Mr. W, a 53-year-old divorced entrepreneur, presents to you for evaluation of poor concentration, decreased self-esteem, and difficulty making decisions that are interfering with his work. A longtime patient of another psychiatrist, Mr. W has a 26-year history of bipolar I disorder. He has not had a manic episode for 5 years but has had several depressive episodes.
During his last manic episode, Mr. W was hospitalized with expansive and irritable mood, racing thoughts, impulsive sexual behavior, psychomotor agitation, elevated self-esteem, marked distractibility, and paranoid ideas about his business partners. His discharge regimen included lithium titrated to 0.9 mEq/L and divalproex sodium, 1,500 mg/d, with lamotrigine, 200 mg/d, added to reduce depressive relapse risk. After several years of stable treatment, Mr. W complained of cognitive impairment. His psychiatrist discontinued lithium and added a low-dose stimulant—methylphenidate, 20 mg bid—to address Mr. W’s complaints of poor concentration.
Mr. W also is taking zolpidem, 10 mg as needed for onset insomnia, and receives weekly psychodynamic psychotherapy. His work performance problems persist despite these treatments, and his company is failing.
A poor course in bipolar disorder—as in Mr. W’s case—is frequently characterized by persistent or relapsing depression. Bipolar disorder is diagnosed by a manic, mixed, or hypomanic episode, but depression and depressive symptoms are most prominent in clinical practice. Likewise, major observational studies blame depression for most of the time spent ill in bipolar types I and II.1-8
A good deal of bipolar symptom burden is associated with subsyndromal depression—defined as having >2 but 5 and depressive symptoms are disproportionately responsible—compared with manic symptoms—for the impact of bipolar illness on patients and their families.9
This article offers clinically useful strategies to minimize subsyndromal depression in patients with bipolar disorder (Table 1). These strategies include an evidence-based approach to medication, the use of validated psychotherapies, regular sleep and socialization schedules, and careful monitoring of mood symptoms.
Table 1
How to minimize bipolar subsyndromal depression
| Monitor symptoms using validated clinician- and patient-rated tools at all visits |
| Use evidence-based treatments first |
| Eliminate ineffective medications |
| Use adequate doses of medications for different mood states |
| Monitor and treat adverse effects of successful treatments |
| Monitor and minimize medications that can worsen symptoms |
| Watch for the impact of medical conditions on mood |
| Be attentive to alcohol and substance use (including caffeine, nicotine, and energy drinks) |
| Monitor psychotherapies for symptom worsening |
| Address comorbid psychiatric conditions |
| Regularize social rhythms |
| Initiate validated psychosocial treatments |
| Engage the patient as a active participant in treatment |
Persistent depression
Randomized, controlled trials designed to obtain FDA approval of bipolar medications inadequately reflect the disabling, confounding nature of bipolar illness. Nearly all of these large studies of acute treatments for mood episodes are placebo-controlled trials with narrow inclusion and broad exclusion criteria. Eliminating subsyndromal symptoms is not their goal, and they are of little help in understanding how to manage residual symptoms.
A more realistic view of bipolar disorder comes from large observational studies that have examined its longitudinal course in outpatients under more or less ideal treatment conditions.10 These studies show that bipolar disorder is almost always recurrent and relapsing, but full recovery and functioning between episodes is not the norm. Most patients never achieve prolonged recovery, complete symptom relief, or return to full functioning.5,8,11
STEP-BD. Most patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) never recovered from a depressed episode during 2 years of prospective follow-up under optimal care. Only 58% of patients who entered the study during an episode of illness achieved 8 consecutive weeks of euthymia.5
Collaborative Depression study. Longitudinal data from the National Institute of Mental Health’s Collaborative Depression Study6,7 showed:
- patients with bipolar I disorder had depressive symptoms in approximately three-quarters of the weeks in which they reported significant symptoms
- patients with bipolar II disorder were depressed in nearly all sick weeks.
The Stanley Foundation Bipolar Network had similar findings, with bipolar disorder patients reporting 3 times as much time spent with depressed mood as with elevated mood.8 Poor social and occupational functioning predicted poor outcomes, suggesting an interplay between subsyndromal depression, poor functioning, and relapse.
Risk factors
Rapid cycling may be a marker for persistent, subsyndromal symptoms. Rapid cycling is defined clinically as 4 distinct mood episodes—switching to the opposite pole or 2 episodes of the same pole separated by ≥8 weeks of partial or full recovery—in the previous 12 months. Rapid cycling usually is diagnosed retrospectively—introducing patients’ recall bias—but may be more of a marker for symptom persistence than for defined episodes.