Fluoxetine

Fluoxetine, sold under the brand names Prozac and Sarafem among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorder (OCD), bulimia nervosa, panic disorder, and premenstrual dysphoric disorder. It may decrease the risk of suicide in those over the age of 65. It has also been used to treat premature ejaculation. Fluoxetine is taken by mouth. Common side effects include trouble sleeping, sexual dysfunction, loss of appetite, dry mouth, rash, and abnormal dreams. Serious side effects include serotonin syndrome, mania, seizures, an increased risk of suicidal behavior in people under 25 years old, and an increased risk of bleeding. If stopped suddenly, a withdrawal syndrome may occur with anxiety, dizziness, and changes in sensation. It is unclear if it is safe in pregnancy. If already on the medication, it may be reasonable to continue during breastfeeding. Its mechanism of action is not entirely clear but believed to be related to increasing serotonin activity in the brain. Fluoxetine was discovered by Eli Lilly and Company in 1972, and entered medical use in 1986. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world is between US$0.01 and US$0.04 per day as of 2014. In the United States, it costs about US$0.85 per day. In 2016 it was the 29th most prescribed medication in the United States with more than 23 million prescriptions. Fluoxetine is frequently used to treat major depressive disorder, obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD), bulimia nervosa, panic disorder, premenstrual dysphoric disorder, and trichotillomania. It has also been used for cataplexy, obesity, and alcohol dependence, as well as binge eating disorder. Fluoxetine seems to be ineffective for social anxiety disorder. Studies do support a benefit in children with autism, though there is but tentative evidence for its benefit in adult autism. The effectiveness of fluoxetine and other antidepressants in the treatment of mild-to-moderate depression is controversial. A review of the comparative efficacy of 21 antidepressant drugs found that fluoxetine was effective for the treatment of depression, however other SSRI’s were more effective. A meta-analysis published by Kirsch in 2008 suggests, in those with mild or moderate symptoms, the efficacy of fluoxetine and other SSRIs is clinically insignificant. A 2009 meta-analysis by Fournier which evaluated patient-level data from six trials of the SSRI paroxetine and the non-SSRI antidepressant imipramine has been further cited as evidence that antidepressants exhibit minimal efficacy in mild to moderate depression. A 2012 meta-analysis using individual patient level-data of fluoxetine for the treatment of depression concluded statistically and clinically significant benefit was seen irrespective of baseline depression severity, and no significant effect was found on baseline severity on observed efficacy. Overall there is no evidence from randomized controlled trials that fluoxetine or other SSRIs decrease the risk of suicide. There is tentative evidence that suggests it may decrease the risk of suicide in those over the age of 65. A 2009 systematic review by the National Institute of Care and Clinical Excellence (NICE) (which considered the Kirsch, but not the later meta-analyses) concluded strong evidence existed for the efficacy of SSRIs in the treatment of moderate and severe depression, with some evidence for their efficacy in the treatment of mild depression. Both the NICE and the Fournier analyses concluded that greater evidence is seen for the efficacy of antidepressants in the treatment of chronic mild depression (dysthymia) than in recent-onset mild depression. NICE recommends antidepressant treatment with an SSRI in combination with psychosocial interventions as second-line treatment for short term mild depression, and as a first line treatment for severe and moderate depression, as well as mild depression that is recurrent or long-standing. The American Psychiatric Association includes antidepressant therapy among its first-line options for the treatment of depression, particularly when 'a history of prior positive response to antidepressant medications, the presence of moderate to severe symptoms, significant sleep or appetite disturbances, agitation, patient preference, and anticipation of the need for maintenance therapy' exist. The efficacy of fluoxetine in the treatment of obsessive–compulsive disorder (OCD) was demonstrated in two randomized multicenter phase III clinical trials. The pooled results of these trials demonstrated that 47% of completers treated with the highest dose were 'much improved' or 'very much improved' after 13 weeks of treatment, compared to 11% in the placebo arm of the trial. The American Academy of Child and Adolescent Psychiatry state that SSRIs, including fluoxetine, should be used as first-line therapy in children, along with cognitive behavioral therapy (CBT), for the treatment of moderate to severe OCD.