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Are Higher Doses of Anti-Depressants Better Than Lower Doses?
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00:00 Intro
00:04 News Report

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In this video, we explore a groundbreaking new study that challenges long-held assumptions about antidepressant dosing. For years, the belief was that higher doses of antidepressants would lead to better outcomes, a notion that stemmed from early research on tricyclic antidepressants. However, the landscape has changed with the newer generation of post-Prozac antidepressants, and recent studies have shown that the benefits of increasing doses may plateau sooner than we thought.

This study, a network meta-analysis of 160 trials, examined antidepressant efficacy across various dosage ranges. While it’s important to note that network meta-analyses come with some limitations—such as assuming that all placebo arms in these trials are similar—the results still align with previous research. Specifically, the study found that the benefits of antidepressants tend to level off after reaching a lower dose range, such as 20-30 mg of fluoxetine, 60 mg of duloxetine, or 30 mg of mirtazapine.

But, as with any scientific rule, there are exceptions. The analysis revealed three notable exceptions where higher doses continued to show improved outcomes: tricyclics (specifically amitriptyline and clomipramine), and reboxetine, a norepinephrine-based antidepressant available outside the U.S.

One major question remains unanswered: What about MAOIs? This class of antidepressants, believed to follow a dose-dependent response similar to tricyclics, has not been thoroughly studied in terms of dose-response curves. Most of the data we have on high-dose MAOIs comes from a 1989 case series that used extremely high doses of tranylcypromine (up to 170 mg daily) in patients with significant treatment resistance. While this approach can sometimes yield positive results, it also requires monitoring for dangerous side effects like orthostatic hypotension and falls.

The bottom line? Unless you're dealing with a tricyclic, MAOI, or reboxetine, pushing antidepressant doses beyond the lower end of the effective range is unlikely to improve outcomes. Instead, it may only increase the likelihood of side effects like insomnia, fatigue, tremor, sexual dysfunction, and apathy. While we’ve all seen patients seemingly improve with higher doses of fluoxetine or other antidepressants, this is likely due to the powerful placebo effect rather than the medication itself.

Make sure to consult with your doctor before making any changes to your antidepressant dosage. And if you're a clinician, take this research into account when considering how high to push the dose for your patients.

Tags: antidepressant dosage, antidepressant dosing guide, tricyclic antidepressants, SSRI dosing, antidepressant side effects, placebo effect in antidepressants, optimal dose of antidepressants, reboxetine antidepressant, how to dose antidepressants, antidepressant fatigue, sexual side effects from antidepressants.