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Diagnosis of major depressive disorder is entirely clinical at present, and based on criteria such as DSM-IV. The classes of medications include antidepressants, selective serotonin reuptake inhibitors (SSRIs), older dual-action reuptake inhibitors, newer dual-action antidepressants, norepinephrine reuptake inhibitors (NRIs) and monoamine oxidase inhibitors. Successful treatment of major depression may require a multi-modal approach including pharmacotherapy, education, and psychotherapy. Patient response to treatment needs systematic monitoring, not only to improve compliance, but to make sound decisions about the need to raise the dose to achieve an optimal antidepressant effect and to monitor side effects. A history of episodes lasting more than 6 months require longer continuation treatment of up to 12 months, and generally continuation treatment will be longer for psychotic depression. Antidepressant and adjunctive pharmacological agents allow successful acute treatment and prevention of future episodes of major depression in most patients.