Why the Bipolar Spectrum is not recognized by the “Bible” By Hunter Yost MD
“The things that your liable to read in the Bible, it ain’t necessarily so… from Porgy and Bess by George Gershwin
First, the back story…
Prior to 1980 when DSM-III was published, there was no Bipolar disorder. In DSM-I and II, (1952 & 1968 respectively) German psychiatrist Emil Kraepelin’s concept of Manic-Depressive Illness (MDI) which essentially meant recurrent severe depressive episodes with or without mania was historically honored. (many episodes of depression over the years and even one episode of mania later on was still MDI).
The new term “bipolar” (depression and manic episodes) introduced in the 1980 DSM-III, is actually a smaller subcategory of the full disease entity of Manic-Depressive Illness. The terms are not synonymous.
From the late 1970’s, the term “bipolar spectrum” is most closely associated with the research of Hagop Akiskal (1944-2021).1 He formalized this term in a 1983 publication entitled, “The bipolar spectrum: New concepts in classification and diagnosis”.2 He and others realized that a larger portion of mood states were not represented in the strictly defined DSM categories.
Extensive explanations for a spectrum model for mood disorders were also elaborated in Goodwin and Jamison’s monumental textbooks, 3,4 and other researchers.5.
Ghaemi et.al.6 succinctly explained: “The bipolar spectrum concept is a return to this earlier Kraepelinian perspective… Bipolar spectrum concepts are historically rooted in Kraepelin’s manic-depressive illness concept, are scientifically testable, and can be clearly formulated. Further, they differ in kind from traumatic/dissociative conditions in ways that can be both historically and scientifically established.”
Phelps et. al.7 defined Bipolar spectrum as “Reflecting its use in the current literature, the term bipolar spectrum will refer herein to the putative continuum between unipolar depression and bipolar I.” (BP I)
According to Angst 8, “In 1977 Akiskal proposed a cyclothymic–bipolar spectrum and in 1981 Klerman suggested a mania spectrum.”
The Bipolar Spectrum is not recognized by DSM which only describes a limited slope criteria of Bipolar I and Bipolar II, but promotes an expanded scope of the newly created category in 1980 called Major Depressive Disorder (MDD). Since then the Mood disorders committee of the DSM has been loath to expand any criteria with even a hint of mania and has been cemented in institutional conservativism regardless of the research in the references below.
The MDD neologism, was introduced to cover the most severe forms of recurrent depression (a true disease) as well as the mildest forms of non-recurrent depression aka persistent depression (not a true disease) in order to ensure coverage by insurance since no company was likely to provide coverage for diagnosis called “minor depression”.
When the Freudian based psychiatrists of that era heard that their favorite billing category of Depressive Neurosis (mild persistent depression and anxiety) was going to be eliminated, Robert Spitzer MD quickly found a term called dysthymia (apparently unaware this was already an established mood temperament in Europe since the late 19th century) and created another new diagnosis called Generalized Anxiety Disorder so the psychoanalysts could use 3 codes to bill for their services. MDD-mild, Dysthymia and GAD. This helped the DSM-III to get approved.
In non-technical jargon, Depressive Neurosis could be described as the “worried well,” “nervous nellies,” “alarmists”, and “high strung insecure types” like characters Woody Allen has played in his movies and clinically would include “risk averse” or high in “harm avoidance” individuals. They respond equally well to psychotherapy or serotonin reuptake inhibitors i.e., SRI’s. This mild form of depression is not incapacitating, the individuals do not need to be hospitalized but are persistently unhappy and rarely suicidal.
The individuals in this large category of “depression/anxiety” are reflexively given SRI medications (introduced in the late 1980’s) by their PCP’s and psychiatrists with little thought of psychotherapy even though it is recommended as a first line treatment instead of medications especially the cognitive-behavioral variety (CBT).
Horse-trading and making the DSM sausage
This horse-trading process was documented by historian Hannah Decker PH.D 9, (Professor of History at the University of Houston, Adjunct Professor in Medical History in the Menninger Dept. of Psychiatry at the Baylor College of Medicine) who gained access to the archives of the American Psychiatric Association (APA) for DSM-III for her book.
It is clear from her research that little science was involved in these decisions but rather compromises by consensus committees. This same decision making process has continued through the current DSM-5 and that is how the sausage is made, a process unique to psychiatry.
As historian Edward Shorter Ph.D.10 (Professor of Psychiatry, Professor of the History of Medicine, Jason A. Hannah Chair in the History of Medicine in the Faculty of Medicine at the University of Toronto) said, “the speed of light was not decided by a consensus committee”. He also was given access to the APA records of the DSM-III deliberations and personally interviewed Rober Spitzer MD, the driving force behind DSM-III, in later years who readily admitted to the horse-trading.
To further quote Shorter10,”…psychiatry, a field that has remained a sandbox of theories about neurotransmitters and commercial opportunities for drug companies”. Big pharma was quite pleased to promote the bloated unscientific category of MDD with dozens of unnecessary antidepressants since the late 1980’s.
To pursue the DSM-III’s single minded focus on reliability, albeit at the expense of validity (is a diagnosis real?), Robert Spitzer and others developed the kappa score to measure of interrater reliability, i.e. how often do psychiatrists agree on a diagnosis. (<0.20=unacceptable, 0.20-0.39=questionable, 0.4-0.59=good, 0.6-0.79=very good, and 0.80-1=excellent).
The kappa for major depression were 0.62 and 0.64 (very good reliability) for DSM-III-R in 2001. However, the kappa scores for major depression in 2013 were 0.28 (questionable reliability) for DSM-5.11
Per Ghaemi12, “Given that a kappa of 0.5 indicates that observers agree and disagree equally frequently, statistical experts have recommended a minimum of 0.6 as acceptable kappa. On that standard, the DSM-5 field trials only had acceptable reliability for alcohol use disorder among major diagnoses. All other kappa’s fell below 0.6, including bipolar disorder (kappa=0.56), and most were below 0.4.”
Had Spitzer developed a statistical measurement of validity first rather than having doctors agree on something that is not real to begin with like MDD and GAD, we would have a much different DSM today.
This history is not taught in psychiatric training programs and several generations of naive young residents are led to believe that MDD and GAD are true diseases found in nature - they are not.
So back to the science…
Akiskal stated the consequences of this change13, “In brief, the entire spectrum of bipolarity in the less-than-manic range is at risk for being relegated to MDD”.
He was right, this led to the over prescribing of antidepressants over the past several decades and the concept of so-called “treatment resistant depression”. When even the mildest and briefest symptoms of mania occur in the midst of a depression, which often go unrecognized or discounted, there is usually a poor response to antidepressants, or even worse, an increase in irritability, agitation and suicidality.
Akiskal and Pinto14 elaborated descriptions for Bipolar I-VI to broaden the understanding of a spectrum concept 8 however this was not adopted by the DSM due to concerns about over diagnosing anything called “bipolar”. However, there were no concerns about overdiagnosing “MDD” leading to the explosion of unnecessary “me too” antidepressants i.e. Prozac and its progeny.
Other prominent spectrum researchers, Phelps et. al.7 suggest, “Data presented herein are consistent with the view of bipolar disorder as existing on a continuum with unipolar depression. These data suggest that at a minimum, the current diagnostic approach to bipolar disorder should be modified to include routine assessment of non-manic bipolar features.”
However, the DSM does not encourage assessment of non-manic bipolar features and compels strict adherence to its narrowly defined categorical list of symptoms ignoring other established diagnostic validators of course, family history and response to treatment.
The DSM does not recognize any validated questionnaires like the Mood Disorder Questionnaire (2002), or the Hypomanic Checklist, HCL-32 (2007) or HCL-15 (2015) item versions which can be used only as screening tools but not to confirm a diagnosis. With the HCL-15 for example, a depressed patient who endorses less than 7 items, has a 93% likelihood of having MDD rather than Bipolar II.
A person who endorses more than 7 items would likely be on a Bipolar Spectrum and should not be prescribed antidepressants but rather mood stabilizers like lithium, valproic acid (Depakote) lamotrigine (Lamictal) or carbamazepine (Tegretol).
I have worked at no hospital or facility that uses these or similar screening tools but instead they use the PHQ-9 which diagnoses only the type depression as defined by the DSM and everyone ends up with and antidepressant and rarely improves. I would explain this to patients as similar to taking the wrong antibiotic for an infection.
In hundreds of electronic hospital and clinic charts I have reviewed, the psychiatrist will dismiss consideration of a bipolar diagnosis by writing, ”patient denies elation and euphoria” as if these are the determining symptoms for the diagnosis. According to Takeshima15, elevated mood, and increased self-esteem are the least frequent symptoms of a mania since these episodes are predominantly of the mixed variety comprising irritability, agitation and distractibility.
Very few people have pure mania (or pure depression) as defined in the DSM. The Koukopoulos Mixed Depression Rating Scale (KMDRS): An International Mood Network (IMN) validation study of a new mixed mood rating scale needs to be used as often as the PHQ-9.16
DSM-III to the current 5th edition deviate from the established historical definitions of mania as psychomotor excitation and depression as psychomotor slowing or retardation. In other words, mood is not the critical factor. It may be elated/euphoric or it may be sad but that is secondary to the psychomotor state.3,4,9
The established diagnostic validators of illness course (age of onset, number and length of episodes), extensive family history, symptoms and response to treatment and biomarkers (of which there are none for psychiatry at present) can confirm a psychiatric diagnosis, but not symptoms alone as required by the DSM.17
In the numbers delineated below by Ghaemi18, up to 80% of people who do not have a pure depressive state i.e. with no manic or mixed symptoms, could be considered to be in the Bipolar spectrum:
· At least 50% of all depressive episodes are mixed with mild manic symptoms, and thus are mixed states, not pure depression.
· Combined with the 15% of classic manic-depressive cycles in bipolar illness, we account for the majority, 65%, of depressive episodes so far. (50%+15%=65%).
· In various studies, it has been found that manic temperaments - hyperthymia or cyclothymia - are present in about 1/3 of persons with recurrent unipolar depressive episodes.
· If so, these calculations would explain one-third or so of the 35% of remaining persons with depressive episodes (i.e., about 12%).
· We now have explained 77% of all persons traditionally diagnosed with severe clinical depressive episodes (50% + 15% + 12%). This would be almost 4 out of 5 of such persons.
· Given this assessment, only 20% of the general population would justifiably qualify for antidepressant treatment having a pure unipolar depression.
The remaining almost 80% would do well on mood stabilizers like lithium, valproate, carbamazepine or lamotrigine but poorly on antidepressants. Recent studies also show effectiveness especially with mixed states of depression or mania with dopamine blockers like Lurasidone (Latuda), cariprazine, (Vraylar), Lumatepterone (Caplyta) or ziprasidone (Geodon).
For the 20% with a pure depression, (historically called melancholic depression with severe psychomotor slowing/retardation), which can be incapacitating and require hospitalization, usually begins in life close to age 30, has episodes lasting 6-18 months and then resolves if untreated according to observations prior to the psychopharmacology era.
The most effective medications and treatment for this type severe recurrent depression are the older antidepressants called tricyclics like amitriptyline (Elavil), nortriptyline (Pamelor), imipramine (Tofranil), or monoamine oxidase inhibitors phenelzine (Nardil), tranylcypromine (Parnate) or electroconvulsive therapy (ECT).
The so-called “SSRI” meds (which are actually not that selective), e.g. fluoxetine (Prozac), sertraline (Zoloft, escitalopram (Lexapro) etc. work best for low-grade depression with anxiety that are more chronic than episodic and do not resolve spontaneously.
For example, sertraline (Zoloft) failed its FDA trials in the late 1980’s for treating severely depressed hospitalized patients but was eventually approved for treatment of mildly depressed outpatients i.e. Depressive Neurosis.
A larger problem with implementing the Bipolar Spectrum is:
· the restrictive DSM criteria discourages clinicians from consideration of non-manic bipolar symptoms.
· inadequate understanding of the concept of mixed states of depression and mania which are more common the pure mania or depression,
· psychiatric training programs do not teach the historical and sorely neglected classical concepts of mood temperaments of Cyclothymia, Hyperthymia or Dysthymia.
Bipolar Spectrum Illness
An approach to characterizing a version of bipolar spectrum concept to distinguish it from “MDD” was proposed by Ghaemi and Dalley19. They called this Bipolar Spectrum Illness to intentionally avoid the nebulous term “disorder” (see medicalmodelredux.com for further explanation of the term disorder20).
Their operationalized definition includes recurrent severe depressions, family history of bipolar disorder, antidepressant induced mania, treatment response, mixed or melancholic features, course with early age of onset and multiple episodes, limited or adverse response to antidepressants (i.e. either no response or psychomotor agitation/irritability/rage and/or increased suicidal expression or attempts). Ghaemi has also suggested the mood temperaments of Hyperthymia and Cyclothymia to be part of this concept.5
I believe the word “bipolar” is problematic –
it limits understanding of the complexity of mood illness.
As mentioned above, the term “bipolar” did not exist as a diagnosis in the U.S. prior to 1980. To distinguish a mood illness on the basis of polarity, either depressed or manic is convenient but simple minded and prevents understanding the broad clinical complexity of Kraepelin’s Manic-Depressive Illness.
Kraepelin said of Manic-Depressive Insanity, “ it includes on the one hand the entire territory of the so-called periodic and circular insanities, and on the other hand, simple mania that hitherto has been kept separate . Over the years I have become increasingly convinced that all these pictures are only the presentations of a single disease process”.21(bold added).
As Goodwin and Jamison put it, “…Kraepelin was right as usual and he was remarkably astute in his observations and predictions about the immensely complex group of disorders collectively known as Manic-Depressive Illness. MDI magnifies common human experiences to larger than life proportions. Among its symptoms are exaggerations of normal sadness and joy, profoundly altered thinking, irritability and rage, psychosis and violence and deeply disrupted patterns of energy and sleep.” 4
Kraepelin’s MDI did not include persistent, i.e. non-recurrent mild depression associated with anxiety, historically called Depressive Neurosis, which is best treated with psychotherapy but responds equally well to serotonin reuptake inhibitors.
Classic Manic-Depressive Illness is a true disease; it includes the full Bipolar Spectrum and recurrent severe clinical depression, mixed states and mood temperaments.
It is unlikely however that the Mood committee of the DSM will reinstate Manic-Depressive Illness and do away with the term “bipolar” as a separate diagnosis which would be my preference. It is also unlikely that the word “disorder” will be eliminated from the DSM even though the rest of the medical field does not have a “cancer disorder”, a “diabetes disorder”, or a “heart disorder” etc. Other medical specialties constantly seek etiologies of diseases to develop better treatments however the DSM-III and subsequent editions was created to intentionally avoid etiologies and the words illness or disease.
So, I propose new terminology to replace the word “bipolar” and the word “mood” due to the DSM’s excessive emphasis on mood states like elation and euphoria rather than level of psychomotor activity:
The Affective States Spectrum
This includes the operational description of Ghaemi and Dalley as described above. The word Affective is chosen in place of the word mood due to its historical usage in DSM-I to III (switched to Mood Disorders in 1994) and in the psychiatric literature prior to the 1990’s including research such as the 1982 Affective States Rating Scale mentioned in Goodwin and Jamison, 1990 and 2007.3,4
This category would exclude however Depressive Neurosis (aka, neurotic Depression) which could be a legitimate separate category and it is historically defined as non-severe and continuous i.e. non-episodic. Currently it is called Persistent Depressive Disorder in DSM-5 which was a newly created term for that edition, demoting the classical term of Dysthymia. (reimbursement is limited)
In closing…
This article, I hope, helps to illuminate some of the biggest misunderstandings in psychiatry held by physicians and the public that lead to misdiagnosis and ineffective treatments for depression. The hegemonic (I prefer Mirriam-Webster’s definition of preponderant influence or authority over others: Domination) hold by the American Psychiatric Association’s DSM since 1980, I believe is the primary cause of these misunderstandings and needs to be significantly revised.
The DSM does not list medical references to support its criteria. We must put our faith in the wisdom of the “expert” consensus committees who have been unfathomably reluctant to expand criteria that have even a whisper of mania, (i.e. psychomotor excitation - irrespective of mood).
In a telling quote from Allan Fransis MD, former task force chair of the DSM-IV in the 1990’s who stated in 2012: “APA has forfeited its right to hold the monopoly over psychiatric diagnosis. Guild interest should never trump public interest”.22
The references below are but a small sample of numerous articles over the past several decades expounding on the vast territory between pure depression and pure mania virtually ignored by the DSM to the detriment of patient care.
1. Akiskal HS, A M Djenderedjian, R H Rosenthal, M K Khani. Cyclothymic disorder: validating criteria for inclusion in the bipolar affective group. Am J Psychiatry. 1977 Nov;134(11):1227-33.
2. Akiskal HS. The bipolar spectrum: New concepts in classification and diagnosis. In: Grinspoon L, ed. Psychiatry Update: The American Psychiatric Association Annual Reiew, Vol 2. Washington, DC: American Psychiatric Press; 1983:271-92.
3. Goodwin F., Jamison K., Manic-Depressive Illness 1990. Oxford Press
4. Goodwin F., Jamison K Manic-depressive Illness – BipolarDisorders and Recurrent Depression. 2007 Oxford press.
5. Nassir Ghaemi, Bipolar Spectrum: A Review of the Concept and a Vision for the Future. Psychiatry Investig 2013;10:218-224.
6. Ghaemi SN, Ko JY, Goodwin FK. Cades disease and beyond: misdiagnosis, antidepressant use, and a proposed definition for bipolar spectrum.
7. Phelps J, Angst J, Katzow J, Sadler J. Validity and utility of bipolar spectrum models. Bipolar Disord 2008: 10: 179–193
8. Angst J. The bipolar spectrum. Brit J Psych 2007; 190: 189–191
9. Decker, Hannah. The Making of DSM-III, a diagnostic manual’s conquest of American Psychiatry. 2013, Oxford University Press.
10. Ed Shorter, What Psychiatry Left Out of the DSM-5: Historical Mental Disorders Today. Routledge; 1st edition ( 2015)
11. Leiblich S. et.al. High heterogeneity and low reliability in the diagnosis of major depression will impair the development of new drugs. BJPsych Open. 2015 Oct; 1(2): e5–e7.
12 Ghaemi N, et.al. Clinical research diagnostic criteria for bipolar illness (CRDC-BP): rationale and validity. International Journal of Bipolar Disorders (2022) 10:23.
13. Akiskal H.S. The Emergence of the Bipolar Spectrum: Validation Along Clinical-Epidemiologic and Familial-Genetic Lines. Psychopharmacol Bull. 2008;40(4):99-115.
14. Akiskal, H.S.A., Pinto, O., 1999. The evolving bipolar spectrum. Protptypes I, II, III and IV. Psychiatr Clin North Am 22, 517–534.
15 . Takeshima M. et. al. DSM-5-defined 'mixed features' and Benazzi's mixed depression: which is practically useful to discriminate bipolar disorder from unipolar depression in patients with depression? Psychiatry Clin Neurosci. 2015 Feb;69(2):109-16
16. Sani G. et.al. The Koukopoulos Mixed Depression Rating Scale (KMDRS): An International Mood Network (IMN) validation study of a new mixed mood rating scale. Journal of Affective Disorders. Volume 232, May 2018, Pages 9-16
17. Robins E., Guze S.B. Establishment of diagnostic validity in psychiatric illness. Its application to schizophrenia. American Journal of Psychiatry, 126, (7) 1970
18. Ghaemi S. Nassir, Clinical Psychopharmacology- Principals and Practice. 2019. Oxford Press.
19. Ghaemi S. Nassir, Shannon Dalley. The bipolar spectrum: Conceptions and misconceptions. The Australian & New Zealand Journal of Psychiatry. March 7, 2014
20. Yost Hunter. What is a Disorder? II. Medicalmodelredux.com. .
21. Kraepelin Emil, Psychiatrie, 6th ed. (1899) vol. 2 359.
22. Allan Fransis in HuffPost 2012, DSM-5 Costs $25 Million, Putting APA in a Financial Hole