Category:Antidepressants - Revision history

MDElliottMD: Retrofit to canonical category structure: history-first lead, indexed members by class, Notes on scope and About these pages, plus three PMID-verified citations

2026-05-21T05:47:30Z

Retrofit to canonical category structure: history-first lead, indexed members by class, Notes on scope and About these pages, plus three PMID-verified citations

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MDElliottMD: Phase 2 retag: add Pharmaceutical root parent (taxonomy restructure 2026-05-20)

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Phase 2 retag: add Pharmaceutical root parent (taxonomy restructure 2026-05-20)

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			[[Category:Pharmaceutical]]

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	'''Antidepressants''' (a term whose accuracy is sometimes questioned — see [[#Terminology\|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 problem.<ref name="williams2022">Williams T, Phillips NJ, Stein DJ, Ipser JC (2022). Pharmacotherapy for post traumatic stress disorder (PTSD). ''Cochrane Database Syst Rev'' 3(3):CD002795. PMID 35234292.</ref>		'''Antidepressants''' (a term whose accuracy is sometimes questioned, see [[#Terminology\|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 problem.<ref name="williams2022">Williams T, Phillips NJ, Stein DJ, Ipser JC (2022). Pharmacotherapy for post traumatic stress disorder (PTSD). ''Cochrane Database Syst Rev'' 3(3):CD002795. PMID 35234292.</ref>

	== Origins ==		== Origins ==

	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).<ref name="lopezmunoz2009">López-Muñoz F, Alamo C (2009). Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. ''Curr Pharm Des'' 15(14):1563–86. PMID 19442174.</ref> 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).<ref name="lopezmunoz2009"/>		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).<ref name="lopezmunoz2009">López-Muñoz F, Alamo C (2009). Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. ''Curr Pharm Des'' 15(14):1563–86. PMID 19442174.</ref> 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).<ref name="lopezmunoz2009"/>

	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.<ref name="lopezmunoz2009"/>		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.<ref name="lopezmunoz2009"/>
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	== Terminology ==		== Terminology ==

	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.<ref name="moncrieff2023">Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA (2023). The serotonin theory of depression: a systematic umbrella review of the evidence. ''Mol Psychiatry'' 28(8):3243–56. PMID 35854107.</ref> Some authors have noted that the "chemical imbalance" phrase owed much to pharmaceutical marketing rather than to settled science.<ref name="lacasse2005">Lacasse JR, Leo J (2005). Serotonin and depression: a disconnect between the advertisements and the scientific literature. ''PLoS Med'' 2(12):e392. PMID 16268734.</ref>		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.<ref name="moncrieff2023">Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA (2023). The serotonin theory of depression: a systematic umbrella review of the evidence. ''Mol Psychiatry'' 28(8):3243–56. PMID 35854107.</ref> Some authors have noted that the "chemical imbalance" phrase owed much to pharmaceutical marketing rather than to settled science.<ref name="lacasse2005">Lacasse JR, Leo J (2005). Serotonin and depression: a disconnect between the advertisements and the scientific literature. ''PLoS Med'' 2(12):e392. PMID 16268734.</ref>

	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.		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.
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	== Mechanisms ==		== Mechanisms ==

	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.<ref name="liu2017">Liu B, Liu J, Wang M, Zhang Y, Li L (2017). From Serotonin to Neuroplasticity: Evolvement of Theories for Major Depressive Disorder. ''Front Cell Neurosci'' 11:305. PMID 29033793.</ref> The mechanism of antidepressant action should therefore be regarded as an area of active investigation rather than a settled question.		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.<ref name="liu2017">Liu B, Liu J, Wang M, Zhang Y, Li L (2017). From Serotonin to Neuroplasticity: Evolvement of Theories for Major Depressive Disorder. ''Front Cell Neurosci'' 11:305. PMID 29033793.</ref> The mechanism of antidepressant action should therefore be regarded as an area of active investigation rather than a settled question.

	== Members ==		== Members ==
	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.		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.

	== Safety ==		== Safety ==

MDElliottMD: Sweep: "indications" -> "problems" sitewide terminology update (preserves MedTemplate param name)

2026-05-19T01:37:46Z

Sweep: "indications" -> "problems" sitewide terminology update (preserves MedTemplate param name)

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	'''Antidepressants''' (a term whose accuracy is sometimes questioned — see [[#Terminology\|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~~.<ref name="williams2022">Williams T, Phillips NJ, Stein DJ, Ipser JC (2022). Pharmacotherapy for post traumatic stress disorder (PTSD). ''Cochrane Database Syst Rev'' 3(3):CD002795. PMID 35234292.</ref>		'''Antidepressants''' (a term whose accuracy is sometimes questioned — see [[#Terminology\|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 problem.<ref name="williams2022">Williams T, Phillips NJ, Stein DJ, Ipser JC (2022). Pharmacotherapy for post traumatic stress disorder (PTSD). ''Cochrane Database Syst Rev'' 3(3):CD002795. PMID 35234292.</ref>

	== Origins ==		== Origins ==

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2026-05-17T19:44:47Z

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	'''Antidepressants''' (a term whose accuracy is sometimes questioned — see [[#Terminology\|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.<ref name="williams2022">Williams T, Phillips NJ, Stein DJ, Ipser JC (2022). Pharmacotherapy for post traumatic stress disorder (PTSD). ''Cochrane Database Syst Rev'' 3(3):CD002795. PMID 35234292.</ref>		'''Antidepressants''' (a term whose accuracy is sometimes questioned — see [[#Terminology\|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.<ref name="williams2022">Williams T, Phillips NJ, Stein DJ, Ipser JC (2022). Pharmacotherapy for post traumatic stress disorder (PTSD). ''Cochrane Database Syst Rev'' 3(3):CD002795. PMID 35234292.</ref>

	== Origins ==		== Origins ==

	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).<ref name="lopezmunoz2009">López-Muñoz F, Alamo C (2009). Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. ''Curr Pharm Des'' 15(14):1563–86. PMID 19442174.</ref> 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).<ref name="lopezmunoz2009"/>		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).<ref name="lopezmunoz2009">López-Muñoz F, Alamo C (2009). Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. ''Curr Pharm Des'' 15(14):1563–86. PMID 19442174.</ref> 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).<ref name="lopezmunoz2009"/>

	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.<ref name="lopezmunoz2009"/>		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.<ref name="lopezmunoz2009"/>
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	== The SSRI era ==		== The SSRI era ==

	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.<ref name="wong2005">Wong DT, Perry KW, Bymaster FP (2005). Case history: the discovery of fluoxetine hydrochloride (Prozac). ''Nat Rev Drug Discov'' 4(9):764–74. PMID 16121130.</ref> 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.<ref name="wong2005"/>		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.<ref name="wong2005">Wong DT, Perry KW, Bymaster FP (2005). Case history: the discovery of fluoxetine hydrochloride (Prozac). ''Nat Rev Drug Discov'' 4(9):764–74. PMID 16121130.</ref> 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.<ref name="wong2005"/>

	== Terminology ==		== Terminology ==

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	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.<ref name="liu2017">Liu B, Liu J, Wang M, Zhang Y, Li L (2017). From Serotonin to Neuroplasticity: Evolvement of Theories for Major Depressive Disorder. ''Front Cell Neurosci'' 11:305. PMID 29033793.</ref> The mechanism of antidepressant action should therefore be regarded as an area of active investigation rather than a settled question.		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.<ref name="liu2017">Liu B, Liu J, Wang M, Zhang Y, Li L (2017). From Serotonin to Neuroplasticity: Evolvement of Theories for Major Depressive Disorder. ''Front Cell Neurosci'' 11:305. PMID 29033793.</ref> The mechanism of antidepressant action should therefore be regarded as an area of active investigation rather than a settled question.

			== Members ==
			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.

	== Safety ==		== Safety ==

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-'''Antidepressants''' include the mechanistic subclasses listed below.
+'''Antidepressants''' (a term whose accuracy is sometimes questioned — see [[#Terminology|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.<ref name="williams2022">Williams T, Phillips NJ, Stein DJ, Ipser JC (2022). Pharmacotherapy for post traumatic stress disorder (PTSD). ''Cochrane Database Syst Rev'' 3(3):CD002795. PMID 35234292.</ref>
 [[Category:MedCategory]]
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2026-05-15T16:07:19Z

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		'''Antidepressants''' include the mechanistic subclasses listed below.

		[[Category:MedCategory]]
		[[Category:Medicines]]

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	~~==SSRIs==~~
	~~[[Fluoxetine]]~~

	~~[[Sertraline]]~~
	~~==SNRIs==~~
	~~[[Duloxetine]]~~