Many forms of treatment for depression are not effective because they tend to have an iatrogenic effect; that is, the doctor or source of treatment is making the depression worse because it forces the individual to dwell on negative events. Whether they are an antecedent or consequence of the depression, cognitive behavioral therapy (CBT) helps the individual to deal with their cognitive symptoms and emotions. CBT focuses on erroneous cognitions that seem to be a part of the depression. The therapy focuses on the patient's sense of control and identifies the tendencies of misattribution, replacing them with other ways of thinking. Group cognitive therapy and mutual support therapy have also been shown to be effective in producing improvements in depressed patients. Other treatments such as electro-convulsive therapy (ECT), which stimulates a controlled seizure in the brain and immediately decreases sensitivity of norepinephrine receptors in the brain, has been shown to be effective immediately in cases of chronic and serious depression. Yet one major side-effect of this form of treatment is severe memory loss.

Other forms of treatment include monoamine oxidase inhibitors, a class of antidepressants that are monamine agonists, blocking the actions of the monamine oxidase and increasing monamine activity). One major problem in treating this disorder is that certain classes of antidepressants such as tricyclics, which include imipramine (Trofanil) and amitriptyline (Elaveil), block the re- uptake of serotonin and norepinephrine, but are deadly if taken in excess. Selective serotonin re-uptake inhibitors (SSRIs), also effective in treating depression, such as Prozac and Zoloft, only block the re-uptake of serotonin. The major side effects of SSRIs are gastro-intestinal discomfort and dry-mouth.