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:<p>Medicines that promote drowsiness (such as sleeping aids and even the antipsychotic quetiapine), as sleep deprivation and depression are highly correlated.<p>The atypical antidepressant wellbutrin&#x2F;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.<p>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.<p>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.