- Early (pre-adolescent) age at onset of first mood disorder episode 6
- Family history of BD, highly recurrent depression, or psychosis 12,13
- Psychosis when depressed. 7,14
A number of other characteristics of depressive illness—including seasonal depression, atypical depressive features, suicidality, irritability, anxiety or substance use comorbidity, postpartum mood episodes, and brief recurrent depressive episodes—have been described in the literature as potential correlates of a bipolar diathesis; none have proved to be robust or pathognomonic of a BD diagnosis, as opposed to a unipolar diagnosis.
Data from the NIMH Collaborative Depression Study suggest that recurrent mania/hypomania after an antidepressant-associated polarity switch is greater when a family history of BD is present; other clinical variables might hold less predictive value. 15 In addition, although some practitioners consider a history of nonresponse to trials of multiple antidepressants suggestive of an underlying bipolar process, polarity is only one of many variables that must be considered in the differential diagnosis of antidepressantresistant depression. Likewise, molecular genetic studies do not support a link between antidepressant nonresponse and the likelihood of a diagnosis of BD. 16
Indefinite Pharmacotherapy for Bipolar Disorder
An important but nagging issue when diagnosing BD after a first manic (or hypomanic) episode is the implied need for indefinite pharmacotherapy to sustain remission and prevent relapse and recurrence.
The likelihood of subsequent depression or mania/hypomania remains high after an index manic/hypomanic episode, particularly for 6 to 8 months after recovery. 8,17 Natural history data suggest that, during the year that follows a first lifetime mania, approximately 40% of patients experience a second manic episode. 8 A second lifetime mania might be especially likely in patients whose index episode involved mood-congruent psychosis, low premorbid work functioning, and an initial manic episode, as opposed to a mixed episode or early age at onset. 8,17
In the absence of randomized, placebo-controlled studies of maintenance pharmacotherapy after a first lifetime manic episode, clinical judgment often drives decisions about the duration of continuing pharmacotherapy after initial symptoms resolve. The Texas Medication Algorithm Project for BD advises that:
General practice at this time is lifetime medication following 2 manic episodes, or 1 episode if it was a severe episode and/or significant family history of bipolar or major depressive disorder is present. For a first episode of bipolar mania with no family history of bipolar or major depressive disorders, medication tapering and discontinuation may be considered after the continuation period is completed (usually 6 months in remission), depending on the severity of the first episode, surrounding factors, and prodromal history. 18
Similarly, in the most recent (2004) Expert Consensus Guideline Series for the Treatment of Bipolar Disorder, 84% of practitioner−respondents favored indefinite mood stabilizer therapy after a second lifetime manic episode. 19 No recommendation was made about the duration of maintenance pharmacotherapy after a first lifetime manic/hypomanic episode.
Avoid or Reintroduce an Antidepressant if Depression Recurs After a First Mania?
Controversies surrounding antidepressant use in BD are extensive; detailed discussion is beyond the scope of this review (Goldberg and Ghaemi provided a broader discussion of risks and benefits of antidepressants in BD). 20 Although the main clinical concern regarding antidepressant use was, at one time, the potential to induce mania or accelerate the frequency of recurrent episodes, more recent, empirical studies suggest that the greater risk of using antidepressants for BD is lack of efficacy. 10,21