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Patients and Families: you're welcome to read this version too, although there's one written for you in simpler English that has more links and details than this one, which is a "trimmed down" version for busy doctors. 

DIAGNOSIS (2001; updated 5/2005) 

"Bipolar II?" -- Do I need to know this in primary care?

Prevalence of bipolar variants in primary care depression may be as high as 30%.Manning  In the psychiatric setting, as many as 50% of patients with depression may have a bipolar variant, according to reports from FranceAllilaire and Switzerland.Angst  Another recent analysis suggests that "agitated depression" is a common presentation of bipolar II. Benazzi

One person in three depressed, primary care patients has bipolar disorder?  One in two, in psychiatry clinics?  Figures as high as these only result when broad definitions of bipolar disorder are used, and these broad interpretations remain controversial amongst general psychiatrists (though much less so amongst mood experts). 

However, you are likely already aware that antidepressants can worsen bipolar disorder and that the FDA recently called for screening all patients who are to receive an antidepressant, for the possible presence of bipolar disorder.  (A patient questionnaire for this purpose, the MDQ, completes the FDA suggested steps with almost no extra time on your part.  It is available for download with no fee or registration in the Primary Care Providers Resource Center of this website; see Diagnostic Aids, MDQ).  Therefore, attempting to identify patients with bipolar disorder, particularly before giving antidepressants, is now regarded as an important part of mood disorder treatment. 

When you have diagnosed bipolar disorder, you may routinely refer out for treatment.  However, in many areas of the U.S., especially here in Oregon, referral to Psychiatry is difficult:  few psychiatrists are taking new patients.   

If you must, you can learn here to use mood stabilizers, the treatment of choice for bipolar medication management.  At minimum, for your patients who have not improved on antidepressants and psychotherapy, consider Bipolar II.  Read on to learn more about this diagnosis.  

What happened to "manic-depressive" (now bipolar I)?

Somewhere along the way you learned about manic-depressive illness: patients with episodes of mania, and episodes of severe depression. You will recall the symptoms of "mania":

  • Mood much better than normal
  • Rapid speech
  • Little need for sleep
  • Racing thoughts, trouble concentrating
  • Continuous high energy
  • Overconfidence
  • Delusions (often grandiose, but including paranoid)

As you know, these patients can also have depressive episodes, which do not fundamentally differ in presentation from other types of depressions.

What happened to "manic-depressive"? As our understanding of bipolar disorder has grown, the nomenclature has changed as well. In recent years the concept of a "mixed state" of bipolar disorder, in which manic symptoms and depressive symptoms are found simultaneously, was added. Obviously this changes the conception of manic-depression from one in which the two mood states alternate, to one in which they can co-occur! Things were getting more complicated.

In the most recent Diagnostic and Statistical Manual (DSM-IV), "Bipolar II" was added. Technically Bipolar II describes a pattern in which patients experience "hypomania" (to be discussed in detail below), alternating with episodes of severe depression. This marked the formal recognition of another variation on how "highs" and "lows" could be experienced.

However, one of the most experienced professionals in this field, who has bipolar disorder herself, has criticized even this advance as too limited and thus profoundly misleading:

    "The clinical reality of manic-depressive illness is far more lethal and infinitely more complex than the current psychiatric nomenclature, bipolar disorder, would suggest. Cycles of fluctuating moods and energy levels serve as a background to constantly changing thoughts, behaviors, and feelings. The illness encompasses the extremes of human experience. Thinking can range from florid psychosis, or "madness," to patterns of unusually clear, fast and creative associations, to retardation so profound that no meaningful mental activity can occur. Behavior can be frenzied, expansive, bizarre, and seductive, or it can be seclusive, sluggish, and dangerously suicidal. Moods may swing erratically between euphoria and despair or irritability and desperation. The rapid oscillations and combinations of such extremes result in an intricately textured clinical picture." (Kay Jamison, Ph.D.)

I had arrived at the same conclusion from listening to patients describe their symptoms. When I used this broader conception with patients, people who had struggled for years often got much better. Thus the motivation for creating this website: to help other practitioners understand the complexity Dr. Jamison describes.

What are the official (DSM-IV) definitions of the "new" bipolar variations?

Some of you may wish to see "official" definitions, before we start getting into variations. The two crucial new concepts are mixed states and hypomania. Here they are, as per DSM criteria.

Mixed States
The combined presence of full manic and full depressive symptoms — at the same time — is Bipolar Mixed State. At the same time? How can that be? Most people have always thought of the two "poles" of "bipolar" to mean something like the North and South Poles:

   
 

 

 

 

 

 

 

Bipolar experts have recognized that this illness is much more complicated . Dr. Susan McElroy of the University of Cincinnati says that two "poles" of "bipolar" disorder are like axes of a graph:

  

and that any point on that graph is possible in the "mixed states" of bipolar disorder.

What does this look like in vivo? Several variations are described in the next section. For now, imagine someone with manic symptoms of rapid thoughts and speech, who instead of feeling euphoric feels terrible: depressed; with negative thoughts, especially about her/himself; full of negative energy, and possibly even delusional (e.g persecutory or paranoid delusions, or delusions of terrible guilt and responsibility). This combined state occurs very commonly in mania, unfortunately.

Technically the DSM-IV recognizes only the upper right hand point on the above graph as "mixed state". However, most bipolar experts agreeFawcett, Angst, Akiskal and Pinto, Perugi et al, Akiskal, Jamison, Ketter (b) that any combination of manic symptoms and depressive symptoms is possible, thus the "nearly infinite" variations described by Dr. Jamison.  For a technical but thorough analysis of the history of "mixed states", and the most current view on the nature of this state, see the symposium summary from APA 2000, on this topic.

Hypomania
Technically, this is literally "little" mania — the familiar symptoms but less so:

  • Mood much better than normal
  • Rapid speech
  • Little need for sleep
  • Racing thoughts, trouble concentrating
  • Continuous high energy
  • Overconfidence

The observant reader will notice "delusions" have disappeared from the list: these are by definition not found in Bipolar II. A patient who has had the above symptoms repeatedly, without having delusions, is much less likely to lose contact with reality (including abnormal perceptions such as auditory hallucinations, which are common in bipolar mania) than a patient who has experienced delusions.

"Bipolar II" is technically the combination of hypomanic phases with separate phases of severe depression.  If the depressive phases are only mild, the term "cyclothymia" is used. Getting confused? I certainly was, until I began to think of these variations as points on a continuum. I’ll discuss that continuum in a moment; but first, consider one more extension of the concept of "bipolar".  

What is the "mood spectrum?"

Until very recently, depression and "manic-depressive illness" were understood as completely independent: a patient either had one or the other. Now the two are seen by many mood specialistsFreeman; McElroy; Perugi; Angst; Akiskal ; Akiskal and Pinto; Goodwin; Fawcett; Jamison as two extremes on a continuum, with variations found at all points in between:

On the left, the "unipolar" extreme represents straightforward depression with no complications. There are many forms of depression, of course. For an overview, see the appendix: "What kinds of depression are recognized?". The depressions discussed further here are of a more genetic, or "chemical" nature; as opposed to those of a more environmental, or situational type. The latter may respond well to time or therapy and not require "bipolar" thinking.

On the right, the "manic-depressive" extreme is defined by the presence of manic episodes, just the kind that most people have seen or heard of -- full delusional mania. 

But consider the following points A and B on this spectrum:

Point A on the continuum describes people who have a complex depression but who still respond well to antidepressant medication or psychotherapy. Around point B, however, there is some sort of threshold where these approaches are no longer completely or continuously effective: either they don’t work at all, offer only partial relief, or help for a while then "stop working" (which may account for some or much of "Prozac poop-out").  Hopefully you're already thinking about the implications of this "spectrum" concept as regards the prescription of antidepressants; for more on that, see my essay on the antidepressant controversy in bipolar spectrum patients.  

Until 1994 and the publication of the DSM-IV, there was no official name for all the variations between B and the "manic-depressive" extreme. It was as though these variations did not exist. In the minds of many, they still don’t, including many psychiatrists who have not adopted this new "spectrum" way of thinking about diagnosis. The DSM-IV itself does not describe this "spectrum" concept. In it, the entire span between B and "manic-depressive" is just "bipolar II". The following section describes some variations as patients experience them. If you would like to hear one person’s experience with many symptoms of a complex bipolar disorder, try this woman’s site, or this testimonial from one of my patients about the horrible experience of one dose of an SSRI  in someone who turns out pretty clearly bipolar. 

For corroboration, everything you just learned herein can also be found in a recent review by Smith and Ghaemi. (Dr. Ghaemi is the head of the bipolar clinic had Emory University, and chairman of the International Society for Bipolar Disorders' Committee on Diagnosis). 

(Will the new rule book, the DSM-5, change this? Short answer: hardly at all.  Really long answer, for nerds like me: a DSM-5 committee got close but did not take up the concept of a "mood spectrum" -- here. ) 

What do these "bipolar variations" look like?

Warning: The following represents my clinical experience taking referrals from primary care physicians: most patients I see have been on 3 or more antidepressants prior to referral. This selects very directly for "bipolar spectrum" patients. However, note that none of these characterizations are found in the DSM, nor are they widely spoken of by mood experts. This is my personal formulation based on 5 years of full-time selection for such patients. This volume may actually exceed the volume seen by academic mood experts, perhaps leading me to conclusions not codified elsewhere.  This section concludes with links to two different patient's testimonials. 

Roller coaster depression
Many people have forms of depression in which their symptoms vary a lot with time: "crash" into depression, then up into doing fine for a while, then "crash" again — sometimes for a reason, but often for no clear reason at all. They feel like they are on some sort of mood "roller coaster". They wonder if they have "manic-depression". But, most people know someone or have heard of someone who had a "manic" episode: decreased need for sleep, high energy, risky behaviors, or even grandiose delusions (‘I can make millions with my ideas"; "I have a mission in space"; "I’m God"). So they think "well, I can’t have that — I’ve never had a manic episode".

However, the new view of bipolar disorder means it’s time to reconsider that conclusion. Hypomania doesn’t look or feel at all like full delusional mania in some patients. Sometimes there is just a clear sense of something cyclic going on. Some mood disorder experts consider recurrent depression to have a high likelihood of manifesting a manic phase at some pointFawcett, especially if the first depression occurred before age twenty.Geller, Rao

Depression with profound anxiety
Many people live with anxiety so severe, their depression is not the main problem. They seem to handle the periods of low energy, as miserable as they are. Often they sleep for 10, 12, even 14 hours a day at those times. But the part they can’t handle is the anxiety: it isn’t "good energy". Many say they feel as though they just have too much energy pent up inside their bodies. They can’t sit still. They pace. And worst of all, their minds "race" with thoughts that go over and over the same thing to no purpose. Or they fly from one idea to the next so fast their thoughts become "unglued", and they can’t think their way from A to C let alone A to Z. When this is severe, people who enjoy books can find themselves completely unable to read: they just go over and over the same paragraph and it doesn’t "sink in". They will get some negative idea in their head and go around and around with it until it completely dominates their experience of the world. Usually these "high negative energy" phases come along with severely disturbed sleep (see Depression with Severe Insomnia, below). Thoughts about suicide are extremely common and the risk may be high.Fawcett(b)

Depressive episodes with irritable episodes
Many people with depression go through phases in which even they can recognize that their anger is completely out of proportion to the circumstance that started it. They "blow up" over something trivial. Those close to them are very well aware of the problem, to put it mildly. Many women can experience this as part of "PMS" . As their mood problems become more severe, they find themselves having this kind of irritability during more and more of their monthly cycle. Similarly, when they get better with treatment, often the premenstrual symptoms are the "last to go". Others can have this kind of cyclic irritability without any relationship to hormonal cycles. Most men endorse this symptom strongly.

Depression that doesn’t respond to antidepressants (or gets worse, or "poops out")
Many people have repeated episodes of depression. Sometimes the first several episodes respond fairly well to antidepressant medication, but after a while the medications seem to "stop working". For others, no antidepressant ever seems to work. And others find that some antidepressants seem to make them feel terrible:  not just mild side effects, but severe reactions, especially severe agitation. These people feel like they’re "going crazy". Usually at this time they also very poor sleep. Many people have the odd experience of feeling the depression actually improve with antidepressants, yet overall —perhaps even months later —they somehow feel worse overall.  In most cases this "worse" is due to agitation, irritability, and insomnia.

In some cases, an antidepressant works extremely well at first, then "poops out".Byrne  The benefits usually last several weeks, often months, and occasionally even years before this occurs.  When this occurs repeatedly with different antidepressants, that may mark a "bipolar" disorder even when little else suggests the diagnosis.Sharma

Depression with periods of severe insomnia
Finally, there are people with depression whose most noticeable symptom is profound insomnia. These people can go for days with 2-3 hours of sleep per night. Usually they fall asleep without much delay, but wake up 2-4 hours later and the rest of the night, if they get any more sleep at all, is broken into 15-60 minute segments of very restless, almost "waking" sleep. Dreams can be vivid, almost real. They finally get up feeling completely unrested. Note that this is not "decreased need for sleep" (the Bipolar I pattern): these people want desperately to sleep better and are very frustrated.

"Soft Signs" of Bipolarity

Here are eleven more factors that have been associated with bipolar disorder.  They are best regarded as markers which suggest considering bipolar disorder as a possible explanation for symptoms:  suggestive of bipolarity, but not sufficient to establish it.  Whether the simultaneous presence of many of these items actually raises the likelihood of bipolar disorder has not been studied, though obviously that is intuitively appealing.   

The list has been adapted from Ghaemi and colleagues; errors in translation to plain English are mine (the list was prepared for the patient version of this section).  In a separate publication the age of which (1983) gives you an idea of how long this seemingly radical notion has been around, one of the most august researchers on bipolar disorder has presented sensitivity and specificity data for several of these factors.Akiskal 

  1. The patient has had four or more episodes of major depression. 
  2. The first episode of major depression occurred before age 26 (71/68) (some experts say before age 20, a few before age 18; most likely, the younger you were at the first episode, the more it is that bipolar disorder, not "unipolar", was the basis for that episode).
  3. A first-degree relative (mother/father, brother/sister, daughter/son) has a diagnosis of bipolar disorder (56/98); or individuals with mood symptoms in at least 3 generations (32/95)
  4. When not depressed, mood and energy are a bit higher than average, all the time ("hyperthymic personality").
  5. When depressed, symptoms are "atypical":  extremely low energy and activity; excessive sleep (e.g. more than 10 hours a day); mood is highly reactive to the actions and actions of others; and (the weakest such sign) appetite is more likely to be increased than decreased (59/88).  Some experts think that carbohydrate craving and night eating are variants of this appetite effect. 
  6. Episodes of major depression are brief, e.g. less than 3 months.
  7. The patient has had psychosis (loss of contact with reality) during an episode of depression. (42/85)
  8. The patient has had post-partum onset of depression (58/84). 
  9. The patient has had hypomania or mania while taking an antidepressant (remember, severe irritability, difficulty sleeping, and agitation may -- but do not always -- qualify for "hypomania"). (32/100)
  10. The patient has had loss of response to an antidepressant (sometimes called "Prozac Poop-out"):  it worked well for a while then the depression symptoms came back, usually within a few months. 
  11. Three or more antidepressants have been tried, and none worked.

There is a very radical idea buried in these 11 items, which we should look at before going on, but you should be aware that this idea is somewhat uncommon even among bipolar experts, and likely to be dismissed with a "hmmmph" by many if not nearly all practicing psychiatrists.  The idea is this:   there might be a version of "bipolar disorder" that does not have any mania at all, not even hypomania.  Ghaemi et al call it "bipolar spectrum disorder".  Akiskal called it "bipolar outcome in the course of depressive illness", and later termed this "soft bipolar".  It is also implicitly recognized in a new (2005 update) bipolar diagnostic system in use at Harvard.

This is strange, you are saying to yourself.  "I thought bipolar disorder was distinguished from 'unipolar' depression by the presence of some degree of hypomania; don't you have to have some hypomania in order to be bipolar?  How could it be 'bi' - polar if there is no other pole!?"

But Dr. Ghaemi and colleagues assert that there are versions of depression that end up acting more like bipolar disorder, even though there is no hypomania at all that we can detect (or, as in item #9, only when an antidepressant has been used).   These conditions do not respond well, in the long run, to antidepressant medications (which "poop out" or actually start making things worse).  They respond better to  "mood stabilizers".  And there is very often a family history which looks more like bipolar than unipolar.  

By this account, there are people whose depression looks so much like unipolar that even a "fine-toothed comb" approach to looking for hypomania will not identify it as part of the "bipolar spectrum", yet who actually should be regarded as "bipolar", in a sense, because of the way they will end up responding to treatment.  

Here's that article link again.Ghaemi   Dr. Ghaemi is the chairman of the committee on diagnosis for the International Society for Bipolar Disorder.  One of his two co-authors for this paper is Dr. Frederick Goodwin, who wrote the "bible" of bipolar disorder for our lifetime (Manic-Depressive Illness, with Dr. Kay Jamison).  These are highly respected researchers amongst mood experts.  Dr. Ghaemi emphasizes the need to rely on evidence in all his papers on diagnosis and treatment and is very frequently cited by other authors on this topic (you'll see quite a few on this website, e.g. see Antidepressant Controversies).  Radical as it sounds, this idea has staying power if only by the reputation of its proponents.  Remember, we're still working from committees not biological markers for all these diagnoses, right?   

Anxious depression could be "bipolar"?!

Warning: leaving DSM-IV territory

The remainder of this "diagnosis" discussion cannot be found in the DSM. I will repeatedly reference mood disorder experts, but many of these views are controversial. You must evaluate for yourself the validity of what follows. I believe that your outcomes with patients will convince you too.

Unfortunately, "hypomania" is quite a misnomer. There are many patients whose "hypomanic" phases are an extreme and very negative experience. As noted by Dr. Jamison, mania can be dysphoric as often as it is euphoric. The "racing thoughts" can have a very negative focus, especially self-denigration; the high energy can be experienced as a severe agitation, to the point where patients feel they must pace the floor for hours at a time. Sleep problems can manifest as insomnia: an inability to sleep, rather than decreased need.  (If you're skeptical and want more information and references about how anxiety can be a bipolar symptom, try that link).  

In my experience most of these patients show up with a combination of agitation, anxiety and dysphoria — and they can’t sleep well.  You’ve seen that many times, right?  Is this "anxious depression?"  Is this some bipolar variant?  How could you tell the difference?  Is there a difference?  What is really going on etiologically?  Unfortunately, this is still almost completely unknown. (See the appendix "What’s the latest on etiology?", which I will try to keep updated frequently, for current data on this fascinating puzzle.)

In the meantime, my opinion:  you can’t easily distinguish "anxious depression" from bipolar II, presenting in a mixed state.  I doubt that there is a distinction to be made, ultimately. For example, there is complete overlap between the symptoms of Generalized Anxiety Disorder and Bipolar II.

For now, the only way to tell is by outcome.  Depression that is not bipolar can get better and stay better: with time, or counseling by you, or formal psychotherapy, or antidepressants.  If your patient gets better - great!  If she/he doesn’t, you may need a new conception of mood disorders in order to identify those patients who can get better with mood stabilizers.

Meanwhile, at least one experienced mood researcher warns that anxiety in someone who is depressed is associated with a high suicide risk.Fawcett(b)  So although there is diagnostic confusion, there are tremendous stakes involved.  Approaching this situation with an open mind seems very warranted, given this risk.

 

Diagnosis: Summary

I hope it may now make sense to you to think of mood symptoms as falling on a continuum between plain depression and "depression plus", the far end of which is Bipolar I, with many variations falling in between. All this requires a redefinition of what one does in "ruling out bipolar", however, as discussed in the next section.

How do you rule out bipolar disorder now?

This used to be simple. The provider determined that the patient had never had a manic episode. When "manic" only meant one thing (classic mania) one could ask "have you ever had a manic episode?" and many patients knew what was being asked. Otherwise, one could ask for a history of:

  • Mood much better than normal
  • Rapid speech
  • Little need for sleep
  • Racing thoughts, trouble concentrating
  • Continuous high energy
  • Overconfidence
  • Loss of contact with reality (delusions)

As you now know, this is a screen for Bipolar I mania. It reflects DSM criteria, and thus misses all the complexity we have just discussed. What you need is a screen for BPII, and it needs to fit within the scope of a busy primary care practice. There is no perfect tool for this. We desperately need a lab test, but there is none on the horizon (and bipolar II may well prove to be a "final common symptom complex" for multiple disorders, each requiring different lab assessments).  If your patient wishes, you could refer her/him to a screening test called the MDQ, recently assembled by a team of mood experts.  It is not as sensitive as I would prefer, but represents solid consensus among bipolar specialists.Hirschfeld et al

If anything about your patient's depression strikes you as atypical, particularly high energy in any form, or a sense of recurrence or cycling, you should have your patient complete an MDQ while you see your next patient.  If it's positive (here's the scoring system) you could refer him/her to my patient site for further education.  This will allow them to begin their own evaluation of this difficult differential. I emphasize that Bipolar disorder is not something one wants to have. At the same time, a patient should have a thorough evaluation for it if this is warranted. 

If your patient returns affirming a suspicion of bipolar disorder, and psychiatric services are limited in your area, you could to a skilled therapist for a diagnostic evaluation, if available.  If the therapist says "bipolar", this would be strong confirmation for the diagnosis:  since there is no psychotherapy with demonstrated efficacy for bipolar II, except as an adjunct to mood stabilizers, there is little "incentive" for therapists to overdiagnose this condition.

So remember, if there is anything that makes you wonder whether this patient’s depression might be more than plain depression, refer them to this website (before or after the MDQ) and let them do the homework. Ask them to bring back printed sections that really make sense to them, for you to evaluate.

From here you can review, read more about diagnosis issues in the Diagnosis Details section, or go on to Treatment.