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Antidepressants for Bipolar Disorder: Page 3 of 3

Antidepressants for Bipolar Disorder: Page 3 of 3

The results from the study by Post and colleagues11 were confirmed in a long-term continuation treatment follow-up phase lasting up to 1 year.13 Hence, more caution appears indicated for patients with bipolar depression for use of venlafaxine than use of bupropion or sertraline as adjunctive treatment to a mood stabilizer, especially if there is a history of rapid cycling. It should be noted that all of these antidepressants are FDA-approved for the treatment of major depression but are not FDA-approved for use in bipolar depression.

Effect of antidepressants in preventing relapse

The other compelling clinical issue in bipolar depression is the risk of recurrence and prevention of relapse. Bipolar disorder is known to be a recurrent disorder, and more than 90% of patients with bipolar disorder experience recurrences.16

However, available data are scarce on the clinical features associated with the risk of recurrence. Interesting findings resulted from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a national longitudinal public health initiative funded by NIMH.17 One of the main aims of the trial was to look for the features associated with risk of recurrence.18 The study prospectively enrolled patients with bipolar disorder who were receiving treatment according to contemporary practice guidelines and observed them for up to 24 months.

Of the 1469 participants who were symptomatic at study entry, 858 subsequently achieved recovery (58.4%). During the 24-month follow-up period, 48.5% of patients experienced recurrences, and depressive episodes developed in more than 34.7%, compared with manic/hypomanic/mixed episodes in 13.8%. Furthermore, in this study, residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence.

Unfortunately, we found just one systematic review investigating the effectiveness of long-term use of antidepressants, which did not provide sufficient evidence to assess the ability of antidepressants to prevent relapse of bipolar disorder.19 The review found 7 randomized controlled trials that enrolled 363 people with BDI or BDII. Data were found only for imipramine, desipramine, bupropion, and fluoxetine (antidepressants) and lithium (a mood stabilizer).

The review provided a narrative overview of the studies, because the variety of comparisons did not allow researchers to perform a meta-analysis or to quantify reliable conclusions. The available evidence suggested that there was no clear benefit for routinely adding long-term antidepressants to ongoing treatment with lithium. Moreover, the same review found that antidepressants may be less effective in preventing relapse when they are prescribed without a mood stabilizer (in this case, lithium).19

Clinical implications

There is some evidence20 that antidepressants are effective in the short-term treatment of bipolar depression, but a large recent trial reported no benefit10 and caution should be paid to the risk of manic switching. Alternative agents, such as quetiapine or lamotrigine, should be considered. When using an antidepressant, it may be prudent to use an SSRI or bupropion rather than a TCA or venlafaxine as first-line treatment. However, the patient history (ie, response to antidepressant treatment without adverse effects, including treatment-emerging manic switch) should be the best guide for choosing the individual treatment strategy.

Looking at the randomized evidence, there is no support for the addition of long-term antidepressants to ongoing treatment with a mood stabilizer for maintenance treatment in persons with bipolar depression. Early discontinuation following resolution of the acute episode should be con-sidered. Recurrence is frequent and associated with the presence of residual mood symptoms at initial recovery. Targeting residual symptoms in maintenance treatment may represent an opportunity to reduce the risk of recurrence. Given the limited evidence, there is a compelling need for further studies with longer follow-up and careful definition of the risk/ benefit profile in terms of efficacy and tolerability.

Recent evidence found conflicting results about possible correlates between suicidality and antidepressant exposure.21,22 This aspect is of crucial importance when using antidepressants not only for bipolar disorder but also for unipolar disorder,23 and it indicates important directions for further research. New pharmacological strategies with agents different from antidepressants are under investigation (quetiapine, lamotrigine, olanzapine, olanzapine plus fluoxetine) and need to be carefully evaluated to improve our therapeutic skills for treating bipolar depression.




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