Are Antidepressants Effective?

Depres­sion has become a major health prob­lem.  In fact, about 10 per­cent of Amer­i­cans over age six now take anti­de­pres­sants.  Does it make sense that depres­sion is treat­ed rou­tine­ly with med­ica­tion?

Depres­sion is not to be ignored or triv­i­al­ized.  It’s a seri­ous, wide­spread con­di­tion that con­tributes to sig­nif­i­cant suf­fer­ing and dis­abil­i­ty.  It mag­ni­fies the impact of oth­er med­ical prob­lems — among them back pain and heart dis­ease.

Businesswoman under stress

And its effect is also mag­ni­fied because depres­sion doesn’t only impact the indi­vid­ual suf­fer­er – it touch­es fam­i­ly mem­bers, too.

In response to this seri­ous health con­di­tion, a vast trea­sure chest has been poured into research­ing and mar­ket­ing med­ica­tions for depres­sion. This is not a small indus­try.  We’re talk­ing seri­ous mon­ey here.

No doubt anti­de­pres­sant med­ica­tions have a role to play under some cir­cum­stances.  But here’s the big ques­tion:

How strong is the sci­en­tif­ic ratio­nale for the cur­rent drug approach to treat­ing depres­sion?

Ide­al­ly, any wide­ly-accept­ed form of med­ical inter­ven­tion should be jus­ti­fied by two syn­er­gis­tic lines of rea­son­ing:

  1. There should be a sci­en­tif­i­cal­ly-plau­si­ble expla­na­tion of how the inter­ven­tion actu­al­ly works to fix the under­ly­ing prob­lem.
  2. Rig­or­ous clin­i­cal stud­ies should doc­u­ment treat­ment effec­tive­ness.

I admit these are tough stan­dards – many well-accept­ed forms of med­ical treat­ment fall short.  After all, med­i­cine is an art.  We can’t throw out every form of ther­a­py that doesn’t meet a stan­dard of sci­en­tif­ic per­fec­tion.

Nonethe­less, in treat­ing depres­sion, there are alter­na­tives to anti­de­pres­sant drugs.  Effec­tive alter­na­tives.  And anti­de­pres­sants have side-effects.  Some­times sig­nif­i­cant side-effects.

Giv­en the alter­na­tives and the risks, do today’s gen­er­a­tion of anti-depres­sant med­ica­tions come close enough to meet­ing these sci­en­tif­ic ideals?

First of all…

Is there a plausible scientific rationale for the drugs’ mechanism of action?

Anti-depres­sants work by pro­long­ing the action of sero­tonin in our brain’s synaps­es.

That sounds great.  But before we get car­ried away with enthu­si­asm for selec­tive sero­tonin reup­take inhibitors (SSRIs), here are two fun­da­men­tal ques­tions:

1.    Is depres­sion caused by a lack of sero­tonin?  Or a loss of sen­si­tiv­i­ty to sero­tonin?


The caus­es of depres­sion are com­plex, and include phys­i­o­log­i­cal, social, psy­cho­log­i­cal, nutri­tion­al, behav­ioral, and envi­ron­men­tal fac­tors.

Drugs com­pa­nies did not devel­op SSRIs because sci­ence dis­cov­ered that a sero­tonin imbal­ance caused depres­sion.  This class of drugs was orig­i­nal­ly devel­oped for oth­er rea­sons.  Their effect on mood showed up as a side-effect.

2.   If you have symp­toms of depres­sion, does your doc­tor test your brain sero­tonin lev­els before pre­scrib­ing these drugs?


In oth­er words, we don’t know if peo­ple with depres­sion have alter­ations in their sero­tonin sig­nal­ing sys­tem, or, if they do, if this alter­ation is the cause of depres­sion or mere­ly an effect.

The phar­ma­ceu­ti­cal com­pa­nies didn’t devel­op a class of drugs to address a rec­og­nized chem­i­cal imbal­ance. They pos­tu­lat­ed a chem­i­cal imbal­ance after the fact to try to explain the mode of action of their drugs.

Maybe that’s okay if a drug has a pow­er­ful ther­a­peu­tic effect.

But how effec­tive are anti­de­pres­sants any­way?  What do the clin­i­cal tri­als show?

Drug com­pa­nies have to per­form a lot of research and jump through many hoops in order to win approval from the FDA for their prod­ucts.  So clin­i­cal stud­ies have been per­formed that show clin­i­cal effec­tive­ness for depres­sion.

But exact­ly how rig­or­ous are those stud­ies?  How effec­tive were the drugs were shown to be?

Here’s one key issue:

To gain FDA approval, a phar­ma­ceu­ti­cal com­pa­ny has to sub­mit two dif­fer­ent stud­ies that show the drug to be effec­tive.  Mean­while, it doesn’t mat­ter if 12 or 50 oth­er neg­a­tive stud­ies were per­formed.   As long as there are two stud­ies show­ing pos­i­tive results, that’s good enough.

For his book The Emperor’s New Drugs: Explod­ing the Anti­de­pres­sant Myth, author Irv­ing Kirsch reviewed 42 research stud­ies, pub­lished and unpub­lished, per­formed on 6 anti­de­pres­sant drugs first approved between 1987 and 1999.

Most of the stud­ies were neg­a­tive, and in the ones that showed a pos­i­tive ben­e­fit, the anti-depres­sants were only mar­gin­al­ly bet­ter than the use of place­bo.

This brings up a sec­ond key issue in eval­u­at­ing the effec­tive­ness of anti­de­pres­sants: place­bo treat­ment does a remark­ably good job for depres­sion.  Place­bos are three times as effec­tive as giv­ing no treat­ment at all.

Com­pared to the anti­de­pres­sant drugs being stud­ied, the place­bo effect account­ed for 75–82% of the total ben­e­fit.  The anti­de­pres­sants, even in those stud­ies which showed a pos­i­tive ben­e­fit, only added anoth­er 18–25% share of improve­ment.

But wait.  It gets even more com­pli­cat­ed.

Kirsch explains a sub­tle bias in the research designs that would tend to over­state the ben­e­fits of anti­de­pres­sants.

In his ear­li­er research he had observed that many oth­er drugs—including seda­tives, syn­thet­ic thy­roid hor­mone, opi­ates, and stimulants—were as effec­tive as anti­de­pres­sants in alle­vi­at­ing the symp­toms of depres­sion.

Kirsch writes, “When admin­is­tered as anti­de­pres­sants, drugs that increase, decrease or have no effect on sero­tonin all relieve depres­sion to about the same degree.”

How could that be?

Here’s his expla­na­tion.  What all these “effec­tive” drugs have in com­mon is that they pro­duce side effects.

In all of these research tri­als, one group of par­tic­i­pants received a place­bo and anoth­er group received the test drug.

Kirsch spec­u­lates that the occur­rence of side effects allowed patients to guess that they were get­ting the active treat­ment.  This enhanced the place­bo effect of the drug: those patients who believed they were in the test drug group were more like­ly to report improve­ment.

To back up his hunch, Kirsch looked at a sub-group of research tri­als that employed “active” place­bos (agents that caused side-effects) instead of inert ones.

For exam­ple, in tri­als using atropine (which caus­es dry mouth) as the “place­bo,” both groups expe­ri­enced side effects of one type or anoth­er, and every­one report­ed the same lev­el of improve­ment.

Now we can grade the anti­de­pres­sant drugs accord­ing to the sci­en­tif­ic stan­dard:

  • There is at best only a high­ly spec­u­la­tive mode of action that’s been pro­posed for the action of SSRIs to treat depres­sion.  It may or may not have any bear­ing on what’s real­ly going on in the brains of depressed peo­ple.
  • The clin­i­cal research tri­als sup­port­ing the use of SSRI’s for depres­sion show only a weak ben­e­fit or, arguably, no actu­al ben­e­fit at all.

If SSRI’s aren’t much good, what’s a depressed per­son to do?

First of all, if you’re cur­rent­ly tak­ing anti­de­pres­sant med­ica­tion, don’t just stop tak­ing it!

If your strat­e­gy to deal with your depres­sion is work­ing, keep it up – you’re doing just fine.

If you have a ques­tion about the effec­tive­ness of your drug reg­i­men or the side-effects you’re expe­ri­enc­ing – talk it over with your doc­tor or phar­ma­cist.  Don’t make a deci­sion about your med­ical treat­ment based on read­ing this arti­cle, or any sin­gle arti­cle.

On the oth­er hand, you should inform your­self about the details of SSRIs, their pos­i­tive and neg­a­tive effects, and what alter­na­tives might exist for you.

Here are some strate­gies that have shown promise in treat­ing depres­sion:

Hope you find one or more of these ideas help­ful.


Deepen Your Body of Knowledge

Mar­cia Angell’s arti­cle in New York Review of Books cov­er­ing Irv­ing Kirsch’s book and two oth­ers on the mis­use of psy­choac­tive med­ica­tion.

Depres­sion and back pain.

Gain con­trol over depres­sion and anx­i­ety

In defense of anti­de­pres­sants

Irv­ing Kirsch’s The Emperor’s New Drugs


About Ronald Lavine, D.C.

Dr. Lavine has more than thirty five years' experience helping patients alleviate pain and restore health using diverse, scientifically-based manual therapy and therapeutic exercise and alignment methods. His website,, provides more information about his approach. Please contact him at or at 212-400-9663.
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