Category:Antidepressants: Difference between revisions

Antidepressants (a term whose accuracy is sometimes questioned — see Terminology below) are a class of medicines used principally in the treatment of major depressive disorder, and also in a range of other conditions including anxiety disorders, post-traumatic stress disorder, obsessive–compulsive disorder, and certain chronic pain syndromes. For post-traumatic stress disorder, selective serotonin reuptake inhibitors are recommended as first-line pharmacotherapy in major treatment guidelines, and two — sertraline and paroxetine — carry specific regulatory approval for that indication.^[1]

The first two medicines specifically recognized as antidepressants were both introduced in the 1950s, and both were discovered by accident. Iproniazid had been developed as a treatment for tuberculosis; clinicians observed that it elevated mood in some patients, and in 1957 Nathan Kline's group reported its effect in depressed patients without tuberculosis. It became the first of the monoamine oxidase inhibitors (MAOIs).^[2] At roughly the same time, imipramine — tested without success as an antipsychotic — was found by the Swiss psychiatrist Roland Kuhn to relieve depression, and became the first of the tricyclic antidepressants (TCAs).^[2]

These accidental discoveries had an influence beyond treatment: the observation that medicines affecting monoamine neurotransmitters could alter mood contributed to the first biological theories of depression.^[2]

The next major shift came with the selective serotonin reuptake inhibitors (SSRIs). Fluoxetine, developed by Eli Lilly and marketed as Prozac, received United States FDA approval in December 1987 and reached the market in January 1988 as the first SSRI.^[3] SSRIs were not necessarily more effective than the older medicines, but were generally regarded as better tolerated and safer in overdose, and they were prescribed very widely in the decades that followed.^[3]

The word "antidepressant" describes a presumed action — the lifting of depression — rather than an established mechanism. Its accuracy has been questioned on two grounds. First, the medicines grouped under the term are pharmacologically diverse and their mechanisms are not fully understood. Second, the popular explanation that depression results from a "chemical imbalance" — typically a deficiency of serotonin — is not supported by current evidence; a 2022 umbrella review found no consistent association between serotonin and depression, and standard psychopharmacology texts have likewise stated that no clear monoamine deficit has been demonstrated.^[4] Some authors have noted that the "chemical imbalance" phrase owed much to pharmaceutical marketing rather than to settled science.^[5]

These criticisms concern the naming and the proposed mechanism; they do not by themselves resolve the separate question of whether the medicines are effective, which is assessed through clinical trials and remains a subject of ongoing research and debate. This wiki retains "antidepressant" as the category name because no widely recognized alternative term exists.

The principal groups of antidepressants include the monoamine oxidase inhibitors (MAOIs), the tricyclic antidepressants (TCAs), the selective serotonin reuptake inhibitors (SSRIs), the serotonin–norepinephrine reuptake inhibitors (SNRIs), and a number of agents not falling neatly into these categories (sometimes grouped as "atypical" antidepressants). The list is not exhaustive.

Most antidepressants are understood to act on monoamine neurotransmitter systems — serotonin, norepinephrine, and dopamine — for example by inhibiting reuptake or by inhibiting their breakdown. How these immediate pharmacological actions relate to changes in mood is not fully established. One commonly cited puzzle is that the effect on neurotransmitter levels occurs within hours, whereas any improvement in depressive symptoms typically takes weeks; this gap has prompted alternative or supplementary models, including hypotheses centered on neuroplasticity.^[6] The mechanism of antidepressant action should therefore be regarded as an area of active investigation rather than a settled question.

The antidepressants are conventionally grouped by their primary mechanism. The monoamine oxidase inhibitors (MAOIs) include phenelzine, tranylcypromine, and isocarboxazid; the tricyclic antidepressants (TCAs) include amitriptyline, nortriptyline, imipramine, and clomipramine. The selective serotonin reuptake inhibitors (SSRIs) — fluoxetine, sertraline, paroxetine, citalopram, escitalopram, and fluvoxamine — and the serotonin–norepinephrine reuptake inhibitors (SNRIs) — venlafaxine, duloxetine, desvenlafaxine, and levomilnacipran — together account for most modern antidepressant prescribing. Further agents act through other mechanisms, including bupropion, mirtazapine, trazodone, vilazodone, vortioxetine, agomelatine, and the recently introduced rapid-acting agents esketamine and zuranolone. The list is not exhaustive.

Reported adverse effects vary considerably between classes, and figures in the literature are population estimates that differ between studies. MAOIs are associated with potentially serious interactions with certain foods and other medicines. TCAs are associated with risk in overdose. SSRIs and SNRIs are commonly associated with gastrointestinal effects, sexual dysfunction, and, on stopping, discontinuation symptoms. Regulators in several countries have required a warning regarding a reported increase in suicidal thoughts and behavior in children, adolescents, and young adults taking antidepressants.^[7] Individual response and tolerability are reported to vary considerably between people.