johnw11

Also, isn't MDMA highly toxic if used frequently? Drug forums seem to recommend the use of MDMA no more often than once every two weeks.

Yes, many do, but is that necessarily inherent to all "happy pills"?

Also, while I don't personally have experience with a lot of illegal drugs, if you ask anyone who does he will tell you that there are drugs that nearly instantly make you happy without having to wait weeks for the drugs to have a subtle effect on your thought processes.

These illegal drugs may or may not be too dangerous to use regularly to treat depression, but it's worth noting the fact that it's clearly not "impossible" to make a true "happy pill"

I would like to point out that there is a whole range of non-SSRI medicines that have significant clinical effects on depression. In particular:

Medicines that promote drowsiness (such as sleeping aids and even the antipsychotic quetiapine), as sleep deprivation and depression are highly correlated.

The atypical antidepressant wellbutrin/bupropion, which impacts a whole bunch of chemicals in the body but notably does not affect seratonin levels. My personal experience from having taken it is that it makes me more energetic, similar to a weak amphetamine.

MAOIs, which again impact a whole bunch of chemicals, including seratonin but notably also melatonin, which is well-known to promote sleep. These are well-known to be highly effective antidepressants, but are rarely used because they require the patient to alter aspects of his lifestyle.

The situation is complicated by the fact that the category of depression consists of a bunch of different symptoms that may be comorbid in many people, but are not necessarily.