Bipolar Disorders

By Stephen Proskauer MD | August 11, 2007

Integrative Diagnosis and Treatment of Bipolar Spectrum Disorders

Bipolar disorders are unique diagnoses in several respects. Most of them went unrecognized as such when I was trained in psychiatry during the late 1960’s and 1970’s and many are still misdiagnosed even today. They encompass a wide range of symptoms and behaviors, from the most subtle disturbances of mood and behavior, to a variety of depressive syndromes that used to be called anxious or agitated depressions, to disabling personality patterns sometimes described as narcissistic or borderline tendencies, all the way to the most severe psychotic manias and depressions that often result in suicide or repeated psychiatric hospitalization. Bipolar symptoms tend to worsen with time if left untreated or managed poorly.

The common feature of all these conditions is instability and poor regulation of emotions, so that afflicted individuals react excessively strongly to small stresses and internal shifts. These reactions when they become extreme can include mood swings from black and hopeless suicidal depression that make it difficult even to get out of bed all the way to states of euphoric or irritable excitement with racing thoughts, compulsive work, sleeplessness, excessive talking, impulsive actions, and at times violent or combative outbursts, especially when others make attempts to restrain the manic behavior. The regular neurophysiological rhythms within the brain seem to be deficient in self-regulatory controls and bounce from one extreme to the other, often, but not always, in regular cycles of hours, days, weeks, months, or seasons.

Many of the less severe bipolar conditions manifest primarily as depression with intervening periods of relative normalcy or hypomania. There are also mixed forms of bipolar illness in which depressive and manic symptoms occur simultaneously or alternate so rapidly as to create a state of constant unpredictability and emotional chaos. Mixed states are extremely difficult to endure, both for patients and those close to them. They are also demanding to treat and carry the highest risk of serious suicide attempts.

Within the bipolar spectrum have fallen the behavior and mood profiles of many famous creative artists and scientists, including Mozart, Beethoven, van Gogh, Sylvia Plath and Leonardo Da Vinci, to name just a few. It is estimated that the genes governing bipolar disorders are present in some form in at least 15% of the human population, and it may be the tendency for bipolarity to be linked with creativity that has preserved these genes and kept them from having been weeded out over time by natural selection. In essence, bipolarity seems to have survival value for the human species. We are fortunate that the very broad range of the bipolar spectrum is more widely appreciated these days and that a number of new treatments are available that offer the promise of preserving a creative quality of life with a minimum of residual symptoms and medication side effects.

Principles of Diagnosis

In my practice, I cast a wide net not confined to the strict DSM-IV definitions of various bipolar disorders. I suspect a bipolar process at work in the presence of depression accompanied by symptoms such as mood instability, anxiety, irritability, distractibility, impulsivity, rapid speech, unwise or sudden decisions about purchases, reckless social or sexual behavior, decreased need for sleep, hyperactivity, temper outbursts, lethargy alternating with agitation, sudden onset of suicidal ideation, and/or impulsive suicidal acts. The manic highs, the dramatic and hazardous periods of euphoria commonly associated with mania, do not necessarily occur at all; this trademark manic symptom is no longer so common and seems to have been eclipsed by hyperirritability in recent years.

Red flags in a depressed patient’s history that should raise the index of suspicion for bipolar include:
(1) family history of anxious depression, bipolar disorder, substance abuse, or psychiatric breakdowns with no clear diagnosis;
(2) early onset of clinical depression prior to age twenty;
(3) history of more than three major depressive episodes, especially if the episodes lasted less than three months;
(4) atypical depressive symptoms – such as gaining (instead of losing) weight and difficulty waking up (instead of early morning awakening) – prominent complaints of anxiety or problems with attention;
(5) unusually fast, temporary, or poor responses to SSRI or SNRI antidepressants (particularly if three or more antidepressants have failed after adequate trials), or paradoxical exacerbation of symptoms in response to antidepressants, including induction of mania or of rapid cycling;
(6) childhood history of temper outbursts, early sleep disturbances, horrible nightmares, and/or separation problems from parents or of a childhood diagnosis of “Attention Deficit Hyperactivity Disorder” (ADHD) accompanied by mood instability that responded poorly to treatment with drugs or even got worse (This is sometimes complicated to sort out, because ADHD often accompanies Bipolar Disorder, so the attention hyperactivity symptoms may improve while mood symptoms persist);
(7) strong seasonal component to the onset of depression, usually, but not always, worse in the winter with a tendency to lessen or become more manic in summer;
(8) history of postpartum depression or psychotic depression or mania;
(9) depressions that periodically interrupt or alternate with highly productive and creative periods in the patient’s life;
(10) a “crash and burn” cycle of life events, such as a chain of divorces, business failures, legal problems, etc., with intervals of apparently successful coping;
(11) a history of substance abuse in which the patient began using drugs or alcohol in an attempt to self-medicate for bipolar symptoms.

The correct diagnosis of bipolar depression has often been delayed for many years, unless a classic manic-depressive pattern fitting the strict DSM-IV criteria for Bipolar Disorder I or II has been detected. Meanwhile, the patient has suffered from incomplete or ineffective treatment, usually with SSRI or SNRI antidepressants. Had all of the red flags listed above been considered as potentially indicative of a bipolar spectrum disorder, the likelihood of appropriate therapy and early recovery could have been much increased. The prevalence of bipolar disorders by the DSM-IV criteria is estimated to be 3-4% of the general population. If broader criteria were used, this figure might rise to at least 10-15% with clinically significant and potentially treatable bipolar illness.

From the research point of view, however, broadening the diagnostic criteria for bipolar spectrum disorders could create a morass of confusion in selecting patients for studies in drug trials and make it all but impossible to compare results with earlier studies done using the strict criteria. A compromise answer to this objection is to maintain the current DSM-IV criteria but expand the controlled study of promising treatments to populations that include the catch-all category, Bipolar Disorder NOS (Not Otherwise Specified), commonly referred to as Atypical Bipolar Disorder. In my experience, there are many patients in this broad diagnostic category who have not responded to treatment for other disorders but who do well on a regimen designed to address their bipolar tendencies.

Principles of Integrative Treatment

The effectiveness of a therapeutic approach has two aspects, efficacy and tolerability of the treatment. Both aspects are important, but their relative value depends on the phase of treatment: (1) acute phase (obtaining relief from the most serious symptoms in the first month or two);
(2) remission phase (facilitating continued improvement up to six months after onset of treatment); and
(3) recovery phase (maintaining stability after six months).

Obviously, if a patient is severely depressed, suicidal or psychotic, side effects are less important in the near term than quick improvement. On the other hand, maintenance therapy over many months or years must be tolerable or patients will eventually discontinue it, however strong the encouragement to persevere with treatment.

Effective maintenance over the long term is at least as important as averting disaster during an acute bipolar decompensation, because of the notorious instability of bipolar disorders and the strong tendency for relapse and recurrence. Bipolar Disorder is a chronic illness like diabetes that must be carefully monitored and treated for life, so it is especially important to choose maintenance drugs that are easily tolerated with little or no risk or unpleasant side effects.

My rule of thumb is to try and avoid any medication that causes my patient as much distress as it relieves at any phase of treatment, however well accepted it may be by the FDA and the psychiatric community. Naturally, as the level of distress decreases from effective treatment, side effects become relatively less tolerable. If a medicine becomes intolerable to my patient for whatever reason, it is clearly not practical to help them recover or maintain well being. Fortunately, there are many choices available and drugs with major side effects for a given patient can be avoided or weeded out by trial and error.

The therapeutic relationship is in itself a key mood stabilizer. It pays off in the long run to have frequent patient visits, especially in the first six months to a year of treatment, in order to forge a trusting relationship, educate the patient about the complexities of bipolar disorders, monitor mood symptoms and medication side effects carefully and deal with psychotherapeutic issues. Since I was trained in psychotherapy and have over four decades practice, I personally prefer to do psychotherapy along with other forms of treatment whenever possible and have come to believe that this factor adds considerably to my effectiveness in treating bipolar illness.

Maintaining the therapeutic alliance involves listening carefully to patient reports of how they are feeling and taking side effects seriously, even if we consider them to be minor relative to the risks of the illness. I tell patients that my goals in treatment are to help them lead as fulfilling a life as possible and to realize their full potential. These are ambitious but crucial aims, since so many bipolar patients are extremely creative and need encouragement to find expression for their gifts once the symptoms have been brought under sufficient control.

Typically, the accurate diagnosis and effective treatment of bipolar disorder has been delayed at least ten years since the patient first sought help for major symptoms. During this time, the patient’s life has often been badly disrupted by the consequences of their symptoms, both the paralyzing effects of black bipolar depression and the destructive impact of manic hostility, impulsivity, and poor judgment, to say nothing of additional discouragement from receiving misguided treatment. The trail of collateral damage leads to loss of hope. After years of chaos, patients often feel that they are doomed and beyond help, which predisposes them to escape into drugs and other addictions as well as to drop out of treatment.

One of my patients had suffered 25 years of mistaken diagnosis and ineffective treatment for “Major Depressive Disorder” at the hands of many psychiatrists and even from a university mood disorders research clinic. Because no one had ever questioned the diagnosis, all the clinicians kept repeating the same failed strategy, trying one round of antidepressants after another. By the time she came to see me, this unfortunate patient was on the verge of suicide. She said I was her last hope. Her chronic depression had been almost disastrously fueled by hopelessness about any possibility of getting effective treatment. When I took a careful history that included the period before she felt depressed, I discovered that she had been hypomanically overfunctioning for at least ten years prior to the time when a series of personal losses had triggered a chronic depression that never switched back to hypomania. Fortunately, she responded quickly to treatment for bipolar depression and finally recovered hope and a measure of well being.

In counseling, to counteract the assault on bipolar patients’ self-esteem from uncontrolled symptoms and the stigma of having a mental illness, I tell them about the many famous artists and writers who have also had this problem so that they come to realize they are in good company. I suggest to them that it is no accident that bipolarity has survived in the human gene pool, since bipolar people are among the most creative and innovative members of the species. I also tell them they are fortunate to live in an era when agents have become available that can control their disruptive symptoms without blunting their creativity or their ability to enjoy life.

Manic patients will often choose to stop their medication rather than blunt the creative flow with chemical straitjackets. The likelihood of compliance with treatment is much increased if the patient knows the doctor cares about their creative life and is willing to adjust dosage or switch medications so that creative energy and expression is preserved and even fostered by being stabilized over the long term so that creative projects can come to fruition.

During the maintenance phase, the danger remains that a patient prone to severe bipolar episodes will decide they have recovered and don’t need maintenance medication anymore. Then, as soon as mania recurs, they lose any insight into their illness and are very resistant to further treatment. This is a very dangerous development and often results in irreversible damage to patients’ lives and relationships and even acute hospitalization or suicide. I warn patients early on about this possibility, but sometimes even that is not enough to prevent flight from treatment unless follow up visits are frequent and the therapeutic relationship is very strong.

A typical psychotherapeutic issue involves learning how to self-regulate in the face of mood instability and to prevent vicious circles of depression or impulsivity from taking over. Often there is grief and emotional repair work from previous losses and childhood trauma that needs to be done, since bipolar patients are often raised in alcoholic or unstable homes by one or more bipolar parents.

As manic instability comes under control and their lives settle down, bipolar patients reach a point where they are flooded with spontaneous realizations and insights about the negative consequences of unwise decisions they made in the past under the influence of their illness. During this period, patients need emotional support to work through the profound remorse and regret that can surface as they achieve bipolar “sobriety.”

After this wave of coming to terms with and taking responsibility for past losses and misfortunes has past, bipolar patients are more ready to pick up the pieces and reconstruct their lives in order to make the best use of their gifts. The therapist’s job at this point is to gently and consistently remind the patient of both their abilities and their vulnerabilities, so as to help them prevent recurrence of future manic or depressive episodes and to avoid lapsing back into prior states of low self-esteem and hopelessness.

I find it helpful to explain my rationale in making medication choices and dosage adjustments to patients as we go along so that they are constantly reminded that I am their consultant and that we make treatment decisions together. This partnership approach to medication management enhances compliance and enables patients to tell me when they discontinue a drug or make dosage changes on their own without fearing my reaction. Sometimes I will give them responsibility to experiment with dosage between appointments within clear guidelines once I am convinced that they can do this sensibly.

Treatment guidelines

(1) Regular healthy meals, sleep hygiene and exercise are all essential and should be discussed with patients. The high level of chaos induced in patients’ lives by rapid mood swings can be partially neutralized by attention to these lifestyle factors.
(2) Dietary supplements are always recommended to my bipolar patients, especially omega-3 oils and multivitamin/mineral preparations. EMpowerPlus, a proprietary blend of 36 nutrients that includes trace organically bound minerals, has been found in pilot studies conducted in Canada to have a robust effect size in bringing bipolar symptoms under control in a small ABAB study design. Larger controlled double blind studies are in the works now. While my clinical experience does not support the use of EMpowerPlus as a monotherapy, I do believe it can reduce the need for medication to the point where some agents can be tapered off and discontinued while others are maintained at reduced dose levels. This further decreases the risk of side effects and enhances the tolerability of treatment. One theory as to the effectiveness of a nutritional approach points to the progressive depletion of trace minerals in our farm soil over the last five or six decades due to the use of chemical fertilizers. It is postulated that genetic defects cause multiple flaws in brain chemistry that render people prone to bipolar illness to be more sensitive than others to these deficiencies of trace minerals in the diet. Therefore, intensive supplementation across a broad range of nutrients acts as a buffer against bipolar symptoms.

(3) Be careful with antidepressants, especially in the absence of mood stabilizers. Patients on SSRIs frequently complain they feel like zombies and these drugs may be ineffective or even make symptoms worse, as discussed above. Bupropion is sometimes more useful and better tolerated in my experience, but this also is best given with a mood stabilizer or at least monitored very carefully if bipolar disorder is suspected.

(4) Avoid whenever possible high doses of maintenance medications that are poorly tolerated because of side effects that interfere with alertness, physical well being, and/or creative expression. These may include some of the most common first-line agents for acute treatment, such as valproate, olanzepine, and even lithium, the most well established of all agents used in treating manic-depressive illness, which can cause kidney and thyroid problems after long term use and serious acute symptoms if blood levels rise too high through overdose or dehydration.

(5) Lamotrigine is excellent and usually well tolerated for bipolar depression, so long as the dose is gradually increased according to the recommended schedule to avoid a dangerous rash or the cognitive blunting (“brain fog”) that sometimes occurs at high doses. One bipolar patient with a history of drug abuse refused to discontinue lamotrigine even after a rash began to develop because it helped her so much to resist her cravings for street drugs. The long term solution was to lower the dose below the rash threshold.

(6) Some of the atypical antipsychotics – particularly aripiprazole, ziprasodone, and quetipine – are extremely useful and usually well tolerated either in monotherapy or in combination with antidepressants, lamotrigine or each other. Their complex and varied receptor profiles allow for great flexibility and inventiveness in choice of agent and dosing. They all have antidepressant properties along with the capacity to prevent mania.

(7) Be prepared to use two, three or even four medications in combination to achieve stability in many cases. It is common for a moderate to severe bipolar depressive patient in my practice to be taking both lamotrigine and an atypical antipsychotic, and not unusual for an antidepressant or two and occasionally a benzodiazepine for anxiety to be part of the cocktail as well. Adjusting the relative doses of these agents with the constantly changing ups and downs typical of the bipolar patient’s course is both an art and a science. Careful follow-up during unstable periods is essential to prevent hospitalization and minimize collateral damage.

(8) Last but not least, keep constantly in mind that bipolar illness, while it is amenable to effective treatment, also carries with it a higher mortality rate than most cancers, the highest incidence and prevalence of completed suicide of all psychiatric disorders. A no-suicide contract is an essential part of the therapeutic alliance in patients who have a history of suicidal thoughts or attempts and any flare-up of suicidality should be taken very seriously.

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