Subsyndromal depression

In STEP-BD, 32% of study entrants reported ≥4 mood episodes in the previous year, yet only 6% of that subgroup had ≥4 episodes after 1 year of prospective follow-up.¹² This suggests:

• patients who retrospectively report rapid cycling may be chronically and persistently ill, rather than experiencing multiple discrete episodes
  
• rapid cycling is a marker for symptom persistence, subsyndromal depression, and lack of sustained remission.
  

• comorbid anxiety disorders (present in ≤50% of patients with bipolar I and II disorder)
  
• active and past substance use disorders (including nicotine dependence)
  
• early age of onset of the mood disorder.^13-16
  

CASE CONTINUED: Restoring the cornerstone

You review Mr. W’s records. Recent lab values were essentially normal, with thyroid stimulating hormone 2.3 mIU/mL and stable renal function. He scores 11 on the Quick Inventory of Depressive Symptoms–self-rated version (QIDS-SR), indicating mild to moderate depressive symptom burden.

His mood chart and interview reveal that he has been depressed and anhedonic most of the day for 4 of the last 10 days. By systematically asking the depression questions in the DSM-IV-TR, you find that he does not meet criteria for depressed mood or anhedonia but has difficulty concentrating most of the day, persistent low self-esteem, and feeling “slowed.”

After you discuss lithium’s pros and cons with Mr. W, he agrees to try this mood stabilizer again. You explain the importance of preventing relapse to mania and of monitoring his cognitive performance at work.

Over time, you titrate lithium to a moderate serum level (0.5 to 0.7 mEq/L) and treat a resulting mild tremor with propranolol, 20 to 40 mg/d. Mr. W is tolerating lamotrigine well, so you continue this medication because of its potential to decrease the probability of relapse to depression. You also continue zolpidem, as needed, but discontinue methylphenidate because you think it may be contributing to sleep difficulties.

Managing medication

Nine drugs are FDA-approved for acute bipolar mania, but treatments for bipolar depression, maintenance treatment, and relapse prevention are far fewer, often partially effective, or effective for a limited number of patients. When depressive symptoms fail to resolve, a reasonable approach is to review patients’ medications and suggest alternatives with proven efficacy for bipolar disorder (Table 2). Patients can then accept or reject various options based on personal preference.

Combination strategies. Antimanic treatment is the cornerstone of treating bipolar I disorder, and preventing manic episodes should be a primary treatment goal. Thus, consider continuing treatments that have prevented mania for your patient—as lithium did in Mr. W’s case—while adding treatments aimed at depression. For example, adding lamotrigine to any antimanic agent is reasonable, especially if doing so does not add substantially to your patient’s side-effect burden.

Minimize antidepressants. Given the predominance and persistence of depressive symptoms in bipolar disorder, one can understand why clinicians and patients might try standard antidepressants without clear evidence supporting this practice. Antidepressants—especially venlafaxine and tricyclic antidepressants—are the most common and likely suspects when patients experience switching to mania, rapid cycling, and symptom persistence.¹⁷ Antidepressants’ negative effect has not been clearly defined, however, and may be patient-specific (related to patient factors rather than intrinsic to the compound).

In my clinical experience, minimizing antidepressant use in bipolar depression hastens rather than delays patients’ recovery. A prudent approach would be to use the minimum dose necessary and discontinue the antidepressant if possible. Also minimize medical pharmacotherapies—including corticosteroids and oral contraceptives—that may worsen mood symptoms, especially in patients with this history.

Avoid under-dosing. Inadequate dosing and duration often are overlooked as causes of treatment resistance in bipolar disorder and other illnesses.¹⁸ Bipolar disorder medications are hardly benign; every drug approved for any phase of bipolar disorder has a black-box warning. Understandably, clinicians and patients try to choose medications and dosages perceived to be most tolerable. Full-dose treatment trials may be warranted, however, given the high probability of incomplete recovery, impaired functioning, and risk of relapse with ineffective dosing.