Can the effectiveness of antidepressants be explained by a placebo effect? A friend of mine showed me a paper (Kirsch, 2014) where the author claims that antidepressants work mostly through a placebo effect (backed up with relevant citations). Antidepressants are generally serotonin enhancers and their mechanism of action hinges on the premise that there is a chemical imbalance of serotonin in the brain. But not only do they not work significantly  better than placebos, but also there are antidepressants that do not enhance serotonin but suppress it. There are some that do nothing to serotonin at all, but their therapeutic effects are all the same, according to Hirsch. So the effect is independent of the chemical composition. That means the chemical imbalance theory is wrong. Is my understanding, as a layperson, correct?

If all of this is legitimate, does that makes any sense to take medicines for an ADHD patient as well? I mean, does the placebo effect, if true, affect ADHD patients, too?

I fear that if people get to see this paper, they may misinterpret the results and may refuse to go to a psychiatrist and get treated even if they have legitimate issues. This is alarming, IMO.

Reference
- Kirsch, Antidepressants and the Placebo Effect, Zeitschrift für Psychologie (2014); 222(3): 128–134
Short answer
Don't believe everything you read.

Background  


The article cited (Kirsch, 2014) appears in a German journal with a mediocre impact factor. Not the most convincing platform.
I'll cite parts of the abstract, starting with 



  But analyses of the published data and the unpublished data that were
  hidden by drug companies reveals that most (if not all) of the
  benefits are due to the placebo effect.


His reference list includes some 40+ references; if I type in "antidepressant AND serotonin" in Scopus (an established academic search engine I often use) I get 23k+ hits. With a bald statement like Hirsch makes, he might be skipping the literature proving him wrong.    


  Some antidepressants increase serotonin levels, some decrease it, and
  some have no effect at all on serotonin. Nevertheless, they all show
  the same therapeutic benefit.  


The new generation of antidepressants, the SNRIs, also have action on nor-epinephrine and may be more effective than the regular SSRIs. Serotonin may and likely is not the whole story. Depression is a complex disease with variable etiologies. Thinking it's all about serotonin is a bit short-sighted.


  Even the small statistical difference between antidepressants and
  placebos may be an enhanced placebo effect, due to the fact that most
  patients and doctors in clinical trials successfully break blind.


Oh come on - when you put forth such a line in the abstract that other researchers can't successfully perform a proper masked clinical trial, only testifies of a lack of proper data to back his [flawed] claims up.   


  The serotonin theory is as close as any theory in the history of
  science to having been proved wrong.


This is a totally subjective thing to say. I don't care where it ranks in a ladder. Especially not in an abstract. Saying stuff like this only testifies he has nothing better to say in the abstract.  


  Instead of curing depression, popular antidepressants may induce a
  biological vulnerability making people more likely to become depressed
  in the future.


This would need carefully planned prospective clinical studies to prove. Until this is addressed, he shouldn't be going down this path.   

Lastly - Hirsch has been criticized proclaiming the same stuff since the 1990's, without changing the contents of his message. Perhaps he should stop theorizing and start experimenting to put his conspiracy theories to the test.

According to Klein (1998), Kirsch bases his claims on a flawed study (Kirsch &amp; Sapirstein, 1998), where Kirsch claims that the substantial majority of drug effect is due to placebo effect and the rest is either measurement error or active placebo effect. Klein criticizes the article, because it was derived from a relative small group of unrepresentative, inconsistently and erroneously selected articles arbitrarily analyzed by an obscure, misleading effect size. Further, he identifies problems with the meta-analytic approach in general, such as the lack of attempts to further segment the placebo response. Lastly, he points to the lack of peer review and the opportunity provided by an electronic journal for rapid publication.   

References
- Kirsch, Zeitschrift für Psychologie (2014); 222(3): 128–34
- Kirsch &amp; Sapirstein, Prevention &amp; Treatment (1998); 1: 0002a
- Klein, Prevention &amp; Treatment (1998); 1: 0006c