Last night I mentioned that diphenhydramine is a somewhat promiscuous molecule, binding to a number of disparate receptors. One of its effects is some inhibition of serotonin reuptake. As you've probably read in countless pop science articles by now, this is one mechanism of action for antidepressants. Take a look at diphenhydramine again:

And Fluoxetine/Prozac:

Note the similarity in structure to diphenhydramine. Also note the trifluoromethyl group (-CF 3 ). You don't really see organofluorine compounds in Nature (it's so reactive it's been caught up in rocks and ores for ages), but they are ubiquitous in medchem. This C&E News article estimates that one in five drugs contains at least one fluorine atom. Fluorine is such a singularly unique element it has its own journals. Fluorine chemistry is a field in and of itself.

For an overview of some of the history of psychopharmacological agents (including the story of diphenhydramine's kinship with modern anti-depressants), take a look at this review article from Psychosomatic Medicine.