Benadryl makes me suicidal for about a week every time I take it. I no longer touch the stuff at all. I have read several studies (and quite a few articles and anecdotal experiences) that have said that this particular medication can cause permanent brain changes in non-depressed people that make them depressed for their entire lifetimes...for bipolar people especially it can be a disaster. The studies focused on the changes to the brain both in the short-term (when you take it and the days following) and both over the long-term are bad. Over the long-term, though, in particular, it can cause irreversible and extremely treatment resistant depression. I will look later for the studies on pubmed and medline so I can post them here.

For some people it doesn't seem to be a huge issue especially when taken only occasionally...but all the bipolar people I personally know who take it regularly struggle with depression most of the time and wonder aloud constantly why their meds don't seem to be working. I'm absolutely convinced there's a connection.