How Half-life May Affect Antidepressant Selection

Hopefully with this scenario, I’m going to teach you how half-life may affect antidepressant selection.  Adherence to antidepressant therapy is a huge issue for our patients.  It is often very challenging in the early stages of treatment to convince patients to continue to take their antidepressant because there usually isn’t an immediate effect.  It can take weeks to months for antidepressants to have the full/desired effect.

Selecting an antidepressant is also a difficult decision and is often done based upon the adverse effect profile, characteristics of the medication, patient perceptions and/or provider familiarity.

A 48 year old female has new onset depression and has been placed on sertraline 50 mg daily.  She has a well known medication history and has been notoriously difficult as far as medication adherence.  She is also on multiple antihypertensives which she has not been consistent about refilling or has historically filled them late.

She is about 1 month in to the sertraline and does not feel that it is helping.  So, what should we do? If we could predict the future, this would be easy.  That’s the “art” of the battle.

There are a ton of different options to consider.  We could increase sertraline. We could ask her to take it for another couple weeks or up to another month or two.

Looking at her history and understanding that adherence might be at play here, especially if she feels it isn’t working, it would very important to try to decipher how much she actually took.  In a scenario like this, it might actually make sense to try switching antidepressants.  The one that I might think about is fluoxetine, which has a longer half life.  The longer half life would potentially be advantageous for a patient who isn’t the most reliable about taking their medications.  Missed doses may not have as large of an impact with the fluoxetine.

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  1. Felipe

    Nicely done Eric. I appreciate your dedication and time. May you continue to be an inspiration to us!

    • Eric Christianson

      Thanks Felipe!

  2. Libby

    Great information :), thank you!

  3. Bill Jones

    It would not be a surprise to me for a patient to not respond to 50 mg of sertraline daily. IF the persistence of getting her refills is documented as good, I would increase the dose. If it is poor, I would try to find a way to get her to “ritualize” taking the drug or find out what barriers exist (how many patients say “I don’t like taking drugs”?) or negotiate for something else (maybe something else can be DC’ed) or HAVE A PLAN that clarly says if you do well with this treatment it can be stopped in 6-12 months. I cannot think of one article that compares antidepressants showing a marked difference in the response rates. Half-life differences sound good, but is there EVIDENCE to show half-life changes the outcome for patients?

    • Eric Christianson

      That’s a great question Bill, and a fair point. Agreed that assessing adherence and figuring out barriers is essential and a necessary first step. Increasing sertraline dose is definitely a consideration. My best evidence for Prozac is that there is a once weekly option compared to other traditional SSRI’s, which I don’t believe have that option. Does that perfectly correlate to a patient that maybe remembers every other day or every third day, probably not, but it gives me more evidence that they might have a response than a patient taking an antidepressant with a shorter half-life. – thanks for the comment

      • Bill Jones

        There is a once weekly option for fluoxetine, but that might be more for marketing purposes than clinical purposes. I might think about that if there was some way to assess reasonably that a WEEKLY dose was taken. I have RARELY recommending prescribing levothyroxine in a ONCE WEEKLY dose that has some evidence that it WORKS and is predicated on the long half-life of levothyroxine. I’d think about that approach if there was a “care giver” who would help give the dose one day a week.

  4. Sean Navin

    Sertraline is the only SSRI that is less effective at lower doses and should be titrated up to obtain the most effectiveness. It may have not been the best initial choice for this patient although educating the patient on the need for titration and titrating early on may have worked for the patient.


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Written By Eric Christianson

July 6, 2016

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