Fluoxetine depression from

Altered removal of a neurotransmitter from the synaptic cleft. The third mechanism by which drugs may alter synaptic activity involves changes in neurotransmitter reuptake or degradation. A very well known example of a drug in this category is Prozac (fluoxetine), which is used to treat depression. The complete etiology is unknown, but it is widely accepted that depression involves a deficiency of monoamine neurotransmitters (e.g., norepinephrine and serotonin) in the CNS. Prozac, a selective serotonin reuptake inhibitor, prevents removal of serotonin from the synaptic cleft. As a result, the concentration and activity of serotonin are enhanced. 

The behavioural effects of two antidepressants with opposite molecular actions, ie. tianeptine (a serotonin reuptake enhancer) and fluoxetine (a serotonin reuptake blocker) have been assessed and it was concluded that, apart from the effects on serotonin reuptake, these dmgs have other mechanisms playing an important role in the anti-depressant action <00AF5>. 

A breakthrough in the treatment of major depression was the discovery of fluoxetine, marketed as Prozac. Fluoxetine has a mechanism of action similar to that of imipramine with an important exception. It is a selective serotonin reuptake inhibitor, an SSRI. This strongly suggests that, in some sense, the symptoms of major depression result from a deficit in serotonin specifically. By inhibiting its reuptake from the synapse, the activity of serotonin is enhanced. Two other important drugs for major depression, sertraline (Zoloft) and paroxetine (Paxil), among several others,... 

As other indications are sought for the SSRls, it is clear that their action extends beyond depression, dysthymia, and the anxiety disorders, and the broad spectrum of therapeutic action of these antidepressants becomes apparent. For example, based on the evidence from placebo-controlled studies [A. Wood 1993], fluoxetine has been licensed in Europe for the treatment of bulimia, and several SSRls are reported to be effective in the treatment of premenstrual syndrome. 

Fluoxetine has been the subject of four reports in the treatment of social phobia. However, no double-blind, control studies have been reported. Preliminary results suggest that fluoxetine is effective in social phobia. Doses ranged from 10 to 100 mg/day. The onset of symptom resolution was variable among subjects. A justifiable approach to treatment with fluoxetine would be to implement an approach similar to that in the treatment of depression. One would start with a dose of 10-20 mg/day and titrate slowly upward over a period of several weeks. A duration of at least 6 weeks would be recommended as a minimum trial of this agent, with 12 weeks perhaps affording a better opportunity to assess the full measure of improvement. 

The olanzapine-fluoxetine combination is currently the only medication approved by the FDA specifically for the treatment of depression in patients with bipolar disorder. This indication was based on data from a double-bhnd, randomized study in which the combination was superior to both olanzapine monotherapy and placebo (Tohen et al. 2003). Treatment-emergent mania or hypomania did not occur more frequently in the olanzapine-fluoxetine combination group than in the placebo group during the acute trial. 

There have been five double-blind studies comparing the antidepressant efficacy of different SSRIs versus different TCAs in patients with HDRS scores of 25 or more (122, 123,124, 125 and 126). Three of these studies permitted inclusion of both inpatients and outpatients ( 122, 123 and 124), whereas the other two were solely done in outpatients (125, 126). Three were placebo-controlled (1.23, 125,126). In these three studies, the SSRI (i.e., fluvoxamine, paroxetine, or sertraline) was either superior to both the f CA and placebo or was comparable with the TCA and superior to placebo. In the other two studies, the SSRI was not different from the TCA and there was no placebo control. There have also been four studies and one metaanalysis of European clinical trials which found no difference in antidepressant efficacy between several different SSRIs and several different tertiary amine TCAs in patients hospitalized for major depression ( 127,128, 129,130 and 131). Finally, there have been two relatively small studies showing that fluoxetine and fluvoxamine both had antidepressant efficacy superior to placebo in patients with melancholia ( 132, 133). Another larger study failed to find a difference between paroxetine and amitriptyline in treating such patients ( 134). 

Depression associated with panic attacks may benefit from the combination of an antidepressant-anxiolytic or the use of an SSRI (e.g., fluoxetine or paroxetine), which may have antipanic properties separate from their antidepressant effects. 

Berman RM, Anand A, Cappiello A, et al. The use of pindolol with fluoxetine in the treatment of major depression final results from a double-blind, placebo-controlled trial. Biol Psychiatry 1999 45 1170-1177. 

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