text:
Selective serotonin reuptake inhibitor
From Wikipedia, the free encyclopedia
Jump to: navigation, search
"SSRI" redirects here. For other uses, see SSRI (disambiguation).
Selective serotonin reuptake inhibitor
Drug class
Serotonin, the target of SSRIs.
Class identifiers
Use
Major depressive disorder, anxiety disorders
ATC code
N06AB
Biological target
Serotonin transporter
Clinical data
Drugs.com
Drug Classes
Consumer Reports
Best Buy Drugs
External links
MeSH
D017367
In Wikidata
Selective serotonin reuptake inhibitors (SSRIs), also known as serotonin-specific reuptake inhibitors or serotonergic antidepressants,[1] are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder and anxiety disorders.
The exact mechanism of action of SSRIs is unknown.[2] SSRIs are believed to increase the extracellular level of the neurotransmitter serotonin by limiting its reabsorption into the presynaptic cell, increasing the level of serotonin in the synaptic cleft available to bind to the postsynaptic receptor. They have varying degrees of selectivity for the other monoamine transporters, with pure SSRIs having only weak affinity for the norepinephrine and dopamine transporters.
SSRIs are the most widely prescribed antidepressants in many countries.[3] The efficacy of SSRIs in mild or moderate cases of depression has been disputed,[4][5][6] and may be outweighed by side effects.[7]
Contents
[hide]
1 Medical uses
1.1 Depression
1.2 Generalized anxiety disorder
1.3 Obsessive–compulsive disorder
1.4 Eating disorders
1.5 Stroke recovery
1.6 Premature ejaculation
2 Adverse effects
2.1 Sexual dysfunction
2.2 Cardiac
2.3 Bleeding
2.4 Fracture risk
2.5 Discontinuation syndrome
2.6 Suicide risk
2.6.1 Children and adolescents
2.6.2 Adults
2.7 Pregnancy and breastfeeding
2.8 Neonatal abstinence syndrome
2.8.1 Persistent pulmonary hypertension
2.8.2 Neuropsychiatric effects in offspring
2.9 Overdose
3 Contraindications and drug interactions
4 List of SSRIs
4.1 Marketed
4.1.1 Antidepressants
4.1.2 Others
4.2 Discontinued
4.2.1 Antidepressants
4.3 Never marketed
4.3.1 Antidepressants
4.4 Related drugs
5 Mechanism of action
5.1 Serotonin reuptake inhibition
5.2 Sigma receptor ligands
5.3 Anti-inflammatory effects
5.4 Pharmacogenetics
5.5 Versus TCAs
6 Society and culture
6.1 Controversy
7 See also
8 References
9 External links
Medical uses[edit]
The main indication for SSRIs is major depressive disorder (also called "major depression", "clinical depression" and often simply "depression"). SSRIs are frequently prescribed for anxiety disorders, such as social anxiety disorder, panic disorders, obsessive–compulsive disorder (OCD), eating disorders, chronic pain and occasionally, for posttraumatic stress disorder (PTSD). They are also frequently used to treat depersonalization disorder, although generally with poor results.[8]
Depression[edit]
Antidepressants are recommended by the National Institute for Health and Care Excellence (NICE) as a first-line treatment of severe depression and for the treatment of mild-to-moderate depression that persists after conservative measures such as cognitive therapy.[9] They recommend against their routine use in those who have chronic health problems and mild depression.[9]
There has been controversy regarding the efficacy of antidepressants in treating depression depending on its severity and duration.
Two meta-analyses published in 2008 (Kirsch) and 2010 (Fournier) found that in mild and moderate depression, the effect of SSRIs is small or none compared to placebo, while in very severe depression the effect of SSRIs is between "relatively small" and "substantial".[4][10] The 2008 meta-analysis combined 35 clinical trials submitted to the Food and Drug Administration (FDA) before licensing of four newer antidepressants (including the SSRIs paroxetine and fluoxetine, the non-SSRI antidepressant nefazodone, and the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine). The authors attributed the relationship between severity and efficacy to a reduction of the placebo effect in severely depressed patients, rather than an increase in the effect of the medication.[10] Some researchers have questioned the statistical basis of this study suggesting that it underestimates the effect size of antidepressants.[11][12]
A 2010 comprehensive review conducted by NICE concluded that antidepressants have no advantage over placebo in the treatment of short-term mild depression, but that the available evidence supported the use of antidepressants in the treatment of dysthymia and other forms of chronic mild depression.[13]
A 2012 meta-analysis of fluoxetine and venlafaxine concluded that statistically and clinically significant treatment effects were observed for each drug relative to placebo irrespective of baseline depression severity.[14]
In 2014 the U.S. FDA published a systematic review of all antidepressant maintenance trials submitted to the agency between 1985 and 2012. The authors concluded that maintenance treatment reduced the risk of relapse by 52% compared to placebo, and that this effect was primarily due to recurrent depression in the placebo group rather than a drug withdrawal effect.[15]
A 2017 systematic review stated that "SSRIs versus placebo seem to have statistically significant effects on depressive symptoms, but the clinical significance of these effects seems questionable and all trials were at high risk of bias. Furthermore, SSRIs versus placebo significantly increase the risk of both serious and non-serious adverse events. Our results show that the harmful effects of SSRIs versus placebo for major depressive disorder seem to outweigh any potentially small beneficial effects".[7]
There does not appear to be a big difference in the effectiveness between medications in the second generation antidepressants (SSRIs and SNRIs).[16]
In children there are concerns around the quality of the evidence on the meaningfulness of benefits seen.[17] If a medication is used, fluoxetine appears to be first line.[17]
Generalized anxiety disorder[edit]
SSRIs are recommended by the National Institute for Health and Care Excellence (NICE) for the treatment of generalized anxiety disorder (GAD) that has failed to respond to conservative measures such as education and self-help activities. GAD is a common disorder of which the central feature is excessive worry about a number of different events. Key symptoms include excessive anxiety about multiple events and issues, and difficulty controlling worrisome thoughts that persists for at least 6 months.
Antidepressants provide a modest-to-moderate reduction in anxiety in GAD,[18] and are superior to placebo in treating GAD.[19] The efficacy of different antidepressants is similar.[18][19]
Obsessive–compulsive disorder[edit]
SSRIs are a second line treatment of adult obsessive–compulsive disorder (OCD) with mild functional impairment and as first line treatment for those with moderate or severe impairment. In children, SSRIs can be considered a second line therapy in those with moderate-to-severe impairment, with close monitoring for psychiatric adverse effects.[20] SSRIs are efficacious in the treatment of OCD; patients treated with SSRIs are about twice as likely to respond to treatment as those treated with placebo.[21][22] Efficacy has been demonstrated both in short-term treatment trials of 6 to 24 weeks and in discontinuation trials of 28 to 52 weeks duration.[23][24][25]
Eating disorders[edit]
Anti-depressants are recommended as an alternative or additional first step to self-help programs in the treatment of bulimia nervosa.[26] SSRIs (fluoxetine in particular) are preferred over other anti-depressants due to their acceptability, tolerability, and superior reduction of symptoms in short-term trials. Long-term efficacy remains poorly characterized.
Similar recommendations apply to binge eating disorder.[26] SSRIs provide short-term reductions in binge eating behavior, but have not been associated with significant weight loss.[27]
Clinical trials have generated mostly negative results for the use of SSRIs in the treatment of anorexia nervosa.[28] Treatment guidelines from the National Institute of Health and Clinical Excellence[26] recommend against the use of SSRIs in this disorder. Those from the American Psychiatric Association note that SSRIs confer no advantage regarding weight gain, but that they may be used for the treatment of co-existing depressive, anxiety, or OCD.[27]
Stroke recovery[edit]
SSRIs have been used in the treatment of stroke patients, including those with and without symptoms of depression. A recent meta-analysis of randomized, controlled clinical trials found a statistically significant effect of SSRIs on dependence, neurological deficit, depression, and anxiety. There was no statistically significant effect on death, motor deficits, or cognition.[29]
Premature ejaculation[edit]
SSRIs are effective for the treatment of premature ejaculation. Chronic administration is more efficacious than on demand use.[30]
Adverse effects[edit]
Side effects vary among the individual drugs of this class. However, certain types of adverse effects are found broadly among most if not all members of this class:
increased risk of bone fractures by 1.7 fold[31]
akathisia[32][33][34][35]
suicidal ideation (thoughts of suicide) (see below)
photosensitivity[36]
Sexual dysfunction[edit]
SSRIs can cause various types of sexual dysfunction such as anorgasmia, erectile dysfunction, diminished libido, genital numbness, and sexual anhedonia (pleasureless orgasm).[37] Sexual problems are common with SSRIs.[38] Poor sexual function is also one of the most common reasons people stop the medication.[39]
Occasionally symptoms of sexual dysfunction may persist after discontinuation of SSRIs.[37][40][41][42]
The mechanism by which SSRIs may cause sexual side effects is not well understood as of 2015. The range of possible mechanisms includes (1) nonspecific neurological effects (e.g., sedation) that globally impair behavior including sexual function; (2) specific effects on brain systems mediating sexual function; (3) specific effects on peripheral tissues and organs, such as the penis, that mediate sexual function; and (4) direct or indirect effects on hormones mediating sexual function.[43] Management strategies include: for erectile dysfunction the addition of a PDE5 inhibitor such as sildenafil; for decreased libido, possibly adding or switching to bupropion; and for overall sexual dysfunction, switching to nefazodone.[44]
A number of (non-SSRI) drugs are not associated with sexual side effects (such as bupropion, mirtazapine, tianeptine, agomelatine and moclobemide.[45][46])
Several small studies have suggested that SSRIs may adversely affect semen quality.[47]
Cardiac[edit]
SSRIs do not appear to affect the risk of coronary heart disease (CHD) in those without a previous diagnosis of CHD.[48] A large cohort study suggested no substantial increase in the risk of cardiac malformations attributable to SSRI usage during the first trimester of pregnancy.[49] A number of large studies of people without known pre-existing heart disease have reported no EKG changes related to SSRI use.[50] The recommended maximum daily dose of citalopram and escitalopram was reduced due to concerns with QT interval prolongation.[51][52][53] In overdose, fluoxetine has been reported to cause sinus tachycardia, myocardial infarction, junctional rhythms and trigeminy. Some authors have suggested electrocardiographic monitoring in patients with severe pre-existing cardiovascular disease who are taking SSRIs.[54]
Bleeding[edit]
SSRIs interact with anticoagulants, like warfarin and aspirin.[55][56][57][58] This includes an increased risk of GI bleeding, and post operative bleeding.[55] The relative risk of intracranial bleeding is increased, but the absolute risk is very low.[59] SSRIs are known to cause platelet dysfunction.[60][61] This risk is greater in those who are also on anticoagulants, antiplatelet agents and NSAIDs (nonsteroidal anti-inflammatory drugs), as well as with the co-existence of underlying diseases such as cirrhosis of the liver or liver failure.[62][63]
Fracture risk[edit]
Evidence from longitudinal, cross-sectional, and prospective cohort studies suggests an association between SSRI usage at therapeutic doses and a decrease in bone mineral density, as well as increased fracture risk,[64][65][66][67] a relationship that appears to persist even with adjuvant bisphosphonate therapy.[68] However, because the relationship between SSRIs and fractures is based on observational data as opposed to prospective trials, the phenomenon is not definitively causal.[69] There also appears to be an increase in fracture-inducing falls with SSRI use, suggesting the need for increased attention to fall risk in elderly patients using the medication.[69] The loss of bone density does not appear to occur in younger patients taking SSRIs.[70]
Discontinuation syndrome[edit]
Main article: SSRI discontinuation syndrome
Serotonin reuptake inhibitors should not be abruptly discontinued after extended therapy, and whenever possible, should be tapered over several weeks to minimize discontinuation-related symptoms which may include nausea, headache, dizziness, chills, body aches, paresthesias, insomnia, and electric shock-like sensations. Paroxetine may produce discontinuation-related symptoms at a greater rate than other SSRIs, though qualitatively similar effects have been reported for all SSRIs.[71][72] Discontinuation effects appear to be less for fluoxetine, perhaps owing to its long half-life and the natural tapering effect associated with its slow clearance from the body. One strategy for minimizing SSRI discontinuation symptoms is to switch the patient to fluoxetine and then taper and discontinue the fluoxetine.[71]
Suicide risk[edit]
Children and adolescents[edit]
Meta analyses of short duration randomized clinical trials have found that SSRI use is related to a higher risk of suicidal behavior in children and adolescents.[73][74][75] For instance, a 2004 U.S. Food and Drug Administration (FDA) analysis of clinical trials on children with major depressive disorder found statistically significant increases of the risks of "possible suicidal ideation and suicidal behavior" by about 80%, and of agitation and hostility by about 130%.[76] According to the FDA, the heightened risk of suicidality is within the first one to two months of treatment.[77][78][79] The National Institute for Health and Care Excellence (NICE) places the excess risk in the "early stages of treatment".[80] The European Psychiatric Association places the excess risk in the first two weeks of treatment and, based on a combination of epidemiological, prospective cohort, medical claims, and randomized clinical trial data, concludes that a protective effect dominates after this early period. A 2014 Cochrane review found that at six to nine months, suicidal ideation remained higher in children treated with antidepressants compared to those treated with psychological therapy.[79]
A recent comparison of aggression and hostility occurring during treatment with fluoxetine to placebo in children and adolescents found that no significant difference between the fluoxetine group and a placebo group.[81] There is also evidence that higher rates of SSRI prescriptions are associated with lower rates of suicide in children, though since the evidence is correlational, the true nature of the relationship is unclear.[82]
In 2004, the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom judged fluoxetine (Prozac) to be the only antidepressant that offered a favorable risk-benefit ratio in children with depression, though it was also associated with a slight increase in the risk of self-harm and suicidal ideation.[83] Only two SSRIs are licensed for use with children in the UK, sertraline (Zoloft) and fluvoxamine (Luvox), and only for the treatment of obsessive–compulsive disorder. Fluoxetine is not licensed for this use.[84]
Adults[edit]
It is unclear whether SSRIs affect the risk of suicidal behavior in adults.
A 2005 meta-analysis of drug company data found no evidence that SSRIs increased the risk of suicide; however, important protective or hazardous effects could not be excluded.[85]
A 2005 review observed that suicide attempts are increased in those who use SSRIs as compared to placebo and compared to therapeutic interventions other than tricyclic antidepressants. No difference risk of suicide attempts was detected between SSRIs versus tricyclic antidepressants.[86]
On the other hand, a 2006 review suggests that the widespread use of antidepressants in the new "SSRI-era" appears to have led to a highly significant decline in suicide rates in most countries with traditionally high baseline suicide rates. The decline is particularly striking for women who, compared with men, seek more help for depression. Recent clinical data on large samples in the US too have revealed a protective effect of antidepressant against suicide.[87]
A 2006 meta-analysis of random controlled trials suggests that SSRIs increase suicide ideation compared with placebo. However, the observational studies suggest that SSRIs did not increase suicide risk more than older antidepressants. The researchers stated that if SSRIs increase suicide risk in some patients, the number of additional deaths is very small because ecological studies have generally found that suicide mortality has declined (or at least not increased) as SSRI use has increased.[88]
An additional meta-analysis by the FDA in 2006 found an age-related effect of SSRI's. Among adults younger than 25 years, results indicated that there was a higher risk for suicidal behavior. For adults between 25 and 64, the effect appears neutral on suicidal behavior but possibly protective for suicidal behavior for adults between the ages of 25 and 64. For adults older than 64, SSRI's seem to reduce the risk of both suicidal behavior.[73]
Pregnancy and breastfeeding[edit]
SSRI use in pregnancy has been associated with a variety of risks with varying degrees of proof of causation. As depression is independently associated with negative pregnancy outcomes, determining the extent to which observed associations between antidepressant use and specific adverse outcomes reflects a causative relationship has been difficult in some cases.[89] In other cases, the attribution of adverse outcomes to antidepressant exposure seems fairly clear.
SSRI use in pregnancy is associated with an increased risk of spontaneous abortion of about 1.7-fold.[90][91] Use is also associated preterm birth.[92]
A systematic review of the risk of major birth defects in antidepressant-exposed pregnancies found a small increase (3% to 24%) in the risk of major malformations and a risk of cardiovascular birth defects that did not differ from non-exposed pregnancies.[93] A study of fluoxetine-exposed pregnancies found a 12% increase in the risk of major malformations that just missed statistical significance.[94] Other studies have found an increased risk of cardiovascular birth defects among depressed mothers not undergoing SSRI treatment, suggesting the possibility of ascertainment bias, e.g. that worried mothers may pursue more aggressive testing of their infants.[95] Another study found no increase in cardiovascular birth defects and a 27% increased risk of major malformations in SSRI exposed pregnancies.[91]
The FDA issued a statement on July 19, 2006 stating nursing mothers on SSRIs must discuss treatment with their physicians. However, the medical literature on the safety of SSRIs has determined that some SSRIs like Sertraline and Paroxetine are considered safe for breastfeeding.[96][97][98]
Neonatal abstinence syndrome[edit]
Several studies have documented neonatal abstinence syndrome, a syndrome of neurological, gastrointestinal, autonomic, endocrine and/or respiratory symptoms among a large minority of infants with intrauterine exposure. These syndromes are short-lived, but insufficient long-term data is available to determine whether there are long-term effects.[99][100]
Persistent pulmonary hypertension[edit]
Persistent pulmonary hypertension (PPHN) is a serious and life-threatening, but very rare, lung condition that occurs soon after birth of the newborn. Newborn babies with PPHN have high pressure in their lung blood vessels and are not able to get enough oxygen into their bloodstream. About 1 to 2 babies per 1000 babies born in the U.S. develop PPHN shortly after birth, and often they need intensive medical care. It is associated with about a 25% risk of significant long-term neurological deficits.[101] A 2014 meta analysis found no increased risk of persistent pulmonary hypertension associated with exposure to SSRI's in early pregnancy and a slight increase in risk associates with exposure late in pregnancy; "an estimated 286 to 351 women would need to be treated with an SSRI in late pregnancy to result in an average of one additional case of persistent pulmonary hypertension of the newborn.".[102] A review published in 2012 reached conclusions very similar to those of the 2014 study.[103]
Neuropsychiatric effects in offspring[edit]
According to a 2015 review available data found that "some signal exists suggesting that antenatal exposure to SSRIs may increase the risk of ASDs (autism spectrum disorders)"[104] even though a large cohort study published in 2013[105] and a cohort study using data from Finland's national register between the years 1996 and 2010 and published in 2016 found no significant association between SSRI use and autism in offspring.[106] The 2016 Finland study also found no association with ADHD, but did find an association with increased rates of depression diagnoses in early adolescence.[106]
Overdose[edit]
See also: Serotonin syndrome
SSRIs appear safer in overdose when compared with traditional antidepressants, such as the tricyclic antidepressants. This relative safety is supported both by case series and studies of deaths per numbers of prescriptions.[107] However, case reports of SSRI poisoning have indicated that severe toxicity can occur[108] and deaths have been reported following massive single ingestions,[109] although this is exceedingly uncommon when compared to the tricyclic antidepressants.[107]
Because of the wide therapeutic index of the SSRIs, most patients will have mild or no symptoms following moderate overdoses. The most commonly reported severe effect following SSRI overdose is serotonin syndrome; serotonin toxicity is usually associated with very high overdoses or multiple drug ingestion.[110] Other reported significant effects include coma, seizures, and cardiac toxicity.[107]
The SSRIs, in decreasing toxicity in overdose, can be listed as follows: > citalopram (due to the potential for QT interval prolongation) > fluvoxamine > escitalopram > paroxetine > sertraline > fluoxetine.[111]
Contraindications and drug interactions[edit]
The following drugs may precipitate serotonin syndrome in people on SSRIs:[112][113]
Linezolid
Monoamine oxidase inhibitors (MAOIs) including moclobemide, phenelzine, tranylcypromine, selegiline and methylene blue
Lithium
Sibutramine
MDMA (ecstasy)
Dextromethorphan
Tramadol
Pethidine/meperidine
St. John's wort
Yohimbe
Tricyclic antidepressants (TCAs)
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Buspirone
Triptan
Mirtazapine
Painkillers of the NSAIDs drug family may interfere and reduce efficiency of SSRIs and may compound the increased risk of gastrointestinal bleeds caused by SSRI use.[56][58][114] NSAIDs include:
Aspirin
Ibuprofen (Advil, Nurofen)
Naproxen (Aleve)
There are a number of potential pharmacokinetic interactions between the various individual SSRIs and other medications. Most of these arise from the fact that every SSRI has the ability to inhibit certain P450 cytochromes.[115][116]
Drug Name
CYP1A2
CYP2C9
CYP2C19
CYP2D6
CYP3A4
CYP2B6
Citalopram + 0 0 + 0 0
Escitalopram 0 0 0 + 0 0
Fluoxetine + ++ +/++ +++ + +
Fluvoxamine +++ ++ +++ + + +
Paroxetine + + + +++ + +++
Sertraline + + +/++ + + +
Legend:
0 — no inhibition.
+ — mild inhibition.
++ — moderate inhibition.
+++ — strong inhibition.
List of SSRIs[edit]
Marketed[edit]
Antidepressants[edit]
Citalopram (Celexa)
Escitalopram (Lexapro)
Fluoxetine (Prozac)
Fluvoxamine (Luvox)
Paroxetine (Paxil)
Sertraline (Zoloft)
[show]
Structures
Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine Sertraline
Others[edit]
Dapoxetine (Priligy)
[show]
Structures
Dapoxetine
Discontinued[edit]
Antidepressants[edit]
Indalpine (Upstène)
Zimelidine (Zelmid)
[show]
Structures
Indalpine Zimelidine
Never marketed[edit]
Antidepressants[edit]
Alaproclate (GEA-654)
Centpropazine
Cericlamine (JO-1017)
Femoxetine (Malexil; FG-4963)
Ifoxetine (CGP-15210)
Omiloxetine
Panuramine (WY-26002)
Pirandamine (AY-23713)
Seproxetine ((S)-norfluoxetine)
[show]
Structures
Alaproclate Cericlamine Femoxetine Ifoxetine Omiloxetine Panuramine Pirandamine Seproxetine
Related drugs[edit]
Although described as SNRIs, duloxetine (Cymbalta), venlafaxine (Effexor), and desvenlafaxine (Pristiq) are in fact relatively selective as serotonin reuptake inhibitors (SRIs).[117] They are about at least 10-fold selective for inhibition of serotonin reuptake over norepinephrine reuptake.[117] The selectivity ratios are approximately 1:30 for venlafaxine, 1:9 for duloxetine, and 1:14 for desvenlafaxine.[117] At low doses, these SNRIs act mostly as SSRIs; only at higher doses do they also prominently inhibit norepinephrine reuptake.[118][119] Milnacipran (Ixel, Savella) and its stereoisomer levomilnacipran (Fetzima) are the only widely marketed SNRIs that inhibit serotonin and norepinephrine to similar degrees, both with ratios close to 1:1.[117][120]
Vilazodone (Viibryd) and vortioxetine (Trintellix) are SRIs that also act as modulators of serotonin receptors and are described as serotonin modulators and stimulators (SMS).[121] Vilazodone is a 5-HT1A receptor partial agonist while vortioxetine is a 5-HT1A receptor agonist and 5-HT3 and 5-HT7 receptor antagonist.[121] Litoxetine (SL 81-0385) and lubazodone (YM-992, YM-35995) are similar drugs that were never marketed.[122][123][124][125] They are SRIs and litoxetine is also a 5-HT3 receptor antagonist[122][123] while lubazodone is also a 5-HT2A receptor antagonist.[124][125]
Chlorphenamine (Chlor-Trimeton) is an over-the-counter antihistamine that also acts as a potent and selective SRI (KD = 15.2 nM).[126][127] It has been suggested for potential use as an over-the-counter antidepressant.[127] The now-withdrawn SSRI zimelidine was derived from chlorphenamine.[127]
Mechanism of action[edit]
Serotonin reuptake inhibition[edit]
In the brain, messages are passed from a nerve cell to another via a chemical synapse, a small gap between the cells. The presynaptic cell that sends the information releases neurotransmitters including serotonin into that gap. The neurotransmitters are then recognized by receptors on the surface of the recipient postsynaptic cell, which upon this stimulation, in turn, relays the signal. About 10% of the neurotransmitters are lost in this process; the other 90% are released from the receptors and taken up again by monoamine transporters into the sending presynaptic cell, a process called reuptake.
SSRIs inhibit the reuptake of serotonin. As a result, the serotonin stays in the synaptic gap longer than it normally would, and may repeatedly stimulate the receptors of the recipient cell. In the short run, this leads to an increase in signaling across synapses in which serotonin serves as the primary neurotransmitter. On chronic dosing, the increased occupancy of post-synaptic serotonin receptors signals the pre-synaptic neuron to synthesize and release less serotonin. Serotonin levels within the synapse drop, then rise again, ultimately leading to downregulation of post-synaptic serotonin receptors.[128] Other, indirect effects may include increased norepinephrine output, increased neuronal cyclic AMP levels, and increased levels of regulatory factors such as BDNF and CREB.[129] Owing to the lack of a widely accepted comprehensive theory of the biology of mood disorders, there is no widely accepted theory of how these changes lead to the mood-elevating and anti-anxiety effects of SSRIs.[citation needed]
Sigma receptor ligands[edit]
SSRIs at the human SERT and rat sigma receptors[130][131][126]
Medication
SERT
σ1
σ2
σ1 / SERT
Citalopram 1.16 292–404 Agonist 5,410 252–348
Escitalopram 2.5 288 Agonist ND ND
Fluoxetine 0.81 191–240 Agonist 16,100 296–365
Fluvoxamine 2.2 17–36 Agonist 8,439 7.7–16.4
Paroxetine 0.13 ≥1,893 ND 22,870 ≥14,562
Sertraline 0.29 32–57 Antagonist 5,297 110–197
Values are Ki (nM). The smaller the value, the more strongly the
drug binds to the site.
In addition to their actions as reuptake inhibitors of serotonin, some SSRIs are also, coincidentally, ligands of the sigma receptors.[130][131] Fluvoxamine is an agonist of the σ1 receptor, while sertraline is an antagonist of the σ1 receptor, and paroxetine does not significantly interact with the σ1 receptor.[130][131] None of the SSRIs have significant affinity for the σ2 receptor, and the SNRIs, unlike the SSRIs, do not interact with either of the sigma receptors.[130][131] Fluvoxamine has by far the strongest activity of the SSRIs at the σ1 receptor.[130][131] High occupancy of the σ1 receptor by clinical dosages of fluvoxamine has been observed in the human brain in positron emission tomography (PET) research.[130][131] It is thought that agonism of the σ1 receptor by fluvoxamine may have beneficial effects on cognition.[130][131] In contrast to fluvoxamine, the relevance of the σ1 receptor in the actions of the other SSRIs is uncertain and questionable due to their very low affinity for the receptor relative to the SERT.[citation needed]
Anti-inflammatory effects[edit]
The role of inflammation and the immune system in depression has been extensively studied. The evidence supporting this link has been showed in numerous studies over the past ten years. Nationwide studies and meta-analyses of smaller cohort studies have uncovered a correlation between pre-existing inflammatory conditions such as type 1 diabetes, rheumatoid arthritis (RA), or hepatitis, and an increased risk of depression. Data also shows that using pro-inflammatory agents in the treatment of diseases like melanoma can lead to depression. Several meta-analytical studies have found increased levels of proinflammatory cytokines and chemokines in depressed patients.[132] This link has led scientists to investigate the effects of antidepressants on the immune system.
SSRIs were originally invented with the goal of increasing levels of available serotonin in the extracellular spaces. However, the delayed response between when patients first begin SSRI treatment to when they see effects has led scientists to believe that other molecules are involved in the efficacy of these drugs.[133] To investigate the apparent anti-inflammatory effects of SSRIs, both Kohler et al. and Więdłocha et al. conducted meta-analyses which have shown that after antidepressant treatment the levels of cytokines associated with inflammation are decreased.[134][135] A large cohort study conducted by researchers in the Netherlands investigated the association between depressive disorders, symptoms, and antidepressants with inflammation. The study showed decreased levels of interleukin (IL)-6, a cytokine that has proinflammatory effects, in patients taking SSRIs compared to non-medicated patients.[136]
Treatment with SSRIs has shown reduced production of inflammatory cytokines such as IL-1β, tumor necrosis factor (TNF)-α, IL-6, and interferon (IFN)-γ, which leads to a decrease in inflammation levels and subsequently a decrease in the activation level of the immune response.[137] These inflammatory cytokines have been shown to activate microglia which are specialized macrophages that reside in the brain. Macrophages are a subset of immune cells responsible for host defense in the innate immune system. Macrophages can release cytokines and other chemicals to cause an inflammatory response. Peripheral inflammation can induce an inflammatory response in microglia and can cause neuroinflammation. SSRIs inhibit proinflammatory cytokine production which leads to less activation of microglia and peripheral macrophages. SSRIs not only inhibit the production of these proinflammatory cytokines, they also have been shown to upregulate anti-inflammatory cytokines such as IL-10. Taken together, this reduces the overall inflammatory immune response.[137][138]
In addition to affecting cytokine production, there is evidence that treatment with SSRIs has effects on the proliferation and viability of immune system cells involved in both innate and adaptive immunity. Evidence shows that SSRIs can inhibit proliferation in T-cells, which are important cells for adaptive immunity and can induce inflammation. SSRIs can also induce apoptosis, programmed cell death, in T-cells. The full mechanism of action for the anti-inflammatory effects of SSRIs is not fully known. However, there is evidence for various pathways to have a hand in the mechanism. One such possible mechanism is the increased levels of cyclic adenosine monophosphate (cAMP) as a result of interference with activation of protein kinase A (PKA), a cAMP dependent protein. Other possible pathways include interference with calcium ion channels, or inducing cell death pathways like MAPK.[139]
The anti-inflammatory effects of SSRIs have prompted studies of the efficacy of SSRIs in the treatment of autoimmune diseases such as multiple sclerosis, RA, inflammatory bowel diseases, and septic shock. These studies have been performed in animal models but have shown consistent immune regulatory effects. Fluoxetine, an SSRI, has also shown efficacy in animal models of graft vs. host disease.[139] SSRIs have also been used successfully as pain relievers in patients undergoing oncology treatment. The effectiveness of this has been hypothesized to be at least in part due to the anti-inflammatory effects of SSRIs.[138]
Pharmacogenetics[edit]
Further information: Pharmacogenetics
Large bodies of research are devoted to using genetic markers to predict whether patients will respond to SSRIs or have side effects that will cause their discontinuation, although these tests are not yet ready for widespread clinical use.[140]
Versus TCAs[edit]
SSRIs are described as 'selective' because they affect only the reuptake pumps responsible for serotonin, as opposed to earlier antidepressants, which affect other monoamine neurotransmitters as well, and as a result, SSRIs have fewer side effects.
There appears to be no significant difference in effectiveness between SSRIs and tricyclic antidepressants, which were the most commonly used class of antidepressants before the development of SSRIs.[141] However, SSRIs have the important advantage that their toxic dose is high, and, therefore, they are much more difficult to use as a means to commit suicide. Further, they have fewer and milder side effects. Tricyclic antidepressants also have a higher risk of serious cardiovascular side effects, which SSRIs lack.
SSRIs act on signal pathways such as cAMP (Cyclic AMP) on the postsynaptic neuronal cell, which leads to the release of Brain-Derived Neurotrophic Factor (BDNF). BDNF enhances the growth and survival of cortical neurons and synapses.[129]
Society and culture[edit]
Controversy[edit]
See also: Biopsychiatry controversy and Biological psychiatry
A study examining publication of results from FDA-evaluated antidepressants concluded that those with favorable results were much more likely to be published than those with negative results.[142]
David Healy has argued that warning signs were available for many years prior to regulatory authorities moving to put warnings on antidepressant labels that they might cause suicidal thoughts.[143] At the time these warnings were added, others argued that the evidence for harm remained unpersuasive[144][145] and others continued to do so after the warnings were added.[146][147]
See also[edit]
Development and discovery of SSRI drugs
Dopamine reuptake inhibitor (DRI)
Noradrenergic and specific serotonergic antidepressant (NaSSA)
Norepinephrine-dopamine reuptake inhibitor (NDRI)
Norepinephrine reuptake inhibitor (NRI)
Serotonin antagonist and reuptake inhibitor
Serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI)
Serotonin-norepinephrine reuptake inhibitor (SNRI)
Serotonin releasing agent (SRA)
Serotonin reuptake inhibitor (SRI)
Trace amine-associated receptor 1 (TAAR1)
References[edit]
Jump up ^ Barlow, David H. Durand, V. Mark (2009). "Chapter 7: Mood Disorders and Suicide". Abnormal Psychology: An Integrative Approach (Fifth ed.). Belmont, CA: Wadsworth Cengage Learning. p. 239. ISBN 0-495-09556-7. OCLC 192055408. CS1 maint: Multiple names: authors list (link)
Jump up ^ http://pi.lilly.com/us/prozac.pdf page 20
Jump up ^ Preskorn SH, Ross R, Stanga CY (2004). "Selective Serotonin Reuptake Inhibitors". In Sheldon H. Preskorn, Hohn P. Feighner, Christina Y. Stanga, Ruth Ross. Antidepressants: Past, Present and Future. Berlin: Springer. pp. 241–62. ISBN 978-3-540-43054-4.
^ Jump up to: a b Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, Fawcett J (January 2010). "Antidepressant Drug Effects and Depression Severity". JAMA. 303 (1): 47–53. PMC 3712503  . PMID 20051569. doi:10.1001/jama.2009.1943.
Jump up ^ Kramer, Peter (7 Sep 2011). "In Defense of Antidepressants". The New York Times. Retrieved 13 July 2011.
Jump up ^ Pies R (April 2010). "Antidepressants Work, Sort of-Our System of Care Does Not". Journal of Clinical Psychopharmacology. 30 (2): 101–4. PMID 20520282. doi:10.1097/JCP.0b013e3181d52dea.
^ Jump up to: a b Jakobsen, Janus Christian; Katakam, Kiran Kumar; Schou, Anne; Hellmuth, Signe Gade; Stallknecht, Sandra Elkjær; Leth-Møller, Katja; Iversen, Maria; Banke, Marianne Bjørnø; Petersen, Iggiannguaq Juhl (2017-02-08). "Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis". BMC Psychiatry. 17. ISSN 1471-244X. PMC 5299662  . PMID 28178949. doi:10.1186/s12888-016-1173-2.
Jump up ^ Medford, Nick. "Understanding and treating depersonalization disorder". Advances in Psychiatric Treatment (2005). Retrieved 2011-11-11.
^ Jump up to: a b "www.nice.org.uk" (PDF). Archived from the original (PDF) on September 28, 2013.
^ Jump up to: a b Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT (February 2008). "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration". PLoS Medicine. 5 (2): e45. PMC 2253608  . PMID 18303940. doi:10.1371/journal.pmed.0050045.
Jump up ^ Horder J, Matthews P, Waldmann R (June 2010). "Placebo, Prozac and PLoS: significant lessons for psychopharmacology". Journal of Psychopharmacology. 25 (10): 1277–88. PMID 20571143. doi:10.1177/0269881110372544.
Jump up ^ Fountoulakis KN, Möller HJ (August 2010). "Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data". The International Journal of Neuropsychopharmacology. 14 (3): 1–8. PMID 20800012. doi:10.1017/S1461145710000957.
Jump up ^ Depression: The NICE Guideline on the Treatment and Management of Depression in Adults (Updated Edition) (PDF). RCPsych Publications. 2010. ISBN 1-904671-85-3.
Jump up ^ Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ (June 2012). "Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine". Archives of General Psychiatry. 69 (6): 572–9. PMC 3371295  . PMID 22393205. doi:10.1001/archgenpsychiatry.2011.2044.
Jump up ^ Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, Fawcett J (January 2010). "Antidepressant drug effects and depression severity: a patient-level meta-analysis". JAMA. 303 (1): 47–53. PMC 3712503  . PMID 20051569. doi:10.1001/jama.2009.1943.
Jump up ^ Gartlehner G, Hansen RA, Morgan LC, Thaler K, Lux L, Van Noord M, Mager U, Thieda P, Gaynes BN, Wilkins T, Strobelberger M, Lloyd S, Reichenpfader U, Lohr KN (December 2011). "Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis". Annals of Internal Medicine. 155 (11): 772–85. PMID 22147715. doi:10.7326/0003-4819-155-11-201112060-00009.
^ Jump up to: a b Hetrick SE, McKenzie JE, Cox GR, Simmons MB, Merry SN (Nov 14, 2012). "Newer generation antidepressants for depressive disorders in children and adolescents.". The Cochrane Database of Systematic Reviews. 11: CD004851. PMID 23152227. doi:10.1002/14651858.cd004851.pub3.
^ Jump up to: a b "www.nice.org.uk" (PDF). Retrieved 2013-02-20.
^ Jump up to: a b Kapczinski F, Lima MS, Souza JS, Schmitt R (2003). Kapczinski, Flavio FK, ed. "Antidepressants for generalized anxiety disorder". The Cochrane Database of Systematic Reviews (2): CD003592. PMID 12804478. doi:10.1002/14651858.CD003592. CS1 maint: Multiple names: authors list (link)
Jump up ^ "Obsessive-compulsive disorder: Core interventions in the treatment of obsessive-compulsive disorder and body dysmorphic disorder" (PDF). November 2005
Jump up ^ Arroll B, Elley CR, Fishman T, Goodyear-Smith FA, Kenealy T, Blashki G, Kerse N, Macgillivray S (2009). Arroll, Bruce, ed. "Antidepressants versus placebo for depression in primary care". The Cochrane Database of Systematic Reviews (3): CD007954. PMID 19588448. doi:10.1002/14651858.CD007954. CS1 maint: Multiple names: authors list (link)
Jump up ^ Busko, Marlene (28 February 2008). "Review Finds SSRIs Modestly Effective in Short-Term Treatment of OCD". Medscape. Archived from the original on April 13, 2013.
Jump up ^ Fineberg NA, Brown A, Reghunandanan S, Pampaloni I (2012). "Evidence-based pharmacotherapy of obsessive-compulsive disorder". The International Journal of Neuropsychopharmacology. 15 (8): 1173–91. PMID 22226028. doi:10.1017/S1461145711001829.
Jump up ^ "Sertraline prescribing information" (PDF). Retrieved 2015-01-30.
Jump up ^ "Paroxetine prescribing information" (PDF). Retrieved 2015-01-30.
^ Jump up to: a b c "Eating disorders in over 8s: management" (PDF). NICE. January 2004.
^ Jump up to: a b "National Guideline Clearinghouse | Practice guideline for the treatment of patients with eating disorders".
Jump up ^ Flament MF, Bissada H, Spettigue W (March 2012). "Evidence-based pharmacotherapy of eating disorders". The International Journal of Neuropsychopharmacology. 15 (2): 189–207. PMID 21414249. doi:10.1017/S1461145711000381.
Jump up ^ Mead GE, Hsieh CF, Lee R, Kutlubaev MA, Claxton A, Hankey GJ, Hackett ML (2012). Mead, Gillian E, ed. "Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery". The Cochrane Database of Systematic Reviews. 11: CD009286. PMID 23152272. doi:10.1002/14651858.CD009286.pub2. CS1 maint: Multiple names: authors list (link)
Jump up ^ Waldinger MD (November 2007). "Premature ejaculation: state of the art". The Urologic Clinics of North America. 34 (4): 591–9, vii–viii. PMID 17983899. doi:10.1016/j.ucl.2007.08.011.
Jump up ^ Wu Q, Bencaz AF, Hentz JG, Crowell MD (January 2012). "Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies". Osteoporosis International. 23 (1): 365–75. PMID 21904950. doi:10.1007/s00198-011-1778-8.
Jump up ^ Stahl SM, Lonnen AJ (2011). "The Mechanism of Drug-induced Akathsia". CNS Spectrums. PMID 21406165.
Jump up ^ Lane RM (1998). "SSRI-induced extrapyramidal side-effects and akathisia: implications for treatment". Journal of Psychopharmacology. 12 (2): 192–214. PMID 9694033. doi:10.1177/026988119801200212.
Jump up ^ Koliscak LP, Makela EH (2009). "Selective serotonin reuptake inhibitor-induced akathisia". Journal of the American Pharmacists Association. 49 (2): e28–36; quiz e37–8. PMID 19289334. doi:10.1331/JAPhA.2009.08083.
Jump up ^ Leo RJ (1996). "Movement disorders associated with the serotonin selective reuptake inhibitors". The Journal of Clinical Psychiatry. 57 (10): 449–54. PMID 8909330. doi:10.4088/JCP.v57n1002.
Jump up ^ September 23, 2012. "SSRIs and Depression". Emedicinehealth.com. Retrieved 2012-09-23.
^ Jump up to: a b Bahrick, Audrey (2008). "Persistence of Sexual Dysfunction Side Effects after Discontinuation of Antidepressant Medications: Emerging Evidence" (PDF). The Open Psychology Journal. 1: 42–50. doi:10.2174/1874350100801010042. Retrieved 30 January 2014.
Jump up ^ Taylor, MJ; Rudkin, L; Bullemor-Day, P; Lubin, J; Chukwujekwu, C; Hawton, K (31 May 2013). "Strategies for managing sexual dysfunction induced by antidepressant medication.". The Cochrane Database of Systematic Reviews. 5: CD003382. PMID 23728643. doi:10.1002/14651858.CD003382.pub3.
Jump up ^ Kennedy, SH; Rizvi, S (April 2009). "Sexual dysfunction, depression, and the impact of antidepressants.". Journal of Clinical Psychopharmacology. 29 (2): 157–64. PMID 19512977. doi:10.1097/jcp.0b013e31819c76e9.
Jump up ^ Waldinger, MD (2015). "Psychiatric disorders and sexual dysfunction.". Handbook of Clinical Neurology / edited by David B. Vodušek and François Boller. Handbook of Clinical Neurology. 130: 469–89. ISBN 9780444632470. PMID 26003261. doi:10.1016/B978-0-444-63247-0.00027-4.
Jump up ^ http://pi.lilly.com/us/prozac.pdf Page 14.
Jump up ^ Reisman, Yacov (2017-06-19). "Sexual Consequences of Post-SSRI Syndrome". Sexual Medicine Reviews. ISSN 2050-0521. PMID 28642048. doi:10.1016/j.sxmr.2017.05.002.
Jump up ^ Gitlin, M. J. (1994-09-01). "Psychotropic medications and their effects on sexual function: diagnosis, biology, and treatment approaches". The Journal of Clinical Psychiatry. 55 (9): 406–413. ISSN 0160-6689. PMID 7929021.
Jump up ^ Balon R (2006). "SSRI-Associated Sexual Dysfunction". The American Journal of Psychiatry. 163 (9): 1504–9; quiz 1664. PMID 16946173. doi:10.1176/appi.ajp.163.9.1504.
Jump up ^ Clayton, Anita H. (2003). "Antidepressant-Associated Sexual Dysfunction: A Potentially Avoidable Therapeutic Challenge". Primary Psychiatry. 10 (1): 55–61.
Jump up ^ Kanaly KA, Berman JR (December 2002). "Sexual side effects of SSRI medications: potential treatment strategies for SSRI-induced female sexual dysfunction". Current Women's Health Reports. 2 (6): 409–16. PMID 12429073.
Jump up ^ Koyuncu H, Serefoglu EC, Ozdemir AT, Hellstrom WJ (September 2012). "Deleterious effects of selective serotonin reuptake inhibitor treatment on semen parameters in patients with lifelong premature ejaculation". Int. J. Impot. Res. 24 (5): 171–3. PMID 22573230. doi:10.1038/ijir.2012.12.
Jump up ^ Oh SW, Kim J, Myung SK, Hwang SS, Yoon DH (Mar 20, 2014). "Antidepressant Use and Risk of Coronary Heart Disease: Meta-Analysis of Observational Studies.". British Journal of Clinical Pharmacology. 78 (4): 727–37. PMID 24646010. doi:10.1111/bcp.12383.
Jump up ^ Huybrechts KF, Palmsten K, Avorn J, Cohen LS, Holmes LB, Franklin JM, Mogun H, Levin R, Kowal M, Setoguchi S, Hernández-Díaz S (2014). "Antidepressant Use in Pregnancy and the Risk of Cardiac Defects". New England Journal of Medicine. 370 (25): 2397–2407. ISSN 0028-4793. PMC 4062924  . PMID 24941178. doi:10.1056/NEJMoa1312828.
Jump up ^ Goldberg RJ (1998). "Selective serotonin reuptake inhibitors: infrequent medical adverse effects". Archives of Family Medicine. 7 (1): 78–84. PMID 9443704. doi:10.1001/archfami.7.1.78.
Jump up ^ FDA. "FDA Drug Safety".
Jump up ^ Citalopram and escitalopram: QT interval prolongation—new maximum daily dose restrictions (including in elderly patients), contraindications, and warnings. From Medicines and Healthcare Products Regulatory Agency. Article date: December 2011
Jump up ^ "ref2" (PDF). Retrieved 2012-09-23.
Jump up ^ Pacher P, Ungvari Z, Nanasi PP, Furst S, Kecskemeti V (Jun 1999). "Speculations on difference between tricyclic and selective serotonin reuptake inhibitor antidepressants on their cardiac effects. Is there any?". Current Medicinal Chemistry. 6 (6): 469–80. PMID 10213794.
^ Jump up to: a b Weinrieb RM, Auriacombe M, Lynch KG, Lewis JD (March 2005). "Selective serotonin re-uptake inhibitors and the risk of bleeding". Expert Opinion on Drug Safety. 4 (2): 337–44. PMID 15794724. doi:10.1517/14740338.4.2.337.
^ Jump up to: a b Taylor, D; Carol, P; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 9780470979693.
Jump up ^ Andrade C, Sandarsh S, Chethan KB, Nagesh KS (December 2010). "Serotonin Reuptake Inhibitor Antidepressants and Abnormal Bleeding: A Review for Clinicians and a Reconsideration of Mechanisms". The Journal of Clinical Psychiatry. 71 (12): 1565–1575. PMID 21190637. doi:10.4088/JCP.09r05786blu.
^ Jump up to: a b de Abajo FJ, García-Rodríguez LA (July 2008). "Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents". Archives of General Psychiatry. 65 (7): 795–803. PMID 18606952. doi:10.1001/archpsyc.65.7.795.
Jump up ^ Hackam DG, Mrkobrada M (2012). "Selective serotonin reuptake inhibitors and brain hemorrhage: a meta-analysis". Neurology. 79 (18): 1862–5. PMID 23077009. doi:10.1212/WNL.0b013e318271f848.
Jump up ^ Serebruany VL (February 2006). "Selective serotonin reuptake inhibitors and increased bleeding risk: are we missing something?". The American Journal of Medicine. 119 (2): 113–6. PMID 16443409. doi:10.1016/j.amjmed.2005.03.044.
Jump up ^ Halperin D, Reber G (2007). "Influence of antidepressants on hemostasis". Dialogues in Clinical Neuroscience. 9 (1): 47–59. PMC 3181838  . PMID 17506225.
Jump up ^ Andrade C, Sandarsh S, Chethan KB, Nagesh KS (2010). "Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms". The Journal of Clinical Psychiatry. 71 (12): 1565–75. PMID 21190637. doi:10.4088/JCP.09r05786blu.
Jump up ^ de Abajo FJ (2011). "Effects of selective serotonin reuptake inhibitors on platelet function: mechanisms, clinical outcomes and implications for use in elderly patients". Drugs & Aging. 28 (5): 345–67. PMID 21542658. doi:10.2165/11589340-000000000-00000.
Jump up ^ Eom, CS; Lee, HK; Ye, S; Park, SM; Cho, KH (May 2012). "Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis". Journal of Bone and Mineral Research. 27 (5): 1186–95. PMID 22258738. doi:10.1002/jbmr.1554.
Jump up ^ Bruyère, O; Reginster, JY (February 2015). "Osteoporosis in patients taking selective serotonin reuptake inhibitors: a focus on fracture outcome". Endocrine. 48 (1): 65–8. PMID 25091520. doi:10.1007/s12020-014-0357-0.
Jump up ^ Hant, FN; Bolster, MB (April 2016). "Drugs that may harm bone: Mitigating the risk". Cleveland Clinic journal of medicine. 83 (4): 281–8. PMID 27055202. doi:10.3949/ccjm.83a.15066.
Jump up ^ Fernandes, BS; Hodge, JM; Pasco, JA; Berk, M; Williams, LJ (January 2016). "Effects of Depression and Serotonergic Antidepressants on Bone: Mechanisms and Implications for the Treatment of Depression". Drugs & aging. 33 (1): 21–5. PMID 26547857. doi:10.1007/s40266-015-0323-4.
Jump up ^ Nyandege, AN; Slattum, PW; Harpe, SE (April 2015). "Risk of fracture and the concomitant use of bisphosphonates with osteoporosis-inducing medications". The Annals of pharmacotherapy. 49 (4): 437–47. PMID 25667198. doi:10.1177/1060028015569594.
^ Jump up to: a b Warden, SJ; Fuchs, RK (October 2016). "Do Selective Serotonin Reuptake Inhibitors (SSRIs) Cause Fractures?". Current osteoporosis reports. 14 (5): 211–8. PMID 27495351. doi:10.1007/s11914-016-0322-3.
Jump up ^ Winterhalder, L; Eser, P; Widmer, J; Villiger, PM; Aeberli, D (December 2012). "Changes in volumetric BMD of radius and tibia upon antidepressant drug administration in young depressive patients". Journal of musculoskeletal & neuronal interactions. 12 (4): 224–9. PMID 23196265.
^ Jump up to: a b "PsychiatryOnline | APA Practice Guidelines | Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition".
Jump up ^ Renoir T (2013). "Selective serotonin reuptake inhibitor antidepressant treatment discontinuation syndrome: a review of the clinical evidence and the possible mechanisms involved". Frontiers in Pharmacology. 4: 45. PMC 3627130  . PMID 23596418. doi:10.3389/fphar.2013.00045.
^ Jump up to: a b Stone MB, Jones ML (2006-11-17). "Clinical review: relationship between antidepressant drugs and suicidal behavior in adults" (PDF). Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee (PDAC). FDA. pp. 11–74. Retrieved 2007-09-22.
Jump up ^ Levenson M, Holland C (2006-11-17). "Statistical Evaluation of Suicidality in Adults Treated with Antidepressants" (PDF). Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee (PDAC). FDA. pp. 75–140. Retrieved 2007-09-22.
Jump up ^ Olfson M, Marcus SC, Shaffer D (August 2006). "Antidepressant drug therapy and suicide in severely depressed children and adults: A case-control study". Archives of General Psychiatry. 63 (8): 865–72. PMID 16894062. doi:10.1001/archpsyc.63.8.865.
Jump up ^ Hammad TA (2004-08-16). "Review and evaluation of clinical data. Relationship between psychiatric drugs and pediatric suicidal behavior" (PDF). FDA. pp. 42; 115. Retrieved 2008-05-29.
Jump up ^ "Antidepressant Use in Children, Adolescents, and Adults".
Jump up ^ "FDA Medication Guide for Antidepressants" (PDF). Retrieved 2014-06-05.
^ Jump up to: a b Cox, Georgina R.; Callahan, Patch; Churchill, Rachel; Hunot, Vivien; Merry, Sally N.; Parker, Alexandra G.; Hetrick, Sarah E. (2014-11-30). "Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents". The Cochrane Database of Systematic Reviews (11): CD008324. ISSN 1469-493X. PMID 25433518. doi:10.1002/14651858.CD008324.pub3.
Jump up ^ "www.nice.org.uk" (PDF).
Jump up ^ Meta-Analysis of Aggression and/or Hostility-Related Events in Children and Adolescents Treated with Fluoxetine Compared with Placebo Journal of Child and Adolescent Psychopharmacology. October 2007; 17(5) 713–718. doi:10.1089/cap.2006.0138.
Jump up ^ Gibbons RD, Hur K, Bhaumik DK, Mann JJ (November 2006). "The relationship between antidepressant prescription rates and rate of early adolescent suicide". The American Journal of Psychiatry. 163 (11): 1898–904. PMID 17074941. doi:10.1176/appi.ajp.163.11.1898.
Jump up ^ "Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitor antidepressants" (PDF). MHRA. 2004-12-01. Retrieved 2007-09-25.
Jump up ^ "Selective Serotonin Reuptake Inhibitors (SSRIs): Overview of regulatory status and CSM advice relating to major depressive disorder (MDD) in children and adolescents including a summary of available safety and efficacy data". MHRA. 2005-09-29. Retrieved 2008-05-29.
Jump up ^ Gunnell D, Saperia J, Ashby D (February 2005). "Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review". BMJ (Clinical Research Ed.). 330 (7488): 385. PMC 549105  . PMID 15718537. doi:10.1136/bmj.330.7488.385.
Jump up ^ Fergusson D, Doucette S, Glass KC, Shapiro S, Healy D, Hebert P, Hutton B (February 2005). "Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials". BMJ (Clinical Research Ed.). 330 (7488): 396. PMC 549110  . PMID 15718539. doi:10.1136/bmj.330.7488.396.
Jump up ^ Rihmer Z, Akiskal H (August 2006). "Do antidepressants t(h)reat(en) depressives? Toward a clinically judicious formulation of the antidepressant-suicidality FDA advisory in light of declining national suicide statistics from many countries". Journal of Affective Disorders. 94 (1–3): 3–13. PMID 16712945. doi:10.1016/j.jad.2006.04.003.
Jump up ^ Hall WD, Lucke J (2006). "How have the selective serotonin reuptake inhibitor antidepressants affected suicide mortality?". The Australian and New Zealand Journal of Psychiatry. 40 (11–12): 941–50. PMID 17054562. doi:10.1111/j.1440-1614.2006.01917.x.
Jump up ^ Malm H (December 2012). "Prenatal exposure to selective serotonin reuptake inhibitors and infant outcome". Therapeutic Drug Monitoring. 34 (6): 607–14. PMID 23042258. doi:10.1097/FTD.0b013e31826d07ea.
Jump up ^ Rahimi R, Nikfar S, Abdollahi M (2006). "Pregnancy outcomes following exposure to serotonin reuptake inhibitors: a meta-analysis of clinical trials". Reproductive Toxicology (Elmsford, N.Y.). 22 (4): 571–575. PMID 16720091. doi:10.1016/j.reprotox.2006.03.019.
^ Jump up to: a b Nikfar S, Rahimi R, Hendoiee N, Abdollahi M (2012). "Increasing the risk of spontaneous abortion and major malformations in newborns following use of serotonin reuptake inhibitors during pregnancy: A systematic review and updated meta-analysis". Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences. 20 (1): 75. PMC 3556001  . PMID 23351929. doi:10.1186/2008-2231-20-75.
Jump up ^ Eke, AC; Saccone, G; Berghella, V (November 2016). "Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and risk of preterm birth: a systematic review and meta-analysis.". BJOG : an international journal of obstetrics and gynaecology. 123 (12): 1900–1907. PMID 27239775. doi:10.1111/1471-0528.14144.
Jump up ^ Einarson TR, Kennedy D, Einarson A (2012). "Do findings differ across research design? The case of antidepressant use in pregnancy and malformations". Journal of Population Therapeutics and Clinical Pharmacology = Journal de la Thérapeutique des Populations et de la Pharamcologie Clinique. 19 (2): e334–48. PMID 22946124.
Jump up ^ Riggin L, Frankel Z, Moretti M, Pupco A, Koren G (April 2013). "The fetal safety of fluoxetine: a systematic review and meta-analysis". Journal of Obstetrics and Gynaecology Canada. 35 (4): 362–9. PMID 23660045.
Jump up ^ Koren G, Nordeng HM (February 2013). "Selective serotonin reuptake inhibitors and malformations: case closed?". Seminars in Fetal & Neonatal Medicine. 18 (1): 19–22. PMID 23228547. doi:10.1016/j.siny.2012.10.004.
Jump up ^ "Breastfeeding Update: SDCBC's quarterly newsletter". Breastfeeding.org. Archived from the original on February 25, 2009. Retrieved 2010-07-10.
Jump up ^ "Using Antidepressants in Breastfeeding Mothers". kellymom.com. Retrieved 2010-07-10.
Jump up ^ Gentile S, Rossi A, Bellantuono C (2007). "SSRIs during breastfeeding: spotlight on milk-to-plasma ratio". Archives of Women's Mental Health. 10 (2): 39–51. PMID 17294355. doi:10.1007/s00737-007-0173-0.
Jump up ^ Fenger-Grøn J, Thomsen M, Andersen KS, Nielsen RG (September 2011). "Paediatric outcomes following intrauterine exposure to serotonin reuptake inhibitors: a systematic review". Danish Medical Bulletin. 58 (9): A4303. PMID 21893008.
Jump up ^ Kieviet N, Dolman KM, Honig A (2013). "The use of psychotropic medication during pregnancy: how about the newborn?". Neuropsychiatric Disease and Treatment. 9: 1257–1266. PMC 3770341  . PMID 24039427. doi:10.2147/NDT.S36394.
Jump up ^ "Persistent Newborn Pulmonary Hypertension".
Jump up ^ Grigoriadis S, Vonderporten EH, Mamisashvili L, Tomlinson G, Dennis CL, Koren G, Steiner M, Mousmanis P, Cheung A, Ross LE (2014). "Prenatal exposure to antidepressants and persistent pulmonary hypertension of the newborn: systematic review and meta-analysis". BMJ (Clinical Research Ed.). 348: f6932. PMC 3898424  . PMID 24429387. doi:10.1136/bmj.f6932.
Jump up ^ 't Jong GW, Einarson T, Koren G, Einarson A (November 2012). "Antidepressant use in pregnancy and persistent pulmonary hypertension of the newborn (PPHN): a systematic review". Reproductive Toxicology. 34 (3): 293–7. PMID 22564982. doi:10.1016/j.reprotox.2012.04.015.
Jump up ^ Gentile S. (2015). "Prenatal antidepressant exposure and the risk of autism spectrum disorders in children. Are we looking at the fall of Gods?". J. Affect. Disord. 182: 132–7. PMID 25985383. doi:10.1016/j.jad.2015.04.048. Epub 2015 May 6.
Jump up ^ Hviid A, Melbye M, Pasternak B (19 December 2013). "Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism". The New England Journal of Medicine. 369 (25): 2406–2415. PMID 24350950. doi:10.1056/NEJMoa1301449. Retrieved 18 December 2013.
^ Jump up to: a b Heli Malm, Alan S. Brown et al. (2016). "Gestational Exposure to Selective Serotonin Reuptake Inhibitors and Offspring Psychiatric Disorders: A National Register-Based Study". Journal of the American Academy of Child & Adolescent Psychiatry. 55: 359–366. doi:10.1016/j.jaac.2016.02.013. CS1 maint: Uses authors parameter (link)
^ Jump up to: a b c Isbister GK, Bowe SJ, Dawson A, Whyte IM (2004). "Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose". Journal of Toxicology. Clinical Toxicology. 42 (3): 277–85. PMID 15362595. doi:10.1081/CLT-120037428.
Jump up ^ Borys DJ, Setzer SC, Ling LJ, Reisdorf JJ, Day LC, Krenzelok EP (1992). "Acute fluoxetine overdose: a report of 234 cases". The American Journal of Emergency Medicine. 10 (2): 115–20. PMID 1586402. doi:10.1016/0735-6757(92)90041-U.
Jump up ^ Oström M, Eriksson A, Thorson J, Spigset O (1996). "Fatal overdose with citalopram". Lancet. 348 (9023): 339–40. PMID 8709713. doi:10.1016/S0140-6736(05)64513-8.
Jump up ^ Sporer KA (1995). "The serotonin syndrome. Implicated drugs, pathophysiology and management". Drug Safety. 13 (2): 94–104. PMID 7576268. doi:10.2165/00002018-199513020-00004.
Jump up ^ White N, Litovitz T, Clancy C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type" (PDF). Journal of Medical Toxicology. 4 (4): 238–250. PMC 3550116  . PMID 19031375. doi:10.1007/BF03161207.
Jump up ^ Ener RA, Meglathery SB, Van Decker WA, Gallagher RM (March 2003). "Serotonin Syndrome and Other Serotonergic Disorders". Pain Medicine. 4 (1): 63–74. PMID 12873279. doi:10.1046/j.1526-4637.2003.03005.x.
Jump up ^ Boyer EW, Shannon M; Shannon, M (2005). "The serotonin syndrome" (PDF). The New England Journal of Medicine. 352 (11): 1112–1120. PMID 15784664. doi:10.1056/NEJMra041867.
Jump up ^ Solomon H. Snyder. "Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans". Proceedings of the National Academy of Sciences. 108: 9262–9267. PMC 3107316  . PMID 21518864. doi:10.1073/pnas.1104836108. Retrieved 2012-09-23.
Jump up ^ Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman’s The Pharmacological Basis of Therapeutics (12th ed.). McGraw Hill Professional. ISBN 978-0071624428.
Jump up ^ Ciraulo, DA; Shader, RI (2011). Pharmacotherapy of Depression (2nd ed.). Springer. p. 49. ISBN 978-1-60327-435-7. doi:10.1007/978-1-60327-435-7.
^ Jump up to: a b c d Shelton R. C. (2009). "Serotonin norepinephrine reuptake inhibitors: similarities and differences". Primary Psychiatry. 16 (4): 25.
Jump up ^ Derek G. Waller; Tony Sampson (4 June 2017). Medical Pharmacology and Therapeutics E-Book. Elsevier Health Sciences. pp. 302–. ISBN 978-0-7020-7190-4.
Jump up ^ Susan G. Kornstein; Anita H. Clayton (5 May 2010). Women's Mental Health, An Issue of Psychiatric Clinics – E-Book. Elsevier Health Sciences. pp. 389–. ISBN 1-4557-0061-4.
Jump up ^ Bruno A, Morabito P, Spina E, Muscatello MR (2016). "The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review". Curr Neuropharmacol. 14 (2): 191–9. PMC 4825949  . PMID 26572745. doi:10.2174/1570159x14666151117122458.
^ Jump up to: a b Mandrioli R, Protti M, Mercolini L (2017). "New-Generation, non-SSRI Antidepressants: Therapeutic Drug Monitoring and Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs". Curr. Med. Chem. PMID 28707591. doi:10.2174/0929867324666170712165042.
^ Jump up to: a b Frank J. Ayd (2000). Lexicon of Psychiatry, Neurology, and the Neurosciences. Lippincott Williams & Wilkins. pp. 581–. ISBN 978-0-7817-2468-5.
^ Jump up to: a b Progress in Drug Research. Birkhäuser. 6 December 2012. pp. 80–82. ISBN 978-3-0348-8391-7.
^ Jump up to: a b Moltzen EK, Bang-Andersen B (2006). "Serotonin reuptake inhibitors: the corner stone in treatment of depression for half a century—a medicinal chemistry survey". Curr Top Med Chem. 6 (17): 1801–23. PMID 17017959. doi:10.2174/156802606778249810.
^ Jump up to: a b Haddad, Peter M. (2000). "Selective Serotonin Reuptake Inhibitors (SSRIs) Past, Present and Future. Edited by S. Clare Standford, R.G. Landes Company, Austin, Texas, USA, 1999". Human Psychopharmacology: Clinical and Experimental. 15 (6): 205–207. ISBN 1-57059-649-2. ISSN 0885-6222. doi:10.1002/1099-1077(200008)15:6<471::AID-HUP211>3.0.CO;2-4.
^ Jump up to: a b Tatsumi M, Groshan K, Blakely RD, Richelson E (1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". Eur. J. Pharmacol. 340 (2–3): 249–58. PMID 9537821. doi:10.1016/s0014-2999(97)01393-9.
^ Jump up to: a b c Hellbom E (2006). "Chlorpheniramine, selective serotonin-reuptake inhibitors (SSRIs) and over-the-counter (OTC) treatment". Med. Hypotheses. 66 (4): 689–90. PMID 16413139. doi:10.1016/j.mehy.2005.12.006.
Jump up ^ Goodman, Louis S. (Louis Sanford); Brunton, Laurence L.; Chabner, Bruce.; Knollmann, Björn C. (2001). Goodman and Gilman's pharmacological basis of therapeutics. New York: McGraw-Hill. pp. 459–461. ISBN 0-07-162442-2.
^ Jump up to: a b Kolb, Bryan and Wishaw Ian. An Introduction to Brain and Behavior. New York: Worth Publishers 2006, Print.
^ Jump up to: a b c d e f g Hindmarch I, Hashimoto K (2010). "Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered". Hum Psychopharmacol. 25 (3): 193–200. PMID 20373470. doi:10.1002/hup.1106.
^ Jump up to: a b c d e f g Albayrak, Yakup; Hashimoto, Kenji (2017). "Sigma-1 Receptor Agonists and Their Clinical Implications in Neuropsychiatric Disorders". Advances in Experimental Medicine and Biology. 964: 153–161. ISSN 0065-2598. doi:10.1007/978-3-319-50174-1_11.
Jump up ^ Kohler, Ole; Krogh, Jesper; Mors, Ole; Eriksen Benros, Michael (26 August 2016). "Inflammation in Depression and the Potential for Anti-Inflammatory Treatment". Current Neuropharmacology. 14 (7): 732–742. doi:10.2174/1570159X14666151208113700.
Jump up ^ Köhler, Stephan; Cierpinsky, Katharina; Kronenberg, Golo; Adli, Mazda (January 2016). "The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants". Journal of Psychopharmacology. 30 (1): 13–22. doi:10.1177/0269881115609072.
Jump up ^ Köhler, Cristiano A.; Freitas, Thiago H.; Stubbs, Brendon; Maes, Michael; Solmi, Marco; Veronese, Nicola; de Andrade, Nayanna Q.; Morris, Gerwyn; Fernandes, Brisa S.; Brunoni, André R.; Herrmann, Nathan; Raison, Charles L.; Miller, Brian J.; Lanctôt, Krista L.; Carvalho, André F. (13 June 2017). "Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis". Molecular Neurobiology. doi:10.1007/s12035-017-0632-1.
Jump up ^ Więdłocha, Magdalena; Marcinowicz, Piotr; Krupa, Renata; Janoska-Jaździk, Marlena; Janus, Marta; Dębowska, Weronika; Mosiołek, Anna; Waszkiewicz, Napoleon; Szulc, Agata (April 2017). "Effect of antidepressant treatment on peripheral inflammation markers – A meta-analysis". Progress in Neuro-Psychopharmacology and Biological Psychiatry. doi:10.1016/j.pnpbp.2017.04.026.
Jump up ^ Vogelzangs, N; Duivis, H E; Beekman, A T F; Kluft, C; Neuteboom, J; Hoogendijk, W; Smit, J H; de Jonge, P; Penninx, B W J H (February 2012). "Association of depressive disorders, depression characteristics and antidepressant medication with inflammation". Translational Psychiatry. 2 (2): e79. doi:10.1038/tp.2012.8.
^ Jump up to: a b Kalkman, Hans O.; Feuerbach, Dominik (July 2016). "Antidepressant therapies inhibit inflammation and microglial M1-polarization". Pharmacology & Therapeutics. 163: 82–93. doi:10.1016/j.pharmthera.2016.04.001.
^ Jump up to: a b Nazimek, Katarzyna; Strobel, Spencer; Bryniarski, Paweł; Kozlowski, Michael; Filipczak-Bryniarska, Iwona; Bryniarski, Krzysztof (June 2017). "The role of macrophages in anti-inflammatory activity of antidepressant drugs". Immunobiology. 222 (6): 823–830. doi:10.1016/j.imbio.2016.07.001.
^ Jump up to: a b Gobin, Veerle; Van Steendam, Katleen; Denys, Damiaan; Deforce, Dieter (May 2014). "Selective serotonin reuptake inhibitors as a novel class of immunosuppressants". International Immunopharmacology. 20 (1): 148–156. doi:10.1016/j.intimp.2014.02.030.
Jump up ^ Rasmussen-Torvik LJ, McAlpine DD (2007). "Genetic screening for SSRI drug response among those with major depression: great promise and unseen perils". Depression and Anxiety. 24 (5): 350–7. PMID 17096399. doi:10.1002/da.20251.
Jump up ^ Anderson IM (April 2000). "Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability". Journal of Affective Disorders. 58 (1): 19–36. PMID 10760555. doi:10.1016/S0165-0327(99)00092-0.
Jump up ^ Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R (January 2008). "Selective publication of antidepressant trials and its influence on apparent efficacy". The New England Journal of Medicine. 358 (3): 252–60. PMID 18199864. doi:10.1056/NEJMsa065779.
Jump up ^ Healy D; Aldred G (2005). "Antidepressant drug use and the risk of suicide" (PDF). International Review of Psychiatry. 17: 163–172. doi:10.1080/09540260500071624.
Jump up ^ Lapierre YD (September 2003). "Suicidality with selective serotonin reuptake inhibitors: Valid claim?". J Psychiatry Neurosci. 28 (5): 340–7. PMC 193980  . PMID 14517577.
Jump up ^ Khan A, Khan S, Kolts R, Brown WA (2003). "Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports.". Am. J. Psychiatry. 160: 790–2. PMID 12668373. doi:10.1176/appi.ajp.160.4.790.
Jump up ^ Kaizar EE, Greenhouse JB, Seltman H, Kelleher K (2006). "Do antidepressants cause suicidality in children? A Bayesian meta-analysis". Clin. Trials. 3 (2): 73–90; discussion 91–8. PMID 16773951. doi:10.1191/1740774506cn139oa.
Jump up ^ Gibbons RD, Brown CH, Hur K, Davis J, Mann JJ (June 2012). "Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine". Arch. Gen. Psychiatry. 69 (6): 580–7. PMC 3367101  . PMID 22309973. doi:10.1001/archgenpsychiatry.2011.2048.
External links[edit]
Serotonin uptake inhibitors at the US National Library of Medicine Medical Subject Headings (MeSH)
[show]
v
t
e
Antidepressants (N06A)
[hide]
Specific reuptake inhibitors and/or receptor modulators
SSRIs
Citalopram
Escitalopram
Fluoxetine#
Fluvoxamine
Indalpine‡
Paroxetine
Sertraline
Zimelidine‡
SNRIs
Desvenlafaxine
Duloxetine
Levomilnacipran
Milnacipran
Tofenacin
Venlafaxine
NRIs
Atomoxetine
Reboxetine
Viloxazine
NDRIs
Amineptine‡
Bupropion
Nomifensine‡
NaSSAs
Mianserin
Mirtazapine
Setiptiline
SARIs
Etoperidone
Nefazodone
Trazodone
SMS
Vilazodone
Vortioxetine
Others
Agomelatine
Amisulpride
Esketamine†
Etryptamine‡
Indeloxazine
flupentixol
Ketamine†
Medifoxamine‡
Metryptamine‡
Oxaflozane‡
Pivagabine‡
Tandospirone
Teniloxazine
Tianeptine
[hide]
Tricyclic and tetracyclic antidepressants
TCAs
Amineptine‡
Amitriptyline#
Amitriptylinoxide
Butriptyline‡
Clomipramine#
Demexiptiline‡
Desipramine
Dibenzepin
Dimetacrine‡
Dosulepin
Doxepin
Imipramine
Imipraminoxide‡
Iprindole‡
Lofepramine
Melitracen
Metapramine‡
Nitroxazepine
Nortriptyline
Noxiptiline
Opipramol
Pipofezine
Propizepine‡
Protriptyline
Quinupramine‡
Tianeptine
Trimipramine
TeCAs
Amoxapine
Maprotiline
Mianserin
Mirtazapine
Setiptiline
Others
Tiazesim
[hide]
Monoamine oxidase inhibitors
Non-selective
Irreversible: Benmoxin‡
Iproclozide‡
Iproniazid‡
Isocarboxazid
Isoniazid#
Linezolid#
Mebanazine‡
Nialamide‡
Octamoxin‡
Phenelzine
Pheniprazine‡
Phenoxypropazine‡
Pivhydrazine‡
Safrazine‡
Tedizolid
Tranylcypromine
Reversible: Caroxazone‡
Mixed: Bifemelane
MAOA-selective
Reversible: Eprobemide
Metralindole
Minaprine‡
Moclobemide
Pirlindole
Tetrindole
Toloxatone
MAOB-selective
Irreversible: Selegiline
[hide]
Adjunctive therapies
Atypical antipsychotics (aripiprazole, brexpiprazole, lurasidone, olanzapine, quetiapine, risperidone)
Buspirone
Lithium (lithium carbonate, lithium citrate)
Thyroid hormones (triiodothyronine (T3), levothyroxine (T4))
[hide]
Miscellaneous
Ademetionine (SAMe)
Hypericum perforatum (St. John's Wort)
Oxitriptan (5-HTP)
Rubidium chloride (RbCl)
Tryptophan
#WHO-EM
‡Withdrawn from market
Clinical trials:
†Phase III
§Never to phase III
[show]
v
t
e
Anxiolytics (N05B)
5-HT1AR agonists
Buspirone
Gepirone†
Tandospirone
GABAAR PAMs
Benzodiazepines: Adinazolam
Alprazolam
Bromazepam
Camazepam
Chlordiazepoxide
Clobazam
Clonazepam
Clorazepate
Clotiazepam
Cloxazolam
Diazepam#
Ethyl loflazepate
Etizolam
Fludiazepam
Halazepam
Ketazolam
Lorazepam#
Medazepam
Nordazepam
Oxazepam
Pinazepam
Prazepam; Others: Alpidem‡
Barbiturates (e.g., phenobarbital)
Carbamates (e.g., meprobamate)
Chlormezanone‡
Ethanol (alcohol)
Etifoxine
Imepitoin; Herbs:
Kava
Skullcap
Valerian
Gabapentinoids
(α2δ VDCC blockers)
Gabapentin
Gabapentin enacarbil
Phenibut
Pregabalin
Antidepressants
SSRIs (e.g., escitalopram)
SNRIs (e.g., duloxetine)
SARIs (e.g., trazodone)
TCAs (e.g., clomipramine)
TeCAs (e.g., mirtazapine)
MAOIs (e.g., phenelzine); Others: Agomelatine
Bupropion
Tianeptine
Vilazodone
Vortioxetine
Sympatholytics
(Antiadrenergics)
Alpha-1 blockers (e.g., prazosin)
Alpha-2 agonists (e.g., clonidine, dexmedetomidine, guanfacine)
Beta blockers (e.g., propranolol)
Others
Benzoctamine
Cannabidiol
Cycloserine
Fabomotizole
Hydroxyzine
Kanna
Lavender
Lorpiprazole
Mebicar
Mepiprazole
Nicotine
Opipramol
Oxaflozane‡
Phenaglycodol
Phenibut
Picamilon
Selank
Tiagabine
Tofisopam
Validolum
#WHO-EM
‡Withdrawn from market
Clinical trials:
†Phase III
§Never to phase III
[show]
v
t
e
OCD pharmacotherapies
Antidepressants
SSRIs (e.g., fluoxetine, fluvoxamine, sertraline)
SNRIs (e.g., venlafaxine)
TCAs (e.g., clomipramine)
MAOIs (e.g., phenelzine)
Others
Antiandrogens (e.g., cyproterone acetate, leuprorelin)
Antipsychotics (e.g., risperidone)
Benzodiazepines (e.g., clonazepam)
Lamotrigine
Memantine
Mirtazapine
N-Acetylcysteine
Ondansetron
Pregabalin
Psychedelics (e.g., psilocybin)
Riluzole
Topiramate
[show]
v
t
e
Monoamine reuptake inhibitors
DAT
(DRIs)
Piperazines: DBL-583
GBR-12783
GBR-12935
GBR-13069
GBR-13098
Nefazodone
Vanoxerine
Piperidines: 4-Fluoropethidine
Benocyclidine (BTCP)
Desoxypipradrol
Dexmethylphenidate
Difemetorex
Ethylphenidate
HDMP-28
Methylphenidate
Pethidine (meperidine)
Phencyclidine
Pipradrol
Tenocyclidine
Pyrrolidines: Diphenylprolinol
MDPV
Naphyrone
Prolintane
Pyrovalerone
Tropanes: Altropane
Benzatropine (benztropine)
Brasofensine
CFT
Cocaine
Dichloropane
Difluoropine
Etybenzatropine (ethybenztropine)
FE-β-CPPIT
FP-β-CPPIT
Ioflupane (123I)
RTI-55
RTI-112
RTI-113
RTI-121
RTI-126
RTI-150
RTI-177
RTI-229
RTI-336
Tesofensine
Troparil
Tropoxane
WF-11
WF-23
WF-31
WF-33
Others: Adrafinil
Amifitadine
Armodafinil
Amfonelic acid
Amineptine
Ansofaxine
BTQ
BTS 74,398
Bupropion
Chaenomeles speciosa
Ciclazindol
Dasotraline
Desmethylsertraline
Desmethylsibutramine
Diclofensine
Didesmethylsibutramine
Dimethocaine
Diphenylpyraline
Dizocilpine (MK-801)
DOV-102,677
DOV-216,303
Efavirenz
Ephenidine
Esketamine
EXP-561
Fencamfamin
Fezolamine
Fluorenol
GYKI-52895
Indatraline
Ketamine
Lefetamine
Levophacetoperane
Liafensine
LR-5182
Manifaxine
Mazindol
Medifoxamine
Mesocarb
Metaphit
MIN-117 (WF-516)
Modafinil
Nefopam
Nomifensine
NS-2359
O-2172
Oroxylin A
Perafensine
Pridefine
Radafaxine
Rimcazole
Sertraline
Sibutramine
Solriamfetol
Tametraline
Tedatioxetine
Tripelennamine
Venlafaxine
NET
(NRIs)
Selective norepinephrine reuptake inhibitors: Amedalin
Alseroxylon
Ciclazindol
Daledalin
Edivoxetine
Esreboxetine
Lortalamine
Mazindol
Nisoxetine
Reboxetine
Talopram
Talsupram
Tandamine
Teniloxazine
Viloxazine
Norepinephrine–dopamine reuptake inhibitors: Amineptine
Bupropion
Fencamine
Fencamfamin
Hydroxybupropion
Lefetamine
Levophacetoperane
LR-5182
Manifaxine
Methylphenidate
Nomifensine
O-2172
Radafaxine
Solriamfetol
Serotonin–norepinephrine reuptake inhibitors: Atomoxetine (tomoxetine)
BTS-54505
CP-39,332
Desvenlafaxine
Duloxetine
Eclanamine
Levomilnacipran
McN-5652
Milnacipran
N-Methyl-PPPA
PPPA
Tofenacin
Venlafaxine
WY-45233
Serotonin–norepinephrine–dopamine reuptake inhibitors: 3,3-Diphenylcyclobutanamine
Amifitadine
Ansofaxine
Bicifadine
Brasofensine
Centanafadine
Cocaine
Dasotraline
Desmethylsertraline
Desmethylsibutramine
Diclofensine
Didesmethylsibutramine
DOV-102677
DOV-216303
EXP-561
Fezolamine
HDMP-28
Indatraline
JNJ-7925476
JZ-IV-10
Liafensine
Mazindol
Naphyrone
Nefazodone
Nefopam
NS-2359
Perafensine
PRC200
Pridefine
SEP-228431
SEP-228432
Sibutramine
Tedatioxetine
Tesofensine
Tropanes (e.g., cocaine)
Tricyclic antidepressants: Amitriptyline
Butriptyline
Cianopramine
Clomipramine
Desipramine
Dosulepin (dothiepin)
Doxepin
Imipramine
Lofepramine
Melitracen
Nortriptyline
Protriptyline
Trimipramine
Tetracyclic antidepressants: Amoxapine
Maprotiline
Mianserin
Oxaprotiline
Setiptiline
Others: Antihistamines (e.g., brompheniramine, chlorphenamine, pheniramine, tripelennamine)
Antipsychotics (e.g., loxapine, ziprasidone)
Arylcyclohexylamines (e.g., ketamine, phencyclidine)
Dopexamine
Ephenidine
Ginkgo biloba
Indeloxazine
Nefazodone
Opioids (e.g., desmetramadol, methadone, pethidine (meperidine), tapentadol, tramadol, levorphanol)
SERT
(SRIs)
Selective serotonin reuptake inhibitors: Alaproclate
Centpropazine
Cericlamine
Citalopram
Dapoxetine
Desmethylcitalopram
Didesmethylcitalopram
Escitalopram
Femoxetine
Fluoxetine
Fluvoxamine
Indalpine
Ifoxetine
Norfluoxetine
Omiloxetine
Panuramine
Paroxetine
PIM-35
Pirandamine
RTI-353
Seproxetine
Sertraline
Zimelidine
Selective serotonin reuptake inhibitors and serotonin receptor modulators: Etoperidone
Litoxetine
Lubazodone
LY-393558
SB-649915
TGBA01AD
Trazodone
Vilazodone
Vortioxetine
Serotonin–norepinephrine reuptake inhibitors: Atomoxetine (tomoxetine)
Bicifadine
BTS-54505
CP-39332
Desvenlafaxine
Duloxetine
Eclanamine
Levomilnacipran
McN-5652
Milnacipran
N-Methyl-PPPA
PPPA
Tofenacin
Venlafaxine
WY-45233
Serotonin–norepinephrine–dopamine reuptake inhibitors: 3,3-Diphenylcyclobutanamine
Amifitadine
Ansofaxine
Bicifadine
Brasofensine
Centanafadine
Cocaine
Dasotraline
Desmethylsertraline
Desmethylsibutramine
Diclofensine
Didesmethylsibutramine
DOV-102677
DOV-216303
EXP-561
Fezolamine
HDMP-28
Indatraline
JNJ-7925476
JZ-IV-10
Liafensine
Mazindol
Naphyrone
Nefazodone
Nefopam
NS-2359
Perafensine
PRC200
Pridefine
SEP-228431
SEP-228432
Sibutramine
Tedatioxetine
Tesofensine
Tropanes (e.g., cocaine)
Tricyclic antidepressants: Amitriptyline
Cianopramine
Clomipramine
Cyanodothiepin
Desipramine
Dosulepin (dothiepin)
Doxepin
Imipramine
Lofepramine
Nortriptyline
Pipofezine
Protriptyline
Others: A-80426
Amoxapine
Antihistamines (e.g., brompheniramine, chlorphenamine, dimenhydrinate, diphenhydramine, mepyramine (pyrilamine), pheniramine, tripelennamine)
Antipsychotics (e.g., loxapine, ziprasidone)
Arylcyclohexylamines (e.g., 3-MeO-PCP, esketamine, ketamine, methoxetamine, phencyclidine)
Cyclobenzaprine
Delucemine
Dextromethorphan
Dextrorphan
Efavirenz
Medifoxamine
Mesembrine
Mifepristone
MIN-117 (WF-516)
N-Me-5-HT
Opioids (e.g., dextropropoxyphene, methadone, pethidine (meperidine), levorphanol, tapentadol, tramadol)
Roxindole
VMATs
Amiodarone
Amphetamines (e.g., amphetamine, methamphetamine, MDMA)
APP
AZIK
Bietaserpine
Deserpidine
Deutetrabenazine
Dihydrotetrabenazine
Efavirenz
GBR-12935
GZ-793A
Ibogaine
Ketanserin
Lobeline
Methoxytetrabenazine
Reserpine
Rose bengal
Tetrabenazine
Valbenazine
Vanoxerine (GBR-12909)
Others
DAT enhancers: Luteolin
DAT modulators: Agonist-like: SoRI-9804
SoRI-20040; Antagonist-like: SoRI-20041
See also: Receptor/signaling modulators • Monoamine releasing agents • Adrenergics • Dopaminergics • Serotonergics • Monoamine metabolism modulators • Monoamine neurotoxins
[show]
v
t
e
Sigma receptor modulators
σ1
Agonists: 3-PPP
4-PPBP
5-MeO-DMT
Alazocine (SKF-10047)
Amantadine
ANAVEX2-73
Arketamine
BD-737
BD-1052
Captodiame
Citalopram
CGRP
Cloperastine
Cocaine
Cutamesine (SA-4503)
Cyclazocine
Dehydroepiandrosterone (DHEA) (prasterone)
Dehydroepiandrosterone sulfate (DHEA-S) (prasterone sulfate)
Dextrallorphan
Dextromethorphan (DXM)
Dextrorphan (DXO)
Dimemorfan
Dimethyltryptamine (DMT)
Ditolylguanidine (DTG)
Donepezil
Eliprodil
Escitalopram
Fabomotizole (afobazole)
Fluoxetine
Fluvoxamine
Ifenprodil
Igmesine (JO-1784)
IPAB
Ketamine
L-687384
MDMA (midomafetamine)
Memantine
Methamphetamine
Methoxetamine
Methylphenidate
Nepinalone
Neuropeptide Y
Noscapine
OPC-14523
Opipramol
Pentazocine
Pentoxyverine (carbetapentane)
PRE-084
Pregnenolone
Pregnenolone sulfate
Pridopidine
Racemethorphan (methorphan)
Racemorphan (morphanol)
UMB-23
UMB-82
Antagonists: 3-PPP
AC-927
BD-1008
BD-1031
BD-1047
BD-1060
BD-1063
BD-1067
BMY-14802 (BMS-181100)
CM-156
Dup-734
E-5842
E-52862 (S1RA)
Haloperidol
LR-132
LR-172
MS-377
NE-100
NPC-16377
Panamesine (EMD-57455)
PD-144418
Pentazocine
Progesterone
Rimcazole (BW-234U)
Sertraline
SR-31742A
Allosteric modulators: Phenytoin; Positive: Methylphenylpiracetam
SOMCL-668
Unknown/unsorted: 3-Methoxydextrallorphan
3-MeO-PCP
4C-T-2
4-IBP
4-IPBS
4-MeO-PCP
5-MeO-DALT
5-MeO-DiPT
Amitriptyline
Azidopamil
Chlorpromazine
Clemastine
Clomipramine
Clorgiline
D-Deprenyl
DiPT
DPT
Ibogaine
Imipramine
KCR-12-83.1
Nemonapride
Noribogaine
RHL-033
RS-67,333
RTI-55
Saffron
Safinamide
Selegiline
Spipethiane
Trifluoperazine
W-18
YKP10A
σ2
Agonists: 3-PPP
Arketamine
BD-1047
BD1063
Ditolylguanidine (DTG)
DKR-1005
DKR-1051
Haloperidol
Ifenprodil
Ketamine
MDMA (midomafetamine)
Methamphetamine
OPC-14523
Opipramol
PB-28
Phencyclidine
Siramesine (Lu 28-179)
UKH-1114
Antagonists: AC-927
BD-1008
BD-1067
CM-156
CT-1812
LR-172
MIN-101
Panamesine (EMD-57455)
SAS-0132
Unknown/unsorted: 3-Methoxydextrallorphan
3-MeO-PCE
4-MeO-PCP
5-MeO-DALT
5-MeO-DiPT
Clemastine
DiPT
DPT
Ibogaine
Nemonapride
Nepinalone
Noribogaine
Pentazocine
RS-67,333
Safinamide
TMA
UMB-23
UMB-82
W-18
Unsorted
Agonists: Berberine
Ethylketazocine
Fourphit
Metaphit
Nalbuphine
Naluzotan
Tapentadol
Tenocyclidine
Antagonists: AHD1
AZ66
Lamotrigine
Naloxone
SM-21
UMB-100
UMB-101
UMB-103
UMB-116
YZ-011
YZ-069
YZ-185
Allosteric modulators: SKF-83959
Unknown/unsorted: 18-Methoxycoronaridine
BMY-13980
Butaclamol
Caramiphen
Carvotroline
Chlorphenamine (chlorpheniramine)
Chlorpromazine
Cinnarizine
Cinuperone
Clocapramine
Dezocine
EMD-59983
Hypericin (St. John's wort)
Fluphenazine
Gevotroline (WY-47384)
Mepyramine (pyrilamine)
Molindone
Perphenazine
Pimozide
Proadifen
Promethazine
Propranolol
Quinidine
Remoxipride
SL 82.0715
SR-31747A
Tiospirone (BMY-13859)
Venlafaxine
See also: Receptor/signaling modulators
Retrieved from "https://en.wikipedia.org/w/index.php?title=Selective_serotonin_reuptake_inhibitor&oldid=803706320"
Categories:
Selective serotonin reuptake inhibitors
Sigma receptor ligands
Hidden categories:
CS1 maint: Multiple names: authors list
CS1 maint: Uses authors parameter
Template:drugs.com link with non-standard subpage
All articles with unsourced statements
Articles with unsourced statements from June 2017
Articles with unsourced statements from August 2017
Navigation menu
Personal tools
Not logged in
Talk
Contributions
Create account
Log in
Namespaces
Article
Talk
Variants
Views
Read
Edit
View history
More
Search
Navigation
Main page
Contents
Featured content
Current events
Random article
Donate to Wikipedia
Wikipedia store
Interaction
Help
About Wikipedia
Community portal
Recent changes
Contact page
Tools
What links here
Related changes
Upload file
Special pages
Permanent link
Page information
Wikidata item
Cite this page
Print/export
Create a book
Download as PDF
Printable version
In other projects
Wikimedia Commons
Languages
العربية
Català
Čeština
Dansk
Deutsch
Eesti
Español
فارسی
Français
한국어
Íslenska
Italiano
עברית
Latviešu
Lietuvių
Magyar
Македонски
Nederlands
日本語
Norsk
Polski
Português
Русский
Simple English
Slovenščina
Српски / srpski
Srpskohrvatski / српскохрватски
Suomi
Svenska
ไทย
Türkçe
Українська
中文
Edit links
This page was last edited on 4 October 2017, at 03:04.
Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization.
Privacy policy
About Wikipedia
Disclaimers
Contact Wikipedia
Developers
Cookie statement
Mobile view

values: mw-page-base noprint

values: mw-head-base noprint

attrs: id class style

values: firstHeading firstHeading en

values: siteSub noprint

values: jump-to-nav mw-jump

values:
/wiki/SSRI_(disambiguation)
mw-disambig
SSRI (disambiguation)

values:
note
hatnote navigation-not-searchable

values: Anatomical Therapeutic Chemical Classification System

values:
/wiki/ATC_code_N06AB
mw-redirect
ATC code N06AB

values: text-align:center;background: #e8e8e8; text-align: center

values:
/wiki/Class_of_drugs
mw-redirect
Class of drugs

values:
/wiki/Presynaptic_cell
mw-redirect
Presynaptic cell

values:
/wiki/Synaptic_cleft
mw-redirect
Synaptic cleft

values:
/wiki/Postsynaptic_receptor
mw-redirect
Postsynaptic receptor

values: National Institute for Health and Care Excellence

values: Edit section: Generalized anxiety disorder

values: Edit section: Obsessive–compulsive disorder

values:
/wiki/Coronary_heart_disease
mw-redirect
Coronary heart disease

values:
/wiki/GI_bleeding
mw-redirect
GI bleeding

values:
/wiki/Intracranial_bleeding
mw-redirect
Intracranial bleeding

values:
/wiki/SSRI_discontinuation_syndrome
mw-redirect
SSRI discontinuation syndrome

values: Food and Drug Administration (United States)

values: Medicines and Healthcare products Regulatory Agency

values:
/wiki/Risk-benefit_analysis
mw-redirect
Risk-benefit analysis

values:
/wiki/Tricyclic_antidepressants
mw-redirect
Tricyclic antidepressants

values: Edit section: Pregnancy and breastfeeding

values: Edit section: Neonatal abstinence syndrome

values:
/wiki/Neonatal_abstinence_syndrome
mw-redirect
Neonatal abstinence syndrome

values: Edit section: Persistent pulmonary hypertension

values: Edit section: Neuropsychiatric effects in offspring

values:
/wiki/Autism_spectrum_disorders
mw-redirect
Autism spectrum disorders

values: Edit section: Contraindications and drug interactions

values:
/wiki/Monoamine_oxidase_inhibitors
mw-redirect
Monoamine oxidase inhibitors

values:
/wiki/St._John%27s_wort
mw-redirect
St. John's wort

values:
/wiki/File:Citalopram.svg
image
Chemical structure of citalopram.

values:
/wiki/File:Escitalopram.svg
image
Chemical structure of escitalopram.

values:
/wiki/File:Fluoxetine.svg
image
Chemical structure of fluoxetine.

values:
/wiki/File:Fluvoxamine.svg
image
Chemical structure of fluvoxamine.

values:
/wiki/File:Paroxetine-2D-skeletal.svg
image
Chemical structure of paroxetine.

values:
/wiki/File:Sertraline.svg
image
Chemical structure of sertraline.

values: padding-left: 0.3em; text-align: left; display: none;

values:
/wiki/File:Dapoxetine.svg
image
Chemical structure of dapoxetine.

values:
/wiki/File:Indalpine.svg
image
Chemical structure of indalpine.

values:
/wiki/File:Zimelidine.svg
image
Chemical structure of zimelidine.

values:
/wiki/File:Alaproclate_structure.svg
image
Chemical structure of alaproclate.

values:
/wiki/File:Cericlamine.svg
image
Chemical structure of cericlamine.

values:
/wiki/File:Femoxetine.svg
image
Chemical structure of femoxetine.

values:
/wiki/File:Ifoxetine.png
image
Chemical structure of ifoxetine.

values:
/wiki/File:Omiloxetine.svg
image
Chemical structure of omiloxetine.

values:
/wiki/File:Panuramine.svg
image
Chemical structure of panuramine.

values:
/wiki/File:Pirandamine.png
image
Chemical structure of pirandamine.

values:
/wiki/File:Seproxetine.svg
image
Chemical structure of seproxetine.

values:
/wiki/Serotonin_receptor
mw-redirect
Serotonin receptor

values: Edit section: Serotonin reuptake inhibition

values: This claim needs references to reliable sources. (June 2017)

values:
noprint Inline-Template Template-Fact
white-space:nowrap;

values: This claim needs references to reliable sources. (August 2017)

values:
/wiki/Type_1_diabetes
mw-redirect
Type 1 diabetes

values:
/wiki/Tumor_necrosis_factor-%CE%B1
mw-redirect
Tumor necrosis factor-α

values:
/wiki/Interferon_%CE%B3
mw-redirect
Interferon γ

values:
/wiki/Inflammatory_bowel_diseases
mw-redirect
Inflammatory bowel diseases

values: Noradrenergic and specific serotonergic antidepressant

values: Serotonin antagonist and reuptake inhibitor

values:
/wiki/Trace_amine-associated_receptor_1
mw-redirect
Trace amine-associated receptor 1

values:
nofollow
external text
//www.worldcat.org/oclc/192055408

values: Category:CS1 maint: Multiple names: authors list

values:
nofollow
external free
http://pi.lilly.com/us/prozac.pdf

attrs: alt src title width height srcset data-file-width data-file-height

values:
/wiki/PubMed_Identifier
mw-redirect
PubMed Identifier

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/20051569

values:
nofollow
external text
//doi.org/10.1001%2Fjama.2009.1943

values:
nofollow
external text
https://zenodo.org/record/890741

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/20520282

values:
nofollow
external text
//www.worldcat.org/issn/1471-244X

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/28178949

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/18303940

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/20571143

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/20800012

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/22393205

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/22147715

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/23152227

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/12804478

values:
nofollow
external text
//doi.org/10.1002%2F14651858.CD003592

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/19588448

values:
nofollow
external text
//doi.org/10.1002%2F14651858.CD007954

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/22226028

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/21414249

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/23152272

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/17983899

values:
nofollow
external text
//doi.org/10.1016%2Fj.ucl.2007.08.011

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/21904950

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/21406165

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/9694033

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/19289334

values:
nofollow
external text
//doi.org/10.1331%2FJAPhA.2009.08083

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/8909330

values:
nofollow
external text
//doi.org/10.4088%2FJCP.v57n1002

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/23728643

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/19512977

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/26003261

values:
nofollow
external text
//www.worldcat.org/issn/2050-0521

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/28642048

values:
nofollow
external text
//doi.org/10.1016%2Fj.sxmr.2017.05.002

values:
nofollow
external text
//www.worldcat.org/issn/0160-6689

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/7929021

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/16946173

values:
nofollow
external text
//doi.org/10.1176%2Fappi.ajp.163.9.1504

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/12429073

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/22573230

values:
nofollow
external text
//doi.org/10.1038%2Fijir.2012.12

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/24646010

values:
nofollow
external text
//doi.org/10.1111%2Fbcp.12383

values:
nofollow
external text
//www.worldcat.org/issn/0028-4793

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/24941178

values:
nofollow
external text
//doi.org/10.1056%2FNEJMoa1312828

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/9443704

values:
nofollow
external text
//doi.org/10.1001%2Farchfami.7.1.78

values: Medicines and Healthcare Products Regulatory Agency

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/10213794

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/15794724

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/21190637

values:
nofollow
external text
//doi.org/10.4088%2FJCP.09r05786blu

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/18606952

values:
nofollow
external text
//doi.org/10.1001%2Farchpsyc.65.7.795

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/23077009

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/16443409

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/17506225

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/21542658

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/22258738

values:
nofollow
external text
//doi.org/10.1002%2Fjbmr.1554

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/25091520

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/27055202

values:
nofollow
external text
//doi.org/10.3949%2Fccjm.83a.15066

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/26547857

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/25667198

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/27495351

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/23196265

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/23596418

values:
nofollow
external text
//doi.org/10.3389%2Ffphar.2013.00045

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/16894062

values:
nofollow
external text
//doi.org/10.1001%2Farchpsyc.63.8.865

values:
nofollow
external text
//www.worldcat.org/issn/1469-493X

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/25433518

values:
nofollow
external text
https://doi.org/10.1089%2Fcap.2006.0138

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/17074941

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/15718537

values:
nofollow
external text
//doi.org/10.1136%2Fbmj.330.7488.385

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/15718539

values:
nofollow
external text
//doi.org/10.1136%2Fbmj.330.7488.396

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/16712945

values:
nofollow
external text
//doi.org/10.1016%2Fj.jad.2006.04.003

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/17054562

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/23042258

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/16720091

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/23351929

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/27239775

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/22946124

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/23660045

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/23228547

values:
nofollow
external text
//doi.org/10.1016%2Fj.siny.2012.10.004

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/17294355

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/21893008

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/24039427

values:
nofollow
external text
//doi.org/10.2147%2FNDT.S36394

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/24429387

values:
nofollow
external text
//doi.org/10.1136%2Fbmj.f6932

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/22564982

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/25985383

values:
nofollow
external text
//doi.org/10.1016%2Fj.jad.2015.04.048

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/24350950

values:
nofollow
external text
//doi.org/10.1056%2FNEJMoa1301449

values:
nofollow
external text
//doi.org/10.1016%2Fj.jaac.2016.02.013

values: Category:CS1 maint: Uses authors parameter

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/15362595

values:
nofollow
external text
//doi.org/10.1081%2FCLT-120037428

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/1586402

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/8709713

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/7576268

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/19031375

values:
nofollow
external text
//doi.org/10.1007%2FBF03161207

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/12873279

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/15784664

values:
nofollow
external text
//doi.org/10.1056%2FNEJMra041867

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/21518864

values:
nofollow
external text
//doi.org/10.1073%2Fpnas.1104836108

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/26572745

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/28707591

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/17017959

values:
nofollow
external text
//www.worldcat.org/issn/0885-6222

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/9537821

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/16413139

values:
nofollow
external text
//doi.org/10.1016%2Fj.mehy.2005.12.006

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/20373470

values:
nofollow
external text
//doi.org/10.1002%2Fhup.1106

values:
nofollow
external text
//www.worldcat.org/issn/0065-2598

values:
nofollow
external text
//doi.org/10.1016%2Fj.pnpbp.2017.04.026

values:
nofollow
external text
//doi.org/10.1038%2Ftp.2012.8

values:
nofollow
external text
//doi.org/10.1016%2Fj.imbio.2016.07.001

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/17096399

values:
nofollow
external text
//doi.org/10.1002%2Fda.20251

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/10760555

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/18199864

values:
nofollow
external text
//doi.org/10.1056%2FNEJMsa065779

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/14517577

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/12668373

values:
nofollow
external text
//doi.org/10.1176%2Fappi.ajp.160.4.790

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/16773951

values:
nofollow
external text
//doi.org/10.1191%2F1740774506cn139oa

values:
nofollow
external text
//www.ncbi.nlm.nih.gov/pubmed/22309973

values: -moz-column-width: 30em; -webkit-column-width: 30em; column-width: 30em; list-style-type: decimal;

values: Noradrenergic and specific serotonergic antidepressants

values: Serotonin antagonist and reuptake inhibitors

values: nowraplinks collapsible uncollapsed navbox-subgroup

values:
/wiki/Tetracyclic_antidepressants
mw-redirect
Tetracyclic antidepressants

values:
/wiki/Thyroid_hormone
mw-redirect
Thyroid hormone

values: nowraplinks collapsible collapsed navbox-inner

values:
/wiki/Positive_allosteric_modulators
mw-redirect
Positive allosteric modulators

values:
/wiki/Alpha-2_agonist
mw-redirect
Alpha-2 agonist

values: nowraplinks collapsible autocollapse navbox-inner

values: Template talk:Monoamine reuptake inhibitors

values:
/wiki/Dopamine_reuptake_inhibitors
mw-redirect
Dopamine reuptake inhibitors

values: Desmethylsibutramine (page does not exist)

values: Didesmethylsibutramine (page does not exist)

values:
/wiki/Histamine_antagonist
mw-redirect
Histamine antagonist

values:
/wiki/Serotonin_reuptake_inhibitors
mw-redirect
Serotonin reuptake inhibitors

values:
/wiki/Vesicular_monoamine_transporters
mw-redirect
Vesicular monoamine transporters

values: 3-Amino-2-phenylpropene (page does not exist)

values: 7-Azido-8-iodoketanserin (page does not exist)

values: Methoxytetrabenazine (page does not exist)

values: 3-Methoxydextrallorphan (page does not exist)

values: nowraplinks hlist collapsible collapsed navbox-inner

values: Category:Selective serotonin reuptake inhibitors

values: Category:Template:drugs.com link with non-standard subpage

values: Category:All articles with unsourced statements

values: Category:Articles with unsourced statements from June 2017

values: Category:Articles with unsourced statements from August 2017

values: Discussion about edits from this IP address [ctrl-alt-n]

values: A list of edits made from this IP address [ctrl-alt-y]

values: You are encouraged to create an account and log in; however, it is not mandatory

values: You're encouraged to log in; however, it's not mandatory. [ctrl-alt-o]

values: Discussion about the content page [ctrl-alt-t]

values: p-namespaces navigation vectorTabs p-namespaces-label

values:
p-variants
navigation
vectorMenu emptyPortlet
p-variants-label

values: Past revisions of this page [ctrl-alt-h]

values: p-views navigation vectorTabs p-views-label

values:
p-cactions
navigation
vectorMenu emptyPortlet
p-cactions-label

values:
mw-wiki-logo
/wiki/Main_Page
Visit the main page

values:
/wiki/Main_Page
Visit the main page [ctrl-alt-z]
z

values: Featured content – the best of Wikipedia

values: Find background information on current events

values:
/wiki/Special:Random
Load a random article [ctrl-alt-x]
x

values: portal navigation p-navigation p-navigation-label

values: Guidance on how to use and edit Wikipedia

values: About the project, what you can do, where to find things

values: A list of recent changes in the wiki [ctrl-alt-r]

values: portal navigation p-interaction p-interaction-label

values: List of all English Wikipedia pages containing links to this page [ctrl-alt-j]

values: Recent changes in pages linked from this page [ctrl-alt-k]

values:
/wiki/Wikipedia:File_Upload_Wizard
Upload files [ctrl-alt-u]
u

values: A list of all special pages [ctrl-alt-q]

values: Permanent link to this revision of the page

values: Link to connected data repository item [ctrl-alt-g]

values: Printable version of this page [ctrl-alt-p]

values: portal navigation p-wikibase-otherprojects p-wikibase-otherprojects-label

values:
uls-settings-trigger
Language settings
0
button
true

values: مثبطات استرداد السيروتونين الانتقائية – Arabic

values: Inhibidor selectiu de la recaptació de serotonina – Catalan

values: Selektivní inhibitor zpětného vychytávání serotoninu – Czech

values: Selektive serotoningenoptagshæmmere – Danish

values: Selektiivsed serotoniini tagasihaarde inhibiitorid – Estonian

values: Inhibidor selectivo de la recaptación de serotonina – Spanish

values: بازدارنده‌های بازجذب سروتونین – Persian

values: Inhibiteur sélectif de la recapture de la sérotonine – French

values: 선택적 세로토닌 재흡수 억제제 – Korean

values: Sértækir serótónín endurupptökuhemlar – Icelandic

values: Inibitori selettivi della ricaptazione della serotonina – Italian

values:
https://he.wikipedia.org/wiki/SSRI
SSRI – Hebrew
he
he
interlanguage-link-target

values: Selektīvie serotonīna atpakaļsaistīšanās inhibitori – Latvian

values: Selektyvieji serotonino reabsorbcijos inhibitoriai – Lithuanian

values: Szelektív szerotoninvisszavétel-gátlók – Hungarian

values: Селективен инхибитор на повторното преземање на серотонинот – Macedonian

values: Selectieve serotonine-heropnameremmer – Dutch

values: 選択的セロトニン再取り込み阻害薬 – Japanese

values: Selektiv serotoninreopptakshemmer – Norwegian

values: Selektywne inhibitory zwrotnego wychwytu serotoniny – Polish

values: Inibidor seletivo de recaptação de serotonina – Portuguese

values: Селективные ингибиторы обратного захвата серотонина – Russian

values: Selective serotonin reuptake inhibitor – Simple English

values: Selektivni zaviralec ponovnega privzema serotonina – Slovenian

values: Selektivni inhibitor preuzimanja serotonina – Serbian

values: Selektivni inhibitor preuzimanja serotonina – Serbo-Croatian

values: Selektiiviset serotoniinin takaisinoton estäjät – Finnish

values: Selektiva serotoninåterupptagshämmare – Swedish

values: Selective serotonin re-uptake inhibitors – Thai

values: Selektif serotonin gerialım inhibitörleri – Turkish

values: Селективні інгібітори зворотного захоплення серотоніну – Ukrainian

values: 选择性5-羟色胺再摄取抑制剂 – Chinese

values: /static/images/wikimedia-button-1.5x.png 1.5x, /static/images/wikimedia-button-2x.png 2x

values: /static/images/poweredby_mediawiki_132x47.png 1.5x, /static/images/poweredby_mediawiki_176x62.png 2x

values:
suggestions
display: none; font-size: 13px;

values: mediawiki ltr sitedir-ltr mw-hide-empty-elt ns-0 ns-subject page-Selective_serotonin_reuptake_inhibitor rootpage-Selective_serotonin_reuptake_inhibitor vector-nav-directionality skin-vector action-view