing as an irritability that is unique to a "mixed depressive state." In other words, let's assume that these scientists were actually doing science.

    The take-home message, however, is none of that. It is, instead, that irritability and agitation are signs of bipolar illness. And you can bet that most psychiatrists won't read the paper or give it the scrutiny you did, and walk away with precisely that idea. Moreover, drug companies who market drugs for bipolar disorder will be more than happy to make that statement (of course, with a reference to Judd et al, 2012, but which no one will ever ask to read).

    Next thing you know, the patients who come in and say "I get so agitated all the time" or "I'm getting irritable again" (and I had three such patients this morning!)-- especially when appointment lengths are only 15 minutes-- are bipolar.

    [Of course, "agitation" and "irritability" aren't the only loaded words in psychiatry. Others that come to mind are "anxiety," "depression," "insomnia," "anger," "poor concentration," "distractibility," "manic," and heck, even "bipolar." I'm sure the list goes on and on. If we fail to ask what patients mean by these words, we're doing nothing more than knee-jerk prescribing, which is precisely what pharma, our employers, payers, PPACA, and, increasingly (and unfortunately), patients, want.]

    1. Steve,

      I have seen patients who say, "I was really MANIC this morning." No they weren't. I wonder where they learned to label their agitation with that word?

  2. Irritability is the least helpful "symptom" in psychiatry. It's nearly ubiquitous in both psychopathology AND normal everyday life, making it wholly unhelpful in distinguishing one disorder from the next, or between psychopathology and normal undulations of mood in response to normal stressors of life.

    Can we all agree to strike "irritability" from the DSM? Has the presence or absence of irritability ever shed light on a single diagnosis?

  3. I am quite sure that you fully vetted your post. I expect nothing less from professionals and actually do read as part of my expectations as someone (not MD or pharma) to do so. Where do we, those afflicted, get most of our info - on the internet, of course. So when I moved recently to the SW, I was given a license plate with the preface ADD -should I drive with my hazards on (maybe)! But please keep in mind, that if I had any other "medical disorder" (I condider the mind a part of the body), you better believe I would read about it anywhere I could to be my own advocate. I would do the same for my car! Do not blame your patients for trying to figure out what is wrong or why their car is leaking oil. It is what most folks would do. Most of us know and trust our MDs, which is more than you can say for your car mechanic, even though, they are reimbursed at at a higher rate...go figure! I have the utmost respect for most MDs, but we do what we can trying not to sound like complete losers...leaky something under the hood...dysphoric depression, mania. irritable, sleepless,"check engine light", "check fluids", etc. It is not to be ridiculed. We are trying to sound somewhat knowledgable and not be ripped off!

    One does not go to their MD for a fun and fantastic proceedure nor does one send their car in for that either. One would hope that those that take care of us hope we are in healing hands and that we will get more than a good 20 years (God forgbid not treatment), and 200,000 miles, as I have done with my car!

    1. This post is about the doctors who buy into transparent nonsense, not about their patients.

      Unfortunately, some psychiatrists these days are not worthy of the trust that patients like yourself put in them.

      It's very difficult for patients to know whether what they read on the internet is accurate or not. I try to include my reasoning for the opinions expressed in this blog.

  4. Your reply is almost true. Sorry to be crude, but I put my money where my mouth is. Do not ever underestimate that we, as paitents, afflicted, are too stupid to figure out when you are being treated well or not. Of course, the internet is full of garbage and I will always defer to my MD's advice. However, I noticed a reference to "transparent doctors", I actually put the greatest trust in my doctors' benevolence and intelligence (and I am a piece of work) by first, an MD and then Pyschiatrist, in fact, any physical health issues, I include him in it, as he gets it. He has wotked in some of the most frightening aspects of mental illness, yet the three women in his life, look at him with total adoration (his family). "Transparent doctors", sure there is inadequacy existing, it exists in all fields, and one must be wise to discern the difference and know intriscally what is best for yourself. At least I still know what is a revolting estimation of doctors, and one should not be patroning in other's good work. And, again, do not understimate one's capaccity to deal with mental illness and sill be most productive. And as for me, yup! Yes, I am more fortunate than others, and have at least been so blessed, I have had the pleasure of being treated by very decent caring and educated doctors. Somehow my psych seems to put it all together, first, as an MD. then as Psych. I expect no less! How does one explain dropping almost 15 pounds due to a cycle of depression, (I am 5'6 and do not need to hover close to 100lbs). Most disgracefully, some think this is really good looking....again, go figure. Cadavers are not something I aspire to be or most disgutinglly do not wished to be complimented on. I am an intelligent and very giving person, and should never be thought of any less. Do I have mental issues...yup! But compared to the rest of my successful and very completely "nuts", giving famuiy, all of whom - we do the best we can - and take care of each other - and have great hopes for our next up-coming genration and hope they will not be terminally blonde and blue eyed!

    Dr. Allen, plese do not take this as a personal offense. I think the most of your opinions and am most happy that there is a forum to post them. Please do not dump all doctors into the same bin.... you guys need to pool together to get respect. I am an advocate for mental health and wish there were more, like yourself, to bring the best to the field.

  5. I apologize for dragging up an old post, but may I ask what your recommendation would be for a patient who wants to describe an emotional state that they only know how to define with the word "irritable?" Are there any circumstances under which a bipolar II diagnosis is warranted? Is there such a thing as "high-functioning bipolar II?"

    If I'm being honest, I am a patient, not a doctor, who has been diagnosed as bipolar II after seeking treatment for postpartum depression. I fear honest disclosure of past depressive episodes and difficulty with SSRIs has contributed to the diagnosis. I've found myself quite skeptical of the diagnosis and treatment I'm receiving.

    1. Thanks for writing.

      Unfortunately, as you know, I can't possibly say what your diagnosis might be without taking my own history.

      In general: If it takes very little to get you into a downer and/or into an angry outburst, unfortunately it won't matter to a bad psychiatrist what you call that; they'll just call it hypomania, which it is not.

      Depending on other factors, I would usually use the term "affective instability," which is usually due to chronic, ongoing relationship stress, not a brain disease.

      Some depressed patients do indeed get more agitated on an SSRI. That is just a side effect that has absolutely nothing to do with bipolar disorder, and is usually an easy side effect to treat. A true bipolar patient might become fully manic on an SSRI, not just agitated or irritable.

      A bipolar II diagnosis is warranted when the patient actually meets the criteria, including and especially the duration criteria and the not-typical-of-their-usual-functioning criteria. I've only seen two such patients in 38 years of practice, and I suspect they were just mild bipolar I's.

      If your doctor has never even asked you about your current relationships, your childhood experiences, and if you are now being or have ever been significantly abused - and just asks you about your symptoms without digging too deep - run as fast as you can and get a second or even a third opinion.

      You can find more info about this on my other blog at:

  6. Thank you so much for your response! I have found your blog very enlightening, and was hopeful that I'd hear back. Looks like it's time to run away from the psychiatrist. I should have been concerned when she labeled me as bipolar before the appointment, and based the diagnosis on secondhand information about my mother, deceased almost 20 years. Unfortunate. I really liked her. (The therapist. Well, and my mother.) Thanks again!

  7. Here's a new article here:

    They say psychomotor agitation in depression is now a sign of a "sub-threshold mixed state."

    1. It's amazing they can pull stuff like that out of their you-know-whats without any real evidence and be taken seriously.