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Understanding and Treating Bipolar Depression

Understanding and Treating Bipolar Depression

Table 1
Table 2
Figure 1
Figure 2

Bipolar disorder is a longitudinal disorder defined by multiple episodes that may occur years apart. As a result, the proper diagnosis requires careful evaluation of both the current symptoms and the patient’s history. The majority of patients with bipolar disorder initially present during an episode of depression, which can be difficult to distinguish from major depressive disorder if there has not been a known manic or mixed episode in the past.1 Not surprisingly, many bipolar patients report a history of diagnostic confusion and delayed treatment.2


Mr Smith, a 32-year-old, is referred by a local family practitioner. He complains of a debilitating depression that has lingered for many months. He has not been able to enjoy his usual hobbies and has been feeling increasingly distant from his wife. He observes that his energy has been so low that his work has suffered; he fears that his job may be in jeopardy.

He has been staying home and sleeping more, and he cannot concentrate. Once an avid reader, he now can barely collect himself to watch television or hold a lengthy conversation. With some prodding, Mr Smith admits to a loss of sexual interest in his wife, which has led to marital problems. While he denies being overtly suicidal, Mr Smith concedes that he has been thinking about his death; he fantasizes about being accidentally killed.

His primary care physician diagnosed major depressive disorder last December and began the first of a series of antidepressant medications that eventually included fluoxetine, mirtazapine, and bupropion. Mr Smith tolerated the medications well but reports that none of them improved his mood. By the middle of March, his physician had grown concerned at his lack of progress and suggested that Mr Smith see a psychiatrist as soon as possible for further evaluation; it is now mid-April, and there has been no remission of symptoms.

When asked about his history, Mr Smith reveals that he has had a series of similar episodes, starting in early childhood. While none of the episodes were as debilitating as his current state, many persisted for more than 2 weeks and interfered with his ability to work as well as with family life.

He recounts that for a few weeks in 1998, his mood became quite elevated; the euphoria was accompanied by increased energy and a loss of any need to sleep. He reports that he felt like he was getting a lot of things accomplished but could not focus sufficiently to finish any of the projects he started. Nonetheless, he recalls the immense self-confidence that he had at the time. Ultimately, he was involved in an altercation with the local police and was hospitalized. Mr Smith does not recall what medications he received at the time. Shortly after being discharged, he discontinued the medications. He is embarrassed about the incident and does not like to discuss it. He denies any history of psychiatric symptoms in his first-degree relatives but notes that his grandmother often had “spells” and was hospitalized for a nervous breakdown.

A careful patient history is critical; on closer questioning, Mr Smith revealed what appears to have been a previous manic episode, as well as several potential signs of bipolar depression. He reports numerous episodes of depression that began when he was young and a possible family history of bipolar disorder. Bipolar symptoms in even a second-degree relative increase a person’s risk for the disorder. The atypical symptoms, such as increased sleep, may also suggest bipolar disorder. Other symptoms of bipolar disorder are listed in Table 1.3-6

It is far from uncommon for patients such as Mr Smith to receive multiple courses of standard antidepressant medications.2 Unfortunately, there are real risks associated with using these medications for bipolar depression. Standard antidepressants may precipitate manic episodes in a minority of bipolar patients and may be ineffective.7 A delayed diagnosis may prolong depression and further affect the patient’s ability to function effectively at home and at work. Prolonged depression may also increase the risk of self-harm.

Some studies suggest that there may be other, less concrete effects of prolonged depression in bipolar patients as well. Correlations have been observed between the number of past affective episodes and subtle cognitive losses in patients with bipolar disorder.8-11 More recently, some preliminary neuroimaging studies have suggested a link between mood episodes and evidence of neuropathic changes in several regions of the brain.12-15

Pharmacotherapeutic treatment options

An accurate diagnosis is, of course, the first step in making treatment decisions. Treatment choices in psychiatry are rarely straightforward, and bipolar depression is no exception to this general rule. Further complicating the process is the limited number of FDA-approved options. The number of FDA-approved medications for bipolar mania has literally tripled over the past decade while the pharmacopeia available for bipolar depression remains quite limited (Table 2).

Only 1 medication and 1 medication combination are approved by the FDA to treat depression in patients with bipolar disorder. Quetiapine (both immediate- and extended-release) was approved on the basis of 2 large initial trials and a follow-up trial of the extended-release formulation.16,17 Olanzapine in combination with fluoxetine was also found to be effective for bipolar depression in 2 large trials and was approved only in this combined formulation.18


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