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Dose increase recommendations vs time for effect?

Posted by Mtom on December 26, 2020, at 12:07:37

I frequently read dosing schedules prescribed for Antidepressants suggest starting at a low to moderate dose, then increasing every 1 to 2 weeks until effect.

What about the fact that it takes most antidepressants 4 to 6 weeks to even kick in (and possibly longer - I've read articles that claim studies have shown for some people it can take up to 8 to 12 weeks to feel better)?

Patients are being told to increase their dose before knowing whether the lower dose would work. Which could in some cases increase the potential for adverse effects. There is of course an urgency to feel better quickly, is this what is driving an increasing dosing schedule which is faster than the time for effect?

I read one paper commenting that some Doctors say that often when they reduce patients from higher to lower doses, the depression returns. The author questioned whether this was in fact a return of the original depression, or antidepressant withdrawal symptoms.

So why is it often prescribed to increase dose after 1 to 2 weeks, and continue this increase schedule up to a specified maximum - when the initial dose (or even the first or second increase if occurring within the first 4 to 6 weeks) have not been given time to assess the effect at these lower doses?

One paper published in the Lancet in July 2019 showed that efficacy starts to decrease above a certain moderate dose, while adverse effects increase. See and scroll down to Figures 2, 3 and 4.

I found the u-shaped efficacy curve for Mirtazapine (Figure 4) particularly interesting as I have experienced this - I have a partial but noticeable response on low doses (below the peak shown in this curve, but I am ultra-sensitive). In an effort to increase my response, my doctors keep encouraging me to increase dose. However every time I've tried, both the side effects and the depression worsen.

A P-Doc I've seen in past mentioned this u-shaped curve is known for many AD medications. So again, why are patients told to keep increasing dose in the early weeks and months of starting an AD without waiting long enough to see if lower to moderate doses are effective?




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