Efficacy and Safety of Fluoxetine in Treating Bipolar II Major Depressive Episode

Abstract

As many as 45% of patients with major depressive episode also meet DSM-IV criteria for bipolar II (BP II) disorder. Although some clinicians advocate using a mood stabilizer in treating BP II depression, antidepressant monotherapy has been less well studied in this disorder. As part of a prospective, placebo-controlled, relapse-prevention study in 839 patients, the efficacy and safety of short- and long-term fluoxetine treatment in patients with BP II major depression compared with patients with unipolar (UP) major depression was retrospectively examined. Eighty-nine BP II patients (mean age, 41+/-11 years) were compared with 89 age- and gender-matched UP patients and with 661 unmatched UP patients (mean age, 39+/-11 years). All received short-term fluoxetine therapy at 20 mg daily for up to 12 weeks. Complete remission was defined as a final Hamilton Rating Scale for Depression score < or = 7 by week 9 that was then maintained for 3 additional weeks. Remitted patients were then randomly assigned to receive double-blind treatment with one of the following: (1) fluoxetine 20 mg daily for 52 weeks; (2) fluoxetine for 38 weeks, then placebo for 14 weeks; (3) fluoxetine for 14 weeks, then placebo for 38 weeks; or (4) placebo for 52 weeks. Antidepressant efficacy was similar in BP and UP patients during short-term therapy. Discontinuation for lack of efficacy was lower in BP II (5%) than in UP (12%) patients (p = not significant [NS]), whereas dropouts for adverse events were similar in BP II (11%) and UP (9%) patients. During long-term relapse-prevention therapy, relapse rates were similar in BP II and UP patients (p = NS). During short-term fluoxetine therapy, three BP II (3.8%) versus no matched UP (p = NS) and 0.3% unmatched UP (p = 0.01) patients had a "manic switch." During long-term fluoxetine therapy, one (2%) BP II and three (1%) unmatched UP patients (one taking placebo) had a manic switch (p = NS). In conclusion, fluoxetine may be a safe and effective antidepressant monotherapy for the short-term treatment of BP II depression with a relatively low manic switch rate. Fluoxetine may also be effective in relapse-prevention therapy in patients with BP II disorder.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…In a separate small 6‐month placebo‐controlled trial, there was a statistical trend for lower relapse rates with fluoxetine compared to placebo 503. Finally, a post hoc analysis of a large 12‐month placebo‐controlled trial found that response rates to fluoxetine were similar in BDII and MDD 468. However, it did not report whether fluoxetine was superior to placebo in BDII.…”

“…The third‐line options include monotherapy with divalproex (level 4)258, 459, 461,462, 463, 464, 465, 466 fluoxetine (mainly for patients with pure depression) (level 3)467, 468, 469 tranylcypromine (level 3),278 or ziprasidone (solely for patients with depression and mixed hypomania) (level 3) 470, 471. Adjunctive agomelatine (level 4),472 bupropion (level 4)276 eicosapentaenoic acid (EPA) (level 4),473, 474, 475 N ‐acetylcysteine (level 4),476 pramipexole (level 3),274 or thyroid hormones (level 4)272 may also be considered.…”

A lamotrigina pode induzir virada maníaca?

“…2 There are no controlled studies about the management of depression in bipolar II patients, and open studies are still scarce in the literature. In the open studies reviewed, we found positive responses with fluoxetine, 14,15 venlafaxine 16 and also with lamotrigine. 17 The case reported here, lamotrigine, corresponding to our expectations, improved the depressive symptoms with no side affects as to cognition.…”

Treatment-resistant bipolar disorder

“…[115][116][117][118][119][120] Fluoxetine was evaluated in three of four studies 115,[118][119][120] with venlafaxine used in the other. 116,117 Questions have been raised about the diagnosis of bipolar II disorder in two of these studies (with the diagnosis being made retrospectively by chart review in the largest study 115 ). Although these findings are controversial, they do open the possibility that the newer antidepressants may be associated with lower switch rates for bipolar II patients than previously recognized and may be safely used.…”