Selective serotonin reuptake inhibitor

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"SSRI" redirects here; for other uses, see SSRI (disambiguation).
This article is about selective serotonin reuptake inhibitors. For serotonin reuptake inhibitors, see serotonin reuptake inhibitor.
Serotonin

Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor[1] (SSRIs) are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. They are also typically effective and used in treating premature ejaculation problems as well as some cases of insomnia.

SSRIs increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin 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 noradrenaline and dopamine transporter.

The first class of psychotropic drugs to be rationally designed, SSRIs are the most widely prescribed antidepressants in many countries.[2]

Contents

[edit] List of SSRIs

Drugs in this class include (trade names in parentheses):

  • citalopram (Celexa, Cipramil, Cipram, Dalsan, Recital, Emocal, Sepram, Seropram, Citox)
  • dapoxetine (no trade name yet; not yet approved by the FDA)
  • escitalopram (Lexapro, Cipralex, Esertia)
  • fluoxetine (Prozac, Fontex, Seromex, Seronil, Sarafem, Fluctin (EUR), Fluox (NZ), Depress (UZB), Lovan (AUS))
  • fluvoxamine (Luvox, Fevarin, Faverin, Dumyrox, Favoxil, Movox)
  • paroxetine (Paxil, Seroxat, Sereupin, Aropax, Deroxat, Rexetin, Xetanor, Paroxat)
  • sertraline (Zoloft, Lustral, Serlain)
  • zimelidine (Zelmid, Normud)

[edit] Related antidepressants

SSRIs form a subclass of serotonin uptake inhibitors, which includes other non-selective inhibitors as well. Serotonin-norepinephrine reuptake inhibitor, serotonin-noradrenaline-dopamine reuptake inhibitors and selective serotonin reuptake enhancers are also serotonergic antidepressants.

[edit] Medical indications

The main indication for SSRIs is clinical depression. SSRIs are frequently prescribed for anxiety disorders like social anxiety, panic disorders, obsessive-compulsive disorder (OCD), eating disorders, chronic pain, and occasionally for Posttraumatic stress disorder (PTSD). Though not specifically indicated by the manufacturers, they are sometimes prescribed to treat irritable bowel syndrome (IBS), Lichen simplex chronicus, and premature ejaculation.

All SSRIs are approved in the US for use with psychiatric disorders as outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV).

The uses for which SSRIs are approved vary by country and is determined by the overseeing medical branch of government in charge of regulating drugs. In the United States, the Food and Drug Administration (FDA) makes these approvals after trials have been submitted by pharmaceutical companies. In Europe, drugs can be approved either by the European Medicines Agency for human consumption throughout the European Union or by the regulatory agencies of individual countries for use within those countries.[citation needed]. In Canada the drug approval process is carried out by Health Canada.

A general disadvantage of SSRIs in treating premature ejaculation is that they require continuous daily treatment to delay ejaculation significantly.[3] For the occasional "on-demand", a few hours before coitus, treatment, clomipramine gave better results than paroxetine in one study,[4] while in another study both sertraline and clomipramine were indistinguishable from the pause–squeeze technique and inferior to paroxetine.[5] The most recent research, conducted in 2007, suggests that on-demand treatment with sildenafil (Viagra) offers a dramatic improvement in ejaculation delay and sexual satisfaction as compared with daily paroxetine,[6] with on-demand sertraline, paroxetine or clomipramine,[5] and with the pause–squeeze technique.[5][6]

[edit] Contraindications and drug interaction

One major contraindication of SSRIs is the concomitant use of MAOIs (monoamine oxidase inhibitors). This is likely to cause severe serotonin syndrome.

People taking SSRIs should also avoid taking pimozide (an antipsychotic diphenylbutylpiperidine derivative). The atypical opioid analgesic tramadol hydrochloride (or Ultram, Ultracet) can, in rare cases, produce seizures when taken in conjunction with an SSRI or tricyclic antidepressant. Liver impairment is another contraindication for medications of this type.

SSRIs may increase blood levels and risk of toxicities of certain medications:

  1. highly protein-bound medications like warfarin (coumadin) and digoxin
  2. antiarrhythmic agents like propafenone (Rythmol) or flecainide (Tambocor)
  3. beta blockers like metoprolol (Toprol xl) or propranolol (Inderal)
  4. tricyclic antidepressants like amitriptyline (Elavil) (may increase risk of serotonin syndrome)
  5. benzodiazepines like alprazolam (Xanax) or diazepam (Valium)
  6. carbamazepine (Tegretol)
  7. cisapride (Propulsid)
  8. clozapine (Clozaril)
  9. ciclosporin (Neoral)
  10. haloperidol (Haldol)
  11. phenytoin (Dilantin)
  12. pimozide (Orap)
  13. theophylline (Theo-dur)

Certain drugs may increase toxicities of SSRIs:

  1. alcohol and other CNS depressants
  2. diuretics (water pills)
  3. MAOIs
  4. sympathomimetic drugs like pseudoephedrine (Sudafed)
  5. lithium
  6. sibutramine (Meridia)
  7. MDMA (ecstasy)
  8. zolpidem (ambien)[7]
  9. Dextromethorphan
  10. tramadol (synergistic serotoninergic effect said to increase risk of seizure)

[edit] Mode of action

SSRIs are believed to act by inhibiting the reuptake of serotonin after being released in synapses. How much an individual will respond to this, however, also depends on genetics. In addition, several other mechanisms are suggested for the desired effect, e.g. neuroprotection and anti-inflammatory and immunomodulatory factors. Taken together, SSRI has several advantages compared with tricyclic antidepressants (TCA)s and 5-HT-prodrugs. However, the latter might be required in addition to SSRIs in certain situations.

[edit] Basic understanding

Further information: Chemical synapse

In the brain, messages are passed between two nerve cells via a synapse, a small gap between the cells. The (presynaptic) cell that sends the information releases neurotransmitters (of which serotonin is one) 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).

To stimulate the recipient cell, SSRIs inhibit the reuptake of serotonin. As a result, the serotonin stays in the synaptic gap longer than it normally would, and may be recognized again (and again) by the receptors of the recipient cell, stimulating it.

[edit] Pharmacodynamics

SSRIs inhibit the reuptake of the neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) into the presynaptic cell, increasing levels of 5-HT within the synaptic cleft.

But there is one counteracting effect: high serotonin levels will not only activate the postsynaptic receptors, but also flood presynaptic autoreceptors, that serve as a feedback sensor for the cell. Activation of the autoreceptors (by agonists like serotonin) triggers a throttling of serotonin production. The resulting serotonin deficiency persists for some time, as the transporter inhibition occurs downstream to the cause of the deficiency, and is therefore not able to counterbalance the serotonin deficiency. The body adapts gradually to this situation by lowering (downregulating) the sensitivity of the autoreceptors [8].

Another adaptive process provoked by SSRIs, however, has potentially harmful effects: the downregulation of postsynaptic serotonin 5-HT2A receptors. After the use of an SSRI, since there is more serotonin available, the response is to decrease the number of postsynaptic receptors over time, and in the long run, this modifies the serotonin/receptor ratio. The augmented amount of serotonin often does not match up with the rate of receptor neurogenesis, and therefore the increased amount of binding of SSRI ligands to the serotonin receptors has the potential to "wear out" those receptors if the SSRI acts as an agonist. Because of this, prolonged agonist SSRI usage followed by discontinuation can promote deeper depression for some individuals. SSRIs which function as antagonists may equally have negative consequences, as antagonists tend to bind to receptors without activating them, thereby inhibiting the generation of signaling. Because of this, these receptors may essentially become inactive out over time due to lack of use.

Most of the serotonin receptors on the surface of the cell are coupled to a G-protein inside it. These proteins activate or inhibit second messengers which in turn affect transcription factors. Transcription factors are proteins that fit to the beginning of a gene and tell the cell to start using it.

These (slowly proceeding) neurophysiological adaptations of the brain tissue are the reason why usually several weeks of continuous SSRI use are necessary for the antidepressant effect to become fully manifested[citation needed], and why increased anxiety is a common side effect in the first few days or weeks of use.

[edit] Pharmacogenetics

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 which will cause their discontinuation, although these tests are not yet ready for widespread clinical use.[9] Single nucleotide polymorphisms of the 5-HT(2A) gene correlate with increased paroxetine discontinuation, but not mirtazapine (a non-SSRI antidepressant) discontinuation[10]

[edit] Neuroprotection

Studies have suggested that SSRIs may promote the growth of new neural pathways or neurogenesis in rats.[11] Also, SSRIs may protect against neurotoxicity caused by other compounds (for instance MDMA and Fenfluramine) as well as from depression itself. SSRIs have been found to induce programmed cell death in Burkitt lymphoma and the brain tumors neuroblastoma and glioma with minimal effect on normal tissue. [12], [13]

[edit] Anti-inflammatory and immunomodulation

Recent studies show pro-inflammatory cytokine processes take place during depression, mania and bipolar disorder, in addition to somatic disease (such as autoimmune hypersensitivity) and it is possible that symptoms manifest in these psychiatric illnesses are being attenuated by pharmacological effect of antidepressants on the immune system.[14][15][16][17][18]

SSRIs have been shown to be immunomodulatory and anti-inflammatory against pro-inflammatory cytokine processes, specifically on the regulation of Interferon-gamma (IFN-gamma) and Interleukin-10 (IL-10), as well as TNF-alpha and Interleukin-6 (IL-6). Antidepressants have also been shown to suppress TH1 upregulation.[19][20][21][22]

Future serotonergic antidepressants may be made to specifically target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.[23]

[edit] SSRIs versus TCAs

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. Because of this, SSRIs lack some of the side effects of the more general drugs.

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.[24] 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 antidepressant also have a higher risk of serious cardiovascular side effects which SSRIs lack.

[edit] SSRIs versus 5-HT-Prodrugs

Further information: Prodrugs

Serotonin cannot be administered directly because when ingested orally, it will not cross the blood-brain barrier, and therefore would have no effect on brain functions. Also, serotonin would activate every synapse it reaches, whereas SSRIs only enhance a signal that is already present, but too weak to come through. In addition, hope for breaching the blood-brain-barrier for causes such as severe depression are underway. The selectivity of the membrane can be reduced for a drug by injecting it in a concentrated sugar solution. The high osmotic pressure of the sugar solution causes the endothelial cells of the capillaries to shrink, which opens gaps between their tight junctions and makes the barrier more permeable. As a result the drug can enter the brain tissue

[edit] SSRIs together with 5-HT-Prodrugs

Biosynthetically serotonin is made from tryptophan, an amino acid. In 1989, the Food and Drug Administration made tryptophan available by prescription only, in response to an outbreak of eosinophilia-myalgia syndrome caused by impure L-tryptophan supplements sold over-the-counter. With current standards, L-tryptophan is again available over the counter in the US as well as supplement 5-HTP which is a direct precursor to serotonin.

[edit] Adverse effects

[edit] General side effects

General side effects are mostly present during the first 1–4 weeks while the body adapts to the drug (with the exception of sexual side effects, which tend to occur later in treatment). In fact, it often takes 6–8 weeks for the drug to begin reaching its full potential (the slow onset is considered a downside to treatment with SSRIs). Almost all SSRIs are known to cause one or more of these symptoms:

Many side effects disappear after the adaptation phase, when the antidepressant effects begin to come to prominence. However, despite being called general, the side effects and their durations are highly individual and drug-specific. Usually the treatment is begun with a small dose to see how the patient's body reacts to the drug, after that either the dose can be adjusted (eg. Prozac in the UK is begun at a 20 mg dose, and then adjusted as necessary to 40 mg or 60 mg). Should the drug prove not to be effective, or the side effects intolerable to the patient, another common route is to switch treatment to either another SSRI, or an SNRI.[26]

Mania or hypomania is a possible side-effect. Users with some type of bipolar disorder are at a much higher risk, however SSRI-induced mania in patients previously diagnosed with unipolar depression can trigger a bipolar diagnosis.

[edit] Sexual side effects

SSRIs can cause various types of sexual dysfunction such as anorgasmia, erectile dysfunction, and diminished libido. Initial studies found that such side effects occur in less than 10% of patients, but since these studies relied on unprompted reporting, the frequency was probably underestimated. In more recent studies, doctors have specifically asked about sexual difficulties, and found that they are present in between 17%[27] and 41%[28] of patients.

Stimulation of postsynaptic 5-HT2 and 5-HT3 receptors decreases dopamine release from the substantia nigra. A number of drugs are not associated with sexual side-effects (bupropion, mirtazapine (Remeron), maprotiline (Ludiomil), tianeptine (Stablon)[29][30] (some of these are also not associated with weight gain). As a result, sexual dysfunction caused by SSRIs can sometimes be mitigated by several different drugs. These include:

On the other hand, the effect of SSRIs to slow down sexual stimulation may be used as treatment; SSRIs have been proposed as a drug to treat premature ejaculation.[31]

[edit] Cardiovascular side effects

Cardiovascular side effects are very rare with SSRI use, with a reported incidence of less than 0.0003 percent.[32] SSRIs inhibit cardiac and vascular sodium, calcium and potassium channels and prolong QT intervals.[33] However, a number of large studies of patients without known pre-existing heart disease have reported no EKG changes related to SSRI use.[34] 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 SSRI's.[35]

[edit] Discontinuation syndrome

Main article: SSRI discontinuation syndrome

Antidepressants such as SSRIs have some dependence producing effects, most notibly a withdrawal syndrome. However, their dependence producing properties are not as significant as benzodiazepines. For example SSRIs have little to no abuse potential unlike benzodiazepines.[36] SSRIs are addictive as discontinuing their use is known to produce both somatic and psychological withdrawal symptoms. Since physical dependence is a reality, discontinuation should be discussed with a medical practitioner before beginning treatment with this class of drugs.

[edit] Post-SSRI sexual dysfunction

Post-SSRI sexual dysfunction (PSSD)[37] is an iatrogenic type of sexual dysfunction caused directly by the previous use of SSRI antidepressants. While apparently uncommon, it can last for months, years, or sometimes indefinitely after the discontinuation of SSRIs.

One or more of the following sexual symptoms persist or begin after the discontinuation of SSRIs:

[edit] Suicidality and aggression

Similarly to other antidepressants, SSRIs can cause suicidality in children.[38][39][40] Analyses of the risks of SSRIs by governing bodies in the United States and United Kingdom have produced warnings about suicidality and aggression when the medications are used with children and adolescents.

A 2004 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%.[38] An additional analysis by the FDA also indicated 1.5-fold increase of suicidality in the 18–24 age group.[39][40] This resulted in a black box warning on SSRI and other antidepressant medications regarding the increased risk of suicidality in patients younger than 24.[41]

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.[42] 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, despite having a favorable risk-benefit ratio for use with depression in adolescents and children, is not licensed for this use.[43]

Other studies on SSRIs and suicide among adolescents are equivocal; rates of suicide attempts in high-risk populations appear to be unaffected by SSRI prescriptions in adults.[44] 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.[45] The introduction of a warning regarding the association between SSRIs and suicide led to a decrease in prescriptions for the medications in 2003 and 2004, and these decreases in prescriptions were associated with an increase in actual number of teenage suicide.[46]

In adults SSRIs overall reduce the incidence of suicide, however, in susceptible patients paradoxical adverse effects can still occur which may precipitate suicide.[47]

[edit] SSRIs and pregnancy

The U.S. Food and Drug Administration issued a warning on July 19, 2006 stating nursing mothers on SSRIs must discuss treatment with their physicians.

When taken by pregnant women, selective serotonin reuptake inhibitors (SSRIs) cross the placenta and have the potential to affect newborns. Sertraline and paroxetine have been associated with congenital malformations. Some evidence suggests that SSRIs are associated with neonatal complications such as neonatal abstinence syndrome (NAS) and persistent pulmonary hypertension (PPHN).

[edit] Neonatal abstinence syndrome

Neonatal abstinence syndrome is a withdrawal syndrome in newborn babies. It has been documented in SSRI treatment. By November 2003, a total of 93 cases of SSRI use associated with either neonatal convulsions or withdrawal syndrome had been reported. Subsequently, the authors of a Lancet study concluded that doctors should avoid or cautiously manage the prescribing of these drugs to pregnant women with psychiatric disorders.[48]

[edit] Permanent neuropsychological changes

Since the early 80's scientists have used a technique called neonatal clomipramine to produce animals used in depression research. If rats are given the tricyclic antidepressant clomipramine when they are 8–21 days old they will develop behavioural changes in adulthood which resembles depression in humans.[49][50] In 1997 Lundbeck found that treatment with the SSRI LU-10-134-C, which only differs from their product citalopram by two atoms could give similar results as clomipramine.[51] Later it was found that neonatal citalopram and escitalopram makes persistent changes in the serotonergic transmission of the brain resulting in behavioral changes, [52][53] which are reversed by treatment with antidepressants.[54] By treating normal and knockout mice lacking the serotonin transporter with fluoxetine scientists showed that normal emotional reactions in adulthood, like a short latency to escape foot shocks and inclination to explore new environments were dependent on active serotonin transporters during the neonatal period.[55][56]

But when young mice were treated with the SNRI desimipramine they developed to normal adults, which suggests that serotonin and noradrenaline has different effects in the developing brain. For humans, the developmental stage sensitive to SSRI:s corresponds with the last trimester to the first years of life. A study showed that 4-year old children perinatally exposed to SSRI:s behave normally, however the young mice and rats also seems to be normal until they reach puberty and develop their behavioural disturbances.[57][58]

The mechanism is currently unknown, but it seems that early life overstimulation of the 5HT-1 receptor which acts like a thermostat for the serotonin production results in low serotonin production after puberty.[59]

[edit] Persistent pulmonary hypertension

Persistent pulmonary hypertension (PPHN) is a serious and life-threatening, but 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. One study has found that PPHN is six times more common in babies whose mothers take an SSRI antidepressant after the 20th week of the pregnancy compared to babies whose mothers do not take an antidepressant.[60]

[edit] Interaction with carbohydrate metabolism

Serotonin is also involved in regulation of carbohydrate metabolism. Few analyses of the role of SSRIs in treating depression cover the effects on carbohydrate metabolism from intervening in serotonin handling by the body.

[edit] Overdose

Main article: Serotonin syndrome

SSRIs appear to be 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.[61] However, case reports of SSRI poisoning have indicated that severe toxicity can occur[62] and deaths have been reported following massive single ingestions,[63] although this is exceedingly uncommon when compared to the tricyclic antidepressants.[61]

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.[64] Other reported significant effects include coma, seizures, and cardiac toxicity.[61]

Treatment for SSRI overdose is mainly based on symptomatic and supportive care. Medical care may be required for agitation, maintenance of the airways, and treatment for serotonin syndrome. ECG monitoring is usually indicated to detect any cardiac abnormalities.

[edit] Criticism

See also: Biopsychiatry controversy and Biological psychiatry

In late 2004 media attention was given to a proposed link between SSRI use and juvenile suicide. For this reason, the use of SSRIs in pediatric cases of depression is now recognized by the United States FDA as warranting a cautionary statement to the parents of children who may be prescribed SSRIs by a family doctor. The FDA's currently required packaging insert for SSRIs includes a warning (known as a "black box warning") that a pooled analysis of placebo controlled trials of 9 antidepressant drugs (including multiple SSRIs) resulted in a risk of suicidality that was twice that of placebo. At the same time, in adults SSRIs do not increase the risk of suicide.[65]

Critics of SSRIs claim that the widely-disseminated television and print advertising of SSRIs promotes an inaccurate message, oversimplifying what these medications actually do and deceiving the public.[66]

The criticism stems from questions about the validity of claims that SSRIs work by 'correcting' chemical imbalances. Without accurately measuring patients' neurotransmitter levels to allow for continuous monitoring during treatment, it is impossible to know if one is correctly targeting a deficient neurotransmitter (i.e. correcting an imbalance), reaching a desirable level, or even introducing too much of a particular neurotransmitter. Thus it has been argued that SSRIs can actually cause chemical imbalances and abnormal brain states. Hence it is purported that when a patient discontinues an SSRI, they may have a chemical imbalance due to the rapid cessation of the drug which is causing the discontinuation syndrome.[67]

One possible mechanism is by inhibition of dopaminergic neurotransmission.[68]

Biopsychiatrists believe that, among other factors, the balance of neurotransmitters in the brain is a biological regulator of mental health. In this theory, emotions within a "normal" spectrum reflect a proper balance of neurochemicals, but abnormally extreme emotions, such as clinical depression, reflect an imbalance. Psychiatrists claim that medications regulate neurotransmitters, and many if not most psychiatrists also claim they treat abnormal personalities by removing a neurochemical excess or replenishing a deficit (though the efficacy of antidepressants and antipsychotics is not undisputed[69]). On the other hand, Elliot Valenstein, a psychologist and neuroscientist, claims that the broad biochemical assertions and assumptions of mainstream psychiatry are not supported by evidence.[70]

One controversial critic of antidepressants, Peter Breggin, a physician who opposes the overuse of prescription medications to treat patients for mental health issues, predicted iatrogenic issues that SSRIs incur on a significant percentage of patients. Another prominent SSRI critic is David Healy.

A widely-reported meta-analysis combined 35 clinical trials submitted to the U.S. Food and Drug Administration (FDA) before licensing of four newer antidepressants (including the SSRIs paroxetine and fluoxetine, and two non-SSRI antidepressants nefazodone and venlafaxine). The authors found that although the antidepressants were statistically superior to placebo they did not exceed the NICE criteria for a 'clinically significant' effect. In particular they found that the effect size was very small for moderate depression but increased with severity reaching 'clinical significance' for very severe depression. The relationship between severity and efficacy was attributed to a reduction of the placebo effect in severely depressed patients, rather than an increase in the effect of the medication.[71] [72] [73] [74] [75][76]

A study in the New England Journal of Medicine on a possible publication bias regarding the efficacy of SSRI medications in the treatment of depression suggests that their effectiveness and risk-benefit ratios may be greatly exaggerated. Of 74 studies registered with the United States FDA, 37 with positive results were published in academic journals, while 22 studies with negative results were not published and 11 with negative results were published in a way that conveyed a positive outcome (one positive study was not published and three negative studies were published with results that were portrayed as negative). Overall, 94% of studies actually published were positive outcomes; when published and unpublished studies were included for analysis, the percentage of positive outcomes was 51%.[77]

[edit] Lawsuits

Hundreds of lawsuits have been filed against drug manufacturers seeking compensation for harm attributed to the use of SSRIs. Suits based on product liability, for example, often allege failure to adequately warn users of potential side effects. Manufacturers have defended many suits on the merits and settled many others. In 2005, the U.S. Food and Drug Administration (FDA) asked manufacturers to include black box warnings on antidepressant drug packaging.[78] The inclusion of the black box warning may have lead to a decrease in prescriptions of SSRIs and an increase in suicide. [79][80]

[edit] See also

[edit] References and notes

  1. ^ 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. pp. 239. ISBN 0495095567. OCLC 192055408. 
  2. ^ (Chapter) Sheldon H. Preskorn, Christina Y. Stanga, Ruth Ross. Selective serotonin reuptake inhibitor. pp. 242.  in Sheldon H. Preskorn, Christina Y. Stanga, John P. Feighner, Ruth Ross (Editors) (2004). Antidepressants: Past, Present, and Future. Springer. ISBN 3540430547. 
  3. ^ Waldinger MD (2007). "Premature ejaculation: state of the art". Urol. Clin. North Am. 34 (4): 591–9, vii–viii. doi:10.1016/j.ucl.2007.08.011. PMID 17983899. 
  4. ^ Waldinger MD, Zwinderman AH, Olivier B (2004). "On-demand treatment of premature ejaculation with clomipramine and paroxetine: a randomized, double-blind fixed-dose study with stopwatch assessment". Eur. Urol. 46 (4): 510–5; discussion 516. doi:10.1016/j.eururo.2004.05.005. PMID 15363569. 
  5. ^ a b c Abdel-Hamid IA, El Naggar EA, El Gilany AH (2001). "Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation". Int. J. Impot. Res. 13 (1): 41–5. doi:10.1038/sj.ijir.3900630. PMID 11313839. 
  6. ^ a b Wang WF, Wang Y, Minhas S, Ralph DJ (2007). "Can sildenafil treat primary premature ejaculation? A prospective clinical study". Int. J. Urol. 14 (4): 331–5. doi:10.1111/j.1442-2042.2007.01606.x. PMID 17470165. 
  7. ^ SSRIs and Depression
  8. ^ http://www.ncbi.nlm.nih.gov/pubmed/9228186?ordinalpos=16&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
  9. ^ PMID 17096399. Rasmussen-Torvik LJ, McAlpine DD. Genetic screening for SSRI drug response among those with major depression: great promise and unseen perils. Depress Anxiety. 2006 Nov 9
  10. ^ PMID 14514498. Murphy GM Jr, Kremer C, Rodrigues HE, Schatzberg AF. Pharmacogenetics of antidepressant medication intolerance. Am J Psychiatry. 2003 Oct;160(10):1830-5.
  11. ^ Malberg JE et al. (2000): "Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus" J. Neurosci. 20 (24), 9104-10
  12. ^ Levkovitz Y et al. (2005). "Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines Evidence for p-c-Jun, cytochrome c, and caspase-3 involvement". Journal of Molecular Neuroscience 27 (1): 29–42. doi:10.1385/JMN:27:1:029. 
  13. ^ Serafeim A et al. (2003). "Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells". Blood 101 (8): 3212–3219. doi:10.1182/blood-2002-07-2044. PMID 12515726. 
  14. ^ O'Brien SM, Scully P, Scott LV, Dinan TG. (2006). Cytokine profiles in bipolar affective disorder: focus on acutely ill patients. J Affect Disord., Feb, 90(2-3), 263-267.
  15. ^ Obuchowicz E, Marcinowska A, Herman ZS. (2005). Antidepressants and cytokines: clinical and experimental studies Psychiatr Pol., Sep-Oct, 39(5), 921-936.
  16. ^ Hong CJ, Yu YW, Chen TJ, Tsai SJ. Interleukin-6 genetic polymorphism and Chinese major depression. Neuropsychobiology, 52(4), 202-205.
  17. ^ Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP. (2005). Abstract cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation, 12(5), 255-269.
  18. ^ Kubera M, Maes M, Kenis G, Kim YK, Lason W. (2005). Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor alpha and interleukin-6. Psychiatry Res., Apr 30, 134(3), 251-258.
  19. ^ Diamond M, Kelly JP, Connor TJ. (2006). Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade. Eur Neuropsychopharmacol., Oct, 16(7):481-490.
  20. ^ Kubera M, Lin AH, Kenis G, Bosmans E, van Bockstaele D, Maes M. (2001). Anti-inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. J Clin Psychopharmacol., Apr, 21(2):199-206.
  21. ^ Maes M. (2001). The immunoregulatory effects of antidepressants. Hum Psychopharmacol., Jan, 16(1):95-103.
  22. ^ Maes M, Kenis G, Kubera M, De Baets M, Steinbusch H, Bosmans E. (2005). The negative immunoregulatory effects of fluoxetine in relation to the cAMP-dependent PKA pathway. Int Immunopharmacol., Mar, 5(3):609-618.
  23. ^ O'Brien SM, Scott LV, Dinan TG. (2004). Cytokines: abnormalities in major depression and implications for pharmacological treatment. Hum Psychopharmacol., Aug, 19(6), 397-403.
  24. ^ Anderson IM (2000): "Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability", J. Affect. Disord. 58(1), 19-3
  25. ^ [http://www.emedicinehealth.com/ssris_and_depression/page5_em.htm SSRIs and Depression
  26. ^ A landmark study in the use of anti-depressants and their role in step-therapy can be found in the STAR*D trial.
  27. ^ Hu XH et al. (2004). "Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate". J Clin Psychiatry 65: 959–65. PMID 15291685. 
  28. ^ Landen M, Hogberg P, Thase ME (2005). "Incidence of sexual side effects in refractory depression during treatment with citalopram or paroxetine". J Clin Psychiatry 66: 100–6. PMID 15669895. 
  29. ^ For the review, see: Clayton AH (2003). "Antidepressant-Associated Sexual Dysfunction: A Potentially Avoidable Therapeutic Challenge". Primary Psychiatry 10 (1): 55–61. 
  30. ^ For another review, see: Kanaly KA, Berman JR (2002). "Sexual side effects of SSRI medications: potential treatment strategies for SSRI-induced female sexual dysfunction". Curr Women's Health Rep 2 (6): 409–16. PMID 12429073. 
  31. ^ Waldinger MD, Olivier B. (July). "Utility of selective serotonin reuptake inhibitors in premature ejaculation". Curr Opin Investig Drugs 5 (7): 743–7. PMID 15298071. 
  32. ^ Grace Brooke Huffman. "Cardiac effects in patients using SSRI antidepressants - selective serotonin reuptake inhibitor - Tips from Other Journals". American Family Physician, August, 1997.
  33. ^ Pacher P, Kecskemeti V."Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?". Curr Pharm Des. 2004;10(20):2463-2475. PMID 15320756
  34. ^ [1] Richard J. Goldberg, MD. Selective Serotonin Reuptake Inhibitors: Infrequent Medical Adverse Effects. Arch Fam Med. 1998;7:78-84.
  35. ^ Pacher P, Ungvari Z, Nanasi PP, Furst S, Kecskemeti V."Speculations on difference between tricyclic and selective serotonin reuptake inhibitor antidepressants on their cardiac effects. Is there any?". Curr Med Chem. 1999 Jun;6(6):469-80. PMID 10213794
  36. ^ van Broekhoven F, Kan CC, Zitman FG (June 2002). "Dependence potential of antidepressants compared to benzodiazepines". Prog. Neuropsychopharmacol. Biol. Psychiatry 26 (5): 939–43. doi:10.1016/S0278-5846(02)00209-9. PMID 12369270. http://linkinghub.elsevier.com/retrieve/pii/S0278-5846(02)00209-9. 
  37. ^ Bahrick AS. Post SSRI Sexual Dysfunction. American Society for the Advancement of Pharmacotherapy Tablet 2006; 7:2-10.
  38. ^ a b Hammad TA (2004-08-116). "Review and evaluation of clinical data. Relationship between psychiatric drugs and pediatric suicidality." (PDF). FDA. 42; 115. http://www.fda.gov/OHRMS/DOCKETS/ac/04/briefing/2004-4065b1-10-TAB08-Hammads-Review.pdf. Retrieved on 2008-05-29. 
  39. ^ a b Stone MB, Jones ML (2006-11-17). "Clinical review: relationship between antidepressant drugs and suicidality in adults" (PDF). Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee (PDAC). FDA. 11–74. http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf. Retrieved on 2007-09-22. 
  40. ^ a b 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. 75–140. http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf. Retrieved on 2007-09-22. 
  41. ^ "FDA Proposes New Warnings About Suicidal Thinking, Behavior in Young Adults Who Take Antidepressant Medications" (htm). FDA. 2007-05-02. http://www.fda.gov/bbs/topics/NEWS/2007/NEW01624.html. Retrieved on 2008-05-29. 
  42. ^ "Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitor antidepressants" (PDF). MHRA. 2004-12-01. http://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con019472.pdf. Retrieved on 2007-09-25. 
  43. ^ "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. http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON019494. Retrieved on 2008-05-29. 
  44. ^ Olfson M, Marcus SC, Shaffer D (August 2006). "Antidepressant drug therapy and suicide in severely depressed children and adults: A case-control study". Arch. Gen. Psychiatry 63 (8): 865–72. doi:10.1001/archpsyc.63.8.865. PMID 16894062. 
  45. ^ Gibbons RD, Hur K, Bhaumik DK, Mann JJ (November 2006). "The relationship between antidepressant prescription rates and rate of early adolescent suicide". Am J Psychiatry 163 (11): 1898–904. doi:10.1176/appi.ajp.163.11.1898. PMID 17074941. http://ajp.psychiatryonline.org/cgi/content/full/163/11/1898. Retrieved on 2008-05-29. 
  46. ^ Gibbons RD, Brown CH, Hur K, et al. (September 2007). "Early evidence on the effects of regulators' suicidality warnings on SSRI prescriptions and suicide in children and adolescents". Am J Psychiatry 164 (9): 1356–63. doi:10.1176/appi.ajp.2007.07030454. PMID 17728420. http://ajp.psychiatryonline.org/cgi/content/full/164/9/1356. 
  47. ^ Nishida T, Wada M, Wada M, Ito H, Narabayashi M, Onishi H (June 2008). "Activation syndrome caused by paroxetine in a cancer patient". Palliat Support Care 6 (2): 183–5. doi:10.1017/S1478951508000278. PMID 18501054. http://journals.cambridge.org/abstract_S1478951508000278. 
  48. ^ [2] Medical News Today - Lancet Press Release. Feb 05 2005
  49. ^ Vogel G, Neill D, Hagler M, Kors D (1990). "A new animal model of endogenous depression: a summary of present findings". Neurosci Biobehav Rev 14 (1): 85–91. doi:10.1016/S0149-7634(05)80164-2. PMID 2183099. http://linkinghub.elsevier.com/retrieve/pii/S0149-7634(05)80164-2. 
  50. ^ Velazquez-Moctezuma J, Aguilar-Garcia A, Diaz-Ruiz O (September 1993). "Behavioral effects of neonatal treatment with clomipramine, scopolamine, and idazoxan in male rats". Pharmacol. Biochem. Behav. 46 (1): 215–7. doi:10.1016/0091-3057(93)90343-R. PMID 7902983. http://linkinghub.elsevier.com/retrieve/pii/0091-3057(93)90343-R. 
  51. ^ Hansen HH, Sánchez C, Meier E (December 1997). "Neonatal administration of the selective serotonin reuptake inhibitor Lu 10-134-C increases forced swimming-induced immobility in adult rats: a putative animal model of depression?". J. Pharmacol. Exp. Ther. 283 (3): 1333–41. PMID 9400008. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9400008. 
  52. ^ Popa D, Léna C, Alexandre C, Adrien J (2008). "Lasting syndrome of depression produced by reduction in serotonin uptake during postnatal development: evidence from sleep, stress, and behavior.". J Neurosci. 14 (2): 3546–3554. doi:10.1523/JNEUROSCI.4006-07.2008. PMID 18385313. http://www.jneurosci.org/cgi/content/abstract/28/14/3546. 
  53. ^ Maciag D, Simpson KL, Coppinger D, et al. (January 2006). "Neonatal antidepressant exposure has lasting effects on behavior and serotonin circuitry". Neuropsychopharmacology 31 (1): 47–57. doi:10.1038/sj.npp.1300823. PMID 16012532. 
  54. ^ Maciag D, Williams L, Coppinger D, Paul IA (February 2006). "Neonatal citalopram exposure produces lasting changes in behavior which are reversed by adult imipramine treatment". Eur. J. Pharmacol. 532 (3): 265–9. doi:10.1016/j.ejphar.2005.12.081. PMID 16483567. 
  55. ^ NEUROSCIENCE: Prozac Treatment of Newborn Mice Raises Anxiety - Holden 306 (5697): 792 - Science
  56. ^ Early-Life Blockade of the 5-HT Transporter Alters Emotional Behavior in Adult Mice - Ansorge et al. 306 (5697): 879 - Science
  57. ^ Inhibition of Serotonin But Not Norepinephrine Transport during Development Produces Delayed, Persistent Perturbations of Emotional Behaviors in Mice - Ansorge et al. 28 (1): ...
  58. ^ Misri S, Reebye P, Kendrick K, Carter D, Ryan D, Grunau RE, Oberlander TF (2006). "Internalizing behaviors in 4-year-old children exposed in utero to psychotropic medications.". Am J Psychiatry 163 (6): 1026–1032. doi:10.1176/appi.ajp.163.6.1026. PMID 16741203. 
  59. ^ Evidence that the deficit in sexual behavior in adult rats neonatally exposed to citalopram is a consequence of 5-HT1 receptor stimulation during development - Dorota Maciag, David Coppinger, and Ian A. Paul 1125(1): 171–175 - Brain Res.
  60. ^ [3] FDA Public Health Advisory - Treatment Challenges of Depression in Pregnancy
  61. ^ a b c Isbister G, Bowe S, Dawson A, Whyte I (2004). "Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose". J Toxicol Clin Toxicol 42 (3): 277–85. doi:10.1081/CLT-120037428. PMID 15362595. 
  62. ^ Borys D, Setzer S, Ling L, Reisdorf J, Day L, Krenzelok E (1992). "Acute fluoxetine overdose: a report of 234 cases". Am J Emerg Med 10 (2): 115–20. doi:10.1016/0735-6757(92)90041-U. PMID 1586402. 
  63. ^ Oström M, Eriksson A, Thorson J, Spigset O (1996). "Fatal overdose with citalopram". Lancet 348 (9023): 339–40. doi:10.1016/S0140-6736(05)64513-8. PMID 8709713. 
  64. ^ Sporer K (1995). "The serotonin syndrome. Implicated drugs, pathophysiology and management". Drug Saf 13 (2): 94–104. doi:10.2165/00002018-199513020-00004. PMID 7576268. 
  65. ^ Gunnell D, Saperia J, Ashby D (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 330 (7488): 385. doi:10.1136/bmj.330.7488.385. PMID 15718537. 
  66. ^ Lacasse JR, Leo J. Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. PLoS Medicine 2005;2:e392.
  67. ^ Moncrieff J, Cohen D. Do Antidepressants Cure or Create Abnormal Brain States? PLoS Medicine 2006;3:e240.
  68. ^ Damsa C, Bumb A, Bianchi-Demicheli F, Vidailhet P, Sterck R, Andreoli A, Beyenburg S. "Dopamine-dependent" side effects of selective serotonin reuptake inhibitors: a clinical review". J Clin Psychiatry. 2004;65:1064-8. PMID 15323590.
  69. ^ Peter Breggin books including Toxic Psychiatry, Talking Back to Prozac, Brain-Disabling Treatments in Psychiatry
  70. ^ Valenstein, Elliot (1998). Blaming the Brain: The Truth about Drugs and Mental Health. The Free Press. 
  71. ^ 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" (htm). PLoS Medicine. http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045. Retrieved on 2008-02-26. 
  72. ^ "The creation of the Prozac myth". The Guardian. February 27 2008. http://www.guardian.co.uk/society/2008/feb/27/mentalhealth.health1. Retrieved on 2008-03-01. 
  73. ^ Day, Michael (26 February 2008). "Prozac does not work in majority of depressed patients". New Scientist. http://www.newscientist.com/article/dn13375-prozac-does-not-work-in-most-depressed-patients.html. Retrieved on 2008-03-01. 
  74. ^ "Anti-depressants 'no better than placebo'". Nursing Times. 26 February 2008. http://www.nursingtimes.net/clinicalnews/2008/02/antidepressants_such_as_prozac_not_clinically_effective.html. Retrieved on 2008-03-01. 
  75. ^ Blue, Laura (February 26, 2008). "Antidepressants Hardly Help". http://www.time.com/time/health/article/0,8599,1717306,00.html. Retrieved on 2008-03-01. 
  76. ^ Anti-depressants' 'little effect' BBC News, February 26, 2008
  77. ^ Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R (January 2008). "Selective publication of antidepressant trials and its influence on apparent efficacy". N. Engl. J. Med. 358 (3): 252–60. doi:10.1056/NEJMsa065779. PMID 18199864. http://content.nejm.org/cgi/content/full/358/3/252. Retrieved on 2008-05-29. 
  78. ^ Center for Drug Evaluation and Research Antidepressant Use in Children, Adolescents, and Adults. Retrieved September 30, 2008.
  79. ^ http://www.cleveland.com/nation/index.ssf/2008/11/after_2_decade_decline_teen_su.html
  80. ^ http://www.psychiatrictimes.com/display/article/10168/54606

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Serotonergics
Receptor
Ligands
Agonists: Azapirones: Alnespirone • Binospirone • Buspirone • Gepirone • Ipsapirone • Perospirone • Tandospirone • Tiospirone • Zalospirone; Lysergamides: Dihydroergotamine • Ergotamine • Methysergide • LSD; Phenethylamines: MDA • MDMA; Piperazines: Eltoprazine • Flesinoxan • Flibanserin; Tryptamines: 5-CT • 5-MeO-DMT • 5-MT • DMT • Psilocin • Psilocybin • Rauwolscine • Yohimbine; Atypical Antipsychotics: Aripiprazole • Asenapine • Clozapine • Quetiapine • Ziprasidone; Others: 8-OH-DPAT • F 11440 • F 13640 • Lesopitron • Lu AA21004 • LY-293,284 • LY-301,317 • MKC-242 • Osemozotan • Piclozotan • PRX-00023 • Repinotan • RU-24969 • S-15535 • Sarizotan • SSR-181,507 • Sunepitron • U-92016A • Urapidil • Vilazodone • Xaliproden
Antagonists: Beta Blockers: Alprenolol • Cyanopindolol • Iodocyanopindolol • Oxprenolol • Pindobind • Pindolol • Propranolol; Piperazines: Nefazodone • Trazodone • WAY-100,135 • WAY-100,635; Others: AV965 • BMY-7378 • Dotarizine • GR-46611 • Isamoltane • Lecozotan • Methiothepin • MPPF • NAN-190 • Robalzotan • S-15535 • SB-649915 • SDZ 216-525 • Spiperone • Spiramide • Spiroxatrine • UH-301 • WAY-100,135 • WAY-100,635 • Xylamidine
Agonists: Lysergamides: Dihydroergotamine • Ergotamine • Methysergide; Piperazines: Eltoprazine • TFMPP; Triptans: Eletriptan • Sumatriptan • Zolmitriptan; Tryptamines: 5-CT • 5-MT; Others: CP-93,129 • CP-94,253 • CP-135,807 • RU-24969
Antagonists: Lysergamides: Metergoline • Methiothepin; Tryptamines: Yohimbine; Others: AR-A000002 • GR-127,935 • Isamoltane • SB-216,641 • SB-224,289 • SB-236,057
Agonists: Lysergamides: Dihydroergotamine • Methysergide; Triptans: Almotriptan • Eletriptan • Frovatriptan • Naratriptan • Rizatriptan • Sumatriptan • Zolmitriptan; Tryptamines: 5-CT • 5-MT; Others: CP-135,807 • CP-286,601 • GR-46611 • L-694,247 • L-772,405 • PNU-109,291 • PNU-142,633
Antagonists: Lysergamides: Metergoline • Methiothepin; Tryptamines: Rauwolscine • Yohimbine; Others: BRL-15572 • GR-127,935 • Ketanserin • LY-310,762 • LY-367,642 • LY-456,219 • LY-456,220 • Ritanserin • Ziprasidone
Agonists: Lysergamides: Methysergide; Triptans: Eletriptan; Tryptamines: Tryptamine
Antagonists: Methiothepin
Agonists: Triptans: Eletriptan • Naratriptan • Sumatriptan; Tryptamines: 5-MT; Others: LY-334,370
Antagonists: Methiothepin
Agonists: Lysergamides: ALD-52 • Ergonovine • Lisuride • LA-SS-Az • LSD • Lysergic acid 2-butyl amide • Methysergide; Phenethylamines: 25I-NBMD • 25I-NBOH • 25I-NBOMe • 2C-B • 2C-B-FLY • 2C-E • 2C-I • 2C-T-2 • 2C-T-7 • 2C-T-21 • 2CBCB-NBOMe • 2CBFly-NBOMe • Bromo-DragonFLY • DOB • DOC • DOI • DOM • MDA • MDMA • Mescaline • Myristicin • TCB-2 • TFMFly; Piperazines: BZP • Quipazine • TFMPP; Tryptamines: 5-CT • 5-MeO-α-ET • 5-MeO-α-MT • 5-MeO-DET • 5-MeO-DiPT • 5-MeO-DMT • 5-MeO-DPT • 5-MT • α-ET • α-Methyl-5-HT • α-MT • Bufotenin • DET • DiPT • DMT • DPT • Psilocin • Psilocybin; Others: AL-34662 • AL-37350A • PNU-22394
Antagonists: Atypical Antipsychotics: Amperozide • Aripiprazole • Clozapine • Iloperidone • Melperone • Olanzapine • Paliperidone • Pimozide • Quetiapine • Risperidone • Sertindole • Ziprasidone • Zotepine; Typical Antipsychotics: Loxapine • Pipamperone; Antidepressants: Amitriptyline • Amoxapine • Etoperidone • Mianserin • Mirtazapine • Nefazodone • Trazodone; Others: 5-I-R91150 • AC-90179 • Altanserin • AMDA • APD-215 • Blonanserin • Cinanserin • Cyproheptadine • Deramciclane • Dotarizine • Eplivanserin • Fananserin • Flibanserin • Ketanserin • KML-010 • Lubazodone • Methiothepin • Nantenine • Pimavanserin • Pizotifen • Ritanserin • Sarpogrelate • Setoperone • Spiperone • Spiramide • SR-46349B • Volinanserin • Xylamidine • Yohimbine
Agonists: Oxazolines: 4-Methylaminorex • Aminorex; Phenethylamines: Chlorphentermine • DOB • DOC • DOI • DOM • Fenfluramine • MDA • MDMA • Norfenfluramine; Tryptamines: 5-CT • 5-MT • α-Methyl-5-HT; Others: BW-723C86 • Cabergoline • mCPP • Pergolide • PNU-22394 • Ro60-0175
Antagonists: Agomelatine • Asenapine • EGIS-7625 • Ketanserin • Lisuride • LY-272,015 • Rauwolscine • Ritanserin • RS-127,445 • Sarpogrelate • SB-200,646 • SB-204,741 • SB-206,553 • SB-215,505 • SB-221,284 • SB-228,357 • SDZ SER-082 • Tegaserod • Yohimbine
Agonists: Phenethylamines: 2C-B • 2C-E • 2C-I • 2C-T-2 • 2C-T-7 • 2C-T-21 • DOB • DOC • DOI • DOM • MDA • MDMA • Mescaline • Myristicin; Piperazines: Aripiprazole • mCPP • TFMPP; Tryptamines: 5-CT • 5-MeO-α-ET • 5-MeO-α-MT • 5-MeO-DET • 5-MeO-DiPT • 5-MeO-DMT • 5-MeO-DPT • 5-MT • α-ET • α-Methyl-5-HT • α-MT • Bufotenin • DET • DiPT • DMT • DPT • Psilocin • Psilocybin; Others: A-372,159 • AL-38022A • CP-809,101 • Lorcaserin • MK-212 • PNU-22394 • Ro60-0175 • Vabicaserin • WAY-629 • WAY-161,503 • YM-348
Antagonists: Atypical Antipsychotics: Clozapine • Iloperidone • Melperone • Olanzapine • Paliperidone • Pimozide • Quetiapine • Risperidone • Sertindole • Ziprasidone • Zotepine; Typical Antipsychotics: Loxapine • Pipamperone; Antidepressants: Agomelatine • Amitriptyline • Amoxapine • Etoperidone • Fluoxetine • Mianserin • Mirtazapine • Nefazodone • Trazodone; Others: Cinanserin • Deramciclane • Dimebolin • Dotarizine • Eltoprazine • FR-260,010 • Ketanserin • Pizotifen • Ritanserin • RS-102,221 • SB-200,646 • SB-206,553 • SB-221,284 • SB-228,357 • SB-242,084 • SB-243,213 • SDZ SER-082 • Xylamidine
Agonists: Piperazines: BZP • Quipazine; Tryptamines: 2-Methyl-5-HT • 5-CT; Others: Chlorophenylbiguanide • RS-56812 • SR-57,227 • SR-57,227-A • YM-31636
Antagonists: Antiemetics: Alosetron • Azasetron • Batanopride • Bemesetron • Cilansetron • Dolasetron • Granisetron • Lerisetron • Ondansetron • Palonosetron • Ramosetron • Renzapride • Tropisetron • Zacopride • Zatosetron; Atypical Antipsychotics: Clozapine • Olanzapine • Quetiapine; Tetracyclic Antidepressants: Amoxapine • Mianserin • Mirtazapine; Others: BRL-46,470 • ICS-205,930 • Lu AA21004 • MDL-72,222 • Memantine
Agonists: Gastroprokinetic Agents: Cisapride • Metoclopramide • Mosapride • Prucalopride • Renzapride • Tegaserod • Zacopride; Others: 5-MT • BIMU-8 • CJ-033,466 • PRX-03140 • RS-67333 • RS-67506 • TD-5108
Antagonists: GR-113,808 • GR-125,487 • L-Lysine • Piboserod • RS-39604 • RS-67532 • SB-203,186
Agonists: Lysergamides: Ergotamine • LSD; Tryptamines: 5-CT; Others: Valerenic Acid
Antagonists: Asenapine • Dimebolin • Methiothepin • Ritanserin • SB-699,551
Agonists: Lysergamides: Ergotamine • LSD
Antagonists: Methiothepin
* Note that the 5-HT5B receptor is not functional in humans.
Agonists: Lysergamides: Lisuride • LSD • Metergoline; Tryptamines: 5-CT • 5-MT • E-6801 • E-6837 • EMD-386,088 • EMDT • LY-586,713 • WAY-181,187 • WAY-208,466
Antagonists: Antidepressants: Amitriptyline • Amoxapine • Clomipramine • Doxepin • Mianserin • Nortriptyline; Atypical Antipsychotics: Aripiprazole • Asenapine • Clozapine • Fluperlapine • Iloperidone • Olanzapine • Tiospirone; Typical Antipsychotics: Chlorpromazine • Loxapine; Others: BGC20-760 • BVT-5182 • BVT-74316 • Dimebolin • EGIS-12233 • GW-742,457 • Ketanserin • Methiothepin • MS-245 • PRX-07034 • Ritanserin • Ro 04-6790 • Ro 63-0563 • SB-258,585 • SB-271,046 • SB-357,134 • SB-399,885
Agonists: Lysergamides: LSD; Tryptamines: 5-CT • 5-MT; Others: 8-OH-DPAT • AS-19 • Bifeprunox • LP-12 • LP-44 • Sarizotan
Antagonists: Antidepressants: Amitriptyline • Amoxapine • Clomipramine • Imipramine • Maprotiline • Mianserin; Atypical Antipsychotics: Amisulpride • Aripiprazole • Clozapine • Olanzapine • Risperidone • Sertindole • Tiospirone • Ziprasidone • Zotepine; Typical Antipsychotics: Chlorpromazine • Loxapine; Others: EGIS-12233 • LY-215,840 • Mesulergine • Metergoline • Methiothepin • Pimozide • Ritanserin • SB-258,719 • SB-258,741 • SB-269,970 • SB-656,104 • SB-656,104-A • SB-691,673 • SLV-313 • SLV-314 • Spiperone • SSR-181,507
Reuptake
Inhibitors
SERT Inhibitors
Selective Serotonin Reuptake Inhibitors (SSRIs): Alaproclate • Citalopram • Dapoxetine • Escitalopram • Femoxetine • Fluoxetine • Fluvoxamine • Indalpine • Litoxetine • Lubazodone • Paroxetine • Sertraline • Vilazodone • Zimelidine; Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Bicifadine • Desvenlafaxine • Duloxetine • Milnacipran • Venlafaxine; Serotonin-Norepinephrine-Dopamine Reuptake Inhibitors (SNDRIs): Brasofensine • Diclofensine • DOV 102,677 • DOV 21,947 • DOV 216,303 • NS2359 • SEP-225289 • SEP-227162 • Tesofensine; Tricyclic Antidepressants (TCAs): Amitriptyline • Butriptyline • Cianopramine • Clomipramine • Desipramine • Dosulepin • Doxepin • Imipramine • Lofepramine • Nortriptyline • Protriptyline • Trimipramine; Tetracyclic Antidepressants (TeCAs): Amoxapine; Piperazines: Nefazodone • Trazodone; Tropanes: Cocaine; Antihistamines: Brompheniramine • Chlorpheniramine • Diphenhydramine • Mepyramine/Pyrilamine • Pheniramine • Tripelennamine; Opioids: Meperidine/Pethidine • Methadone • Propoxyphene • Tramadol; Others: Cyclobenzaprine • Dextromethorphan • Mesembrine • SB-649915 • Sibutramine • Ziprasidone
TRPC6 Activators
VMAT Inhibitors
Releasing
Agents
Aminoindanes: ETAI • MDAI • MDMAI • MMAI • TAI; Aminopropanes: Indanylaminopropane • Naphthylaminopropane; Benzofurans: 5-APDB; Oxazolines: 4-Methylaminorex • Aminorex; Phenethylamines: 2-Methyl-MDA • 3-Methoxy-4-methylamphetamine • 4-Bromomethcathinone • 4-Fluoroamphetamine • 4-Fluoromethamphetamine • 4-Methylamphetamine • 4-Methylmethamphetamine • 4-Methylthioamphetamine • 5-Methyl-MDA • BDB • BOH • Butylone • Chlorphentermine • Diethylcathinone • Dimethylcathinone • EBDB • Ethylone • Fenfluramine • Flephedrone • MBDB • MDA • MDEA • MDMA (Ecstasy) • MDOH • MDPEA • Mephedrone • Methylone • MMDA • MMDMA • Norfenfluramine • para-Bromoamphetamine • para-Chloroamphetamine • para-Chloromethamphetamine • para-Iodoamphetamine • para-Methoxyamphetamine • para-Methoxyethylamphetamine • para-Methoxymethamphetamine; Quinolines: PK 7059 • Viqualine; Tryptamines: α-ET • α-MT
Enzyme
Inhibitors
TPH Inhibitors
Others
Others
Activity Enhancers: BPAP • PPAP; Reuptake Enhancers: Tianeptine
Retrieved from "http://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor"
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