Category:Antidepressants

The antidepressants are the medicines given to relieve depression, and the first of them were discovered by accident. In the mid-1950s, at the cantonal psychiatric clinic of Münsterlingen on the Swiss shore of Lake Constance, the psychiatrist Roland Kuhn was asked to test a compound known in the Geigy company's laboratories only as G 22355. It was a close chemical relative of chlorpromazine, the antipsychotic that had lately transformed psychiatry, and Geigy expected it too would calm psychosis. In Kuhn's psychotic patients it did little. His depressed patients were another matter: given the same medicine they began to lift, woke earlier, spoke more, and described the return of feeling. Kuhn reported the observation in 1957, and the medicine, imipramine, became the first of the tricyclic antidepressants.^[1][2]

The other founding antidepressant arrived by a similar accident, and at almost the same moment. Iproniazid had been developed to treat tuberculosis, and physicians in the tuberculosis sanatoria of the early 1950s noticed that their patients became not only less feverish but visibly elated. In 1957 a group led by the American psychiatrist Nathan Kline reported that iproniazid lifted depression in patients who had no tuberculosis at all, and called it a "psychic energizer." It became the first of the monoamine oxidase inhibitors, the MAOIs.^[2] Two classes of medicine, found within months of one another, neither of them sought: it was a pattern that would recur for decades.

The accidents were more than luck. Both founding medicines turned out to act on the monoamine neurotransmitters, serotonin, norepinephrine, and dopamine, and the finding that medicines altering these could lift mood gave psychiatry its first biological theory of depression. In 1965 the American psychiatrist Joseph Schildkraut set out the catecholamine hypothesis: that depression might reflect a deficiency of catecholamines, norepinephrine above all, at key sites in the brain.^[3] The hypothesis, soon broadened into a more general monoamine theory that gave serotonin equal weight, shaped the design of antidepressants for decades. Its most familiar product was the selective serotonin reuptake inhibitor: fluoxetine, developed at Eli Lilly and sold as Prozac, reached the United States market in early 1988 as the first SSRI sold there. The SSRIs were not built to outperform the medicines they replaced but to be cleaner, more selective in their chemistry, easier to tolerate, and far safer taken in overdose, and they made antidepressant prescribing ordinary.^[4]

The name carries a claim the science has not fully kept. "Antidepressant" describes a hoped-for effect, the lifting of depression, rather than an established mechanism, and the medicines gathered under the word are a pharmacologically mixed group whose workings are still not fully understood. The popular account, that depression is a "chemical imbalance" and most often a shortage of serotonin, has not held up: a 2022 umbrella review found no consistent evidence linking serotonin to depression,^[5] and earlier work had traced how much of the "chemical imbalance" language owed to pharmaceutical advertising rather than to settled science.^[6] Whether the medicines work, though, is a separate question from whether the serotonin story is true, and it is answered, as far as it can be, by trials: a 2018 network meta-analysis of 21 antidepressants found every one of them more effective than placebo for acute major depression, although the differences between medicines were modest.^[7] A puzzle still sits between the chemistry and the cure: reuptake is blocked within hours, while any improvement in mood takes weeks, a gap that has turned newer models toward neuroplasticity rather than neurotransmitter levels alone.^[8]

Antidepressant use now reaches far beyond depression. These medicines are used in the anxiety disorders, in obsessive-compulsive disorder, and in post-traumatic stress disorder, where the SSRIs sertraline and paroxetine hold specific regulatory approval,^[9] and several are used in chronic pain. They are not without hazard: in the United States the boxed warning carried on antidepressant labels states that these medicines can increase suicidal thoughts and behavior in children, adolescents, and young adults.^[10] This category collects the wiki's antidepressant pages and groups them, as the field itself does, by the mechanism each medicine is understood to use.

The antidepressants are grouped by their principal pharmacology. The two founding classes of the 1950s come first, then the reuptake inhibitors that account for most prescribing today, and last the agents that work by other routes.

• Monoamine oxidase inhibitors (MAOIs): the first class, raising monoamine levels by blocking the enzyme that breaks them down. phenelzine, tranylcypromine, isocarboxazid, and the reversible inhibitor moclobemide. Effective, but constrained by interactions with certain foods and medicines.
• Tricyclic antidepressants (TCAs): the other founding class. amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, doxepin, trimipramine, protriptyline, amoxapine, and the closely related tetracyclic maprotiline. Effective, but with anticholinergic effects and danger in overdose.
• Selective serotonin reuptake inhibitors (SSRIs): the most widely prescribed group. fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine.
• Serotonin–norepinephrine reuptake inhibitors (SNRIs): dual reuptake action; several are also used in chronic pain. venlafaxine, desvenlafaxine, duloxetine, levomilnacipran, milnacipran.
• Norepinephrine–dopamine reuptake inhibitors (NDRIs) and norepinephrine reuptake inhibitors (NRIs): reuptake inhibitors that spare serotonin. bupropion, an NDRI also used for smoking cessation; and the norepinephrine reuptake inhibitors reboxetine, viloxazine, and atomoxetine.
• Noradrenergic and specific serotonergic antidepressants (NaSSAs): they work by blocking receptors rather than blocking reuptake. mirtazapine.
• Serotonin antagonist and reuptake inhibitors (SARIs): trazodone, nefazodone.
• Multimodal serotonergic agents: they combine reuptake inhibition with direct actions at serotonin receptors. vortioxetine, vilazodone.
• Melatonergic agents: agomelatine.
• Atypical and rapid-acting agents: newer medicines that act outside the monoamine-reuptake model. They include the NMDA-receptor antagonists esketamine and dextromethadone and the dextromethorphan-bupropion combination Auvelity; the neuroactive steroids brexanolone and zuranolone, which act at GABA receptors; and the atypical agent tianeptine.

This category indexes the medicines that belong to a recognized antidepressant class or are regulatorily approved to treat depression, grouped by antidepressant mechanism. The boundary is pharmacological lineage rather than present-day use. Several medicines indexed here are now used as much for other conditions: atomoxetine and viloxazine are today mostly attention-deficit medicines, duloxetine, milnacipran, and the tricyclics are widely used in chronic pain, and many of the SSRIs and SNRIs are first-line for anxiety disorders. They are indexed here because their pharmacology is antidepressant-class, not because depression is their only use.

Some medicines treat depression without being antidepressants. Lithium and several antipsychotics are used in depressive illness, as augmentation or in bipolar disorder, but they belong to other classes and are indexed under Mood Stabilizers and Antipsychotics / Neuroleptics. The rapid-acting medicines esketamine, brexanolone, and zuranolone are indexed here as approved antidepressants even though they act outside the monoamine-reuptake model on which the older classes were built. Following the wiki's multi-membership convention, a medicine may be indexed in more than one category where its pharmacology or its uses warrant.

Each medicine indexed here has its own page, built on the wiki's standard structure for a medicine: a history-first account, then pharmacology, indications, adverse effects, and interactions. The sub-class categories named in the index above collect the members of each pharmacological group.

This is one of the wiki's MedCategory class-overview pages. It carries the MedCategory and MedCategoryFull marker tags; the second suppresses the member list that MediaWiki would otherwise generate automatically, so that the curated index above is the only one the reader sees. The category sits beneath Medicines and beneath Pharmaceutical, the origin category for medicines that came into use through scientific discovery rather than traditional practice. The antidepressants, found in the clinic and refined in the laboratory, are pharmaceutical-origin medicines in full.