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I have been unable to find the exact reference, but I recall once reading that 5 mg of fluoxetine was shown to be comparable in effectiveness to 20 mg in Lilly's initial studies for the FDA (for MDD), but that the 20 mg dose was approved as the recommended starting dose in order to account for outliers. (Perhaps someone can clarify this).
Relatedly:
"The results of three dose-effect studies... [demonstrated that] a dose of 5 mg per day was as effective as any of the higher doses." N Engl J Med 1994; 331:1354-1361.
5 mg helped 54% with major depression; 20 mg helped 64%. Fewer adverse effects with the 5 mg dose. Conclusion: "No lower limit for an effective dose of this potent serotonin uptake inhibitor has been demonstrated in moderately depressed outpatients. Psychopharmacology Bulletin 1998:
In the 5 mg, 20 mg, and 40 mg fixed-dose study, there were no differences in effectiveness between the active treatment groups, all of which were superior to placebo. Side effect dropouts increased significantly with dosage....With endpoint analysis, numerically, 5 mg/day outperformed 40 mg/day which outperformed 20 mg/day...These data point to 5 mg/day as optimal, although there is no evidence that doses below 5 mg/day are not equally effective."
Journal of Clinical Psychiatry, 1992
"We conclude that starting fluoxetine at doses lower than 20 mg is a useful strategy because of the substantial fraction of patients who cannot tolerate a 20-mg dose but appear to benefit from lower doses.... Patients often benefitted clinically from treatment at lower doses, and failure to tolerate 20 mg/day of fluoxetine should not be taken as evidence that the agent cannot be used efficaciously in these patients.
Journal of Clinical Psychiatry, 1993
I am curious of others' thoughts regarding the dosing of Prozac. Might it have the reputation of being "(perhaps overly) stimulating/anxiogenic" and hence not the best choice with regard to anxiety (primary or iatrogenic) due to an inappropriately high recommended starting dose (20mg)? It is, after all indicated for panic disorder and OCD.
It seems that there is a significant disparity between 5-80mg/dy, and I'm curious as to the clinical relevance of this vis-a-vis treating various disorders (i.e. anxiety vs. eating vs. depressive disorders).
Lastly, while Prozac is known to be unique among the SSRI's with regard to its 5-HT2C antagonism (which increases dopamine and norepinephrine in the prefrontal cortex and nucleus accumbens), my understanding is that this may only be clinically relevant at the higher end of the dosing spectrum (if at all). Is this accurate, and how does the 5-HTC antagonism correlate clinically? For example, might the related potential increase in dopaminergic activity be especially helpful for anhedonia or perhaps confer a lower propensity for sexual dysfunction or SSRI-related apathy?
Relatedly:
"The results of three dose-effect studies... [demonstrated that] a dose of 5 mg per day was as effective as any of the higher doses." N Engl J Med 1994; 331:1354-1361.
5 mg helped 54% with major depression; 20 mg helped 64%. Fewer adverse effects with the 5 mg dose. Conclusion: "No lower limit for an effective dose of this potent serotonin uptake inhibitor has been demonstrated in moderately depressed outpatients. Psychopharmacology Bulletin 1998:
In the 5 mg, 20 mg, and 40 mg fixed-dose study, there were no differences in effectiveness between the active treatment groups, all of which were superior to placebo. Side effect dropouts increased significantly with dosage....With endpoint analysis, numerically, 5 mg/day outperformed 40 mg/day which outperformed 20 mg/day...These data point to 5 mg/day as optimal, although there is no evidence that doses below 5 mg/day are not equally effective."
Journal of Clinical Psychiatry, 1992
"We conclude that starting fluoxetine at doses lower than 20 mg is a useful strategy because of the substantial fraction of patients who cannot tolerate a 20-mg dose but appear to benefit from lower doses.... Patients often benefitted clinically from treatment at lower doses, and failure to tolerate 20 mg/day of fluoxetine should not be taken as evidence that the agent cannot be used efficaciously in these patients.
Journal of Clinical Psychiatry, 1993
I am curious of others' thoughts regarding the dosing of Prozac. Might it have the reputation of being "(perhaps overly) stimulating/anxiogenic" and hence not the best choice with regard to anxiety (primary or iatrogenic) due to an inappropriately high recommended starting dose (20mg)? It is, after all indicated for panic disorder and OCD.
It seems that there is a significant disparity between 5-80mg/dy, and I'm curious as to the clinical relevance of this vis-a-vis treating various disorders (i.e. anxiety vs. eating vs. depressive disorders).
Lastly, while Prozac is known to be unique among the SSRI's with regard to its 5-HT2C antagonism (which increases dopamine and norepinephrine in the prefrontal cortex and nucleus accumbens), my understanding is that this may only be clinically relevant at the higher end of the dosing spectrum (if at all). Is this accurate, and how does the 5-HTC antagonism correlate clinically? For example, might the related potential increase in dopaminergic activity be especially helpful for anhedonia or perhaps confer a lower propensity for sexual dysfunction or SSRI-related apathy?
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