APA Practice Guidelines

2. Depressive episodes

cont. from

The primary goal of treatment in bipolar depression, as with nonbipolar depression, is remission of the symptoms of major depression with return to normal levels of psycho-social functioning. An additional focus of treatment is to avoid precipitation of a manic or hypomanic episode.

The first-line pharmacological treatment for bipolar depression is the initiation of either lithium or lamotrigine. The better supported of these is lithium. While standard antidepressants such as SSRIs have shown good efficacy in the treatment of unipolar depression, for bipolar disorder they generally have been studied as add-ons to medications such as lithium or valproate; antidepressant monotherapy is not recommended, given the risk of precipitating a switch into mania. For severely ill patients, some clinicians will initiate treatment with lithium and an antidepressant simultaneously, although there are limited data to support this approach. In patients with life-threatening inanition, suicidality, or psychosis, ECT also represents a reasonable alternative. In addition, ECT is a potential treatment for severe depression during pregnancy. Selection of the initial treatment should be guided by clinical factors such as illness severity, by associated features (e.g., rapid cycling, psychosis), and by patient preference, with particular attention to side effect profiles.

Small studies have suggested that interpersonal therapy and cognitive behavior therapy may also be useful when added to pharmacotherapy during depressive episodes in patients with bipolar disorder. There have been no definitive studies to date of psychotherapy in lieu of antidepressant treatment for bipolar depression. However, a larger body of evidence supports the efficacy of psychotherapy in the treatment of unipolar depression.

For patients who, despite receiving maintenance medication treatment, suffer a breakthrough depressive episode, the first-line intervention should be to optimize the dose of the maintenance medication. Optimization of dosage entails ensuring that the serum drug level is in the therapeutic range and in some cases achieving a higher serum level (although one still within the therapeutic range).

For patients who do not respond to optimal maintenance treatment, next steps include adding lamotrigine, bupropion, or paroxetine. Alternative next steps include adding other newer antidepressants (e.g., another SSRI or venlafaxine) or an MAOI. Although there are few empirical data that directly compare risk of switch or efficacy among antidepressants in the treatment of bipolar disorder, tricyclic antidepressants may carry a greater risk of precipitating a switch into hypomania or mania. Also, while MAOIs have generally demonstrated good efficacy, their side effect profile may make other agents preferable as initial interventions. ECT should be considered for patients with severe or treatment-resistant depressive episodes or for those episodes with catatonic features.

Patients with psychotic features during a depressive episode usually require adjunctive treatment with an antipsychotic medication. ECT represents a reasonable alternative.

Studies of bipolar depression rarely separate results for patients with bipolar I disorder from those of patients with bipolar II disorder. It is not known whether specific pharmacotherapy regimens differ in efficacy for treatment of bipolar I versus bipolar II depression. However, existing data suggest that for patients with bipolar II disorder, antidepressant treatment-either alone or in combination with a maintenance medication-is less likely to result in a switch into a hypomanic episode relative to those with bipolar I disorder.

3. Rapid cycling

The initial intervention for patients who experience rapid-cycling episodes of illness is to identify and treat medical conditions that may contribute to cycling, such as hypothyroidism or drug or alcohol use. Since antidepressants may also contribute to cycling, the need for continued antidepressant treatment should be reassessed; antidepressants should be tapered if possible. The initial treatment for patients who experience rapid-cycling episodes of illness should include lithium or valproate; an alternative treatment is lamotrigine. In many instances, combinations of medications are required (39,40); possibilities include combining two of these agents or combining one of them with an antipsychotic. Because of their more benign side effect profile, atypical antipsychotics are preferred over typical antipsychotics.

continue: Maintenance Treatment

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Written 4/02. Reviewed: 03/2006