The first antidepressants, dating back to the fifties, were opioids and amphetamines. Yes, they worked, but they were highly addictive and had major side effects. Then by accident, Imipramine (the first of a class known as tricyclics) was discovered, and the antidepressant boom was born.

These early drugs were very effective, — in fact, as effective as modern treatments — but there were many, sometimes intolerable, side effects. Also, they were difficult to prescribe as the dose needed to be gradually titrated upward.

All that changed with the approval of Prozac in 1987. Now antidepressants are some of the most commonly prescribed medications in the world. But with dozens of meds on the market, the question I often hear is, "Which antidepressant works the best?"

With the many classes and sub-types of antidepressants, numerous clinical trials and millions of patients who have taken these meds throughout the years, it stands to reason that one or two medications would stand out as being the best, and safest. In fact, how could that not be the case?

Well, it’s not. Statistically, they all yield amazingly similar results. In other words, when looking at the response rate across the board, all the antidepressants are eerily the same. This is even more amazing when you consider that these antidepressant classes focus on different neurotransmitters from serotonin to dopamine to norepinephrine. How could it be that they are all equally effective? The answer is unclear, but my thought is that there could be some unknown mechanism that underlies all of their efficacy which we are just not yet aware of.

Of course, this doesn’t mean that a certain antidepressant won’t work best for you. The problem is that we have no way of predicting in advance which med that might be. Many providers will treat someone with poor sleep with a sedating antidepressant, another who lacks energy with one that is more energizing, and yet another with weight loss with one that increases appetite. But this is all anecdotal and theoretical, so this is where the art of medicine comes into play, coupled with plain old trial and error.

Something new and interesting that may take the guess work out of prescribing is genetic testing. This is a way to determine how your body will process a drug, since each and every person's inherited genetic traits cause variations. At this time it’s expensive, and it's doubtful whether it’s cost-effective, when compared to trial and error. However as we learn more about genes and medication, it may have potential for the future.

All of the latest and greatest antidepressants do have one thing in common — they are extremely expensive. Generics are always the first, best choice, as they are effective copies of the originals for a fraction of the cost — sometimes as little as $4 per month. Of course, some antidepressants are covered by health insurance, but even so, why go with a more expensive alternative if there is no demonstrable benefit?

So back to our original question, "Which antidepressant is the best?" Start with the cheapest one and go from there.

About the Author

Dr. Dale Archer

Dale Archer, M.D., is a clinical psychiatrist and the author of Better Than Normal: How What Makes You Different Can Make You Exceptional.

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