The Expanding Spectrum of Bipolar Disorder

The introduction of the SSRI antidepressants in 1988 (Prozac being the first), brought a revolution in the treatment of mental illness in this country. Prozac and its many cousins such as Zoloft, Paxil, Effexor, and Celexa, were quite different from older antidepressants. They were much safer if taken in overdose, they were easier to sort out the correct dose, and their side-effects were fewer. Millions of patients who had struggled with untreated depression now started taking medication for their problem. Because these drugs were easy to prescribe and fairly safe, primary care doctors began offering them to patients in record numbers.

We should be careful not to overstate the effectiveness of these drugs. A placebo (sugar pill) will help 30% of depressed patients and antidepressants help about 50%. Antidepressants combined with effective psychotherapy will help up to 80%. So although these drugs are not a panacea, they are widely prescribed because mental health issues are so common. They account for about one third of a typical
primary care physician’s practice.

An unintended effect of this widespread use of antidepressants was to advance our understanding of bipolar disorder. Antidepressants often, but not always, make depressed bipolar patients worse, particularly if they are not on a mood stabilizing drug like lithium. Mood stabilizers include lithium, of course, but also drugs that are borrowed from neurology and treat seizures, such as Depakote and Lamictal. Agents like these are valuable in the management of bipolar disorder.

A few years before the introduction of Prozac, experts in the field of mood disorders began describing patients with what was felt to be a more mild form of bipolar disorder. They named this version Bipolar II to distinguish it from the Bipolar I that we think of as classic manic-depressive illness.

Patients with bipolar II never really have full-blown mania. They might not end up in a psych hospital or gamble away their life savings, but they have many other features which make them look more like bipolar patients than typical depressed patients.

Many of these individuals have periods of hypomania (literally, “below” mania), where they feel charged up, require less sleep, talk and think faster, and have increased productivity. Sometimes, their judgment is impaired during these times. The hypomanic periods are not necessarily seen by patients as a problem, they might be “better than well” or just a little jumpy and agitated. But later they often “crash” and then a depression sets in. We should remember that for bipolar patients, the problem is mostly depression, not mania. Manic or hypomanic periods tend to be uncommon and short-lived. The typical bipolar patient is much more likely to feel depressed than manic at any given time.

Not only do certain depressed patients with bipolar disorder not improve on regular antidepressants, but some get worse, switching more rapidly from depression to mania, or being both manic and depressed at the same time, so that they are restless, pacing, not sleeping, anxious, but also depressed and not enjoying the euphoria or expansive mood of pure mania.

The environment during the past 15 years was ripe for a test of the theory that bipolar disorder is actually widespread in the population, with the milder versions being quite common. The experiment was to unleash millions of prescriptions for antidepressants from primary care doctors, usually in the form of SSRIs like Prozac and Zoloft on depressed Americans. If there were a lot of Bipolar II patients out there, some would get worse; they would pop out of the woodwork. And they did.

The FDA is now recommending that physicians screen patients for bipolar disorder before starting antidepressants. This is based on reports of antidepressants causing mania in depressed bipolar individuals. Sometimes, patients with bipolar illness only get diagnosed after they take an antidepressant and became agitated or hypomanic. One estimate is that a third of all depressed patients actually suffer from some form of bipolar disorder. It would make bipolar illness much more common than is currently appreciated.  Traditional manic-depressive illness (Bipolar I) makes up about 1% of the population.

One of the challenges is that if a patient feels agitated, anxious, and depressed, it could be straightforward anxiety and depression, or it could be Bipolar II in a mixed state of hypomania and depression. It can be hard to tell the difference, and there might be little observable difference, really. But the treatment approach is not the same. Bipolar patients need mood stabilizers first, depressed unipolar patients needs antidepressants. Not only are we now recognizing bipolar illness in its milder form, but we are also discovering and identifying many variants which fit in the broad spectrum of bipolar illness. Appreciating this expanding landscape of bipolar illness is critical to helping patients with disorders of mood.

The first carve out was for Bipolar II, which is periods of depression alternating with periods of hypomania, without any fullblown mania to meet the criteria for Bipolar I. But there are other variants as well. Some depressed patients never show any evidence of mania or agitation unless they take an antidepressant. In this case, the antidepressant is said to unmask their latent bipolar illness. Others don’t have their first hypomanic episode until they’ve had many years of depression, and the diagnosis is only clearly made in retrospect.

The hyperthymic temperament refers to individuals who are engaging, energetic, charismatic, love to socialize, and often need little sleep. They walk through life with their 100 watt light bulb burning at 150 watts. The name hyperthymic temperament is used to compare them to dysthymic individuals. Dysthymia means mild depression, so hyperthymia is the opposite. Saying that these individuals have a “hyperthymic temperament” means that it is in their nature to be this way. They don’t really have discreet periods of mania or hypomania, they are pretty much always like this.

Hyperthymic individuals are common in the entertainment industry and they also make fine CEOs. You might wonder, why aren’t we all like this? What could be wrong about going through life better, more energetic, more alive, more charismatic? Well, some individuals like this are lucky and they get through life without difficulties. For them, it is not really an illness. But others ultimately develop depression. They have “borrowed” for that extra energy for so long that they finally run out, or they have a moderate life upheaval (divorce, loss of job) that would surely upset most people, but they are particularly unable to recover. In patients with a hyperthymic temperament, the extra “boost” comes at a risk of later depression. These individuals may be less protected if things go very wrong in their lives.

Other patients subjectively “feel” bipolar to an experienced clinician, even though they’ve never even had hypomania. Their depressions are characterized by increased (instead of decreased) sleep and appetite. They may have a personal or family history of alcoholism. There may be suicides or bipolar illness in the family. Their depression could be accompanied by severe, sometimes lifetime insomnia. They may be particularly driven, full of energy, and successful when not depressed. They might have not responded to multiple prior antidepressants.

It is important to distinguish bipolar illness from “mood swings.” Mood swings are dramatic changes in mood that happen over the course of hours or a day. The changes in mood in bipolar illness last for weeks, months, or longer. Even so-called rapid cycling bipolar patients are people with several switches in mood in a year, not several in a day. Patients with very unstable moods that change unpredictably and dramatically during a single day are much more likely to have borderline personality disorder than bipolar disorder. Only a minority of psychiatrists think that multiple mood swings during the day constitutes bipolar illness. Also, as we now realize, the idea that mood must undergo dramatic shifts in order to qualify a patient as bipolar is no longer true. Some patients remain in one state or the other for years.

So we see that the concept of bipolar illness has undergone a huge transformation. First, the idea that you had to have full-blown mania was dropped. Then the idea that you had to switch between one mood state and another was given up, and now we are not even sure that you need any hypomania to qualify as bipolar. From a clinical perspective, why do we care? We care because we want to identify patients who should be treated with mood stabilizers before you consider using antidepressants, if you use them at all.

Often, once you stabilize mood, depression lifts because patients are so much calmer. Other times, a depressed bipolar patient can be given a second drug, such as an antidepressant, or a mood stabilizer with antidepressant properties (lithium and Lamictal are two examples) to help his or her symptoms. Although patients with traditional depression are usually treated with antidepressants, sometimes a mood stabilizer can be added to augment, or help, the antidepressant work better.  A related example is that light therapy can help depressed patients who do not suffer at all from seasonal affective disorder. This underscores the weaknesses in our current classification of depression.

Intellectually, the error that was made with bipolar disorder was that the most dramatic feature of a minority of sufferers (full-blown mania) caught the biggest attention of researchers and clinicians, and it blinded us to the subtleties of this condition.

The analogy I would make is if you were from another planet and studying plant life on earth. If you saw a rosebush you would assume that those big, blooming roses were what defined it. But with more examination, including DNA analysis, you might realize that other rosebushes are not in bloom and some never bloom, but they are still rosebushes nonetheless.

A better way to consider bipolar illness, from the perspective of a practicing physician, is to simply focus on the treatment decision. Whether you need mania to “qualify” as bipolar illness is of less interest than what drug we can prescribe to help a patient sitting in the office. A practical approach would be to divide patients into two groups. One is those more likely to respond to traditional antidepressants and the other is a group that might do worse or not respond to antidepressants and should be treated with a mood stabilizer first, with an antidepressant sometimes added later on. Instead of calling these two groups unipolar and bipolar depression, maybe we should call them Frank I and Frank II, which would be my preference, along with a Nobel Prize, of course, but would also serve to de-emphasize the focus on mania and put it more on the responsiveness to treatment.

The analogy I would make is if you were from

another planet and studying plant life on earth.

If you saw a rosebush you would assume that those big,

blooming roses were what defined it.

Some mental health professionals feel that bipolar illness is now reaching bandwagon status and that it is being over diagnosed by a few psychiatrists and psychologists. This might be true, but the opposite problem, missing bipolar illness altogether, is a much more frequent concern.

Either type of depression can also be treated with psychotherapy, but Bipolar II patients in a hypomanic phase are probably best treated primarily with medication. Bipolar patients also benefit by having regular sleep/wake cycles, predictable schedules, and avoiding extremes of work or recreation. Individuals in the bipolar spectrum often thrive on huge job assignments or the challenge of planning an enormous party, but then “crash” afterwards. Many naturally gravitate to these extremes which actually make their illness worse.  Bipolar patients who monitor their own mood (or get the help of family members) and take action early on do better than those who leave it up to their doctors.

One error I have seen commonly is that a patient presents to the doctor complaining of anxiety and depression and is appropriately put on an antidepressant. Soon afterwards, the patient starts complaining he or she is worse, with agitation, nervousness, restlessness, skin tingling, etc. The clinician might think these symptoms are part of the original illness, and maybe add a tranquilizer like Valium or increase the dose of the antidepressant. Other physicians might switch the patient several times to other SSRI antidepressants, thinking that it was an adverse reaction to just one particular drug. But the problem is that the development of these symptoms should be the “ah, ha!” that makes us realize we might be dealing with a bipolar spectrum disorder. The antidepressant should be immediately stopped and a mood stabilizer tried instead.

Primary care doctors are the de facto mental health providers in our country. There are simply not enough psychiatrists to take care of everyone with a mental health issue, and because these problems are so common, it is not appropriate for primary care physicians to refer all these patients to specialists. Like high blood pressure and diabetes, most mental health falls squarely within the scope of primary care. Also, patients are generally more comfortable in their primary care doctor’s office than they would be seeing a psychiatrist. The TV view of a bearded, accented intellectual making you lie down on a couch and talk about your mother is still with us.

Because primary care doctors treat the vast majority of all depressed patients, I feel it is incumbent on us to step up to the plate on bipolar illness. It is a challenge because most of my primary care colleagues are unbelievably overburdened. But when mental health makes up a third of your practice, as it does for most primary care docs, you have to be able to treat it properly. Only providing antidepressants and not looking for or treating bipolar illness is missing half (or maybe a third) of the boat.