NationMaster - Encyclopedia: Fluoxetine

Fluoxetine hydrochloride (Prozac) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. Fluoxetine is approved for the treatment of clinical depression (including pediatric depression), obsessive-compulsive disorder (in both adult and pediatric populations), bulimia nervosa, anorexia nervosa, panic disorder and premenstrual dysphoric disorder.^[1] Despite the availability of newer agents, it remains extremely popular. Over 22.2 million prescriptions for generic formulations of fluoxetine were filled in the United States in 2007, making it the third most prescribed antidepressant.^[2] In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... Look up oral in Wiktionary, the free dictionary. ... Image File history File linksMetadata Download high-resolution version (2592x1944, 1540 KB) Summary Licensing File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Fluoxetine Metadata This file contains additional information, probably added from the digital camera or scanner used... Image File history File linksMetadata Download high-resolution version (2592x1944, 1540 KB) Summary Licensing File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Fluoxetine Metadata This file contains additional information, probably added from the digital camera or scanner used... Prozac, a selective serotonin reuptake inhibitor (SSRI) Serotonin-norepinephrine reuptake inhibitor, Venlafaxine An antidepressant is a psychiatric medication or other substance (nutrient or herb) used for alleviating depression or dysthymia (milder depression). ... SSRI redirects here; for other uses, see SSRI (disambiguation). ... On the Threshold of Eternity. ... Bulimia nervosa is an eating disorder characterised by recurrent binge eating, followed by compensatory behaviors, referred to as purging.[1] The most common formâ€”practised more than 75% of people with bulimia nervosaâ€”is self-induced vomiting; fasting, the use of laxatives, enemas, diuretics, and overexercising are also common. ... For other uses, see Anorexia. ... Panic Disorder is a psychiatric condition characterized by recurring panic attacks in combination with significant behavioral change or at least a month of ongoing worry about the implications or concern about having other attacks. ... Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome, afflicting 8% of all women. ...

History

According to David Wong,^[3] the work which eventually led to the discovery of fluoxetine began at Eli Lilly in 1970 as a collaboration between Bryan Molloy and Robert Rathburn. It was known at that time that the antihistamine diphenhydramine shows some antidepressant-like properties. 3-Phenoxy-3-phenylpropylamine, a compound structurally similar to diphenhydramine, was taken as a starting point, and Molloy synthesized dozens of its derivatives. Testing the physiological effects of these compounds in mice resulted in nisoxetine, a selective norepinephrine reuptake inhibitor currently widely used in biochemical experiments.^[3] One of the worlds largest corporations, Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company with headquarters in Indianapolis,Indiana, USA. A Fortune 500 corporation, the company had revenues of $12. ... An H1 antihistamine is a histamine antagonist which serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions, through action at the H1 receptor. ... Diphenhydramine hydrochloride (trade name Benadryl as produced by Johnson & Johnson, or Dimedrol outside the U.S. & Canada. ... Norepinephrine reuptake inhibitors (NRIs) are compounds that increase amounts of the neurotransmitter norepinephrine in the brain by inhibiting its reuptake at synapses. ...

Later, hoping to find a derivative inhibiting only serotonin reuptake, Wong proposed to re-test the series for the in-vitro reuptake of serotonin, norepinephrine and dopamine. This test, carried out by Jong-Sir Horng in May 1972,^[3] showed the compound later named fluoxetine to be the most potent and selective inhibitor of serotonin reuptake of the series.^[4] For the professional wrestling stable, see Ravens Nest#Serotonin. ... In vitro (Latin: within the glass) refers to the technique of performing a given experiment in a test tube, or, generally, in a controlled environment outside a living organism. ... For other uses, see Dopamine (disambiguation). ...

A controversy ensued after Lilly researchers published a paper entitled "Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug"^[3] implicitly claiming fluoxetine to be the first selective serotonin reuptake inhibitor (SSRI). Two years later they had to issue a correction, admitting that the first SSRI was zimelidine developed by Arvid Carlsson and colleagues.^[5] Fluoxetine made its appearance on the Belgian market in 1986^[6] and was approved for use by the FDA in the United States in December 1987.^[7] Fluoxetine was the fourth SSRI to make it to market, after zimelidine, indalpine and fluvoxamine. However, the first two were withdrawn due to the side effects, and a vigorous marketing campaign by Eli Lilly made sure that in the popular culture fluoxetine has been perceived as a scientific breakthrough and associated with the title of the first SSRI. SSRI redirects here; for other uses, see SSRI (disambiguation). ... // General Remars and History Zimelidine is a pyridylallylamine and has a structure different from other antidepressants. ... Arvid Carlsson (b. ... FDA redirects here. ... // General Remars and History Zimelidine is a pyridylallylamine and has a structure different from other antidepressants. ... Indalpine is a serotonin uptake inhibitor. ... Fluvoxamine (brand name as LuvoxÂ®, FaverinÂ®, FevarinÂ® and DumyroxÂ®) is an antidepressant which functions pharmacologically as a selective serotonin reuptake inhibitor. ...

Eli Lilly's patent on Prozac (fluoxetine) expired in August, 2001,^[8] prompting an influx of generic drugs onto the market. One of the worlds largest corporations, Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company with headquarters in Indianapolis,Indiana, USA. A Fortune 500 corporation, the company had revenues of $12. ...

Indications

Fluoxetine has been approved by the FDA for the treatment of clinical depression, obsessive compulsive disorder, bulimia nervosa and panic disorder.^[9] Fluoxetine was shown to be effective for depression in 6-week long double-blind controlled trials where it also alleviated anxiety and improved sleep. Fluoxetine was better than placebo for the prevention of depression recurrence when the patients, who originally responded to fluoxetine, were treated for a further 38 weeks. Efficacy of fluoxetine for geriatric as well as pediatric depression was also demonstrated in placebo-controlled trials.^[9]

The peculiar pharmacokinetics of fluoxetine with its brain levels rising extremely slowly over at least first 5 weeks of treatment (see Fluoxetine#Pharmacokinetics) makes it unclear whether the 20-mg/day optimal dose established in the short term (6-8 weeks) trials is applicable for the longer term supportive treatment. One 60-mg dose of fluoxetine per week was found to be equivalent to 20 mg/day for the continuation treatment of responders to 20 mg/day of fluoxetine.^[10]^[11] Furthermore, 5 mg/day fluoxetine was shown to be better than placebo and similar to 20 mg/day,^[12] and one weekly dose of 80 mg fluoxetine was equivalent to 60 mg/day fluoxetine or 150 mg/day amitriptyline.^[11] On the other hand, increase of the dose to 60 mg/day in non-responders from 20 mg/day brought no additional benefits as compared to continuing the 20 mg/day treatment.^[12] Prozac redirects here. ... Amitriptyline (or Amitryptyline) hydrochloride (sold as Elavil, Tryptanol, Endep, Elatrol, Tryptizol, Trepiline, Laroxyl) is a tricyclic antidepressant drug. ...

The recent research suggests that a significant part of the resistance to the SSRIs paroxetine (Paxil) and citalopram (Celexa) can be explained by the genetic variation of Pgp transporter. Paroxetine and citalopram, which are Pgp substrates, are actively transported from the brain by this protein. Fluoxetine is not a substrate of Pgp, and thus a switch from paroxetine or citalopram to fluoxetine may be beneficial to the non-responders.^[13]^[14] Paroxetine (Paxil, Seroxat, Pexeva) is a selective serotonin reuptake inhibitor (SSRI) antidepressant. ... Citalopram is an antidepressant drug used to treat depression associated with mood disorders. ... P-glycoproteins are a type of protein that appear to have developed as a mechanism to protect the body from harmful substances by acting as efflux transporters. ...

OCD was successfully treated by fluoxetine in two adult and one pediatric placebo-controlled 13-week trials. The higher doses of fluoxetine appeared to result in better response, while the reverse relationship was observed in the treatment of depression.^[9] Fluoxetine dramatically, by 40-50%, decreased the frequency of panic attacks in two controlled trials of panic disorder patients. In three double-blind trials fluoxetine significantly decreased the number of binge-eating and purging episodes of bulimia nervosa. Continued year-long treatment of the patients, who originally responded to fluoxetine, was more effective than placebo for the prevention of bulimia nervosa episodes.^[9] OCD redirects here. ... Bulimia nervosa is an eating disorder characterised by recurrent binge eating, followed by compensatory behaviors, referred to as purging.[1] The most common formâ€”practised more than 75% of people with bulimia nervosaâ€”is self-induced vomiting; fasting, the use of laxatives, enemas, diuretics, and overexercising are also common. ...

Adverse effects

According to the manufacturer of Prozac brand of fluoxetine Eli Lilly, fluoxetine is contraindicated in individuals taking monoamine oxidase inhibitors, pimozide (Orap) or thioridazine (Mellaril).^[9] The prescribing information recommends that the treatment of the patients with liver impairment "must be approached with caution". The elimination of fluoxetine and its metabolite norfluoxetine is about twice slower in these patients, resulting in the proportionate increase of exposure to the drug.^[9] One of the worlds largest corporations, Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company with headquarters in Indianapolis,Indiana, USA. A Fortune 500 corporation, the company had revenues of $12. ... Contraindicated is a medical term to indicate a situation in which a medication or treatment should not be administered. ... MAOI redirects here. ... Pimozide (sold as OrapÂ®) is an antipsychotic drug. ... Thioridazine is a piperidine antipsychotic drug previously widely used in the treatment of schizophrenia and psychosis. ...

Among the common adverse effects associated with fluoxetine and listed in the prescribing information, the effects with the greatest difference from placebo are nausea (22% vs 9% for placebo), insomnia (19% vs 10% for placebo), somnolence (12% vs 5% for placebo), anorexia (10% vs 3% for placebo), anxiety (12% vs 6% for placebo), nervousness (13% vs 8% for placebo), asthenia (11% vs 6% for placebo) and tremor (9% vs 2% for placebo). Those that most often resulted in interruption of the treatment were anxiety, insomnia, and nervousness (1-2% each), and in pediatric trials—mania (2%).^[9] An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted, negative consequences associated with the use of given medications. ... For other uses, see Placebo (disambiguation). ... For other uses, see Nausea (disambiguation). ... This article is about the sleeping disorder. ... Somnolence (or drowsiness) is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods. ... Anorexia can refer to: Anorexia nervosa, an eating disorder in which people do not eat correctly due to the obsessive fear of weight gain Anorexia (symptom), the general symptom of decreased appetite Sexual anorexia, a term used to describe a lack of appetite for sex. ... Anxiety is a physiological state characterized by cognitive, somatic, emotional, and behavioral components[1]. These components combine to create the feelings that we typically recognize as anger and known as fear, apprehension, or worry. ... Asthenia (Greek: Î±ÏƒÎ¸ÎÎ½ÎµÎ¹Î±, lit. ... For the film, see Tremors (film). ...

In addition, rash or urticaria, sometimes serious, was observed in 7% patients in clinical trials; one-third of these cases resulted in discontinuation of the treatment. Postmarketing reports note several cases of complications developed in patients with rash. The symptoms included vasculitis and lupus-like syndrome. Death has been reported to occur in association with these systemic events.^[9] Vasculitis (plural: vasculitides), a group of diseases featuring inflammation of the wall of blood vessels including veins (phlebitis), arteries (arteritis) and capillaries due to leukocyte migration and resultant damage. ... Systemic Lupus Erythematosus (SLE or lupus) is a chronic autoimmune disease that can be fatal, though with recent medical advances, fatalities are becoming increasingly rare. ...

Akathisia, that is inner tension, restlessness, and the inability to stay still, often accompanied by "constant pacing, purposeless movements of the feet and legs, and marked anxiety," is a common side effect of fluoxetine.^[15]^[16] Akathisia usually begins after the initiation of the treatment or increase of the dose and disappears after fluoxetine is stopped or its dose is decreased, or after treatment with propranolol.^[17]^[18]^[15] There are case reports directly linking akathisia with suicidal attempts, with patients feeling better after the withdrawal of fluoxetine, and again developing severe akathisia on repeated exposure to fluoxetine. These patients described "that the development of the akathisia made them feel suicidal and that it had precipitated their prior suicide attempts."^[18] The experts note that because of the link of akathisia with suicide and the distress it causes to the patient, "it is of vital importance to increase awareness amongst staff and patients of the symptoms of this relatively common condition".^[19]^[20] More rarely, fluoxetine has been associated with related movement disorders acute dystonia and tardive dyskinesia.^[16]^[21]^[22] Akathisia (or acathisia) is an often extremely unpleasant subjective sensation of inner restlessness that manifests itself with an inability to sit still or remain motionless, hence the origin of its name: Greek a (without) + kathesis (sitting). ... Propranolol (INN) (IPA: ) is a non-selective beta blocker mainly used in the treatment of hypertension. ... Dystonia is a neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. ... Tardive dyskinesia is a serious neurological disorder caused by the long-term and/or high-dose use of dopamine antagonists, usually antipsychotics and among them especially the typical antipsychotics. ...

Other side effects may occur, including sexual dysfunction. Possible sexual side effects can include anorgasmia, reduced libido and impotence.^[23] Sexual dysfunction or sexual malfunction (see also sexual function) is difficulty during any stage of the sexual act (which includes desire, arousal, orgasm, and resolution) that prevents the individual or couple from enjoying sexual activity. ... Anorgasmia (also known as Retarded Ejaculation in males) is a form of sexual dysfunction, sometimes classified as a psychiatric disorder, where the patient cannot achieve orgasm, even with adequate stimulation. ... For other uses, see Libido (disambiguation). ...

Fluoxetine taken during pregnancy also increases rate of poor neonatal adaptation.^[23] Because fluoxetine is excreted in human milk, nursing while on fluoxetine is not recommended.^[24] The American Association of Pediatrics classifies fluoxetine as a drug for which the effect on the nursing infant is unknown but may be of concern.^[25]

Discontinuation syndrome

Several case reports in the literature describe severe withdrawal or discontinuation symptoms following an abrupt interruption of fluoxetine treatment.^[26] Considering the number of fluoxetine prescriptions dispensed over the years, this is exceedingly rare. It is generally believed that the side effects of the fluoxetine discontinuation are mild,^[26] and one of the recommended strategies for the management of discontinuation syndrome with other SSRIs is to substitute fluoxetine for the original agent.^[27]^[28] The double-blind controlled studies support this opinion. No increase in side effects was observed in several studies when the treatment with fluoxetine was blindly interrupted for a short time (4-8 days) and then re-instated, this result being consistent with its slow elimination from the body. More side effects occurred during the interruption of sertraline in these studies, and significantly more—during the interruption of paroxetine.^[29] In a longer, 6 week-long, blind discontinuation study, insignificantly higher (32% vs 27%) overall rate of new or worsened side effects was observed in the group that discontinued fluoxetine than in the group that continued treatment. However, significantly higher 4% rate of somnolence at week 2 and 5-7% rate of dizziness at weeks 4-6 were reported by the patients in the discontinuation group. This prolonged course of the discontinuation symptoms, with dizziness persisting to the end of the study, is also consistent with the long half-life of fluoxetine in the body.^[30] SSRI discontinuation syndrome, also known as SSRI withdrawal syndrome or SSRI cessation syndrome, is a condition that can occur during or following the interruption, lowering of dose or discontinuation of regular SSRI or SNRI antidepressant drug usage. ...

Suicidality in antidepressant trials

The FDA requires all antidepressants, including fluoxetine, to carry a black box warning stating that antidepressants may increase the risk of suicide in persons younger than 25. This warning is based on statistical analyses conducted by two independent groups of the FDA experts that found a 2-fold increase of the suicidal ideation and behavior in children and adolescents, and 1.5-fold increase of suicidality in the 18–24 age group. The suicidality was slightly decreased for those older than 24, and statistically significantly lower in the 65 and older group.^[31]^[32]^[33] This analysis was criticized by Donald Klein who noted that suicidality, that is suicidal ideation and behavior, is not necessarily a good surrogate marker for completed suicide, and it is still possible that antidepressants may prevent actual suicide while increasing suicidality.^[34] This opinion goes against the general consensus that "suicidal ideation has been associated with suicide attempt in retrospective studies and with suicide in prospective studies."^[35] It has been suggested that this article or section be merged with Black_Box_Warning. ...

Suicidality and fluoxetine

Suicidal ideation and behavior in clinical trials are rare. For the above analysis the FDA combined the results of 295 trials of 11 antidepressants for psychiatric indications in order to obtain statistically significant results. Considered separately, fluoxetine use in children increased the odds of suicidality by 50% (not statistically significant),^[36] and in adults decreased the odds of suicidality by approximately 30% (statistically significant).^[32]^[33] Similarly, the analysis conducted by the UK MHRA found a 50% increase of odds of suicide-related events, not reaching statistical significance, in the children and adolescents on fluoxetine as compared to the ones on placebo. According to the MHRA data, for adults fluoxetine did not change the rate of self-harm and statistically significantly decreased suicidal ideation by 50%.^[37]^[38] Suicidal ideation is common medical term for the mere thoughts about and of plans of committing suicide, not the actual following through or act itself. ... In statistics, a result is significant if it is unlikely to have occurred by chance, given that a presumed null hypothesis is true, but is not improbable if the null hypothesis is false. ... The logo of the MHRA. The Medicines and Healthcare products Regulatory Agency (MHRA) is the UK government agency which is responsible for ensuring that medicines and medical devices work and are acceptably safe. ...

Pharmacokinetics

The bioavailability of fluoxetine is relatively high (72%), and peak plasma concentrations are reached in 6 to 8 hours. It is highly bound to plasma proteins, mostly albumin. In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... A drugs efficacy may be affected by the degree to which it binds to the proteins within blood plasma. ... It has been suggested that this article or section be merged into serum albumin. ...

Fluoxetine is metabolized in the liver by isoenzymes of the cytochrome P450 system, including CYP2D6.^[1] The role of CYP2D6 in the metabolism of fluoxetine may be clinically important, as there is great genetic variability in the function of this enzyme among people. Only one metabolite of fluoxetine, norfluoxetine (demethylated fluoxetine), is biologically active. Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... The liver is the largest internal organ in the human body, and is an organ present in vertebrates and some other animals. ... Isozymes, (or isoenzymes) are isoforms (closely related variants) of enzymes. ... Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ... Cytochrome P450 2D6 (CYP2D6), a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. ... A metabolite is the product of metabolism. ... Demethylation is the chemical process resulting in the removal a methyl group (CH3) from a molecule. ...

The extremely slow elimination of fluoxetine and its active metabolite norfluoxetine from the body distinguishes it from other antidepressants. With time, fluoxetine and norfluoxetine inhibit their own metabolism, so fluoxetine elimination half-life changes from 1 to 3 days, after a single dose—to 4 to 6 days, after long-term use. Similarly, the half-life of norfluoxetine is longer (16 days) after long-term use.^[1]^[39]^[11] Therefore, the concentration of the drug and its active metabolite in the blood continues to grow through the first few weeks of treatment, and their steady concentration in the blood is achieved only after four weeks.^[40]^[41] Moreover, the brain concentration of fluoxetine and its metabolites keeps increasing through at least the first five weeks of treatment.^[42] That means that the full benefits of the current dose a patient receives are not realized for at least a month since its initiation. For example, in one 6-week study, the median time to achieving consistent response was 29 days.^[40] Likewise, complete excretion of the drug may take several weeks. During the first week after the treatment discontinuation, the brain concentration of fluoxetine decreases only by 50%,^[42] The blood level of norfluoxetine 4 weeks after the treatment discontinuation is about 80% of the level registered by the end of the first treatment week, and 7 weeks after the discontinuation norfluoxetine is still detectable in the blood.^[11] The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ...

A PET study compared the action of a single dose of fluoxetine on exclusively heterosexual and exclusively homosexual men who attested that their past and present sexual behavior, desires, and fantasies were directed entirely toward women or men, respectively. The study found that in some areas of the brain the metabolic response in these two groups was different. "Both groups, however, did exhibit similar widespread lateralized metabolic responses to fluoxetine (relative to placebo), with most areas of the brain responding in the same direction." They "did not differ on behavioral measures or blood levels of fluoxetine".^[43] Homosexuality refers to sexual interaction and / or romantic attraction between individuals of the same sex. ...

Interactions

The simultaneous use of fluoxetine with triptans, tramadol or other serotonergic agents can result in a rare, but potentially life-threatening adverse drug reaction called serotonin syndrome. Triptans are a family of tryptamine drugs used in the treatment of migraine and cluster headaches. ... Tramadol (INN) (IPA: ) is an atypical opioid which is a centrally acting analgesic, used for treating moderate to severe pain. ... Serotonergic means related to, capable of producing, altering, or releasing serotonin, a neurotransmitter, and can refer to the following classes of chemicals: Selective serotonin reuptake inhibitor - A common class of serotonergic antidepressants Noradrenergic and specific serotonergic antidepressant - Another class of serotonergic antidepressants serotonergic psychedelics - The serotonergic hallucinogenic drugs This is... Serotonin syndrome is a rare, but potentially life-threatening adverse drug reaction that results from intentional self-poisoning, therapeutic drug use, inadvertent interactions between drugs, or the recreational use of certain drugs. ...

Controversy

"In 1989, Joseph Wesbecker shot dead eight people and injured 12 others before killing himself at his place of work in Kentucky. Wesbecker had been taking the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine for four weeks before these homicides, and this led to a legal action against the makers of fluoxetine, Eli Lilly.^[44] The case was tried and settled in 1994, and as part of the settlement a number of pharmaceutical company documents about drug-induced activation were released into the public domain. Subsequent legal cases...have further raised the possibility of a link between antidepressant use and violence."^[45] The Standard Gravure shooting occurred on September 14, 1989. ...

A meta-analysis published in February 2008 combined 35 clinical trials of four newer antidepressants (fluoxetine, paroxetine (Paxil), nefazodone (Serzone) and venlafaxine (Effexor)). These antidepressants belonging to three different pharmacological groups were considered together, and the authors did not analyze them separately. The authors concluded that "although the difference [between the placebo and antidepressants] easily attained statistical significance", it did not meet the criterion for clinical significance, as used by National Institute for Health and Clinical Excellence (UK), "for any but the most severely depressed patients."^[46] Some articles in the press using the titles "The creation of the Prozac myth"^[47] and "Prozac does not work in majority of depressed patients"^[48]^[49] presented these general findings about the relative efficacy of antidepressants and placebo as the findings about ineffectiveness of fluoxetine. A meta-analysis is a statistical practice of combining the results of a number of studies. ... Paroxetine (Paxil, Seroxat, Pexeva) is a selective serotonin reuptake inhibitor (SSRI) antidepressant. ... Nefazodone hydrochloride (trade name Serzone) is an antidepressant drug marketed by Bristol-Myers Squibb. ... Venlafaxine (Effexor, Efexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class first introduced by Wyeth in 1993. ... In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. ... The National Institute for Health and Clinical Excellence or NICE is an agency of the National Health Service in the United Kingdom. ...

References

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^ Zajecka J, Fawcett J, Amsterdam J, Quitkin F, Reimherr F, Rosenbaum J, Michelson D, Beasley C (1998). "Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled study". J Clin Psychopharmacol 18 (3): 193–7. PMID 9617977.
^ Levenson M, Holland C. Antidepressants and Suicidality in Adults: Statistical Evaluation. (Presentation at Psychopharmacologic Drugs Advisory Committee; December 13, 2006). Retrieved on 2007-05-13.
^ ^a ^b Stone MB, Jones ML (November 17, 2006). Clinical Review: Relationship Between Antidepressant Drugs and Suicidality in Adults (PDF). Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee (PDAC) 11-74. FDA. Retrieved on 2007-09-22.
^ ^a ^b Levenson M, Holland C (November 17, 2006). Statistical Evaluation of Suicidality in Adults Treated with Antidepressants (PDF). Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee (PDAC) 75-140. FDA. Retrieved on 2007-09-22.
^ Klein DF (2006). "The flawed basis for FDA post-marketing safety decisions: the example of anti-depressants and children". Neuropsychopharmacology 31 (4): 689–99. doi:10.1038/sj.npp.1300996. PMID 16395296.
^ Mann JJ, Ellis SP, Waternaux CM, Liu X, Oquendo MA, Malone KM, Brodsky BS, Haas GL, Currier D (2008). "Classification Trees Distinguish Suicide Attempters in Major Psychiatric Disorders: A Model of Clinical Decision Making". J Clin Psychiatry: e1–e9. PMID 18190232.
^ Tarek A. Hammad (September 13, 2004). Results of the Analysis of Suicidality in Pediatric Trials of Newer Antidepressants (PDF). Presentation at the Meeting of Psychopharmacologic Drugs Advisory Committee and the Pediatric Advisory Committee on September 13, 2004 25, 28. FDA. Retrieved on 2008-01-06.
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Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 104th day of the year (105th in leap years) in the Gregorian calendar. ... Zoloft bottles, with blue and green tablets Sertraline hydrochloride (also sold under brand names Zoloft, Lustral, Apo-Sertral, Asentra, Gladem, Serlift, Stimuloton, Xydep, Serlain, Concorz) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. ... Lexapro pills Escitalopram (Lexapro, Lexaprin, Cipralex, Sipralexa, Entact and Seroplex)[1] is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini/Common Era, in accordance with the Gregorian calendar. ... is the 49th day of the year in the Gregorian calendar. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini/Common Era, in accordance with the Gregorian calendar. ... is the 89th day of the year (90th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 201st day of the year (202nd in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 172nd day of the year (173rd in leap years) in the Gregorian calendar. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini/Common Era, in accordance with the Gregorian calendar. ... is the 9th day of the year in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 133rd day of the year (134th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 265th day of the year (266th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 265th day of the year (266th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini/Common Era, in accordance with the Gregorian calendar. ... is the 6th day of the year in the Gregorian calendar. ... The Committee on the Safety of Medicines (CSM) was an independent advisory committee that for 40 years advised the UK Licensing Authority on the quality, efficacy and safety of medicines. ... The logo of the MHRA. The Medicines and Healthcare products Regulatory Agency (MHRA) is the UK government agency which is responsible for ensuring that medicines and medical devices work and are acceptably safe. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 268th day of the year (269th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... For the Australian university, see University of Newcastle, Australia. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 104th day of the year (105th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini/Common Era, in accordance with the Gregorian calendar. ... is the 57th day of the year in the Gregorian calendar. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini/Common Era, in accordance with the Gregorian calendar. ... is the 60th day of the year (61st in leap years) in the Gregorian calendar. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini/Common Era, in accordance with the Gregorian calendar. ... is the 60th day of the year (61st in leap years) in the Gregorian calendar. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini/Common Era, in accordance with the Gregorian calendar. ... is the 60th day of the year (61st in leap years) in the Gregorian calendar. ...

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In pharmacology, a psychoanaleptic is a medication which produces an arousing effect upon the patient. ... Prozac, a selective serotonin reuptake inhibitor (SSRI) Serotonin-norepinephrine reuptake inhibitor, Venlafaxine An antidepressant is a psychiatric medication or other substance (nutrient or herb) used for alleviating depression or dysthymia (milder depression). ... A section of the Anatomical Therapeutic Chemical Classification System containing Psychoanaleptics. ... MAOI redirects here. ... Iproclozide is a monoamine oxidase inhibitor antidepressant. ... Iproniazid is a monamine oxidase inhibitor (MAOI) that was developed as the first anti-depressant (Also first psychiatric drug). ... Isocarboxazid is a nonselective hydrazine-derived monoamine oxidase inhibitor used in treatment resistant depression. ... Nialamide (EsprilÂ®, NiamidÂ®, NiaquitilÂ®, NuredalÂ®, NyazinÂ®, and PsicodistenÂ®) was one of the first MAOI (monoamine oxidase inhibitor) antidepressants. ... Pargyline is a monoamine oxidase B (MAO-B) inhibitor indicated for the treatment of moderate to severe hypertension. ... Phenelzine (brand name Nardil) is an antidepressant drug that belongs to the monoamine oxidase inhibitor (MAOI) class of drugs. ... Rasagiline (trade name AzilectÂ®) is a irreversible inhibitor of monoamine oxidase used as a monotherapy in early Parkinsons disease or as an adjunct therapy in more advanced cases. ... Selegiline (l-deprenyl, EldeprylÂ® or AniprylÂ® [veterinary]) is a drug used for the treatment of early-stage Parkinsons disease and senile dementia. ... Toloxatone is a monoamine oxidase inhibitor antidepressant. ... Tranylcypromine (sold under the brand name ParnateÂ®) is a monoamine oxidase inhibitor (MAOI) used as an antidepressant drug. ... These drugs, a subset of monoamine oxidase inhibitors (MAOIs), inhibit only isoenzyme A and are reversible. ... Brofarmine is a psychiatric drug primarily used to treat depression and anxiety. ... Î²-Carboline (9H-pyrid-[3,4-b]-indole) is an organic amine that is the prototype of a class of compounds known as Î²-Carbolines. ... Harmala, also known at various times as Telepathine and Banisterine, is a blanket term for a group of naturally occurring beta-carbolines including harmine, harmaline, and others. ... Moclobemide (sold as AurorixÂ®, ManerixÂ®) is a psychiatric drug primarily used to treat depression and social anxiety. ... A neurotransmitter uptake inhibitor is a drug which inhibits the reuptake of the neurotransmitter, thus extending the duration of its effect. ... A serotonin uptake inhibitor is a drug which acts as a neurotransmitter uptake inhibitor on serotonin receptors. ... SSRI redirects here; for other uses, see SSRI (disambiguation). ... Alaproclate is an antidepressant that increases serotonin levels by inhibiting the uptake of 5-HT. Today, its primarily used to stagment the cravings for cocaine. ... Citalopram is an antidepressant drug used to treat depression associated with mood disorders. ... Dapoxetine is the International Nonproprietary Name of a drug currently being considered for approval by the FDA for the treatment of premature ejaculation in men, which would make it the first drug approved for such treatment. ... Lexapro pills Escitalopram (Lexapro, Lexaprin, Cipralex, Sipralexa, Entact and Seroplex)[1] is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. ... Fluvoxamine (brand name as LuvoxÂ®, FaverinÂ®, FevarinÂ® and DumyroxÂ®) is an antidepressant which functions pharmacologically as a selective serotonin reuptake inhibitor. ... Paroxetine (Paxil, Seroxat, Pexeva) is a selective serotonin reuptake inhibitor (SSRI) antidepressant. ... Zoloft bottles, with blue and green tablets Sertraline hydrochloride (also sold under brand names Zoloft, Lustral, Apo-Sertral, Asentra, Gladem, Serlift, Stimuloton, Xydep, Serlain, Concorz) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. ... // General Remars and History Zimelidine is a pyridylallylamine and has a structure different from other antidepressants. ... Chemical structure of the tricyclic antidepressant amitriptyline. ... There are also several chemically unrelated tetracyclic antibiotics based on Tetracycline. ... Clomipramine (brand-name AnafranilÂ®) is a tricyclic antidepressant. ... Nefazodone hydrochloride (trade name Serzone) is an antidepressant drug marketed by Bristol-Myers Squibb. ... Trazodone (trade names Desyrel, Molipaxin, Trittico, Thombran, Trialodine) is a psychoactive compound with sedative, anxiolytic, and antidepressant properties. ... Norepinephrine reuptake inhibitors (NRIs) are compounds that increase amounts of the neurotransmitter norepinephrine in the brain by inhibiting its reuptake at synapses. ... A adrenergic uptake inhibitor is a drug which blocks the reuptake of adrenergic neurotransmitters. ... Atomoxetine is the first non-stimulant drug approved for the treatment of attention-deficit hyperactivity disorder (ADHD). ... To meet Wikipedias quality standards, this article may require cleanup. ... Reboxetine is an antidepressant drug used in the treatment of clinical depression, panic disorder and ADD/ADHD. Its mesilate ( methanesulfonate) salt is sold under tradenames including EdronaxÂ®, NoreboxÂ®, ProliftÂ®, SolvexÂ® or VestraÂ®. Reboxetine has two chiral centers, but it only exists as two enantiomers, (R,R)-(-)- and (S,S)-(+)-reboxetine. ... Viloxazine is a bicyclic antidepressants[2] that inhibits the reuptake of serotonin, and to a lesser extent, dopamine and norepinephrine. ... Chemical structure of the tricyclic antidepressant amitriptyline. ... There are also several chemically unrelated tetracyclic antibiotics based on Tetracycline. ... Amitriptyline (or Amitryptyline) hydrochloride (sold as Elavil, Tryptanol, Endep, Elatrol, Tryptizol, Trepiline, Laroxyl) is a tricyclic antidepressant drug. ... Amoxapine (Asendin®; Asendis®; Defanyl®; Demolox®; Moxadil®) is a tricyclic antidepressant of the dibenzoxazepine class. ... Butriptyline (Dl-10,11-Dihydro-N,N,beta-trimethyl-5H-dibenzo[a,d]cycloheptene-5-propylamine) is a tricyclic antidepressant with sedative properties and uses similar to that of amitriptyline. ... Desipramine is a tricyclic antidepressant (TCA) that inhibits the reuptake of norepinephrine. ... Lofepramine (trademarked Gamanil) is a tricyclic antidepressant prescribed primarily for sleeping and eating disorders. ... Dibenzepin (NoverilÂ®) is a muscarinic antagonist. ... Dosulepin hydrochloride (sometimes known outside the USA as dothiepin hydrochloride) is an antidepressant of the tricyclic family. ... Doxepin is a tricyclic antidepressant, known under many brand-names such as AponalÂ®, the original preparation by Boehringer-Ingelheim, now part of the Roche group; AdapineÂ®, SinquanÂ® and SinequanÂ® (Pfizer Inc. ... Imipramine (sold as Antideprin, Deprenil, Deprimin, Deprinol, Depsonil, Dynaprin, Eupramin, Imipramil, Irmin, Janimine, Melipramin, Surplix, Tofranil) is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group. ... Iprindole (C19H28N2), a 5-HT2 antagonist, is a tricyclic antidepressant that can be fatal when combined with MDMA. Categories: | ... Melitracen (or melitracene) is a tricyclic antidepressant. ... -1... Protriptyline (VivactilÂ®) is a tricyclic antidepressant indicated for depression and ADHD. Categories: | ... Trimipramine is an tricyclic antidepressant with sedative and anxiolytic properties. ... To meet Wikipedias quality standards, this article may require cleanup. ... Dopamine Dopamine Reuptake Inhibitors (DARI), Dopamine Uptake Inhibitors, Dopamine Transporter Inhibitors are compounds that inhibit the reuptake of extracellular dopamine back into the presynaptic cell by blocking the cell membrane-spanning dopamine transporter. ... Phenmetrazine is an amphetamine-like drug. ... Vanoxerine, also known as GBR-12909, is a piperazine derivative which is a potent and selective dopamine reuptake inhibitor. ... Chemical structure of the tricyclic antidepressant amitriptyline. ... Amineptine is an atypical tricyclic antidepressant that selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting antidepressant effect. ... Serotonin Norepinephrine Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant used in the treatment of clinical depression and other affective disorders. ... Desvenlafaxine succinate, marketed under the name Pristiq, is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class from Wyeth. ... Duloxetine (brand names Cymbalta, Yentreve, and in parts of Europe, Xeristar or Ariclaim) is a drug which primarily targets major depressive disorder (MDD), generalized anxiety disorder (GAD), pain related to diabetic peripheral neuropathy and in some countries stress urinary incontinence (SUI). ... Milnacipran is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. ... Nefazodone hydrochloride (trade name Serzone) is an antidepressant drug marketed by Bristol-Myers Squibb. ... Venlafaxine (Effexor, Efexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class first introduced by Wyeth in 1993. ... A Norepinephrine-dopamine reuptake inhibitor is a class of drugs that is both: Dopamine reuptake inhibitor Norepinephrine reuptake inhibitor An example is Bupropion. ... Bupropion (INN; also amfebutamone,[1] brand names Wellbutrin, Zyban, Budeprion and Buproban) is an atypical antidepressant, which acts as a norepinephrine reuptake inhibitor and dopamine reuptake inhibitor,[2] and a nicotinic antagonist. ... Nomifensine is a dopamine reuptake inhibitor that increases the amount of synaptic dopamine available to receptors by blocking dopamines re-uptake transporter. ... Serotonin-norepinephrine-dopamine-reuptake-inhibitors (SNDRI) are a class of psychoactive antidepressants. ... Brasofensine is a serotonin-noradrenaline-dopamine reuptake inhibitor. ... Tesofensine is a serotonin-noradrenaline-dopamine reuptake inhibitor, which also seems to increase the action of acetylcholine in the brain, probably due to downstream effects. ... Tianeptine (INN) (StablonÂ®, CoaxilÂ®, TatinolÂ®), is structurally similar to the tricyclic antidepressants. ... Tianeptine (INN) (StablonÂ®, CoaxilÂ®, TatinolÂ®), is an SSRE, or Selective Serotonin Reuptake Enhancer, structurally similar to the tricyclic antidepressants. ... An Adrenergic antagonist is a pharmaceutical substance that acts to inhibit the action of the adrenergic receptors. ... There are also several chemically unrelated tetracyclic antibiotics based on Tetracycline. ... Mianserin is a tetracyclic antidepressant that has antihistaminic and hypnosedative, but almost no anticholinergic, effect. ... Mirtazapine is an antidepressant introduced by Organon International in 1994 used for the treatment of moderate to severe depression. ...

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