Kirsh’s found that trial subjects who got antidepressants and those who got placebo reported or displayed changes that led to approximately the same degree of improvement whether symptoms are metered by HAM-D, MADRS, or possibly clinical impression. In no way does that mean the trialed antidepressant didn’t improve anyone’s mood. It suggests that antidepressant trials are designed in every aspect to effect reductions in depression scores for all subjects. In subjects assigned to take the antidepressant, an additive effect of a mood-improving milieu and drug is not certain to occur, but if it does, it won’t necessarily mean greater improvement in depression scores for the drug subjects vs the placebo subjects. There is a ceiling on how much a pill can elevate a subject’s mood. Elevating it past the ceiling renders the patient hypomanic or manic, to be adverse-effected out of the trial and the data. But I don’t think that’s what happens. It’s probably more like adding milk to 100 cups of coffee (milieu, affecting all subjects) and sugar to 50 cups (the antidepressant, affecting half of the subjects) and reporting the change in volume but not the change in sweetness. (Which is like using HAM-D, in which only one question investigates mood directly.) HAM-D: http://healthnet.umassmed.edu/mhealth/HAMD.pdf Per Bech, MD, Rating scales in depression: limitations and pitfalls: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181766/ P.S. I’ve commented elsewhere that the drugs do have genuine chemical properties that do alter mood, often radically for the better. I say that because I’ve taken a few of them. I’ve also stolen, long ago, pills from my parents’ pharmacy-sized jar of little yellow amphetamine pills, taken Librium and Quaaludes, snorted coke and black beauties, eaten psilocybin, smoked legendary Thai stick, received morphine and Dilaudid intravenously, and attempted to trip on LSD. All but Dilaudid and LSD caused a pleasant and marked departure from the ordinary. (I didn’t take enough LSD, or it was bogus.) Prozac, Effexor, and Wellbutrin also caused pleasant departures from the ordinary. Effexor comes on in 20 minutes, or did for me, the first time.