Use of Antidepressants in Treating Bipolar Disorder

Patients with bipolar disorder, particularly those who are undiagnosed or in the early phases of their illness, often first seek medical help complaining of depression. Inexperienced or inadequately informed medical personnel often take these complaints at face value and prescribe an antidepressant, which frequently induces an episode of mania in the patient. It is crucial that physicians, in addition to looking for physical causes of depression (such as thyroid conditions), also explore the patient's personal and family medical history for signs of bipolar disorder. Consultation with the patient's nearest loved ones can be critical, as some early signs of the disorder may not seem to be worth mentioning to the depressed patient.

The conservative approach is first to establish a mood stabilizing medication prior to beginning the antidepressant. The mood stabilizer has the effect of moderating or opposing the mania-inducing effects of the antidepressant. (Antidepressants taken without a mood stabilizer are known as "unopposed antidepressants.") There are situations where unopposed antidepressants may be acceptable, as when suicide is an imminent treat, but in any case the important fact is that antidepressants should be prescribed to persons with bipolar disorder with extreme caution, and only by skilled psychiatrists or psychopharmacologists.

Authoritative References:

From the web site: Antidepressants in Bipolar Disorder: The Controversies

Article: Antidepressants in Bipolar Disorder: Are They Safe? Are They Effective?, by S. Nassir Ghaemi, M.D.

Article: “Cade’s Disease” and Beyond: Misdiagnosis, Antidepressant Use, and a Proposed Definition for Bipolar Spectrum Disorder, by Nassir Ghaemi, MD, James Y Ko, AB, Frederick K Goodwin, MD

Article: Bipolar Disorder, by S. Nassir Ghaemi, MD

Abstract: Antidepressants in bipolar disorder: the case for caution, Ghaemi SN, Hsu DJ, Soldani F, Goodwin FK in Bipolar Disord. 2003 Dec;5(6):421-433

From the APA (American Psychiatric Association) Practice Guideline For The Treatment Of Patients With Bipolar Disorder, Section II.B.6: Pharmacologic Treatments, Antidepressants)

Virtually every available antidepressant agent has been associated with the emergence of mania in bipolar patients. The study of this issue is complicated, however, by the fact that patients with depression have a baseline risk of switching to mania. This risk has been difficult to characterize because of variations in patient groups and treatment regimens across studies. Of further concern is the fact that some investigators have reported an association between the use of antidepressants and the development of rapid cycling and mixed affective states. It has therefore been hypothesized that antidepressants may worsen the overall course of bipolar disorder. Unfortunately, the phenomenon of antidepressants inducing the switch to mania, hypomania, rapid cycling, or mixed affective states has not been systematically evaluated in most studies of antidepressants and bipolar depression. It is therefore unknown whether different antidepressants are more or less likely to induce the switch process, although recent preliminary data suggest that bupropion may be less likely than tricyclic antidepressants to induce a switch.

In general, psychiatrists should be cautious in prescribing antidepressants for patients with bipolar disorder. However, as some bipolar patients continue to develop depression despite optimal use of mood stabilizers, antidepressants are often necessary for acute and/or prophylactic treatment. Patients who require antidepressant treatment should receive the lowest effective dose for the shortest time necessary.

From Mental Health Infosource, Ask the Expert - Antidepressants as a Treatment for Bipolar Disorder, by Ron Pies, M.D., clinical professor of psychiatry at Tufts University and popular Psychiatric Times columnist. The linked site contains fuller information on this subject.

There is still a fair amount of controversy as to whether antidepressants can affect cycle length or "switching" in bipolar illness; and if so, how much and in which subtypes of bipolar disorder. The consensus seems to be--and I concur with this--that at least some bipolar patients are sensitive to antidepressants, particularly tricyclics, and that their course can worsen substantially with use of these agents.

Excerpts from BPSO Discussions

The following discussion should not be regarded as authoritative, it is simply the personal experience of the individual authors. Always consult a trained mental health professional before making any decision regarding treatment choice or changes in treatment. Never discontinue treatment or medication without first consulting your physician, clinician or therapist.

People who become manic on unoppposed antidepressants most definitely have a genetic predisposition to the illness.

A skilled psychiatrist or pharmacologist who takes comprehensive patient histories might have discerned earlier unrecognized hypomania. But Bipolar II (depression with hypomania) is notoriously difficult to diagnose. Earlier episodes of hypomania may have been so fleeting as to be undetectable. Taking a careful, comprehensive family history can be a substantial aid to diagnosis.

Any pdoc worth his (or her) salt knows that unopposed antidepressants can and do precipitate (hypo)mania in people who are genetically predisposed to Bipolar Disorder. Yet antidepressants are often prescribed by doctors without the requisite skills. My feeling is that no one should ever take an antidepressants unless s/he has been thoroughly evaluted by a skilled psychopharmacologist.

There is a growing literature suggesting that not only can antidepressants precipitate mania in bipolars, they can also worsen the course of the illness, in terms of shortening the time between cycling and prompting other responses, such as Panic Disorder. There is some evidence that certain antidepressants are worse than others -- the trend is well established for all the tricyclics (which means that extreme caution should also be taken with Effexor, which includes a tricyclic component) and less well established for the SSRIs, which is the category that Paxil falls under. The half-life of the drug is totally unrelated (based on the studies I've read) to its effect on bps. The antidepressants which seem least likely to promote this response are Wellbutrin and the MAOIs but if any antidepressant has caused mania, extreme caution should be exercised in the use of any other antidepressant, regardless of its classification.

Antidepressants are essential to the successful treatment of bipolar depression. Without them, many people with bipolar illness will suffer miserably and perhaps complete suicide.

Obviously, antidepressants, like all psychotropic medications, should be prescribed and monitored with the greatest of care. And they should not be taken by someone with bipolar disorder who is not also taking either at least one mood stabilizer or (in some cases) an atypical neuroleptic.

Harrison Pope, Jr. discusses this issue [using antidepressants] in an interview in the May 1994 issue of Currents in Affective Illness. The article is entitled "An Algorithmic Approach to Mania and Depression in Bipolar Disorder." With respect to the question whether antidepressants accelerate mood cycling in bipolar patients, he says:

At McLean Hospital, there exists a range of clinicians, from very conservative psychopharmacologists, who are reluctant to introduce antidepressants out of concern that they may exacerbate the course of bipolar disorder, to others, who argue that the jury is still out on the issue and use antidepressants without hesitation when indicated for depression.

In practice, the question is rendered moot by the fact that when one has a profoundly depressed bipolar patient, one can not withhold antidepressants and allow the patient to suffer from depression out of concern that introducing a treatment that will alleviate the patient's present state may perhaps exacerbate the subsequent course of the illness. When a patient is suffering, one intervenes.

Whether and how much of an antidepressant should be prescribed depends on the nature of the individual patient's illness. In patients with Bipolar I, whose illness often shifts dramatically toward mania in Fall and Spring if it were untreated or inadequately treated, antidepressants must be used with great caution, adding, decreasing, or stopping them as the symptoms and time of year warrant. Without an antidepressant, however, the patient's mood may remain flat, and energy less than optimal. A patient with Bipolar II is entirely different and a higher dosage of antidepressant can often be tolerated with no ill effect.

Gerald Klerman, MD, one of the more highly respected clinicians and researchers in this area of medicine (now unfortunately deceased) classified the primary forms of bipolar disorder as follows:

With respect to Bipolar IV, Klerman wrote: Bipolar IV includes those depressed individuals who have elated episodes precipitated by antidepressants. In assessing the evidence indicating that antidepressant agents precipitate a switch from depression to mania, Bunney [1978] reviewed 80 published reports in which mania or hypomana was noted while patients were receiving tricyclic drugs or MAOIs for depression. Approximately 10 percent of the 3923 patients experienced preciptation of a manic episode; the majority of these patients had a prior diagnosis of bipolar disorder. It has been theorized that changes in brain metabolism and receptor sensitivity are involved in the switch process. [Psychiatric Annals 17-January 1987]

The DSM-III-r categorizes antidepressant-induced mania as organic mood disorder.

Antidepressants often induce mania or hypomania, and the almost always increase the rate of cycling in bipolarss. The theory is that antidepressants contribute to what is called the "kindling effect", thereby increasing the rate of cycling and the severity of the course of illness. The risk is greatest for bipolars who are already rapid cyclers. Read the lastest APA guidelines on the treatment of Bipolar (American Journal of Psychiatry, 151 December 1994 Supplement); a recent article in Archives of General Psychiatry (55, January 1998, pp. 23-25) called "Understanding Manic-depressive Illness") for a general overview. Many bipolars do take antidepressants. Sometimes this can work for a short period -- but there is an inherent danger in keeping a bipolar on antidepressants indefinitely. The risk can be minimized somewhat by the concurrent use of a mood stabilizer (i.e., not just an anti-manic drug like lithium, but also something like Depakote or Tegretol).

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