Accepted wisdom for a number of years has been that all modern anti-depressants work equally well, and that drug selection depends more on the side effect profile desired. Thus a lethargic patient might benefit from an activating antidepressant like Prozac, and an anxious patient would be better off with Paxil. Often prescribing practices are based on individual doctors’ preferences and biases. But a newly published study suggests that this may be wrong. There may be antidepressants that not only work better, but are easier for patients to tolerate.

A terrific new study was recently published in the Lancet medical journal. A team of international researchers, led by Andrea Cipriani at the University of Verona in Italy, reviewed 117 studies of antidepressants which included 25928 patients, two-thirds of whom were women. These studies, done all around the world, compared various antidepressants to either placebo or other antidepressants.

The researcher compared the results of 12 new generation antidepressants in terms of efficacy and acceptabiltiy. They defined efficacy as the proportion of patients who improved at least 50% on a depression rating scale by 8 weeks of treatment. They defined acceptability as the proportion of patients who did not drop out of the study. They made an attempt to adjust for dosages, and did very sophisticated statistical analyses to compare all of the drugs. They used fluoxetine (Prozac) as the common comparison drug, since it has been on the market for the longest time.

What were the results? The winners in terms of short term effectiveness were: (drum roll) mirtazapine (Remeron), escitalopram (Lexapro), venlafaxine (Effexor), and sertraline (Zoloft). The winners in terms of acceptability were: escitalopram (Lexapro), sertraline (Zoloft), citalopram (Celexa), and bupropion (Wellbutrin) were better tolerated than other new-generation antidepressants. Note that the overall winners for effectiveness combined with tolerability were escitalopram (Lexapro) and sertraline (Zoloft). Two of the best drugs in terms of effectiveness (mirtazapine (Remeron) and venlafaxine (Effexor)) were not among the best tolerated medicines.

The losers in terms of both effectiveness and tolerability were reboxetine (Edronax), ?uvoxamine (Luvox), paroxetine (Paxil), and duloxetine (Cymbalta). The worst drug of all was reboxetine (Edronax).

So what about cost? I’ve developed a spreadsheet of all of the drugs’ costs based on a 30 day supply, paying full retail price at Costco pharmacy, and using generic equivalents when available. Of the winners in terms of effectiveness and tolerability, the clear cost winner was sertraline (Zoloft), at $12 a month. The other winner, escitalopram (Lexapro), was a loser in terms of cost at $88 a month! The other winners in terms of effectiveness were quite cost effective too, with mirtazapine (Remeron) at $14 a month, and venlafaxine (Effexor) at $28 a month.

So what should doctors and patients do? For patients, the two best drugs appear to be escitalopram (Lexapro) and sertraline (Zoloft), with sertraline the clear winner if you pay much for prescription drugs. Doctors might want to consider costs as well, as this can help with overall health care inflation. If you can tolerate the side effects, consider trying mirtazapine (Remeron), or venlafaxine (Effexor).

Now there are of course a few caveats about this study. It is possible that another meta-analysis could find different results. One criticism was that the study only looked at effectiveness over 8 weeks of treatment. It is possible that some drugs work more slowly, and at 12 or 16 weeks might have different results. But most patients want results in two months or less, so this is not a major criticism.

Another issue is funding bias. Although none of the authors of this study were paid by drug companies, many of the studies they analyzed were funded by drug companies, and may have reflected some bias. But for now, this is the best information we have in terms of effectiveness and toleration of antidepressant medications.

So who’s the winner? Sertraline (Zoloft) was the clear winner by effectiveness, tolerability, and cost!

Should you change medications if you are not on one of the winners? No, of course not. If your medication is working, don’t change it. But if it’s not working, then talk with your doctor about switching.

And no, I don’t receive any funding or sponsorship from any drug companies…

Here’s the table of drug price comparisons.
Comparison of Antidepressant Costs for 30 Day Supply (Costco Pharmacy, Generic Equivalents if possible)
Bolded Drugs were most effective

Drug            Generic Name         Cost          Dose(mg)

Celexa             citalopram                   $3                 40
Prozac             fluoxetine                    $6                  20
Zoloft             sertraline                       $12             100
Remeron     mirtazapine                    $14               30
Luvox              fluvoxamine               $24             100
Effexor         venlafaxine                    $28                75
Welbutrin      bupropion                   $74             200
Lexapro       escitalopram                 $88                10
Paxil                paroxetine                   $91             37.5
Cymbalta       duloxetine                   $128              60

Copyright © 2009 Andrew Gottlieb, Ph.D. /The Psychology Lounge/TPL Productions