Acute Bipolar Depression

Acute Bipolar Depression

General Management Considerations

Bipolar depression is usually indistinguishable from other forms of major depression, except that the episodes are typically shorter and more frequent. Other clues that the disorder may be bipolar include onset at a young age, a positive family history for bipolar disorder (particularly in first-degree relatives), and the occurrence of a hypomanic phase before the onset of the depressive episode.

For the most part, the treatment of a bipolar patient during an acute episode of depression is similar to that of a nonbipolar patient. The same concerns about protecting the patient from suicide and maintaining physical health and safety apply, and for the most part, the same antidepressants or ECT will be useful (Table 78.7). Because of fears about speeding up cycling and/or precipitat-ing mania in patients with bipolar disorder, most doctors avoid prescribing tricyclics in bipolar depression. The short section that follows addresses issues unique to treatment of bipolar depression.

Pharmacotherapy

There is a widespread clinical impression that administering some antidepressants to bipolar patients can trigger switches into mania. Some experts also believe that antidepressants speed up mood cycles, although this point is more controversial. Because of both concerns, psychiatrists are often cautious about prescrib-ing an antidepressant at the first sign of depression in a bipolar patient. If symptoms are mild and short-lived, many clinicians choose watchful waiting, while maintaining close contact to de-tect clinical deterioration.

Current guidelines by the American Psychiatric Associa-tion list lithium, as well as the anticonvulsant lamotrigine, as first-line monotherapy for acute bipolar depression (Hirschfeld et al., 2002). This is a result of recent research that suggests that lamotrigine may be an effective treatment for bipolar depression, while carrying a low risk of triggering a switch into mania.

Lamotrigine is completely absorbed after oral administra-tion, with a bioavailability of 98%, which is not affected by food. Peak plasma concentrations occur between 1.4 and 4.8 hours after administration. Lamotrigine is approximately 55% protein bound, making clinical interactions with other protein-bound drugs unlikely. Its half-life is 14 to 49 hours, with steady-state levels reached in 3 to 10 days.

Lamotrigine is metabolized predominately by glucuronic acid conjugation in the liver, with the conjugate and the remaining 10% of the unmetabolized drug excreted in the urine. Clearance is markedly increased with the administration of other drugs that induce hepatic enzymes, including phenytoin, carbamazepine and phenobarbital (Table 78.8). Adding lamotrigine to carbamazapine

can decrease steady-state concentrations of lamotrigine by approximately 40%. Adding lamotrigine to valproate, however, can decrease steady-state levels of valproate by approximately 25%, while the steady-state levels of lamotrigine increases approximately twofold. In this case, the starting dose of lamotrigine should be lowered, and the titration made slowly.

The only contraindication to lamotrigine use is hypersen-sitivity to the drug, though there is a box warning about derma-tologic events, particularly rashes. These rashes, that occurred in approximately 10% of patients, generally occur after 2 to 8 weeks and are usually macular, papular, or erythematous in nature. Of those who develop a rash, one in 1000 adults can precede to a Stephens–Johnson type syndrome. Because it is impossible to distinguish which rashes will develop into this serious condition, it is advised to discontinue the medication at any sign of drug-induced rash. Otherwise the most frequently encountered side effects include dizziness, ataxia, somnolence, headache, blurred vision, nausea, vomiting and diplopia.

To reduce the risk of rash and other side effects lamotrigine should be started at low doses and titrated slowly, especially if combined with valproate therapy. Patients are commonly started on 25 to 50 mg p.o.q.d. doses for 2 weeks, with doses increased by 25 to 50 mg every 1 to 2 weeks until maintenance levels between 100 to 250 mg/day are reached. Maximum doses are lower with valproate at about 100 to 150 mg/day. Initial labs for those un-dergoing lamotrigine therapy should include liver function tests, renal function tests, a pregnancy test if applicable and a complete medical work-up.

Probably all available antidepressant drugs are effective in alleviating the symptoms of depression in a bipolar patient, and in fact a recent 1-year retrospective chart review by Altshuler and colleagues (2001) suggests that antidepressant discontinuation may increase the risk of depressive relapse in bipolar patients.

When a patient is known to have bipolar disorder, admin-istration of an antidepressant to reverse an acute depression is almost always used together with one of the mood-stabilizing agents, usually lithium, valproate, carbamazepine (or a combina-tion), or possibly one of the newer putative agents. Most bipo-lar patients will be taking these drugs in maintenance therapy. Moreover, mood stabilizers may enhance the effectiveness of the antidepressant and might protect against the possibility of a switch into mania.

Nonpharmacotherapy: Electroconvulsive Therapy

ECT is a useful alternative to antidepressants, particularly when a patient appears not to be responding quickly or is intolerant of the medication. Early studies that claimed that ECT works faster than medication in depressed patients are now considered to be methodologically flawed. However, two later studies found a more rapid decrease in depressive symptoms with ECT than is usually observed with medications. In a total of 72 patients with major depression, approximately six ECT treatments administered in a period of about 2 weeks led to a decrease in mean Hamilton De-pression Rating Scale scores from between 24 and 30 to below 10 (Abrams et al., 1991; Pettinati, 1994). The authors attributed the efficacy of treatment to the use of high suprathreshold dosages. Sackeim and colleagues (1993) found that higher dosage results in more rapid improvement in both bipolar and unipolar depressed patients. There are indications that bilateral electrode placement is superior to unilateral placement (Abrams et al., 1991; Sackeim et al., 1993), but there may be an increased risk of severe cogni-tive side effects with bilateral ECT at ultrahigh dosages.