The notion that bipolar and unipolar depression might be distinct illnesses was first proposed in the middle of the 20th century. Before this time, manic-depressive illness was considered to encompass a broad range of psychopathology, including recurrent unipolar depression. We now recognize that there are substantial differences between depression arising from bipolar disorder and with depression arising from unipolar disorder.
Up to one-third of all patients seeking treatment for depression suffer from bipolar disorder. This includes patients within the bipolar spectrum of bipolar I, bipolar II, and cyclothymia. Unfortunately, many patients with bipolar depression are treated as though they had unipolar depression, sometimes with disastrous results — for example, if the antidepressant precipitates a switch into mania. Thus, recognition of bipolarity is critical to patient care.
The overwhelming majority of clinical and research attention on bipolar disorder has focused on the stabilization of acute mania and its management over the long-term. Much less clinical and research attention has been focused on the diagnosis and management of bipolar depression. This is unfortunate, because many bipolar patients report that their depression episodes are actually more painful, debilitating, and protracted than their manic episodes.
This chapter will overview the phenomenology, diagnosis, and clinical course of bipolar depression and will review various treatment approaches including phar-macotherapy, alternative treatments, and psychosocial interventions. This chapter will also address special issues specific to the treatment of bipolar depression and conclude with clinical recommendations for effective treatment.
The presenting clinical picture of an episode of depression in a bipolar patient often provides few clues of bipolarity. However, bipolar depression is more likely to have an earlier age of onset and a more rapid onset than unipolar depression. Anergia and psychotic features are more frequent in bipolar depression, but other symptoms generally do not differ in frequency from unipolar depression.
Nevertheless, bipolar depression is often more severe than unipolar depression and is usually more difficult to treat.
Differences in the clinical picture of depression exist among bipolar subtypes. Depressed patients with bipolar I have less anxiety and are more likely to have psychotic features. Patients with bipolar II are more likely to have fatigue, hypersomnia, decreased appetite, decreased interest, and more anxiety symptoms.
The presenting picture of bipolar depression is not distinct and provides few clues of bipolarity. The first symptom of bipolar disorder in approximately half of the patients is depression. A remarkable finding that is consistent through many surveys of patients with bipolar disorder is that patients have to wait for an average of 10 years from their first symptoms to first medication. About 70% of patients with bipolar disorder have been misdiagnosed before receiving a correct diagnosis. The most frequent incorrect diagnosis is usually unipolar depression. It is imperative that clinicians ask about a history of bipolarity in all patients evaluated for depression. A history of mood swings; substance abuse, or poor impulse control suggests that bipolarity may be present.
The sequence order of bipolar episodes is helpful in predicting prognosis. Episodes that begin with mania (i.e., mania, followed by depression) have a much better prognosis than those beginning with depression and switching into mania. Depressive and mixed episodes appear to have equal prognosis. Patients with multiple switching within episodes and with long depressive episodes tend to have a poorer prognosis.
Bipolar disorder can have devastating effects on personal, occupational, and family life. Treatments that address these problems can be extremely helpful. Several psychotherapies and other psychosocial treatments have been developed or adapted for bipolar disorder. Among these are behavioral family management, a psychoeducational approach, and a modified cognitive behavioral package.
These psychosocial approaches have several features in common. They include educational components on the nature and course of bipolar disorder and communication components that enhance the communication between patients and family members. This enhanced communication helps patients resolve interpersonal problems resulting from the disorder. The psychosocial approaches also focus on current issues, not on early life experience and aim to help patients to manage their illness more effectively and to foster early identification of signs of relapse and recurrence.
A unique psychosocial issue for the management of bipolar disorder is attendance to regularization of body and social rhythms. Changes in social rhythms, especially abrupt ones, can trigger or exacerbate episodes. Disruptions in sleep or a highly stimulating environment can also have harmful consequences. Thus, it is imperative to successful treatment that bipolar patients learn to understand and manage their illness. Psychosocial interventions may help patients accomplish this task.
Electroconvulsive therapy (ECT) may be the most effective available antidepressant treatment. Although there are no data yet confirming the effectiveness of ECT for the treatment of bipolar depression, ECT is particularly effective in patients with psychotic depression, which is more prevalent among bipolar patients. Therefore, ECT should be seriously considered in bipolar patients with depression, particularly psychotic or treatment-resistant depression. Switching into mania can occur following ECT treatment of bipolar depressed patients. However, continuation with ECT will treat mania as well.
A substantial problem in the pharmacotherapy of bipolar depression is the risk of precipitating mania or hypomania (i.e., “switching”). Data from a number of studies in the 1970s and 1980s suggest that MAOIs and tricyclic antidepressants — when used without concurrent mood stabilizers — are very likely to induce switching in patients with bipolar depression. However, some findings from longitudinal studies do not support this. In a six-decade record review of patients treated at the Burgholzli in Zurich, Angst concluded that there is no evidence for treatment-induced switching. Although the evidence is modest, many clinicians believe that the newer agents, particularly bupropion and the SSRIs, are less likely to induce switches than the tricyclic antidepressants or MAOIs.
Another concern in the pharmacotherapy of bipolar depression is the induction of rapid cycling with antidepressant treatment. This is more likely to occur in women, particularly those with an early age of onset of their bipolar depression. Concurrently administered mood stabilizers may not prevent or alleviate anti-depressant-induced rapid cycling. Discontinuation of antidepressants will often stop the cycling, however.
Antidepressants may reduce cycle length (i.e., the period of time from the beginning of one episode of illness to the beginning of the next) in bipolar patients. Wehr et al. found dramatic decreases in the cycle lengths of bipolar depressed patients treated with tricyclic antidepressants.
Conclusions And Recommendations
Over the years, most clinical and research attention in bipolar disorder has been concentrated on the management of acute bipolar mania. Considerably less attention was devoted to the management of bipolar depression. This is unfortunate, as recent survey results reveal that bipolar depression causes more severe symptoms and greater psychosocial impairment than mania. Specifically, patients diagnosed with bipolar disorder experience symptoms of depression for a significantly greater proportion of time than symptoms of mania. Likewise, depression accounts for significantly more disruptive days than mania. The psychosocial impairment in terms of work/school, social/leisure, and family life associated with depression is also significantly greater than that associated with mania. Depression symptoms are also cited significantly more often than mania as causing patients to feel ashamed of work, feeling upset, and being disinterested in work. Furthermore, patients are more likely to have consulted a physician while suffering from depression compared with mania. Bipolar depression is also under-recognized, with patients often receiving a diagnosis of unipolar depression. At the same time, a recent study has shown that patients with bipolar depression report significantly more disruption in work, social, and family life than patients with unipolar depression. Therefore, the successful treatment of bipolar disorder requires improved recognition of bipolar depression and effective treatment.
Among the treatment options for bipolar depression available today, several agents should be considered for first-line treatment of bipolar I depression: lithium, lamotrigine, olanzapine/fluoxetine combination, and quetiapine. These recommendations result from new data emerging since the publication of the APA Practice Guideline for the Treatment of Patients with Bipolar Disorder in 2002. Monotherapy with antidepressants is not recommended because of the risk of manic switching and destabilization induced by antidepressants in bipolar patients. In severe bipolar depression, an antidepressant may be started simultaneously with a mood stabilizer. In patients who fail to respond to the initial combination therapy of a mood stabilizer and an SSRI, combination of a different mood stabilizer with an MAOI is appropriate. In patients with severe bipolar depression with psychotic features, or in patients at risk of suicide, when a rapid response is necessary, ECT should be seriously considered.