Ask the Pharmacist: Why some antidepressants work, and others don’t

Suzy Cohen
Two drawings of brains represented by colorful blocks, with one jumbled and the other orderly.

First let me say I am not a fan of medicating normal, regular sadness that we encounter in our life, such as the melancholy associated with losing a job, or when someone unfriends you, or for hormonal cycles. There are people who are truly depressed and suppressing the urge to harm themselves. We need to be loving and gentle with them, and if they need medicine, then so be it.

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Medication treatment should be based upon the neurotransmitters that are imbalanced. Doctors tend to throw a dart in the dark by prescribing popular drugs without measuring metabolites of neurotransmitters (for example Homovanillate or 5-HIAA) which provide a glimpse behind the curtain. 

So, let’s get to it, what do you think is better, an SNRI or an SSRI? Or a MOA inhibitor? The answer is unclear. One category of meds will work great for you and be an epic fail for your friend.

Why is that?

Because Zoloft (sertraline) works by making serotonin linger longer, and that’s great if you have reduced serotonin activity. But what if that’s not your problem? What if you’re depressed because you have low DHEA, a youth hormone that declines after 40. What if it’s low testosterone or estrogen. And what if your levels of serotonin are fine, but you have super low levels of norepinephrine or dopamine? In the latter case, Zoloft would not work, and might be harmful, whereas Wellbutrin (bupropion) would be great! 

Some of you could benefit from a med that raises serotonin, dopamine AND norepinephrine.  Remeron (mirtazapine) works in this regard. There are so many possibilities, so do not lose hope! 

Someone else reading this needs lifting of serotonin and norepinephrine but not the dopamine. Effexor (venlafaxine) is an SNRI that does exactly that!

What I’m trying to say is that each of you respond to the medication that restores activity of the neurotransmitter you are deficient in. Not everyone with depression is deficient in one specific thing.

I have readers today that are in bad shape and feeling isolated and hopeless. I want to help you. Keep doing a little more ‘trial and error’ with medications (and other therapies outside the pill). There are tests you can take today to measure metabolites. I have a more comprehensive version of this article which you can receive via email if you sign up for my newsletter at

In closing, I couldn’t possibly know what’s right for everyone because neurotransmitter levels are like fingerprints in people. Sometimes depression is caused by folate or B12 deficiency, or thyroid illness. Sometimes it’s from very high inflammatory compounds, or from a biotoxin like mold. This may surprise you but sometimes it’s medication-induced, like from “The Pill.”

If you feel like you’re at your wits end and you’ve tried everything and it's just time to go (and stop being a burden to others) then you need to stop thinking that immediately because it simply isn’t so. You haven’t tried everything. There are people who love you and need you. The National Suicide Prevention Line is 800-273-8255 or text HELLO to 741741.

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Suzy Cohen is a registered pharmacist. The information presented here is not intended to treat, cure or diagnose any condition. Visit