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Antidepressants: Finding the Right Fit

Debra Gordon

Last updated: December 1, 2016 3:34 pm

About 16 percent of adults will be diagnosed with depression in their lifetime and most will start taking some kind of antidepressant. Yet about 40 percent won’t get better on that first medication, and more than 60 percent will experience at least one side effect, often so severe that they quit taking the medication.

Which leads to your healthcare provider switching you to another antidepressant. And, perhaps, another one. Or adding one. Or adding an anti-psychotic. Until it begins to feel as if treating your depression isn’t much different than throwing darts, hoping that at least one hits a bull’s eye. This is all made worse by the fact that it can take six to eight weeks to get the full benefits of an antidepressant that does work; and you often have to be weaned off one before starting another. So finding the right treatment can take months—during which you’re still feeling miserable.

You’re not the only one frustrated; it’s frustrating for your healthcare provider, too, who has to choose from among more than a dozen approved antidepressants as well as other drugs that are often used “off-label” to treat the condition. Plus, there’s no blood test or even imaging test that can quickly tell them if the drug will work. It’s all hit or miss.

There’s also so much we don’t know about the drugs, despite more than two decades of research on newer, targeted medications like Prozac (fluoxetine). For instance, we don’t know how these medications work after the acute phase of depression has passed. Yet guidelines call for remaining on antidepressants for at least six months. Some people need them for years or even a lifetime to prevent recurrences.

The good news is that research is beginning to trickle out that can provide some road marks that may help you and your healthcare professional choose the right medication for you.

For instance, a review of 117 randomized trials of 12 newer antidepressants involving nearly 26,000 participants found that mirtazapine (Remeron®), escitalopram (Lexapro®), venlafaxine (Effexor®), and sertraline (Zoloft®) were significantly more effective than duloxetine (Cymbalta®), fluoxetine (Prozac®), fluvoxamine (Luvox®), or paroxetine (Paxil®). Those with the fewest side effects were Lexapro and Zoloft. Overall, the researchers concluded, Zoloft “might be the best choice” when starting someone on an antidepressant given its safety, effectiveness, and cost.

The table below depicts the results of another major analysis comparing many of the available antidepressants:

Bupropion (Wellbutrin®) Citalopram (Celexa®) Cymbalta Prozac Remeron Paxil Zoloft Tricyclics Effexor
Faster onset

Greatest risk of side effects that will make you quit
Least likely to have sexual side effects
Most likely to cause sexual side effects
Most likely to cause weight gain
Most likely to cause diarrhea
Highest risk of nausea and vomiting
Most likely to cause “discontinuation syndrome” (headache, dizziness, nausea)
Least likely to cause discontinuation syndrome
Consider for uncomplicated major depression with no anxiety disorder
Consider for depression with anxiety disorder
Consider for depression with pain ✔* ✔*
Avoid if you have osteoporosis or gastrointestinal bleeding

*Neuropathic pain, migraines, tension headaches
Sources: Agency for Healthcare Research and Quality. Choosing Antidepressants for Adults. Clinician’s Guide.

In the end, it is up to you and your doctor or nurse practitioner to decide which antidepressant is right for you. But this information could, at the very least, provide a roadmap for that discussion.