An antidepressant is a psychiatric medication used for alleviating major depression or dysthymia ('milder' depression). Drug groups known as MAOIs, tricyclics, and second-generation antidepressants such as SSRIs are particularly associated with the term. These medications are now amongst the drugs most commonly prescribed by psychiatrists and other physicians, and their effectiveness and adverse effects are the subject of many studies and competing claims.

Most antidepressants have a delayed onset of action and are usually taken over the course of weeks, months, or sometimes years. They are generally considered distinct from stimulants, and drugs used for an immediate euphoric effect only are not generally considered antidepressants. Despite the name, antidepressants are often used in the treatment of other conditions, including anxiety disorders, bipolar disorder, obsessive compulsive disorder, eating disorders, and chronic pain. Some have also become known as lifestyle drugs or "mood brighteners".

Other medications that are not usually called antidepressants, including antipsychotics in low doses and benzodiazepines, may also be used to manage depression, though in the case of "Benzos", there is a serious risk of physical dependence. An extract of the herb St John's Wort is commonly used as an antidepressant, labeled as a dietary supplement in some countries. The term antidepressant is sometimes applied to any therapy (e.g. psychotherapy, electro-convulsive therapy, acupuncture) or process (e.g. sleep disruption, increased light levels, regular exercise) found to improve clinically depressed mood.

An inert placebo tends to have a significant antidepressant effect, so establishing something as an antidepressant in a clinical trial involves demonstrating a significant additional effect.

History

Various opiates were commonly used as antidepressants until the mid-1950s, when they fell out of favor due to their addictive nature, tolerance buildup issues and their side-effect profile. Extracts from the herb St John's Wort have long been used (as a "nerve tonic") to alleviate depression.

Isoniazid and iproniazid

In 1951, two physicians from the Sea View Hospital on Staten Island, Irving Selikoff and Edward Robitzek, began clinical trials to evaluate two new anti-tuberculosis agents from Hoffman-LaRoche, isoniazid and iproniazid. Only the patients with poor prognosis were initially treated; nevertheless, their condition improved dramatically. In addition, Selikoff and Robitzek noted "a subtle general stimulation... The patients exhibited renewed vigor and indeed this occasionally served to introduce disciplinary problems." The promise of the cure for tuberculosis brought by the results of the Sea View Hospital trials was also excitedly discussed in the mainstream press. In 1952, learning of the stimulant-like side effects of the isoniazid, the Cincinnati psychiatrist Max Lurie decided to try it on his patients. In the following year, he and Harry Salzer reported that isoniazid improved the depression in two thirds of their patients and also coined the term antidepressant to describe its action. A similar story happened in Paris, where Jean Delay, the head of psychiatry at Sainte-Anne Hospital, found out from his pulmonology colleagues from Cochin Hospital about the side effects of isoniazid. In 1952, that is even earlier than Lurie and Salzer, Delay with the resident Jean-Francois Buisson also reported the positive action of isoniazid on depressed patients. For the reasons unrelated to the efficacy, isoniazid as antidepressant was soon overshadowed by more toxic iproniazid, although it remains one of the mainstays of the tuberculosis treatment. The mode of antidepressant action of isoniazid is still unclear. It is speculated that its effect is due to the inhibition of diamine oxidase coupled with a weak inhibition of monoamine oxidase A.