Флуоксетин — Википедия

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Флуоксетин — Википедия

Fluoxetine , sold under the brand names Prozac and Sarafem among others, is an antidepressant of the selective serotonin reuptake inhibitor SSRI class. Common side effects include indigestion, trouble sleeping, sexual dysfunction, loss of appetite, dry mouth, rash, and abnormal dreams. Fluoxetine was discovered by Eli Lilly and Company in , and entered medical use in Fluoxetine is frequently used to treat major depressive disorder , obsessive—compulsive disorder OCD , post-traumatic stress disorder PTSD , bulimia nervosa , panic disorder , premenstrual dysphoric disorder , and trichotillomania. The effectiveness of fluoxetine and other antidepressants in the treatment of mild-to-moderate depression is controversial. A systematic review by the National Institute of Care and Clinical Excellence NICE which considered the Kirsch, but not the later meta-analyses concluded strong evidence existed for the efficacy of SSRIs in the treatment of moderate and severe depression, with some evidence for their efficacy in the treatment of mild depression. NICE recommends antidepressant treatment with an SSRI in combination with psychosocial interventions as second-line treatment for short term mild depression, and as a first line treatment for severe and moderate depression, as well as mild depression that is recurrent or long-standing. The American Psychiatric Association includes antidepressant therapy among its first-line options for the treatment of depression, particularly when 'a history of prior positive response to antidepressant medications, the presence of moderate to severe symptoms, significant sleep or appetite disturbances, agitation, patient preference, and anticipation of the need for maintenance therapy' exist. The efficacy of fluoxetine in the treatment of obsessive—compulsive disorder OCD was demonstrated in two randomized multicenter phase III clinical trials. The efficacy of fluoxetine in the treatment of panic disorder was demonstrated in two week randomized multicenter phase III clinical trials that enrolled patients diagnosed with panic disorder, with or without agoraphobia. A systematic review of seven trials which compared fluoxetine to a placebo in the treatment of bulimia nervosa ; six of which found a statistically significant reduction in symptoms such as vomiting and binge eating. Fluoxetine is used to treat premenstrual dysphoric disorder. In children and adolescents, fluoxetine is the antidepressant of choice due to tentative evidence favoring its efficacy and tolerability. Evidence supporting an increased risk of major fetal malformations resulting from fluoxetine exposure is limited, although the Medicines and Healthcare Products Regulatory Agency MHRA of the UK has warned prescribers and patients of the potential for fluoxetine exposure in the first trimester during organogenesis, formation of the fetal organs to cause a slight increase in the risk of congenital cardiac malformations in the newborn. However, a systematic review and meta-analysis of 21 studies — published in the Journal of Obstetrics and Gynaecology Canada — concluded, 'the apparent increased risk of fetal cardiac malformations associated with maternal use of fluoxetine has recently been shown also in depressed women who deferred SSRI therapy in pregnancy, and therefore most probably reflects an ascertainment bias. Overall, women who are treated with fluoxetine during the first trimester of pregnancy do not appear to have an increased risk of major fetal malformations. Per the FDA, infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn. Limited data support this risk, but the FDA recommends physicians consider tapering SSRIs such as fluoxetine during the third trimester. Sexual dysfunction, including loss of libido, anorgasmia , lack of vaginal lubrication, and erectile dysfunction , are some of the most commonly encountered adverse effects of treatment with fluoxetine and other SSRIs. Antidepressant discontinuation syndrome may occur within days or weeks of stopping an antidepressant. Symptoms may include dizziness, disturbance of balance, headache, nausea, insomnia, vivid dreams, sensations of tingling or numbness , irritability, hallucinations , fatigue , depression-like symptoms, and suicide. Antidepressant discontinuation syndrome is often mistaken for recurrent depression, prompting re-administration of the drug. Antidepressant discontinuation syndrome may be reduced or prevented by tapering the medication over several weeks or months. In the FDA required all antidepressants to carry a black box warning stating that antidepressants may increase the risk of suicide in people younger than The suicidality was slightly decreased for those older than 24, and statistically significantly lower in the 65 and older group. There is less data on fluoxetine than on antidepressants as a whole. For the above analysis on the antidepressant level, the FDA had to combine the results of trials of 11 antidepressants for psychiatric indications to obtain statistically significant results. Fluoxetine can affect the electrical currents that heart muscle cells use to coordinate their contraction, specifically the potassium currents I to and I Ks that repolarise the cardiac action potential. When fluoxetine is taken alongside other drugs that prolong the QT interval, or by those with a susceptibility to long QT syndrome , there is a small risk of potentially lethal abnormal heart rhythms such as Torsades de Pointes. In overdose, most frequent adverse effects include: \\\\\\\\\\\\[67\\\\\\\\\\\\]. Contraindications include prior treatment within the past 5—6 weeks, depending on the dose \\\\\\\\\\\\[68\\\\\\\\\\\\] \\\\\\\\\\\\[69\\\\\\\\\\\\] with MAOIs such as phenelzine and tranylcypromine , due to the potential for serotonin syndrome. In some cases, use of dextromethorphan -containing cold and cough medications with fluoxetine is advised against, due to fluoxetine increasing serotonin levels, as well as the fact that fluoxetine is a cytochrome P 2D6 inhibitor, which causes dextromethorphan to not be metabolized at a normal rate, thus increasing the risk of serotonin syndrome and other potential side effects of dextromethorphan. Fluoxetine and norfluoxetine inhibit many isozymes of the cytochrome P system that are involved in drug metabolism. Its use should also be avoided in those receiving other serotonergic drugs such as monoamine oxidase inhibitors , tricyclic antidepressants , methamphetamine , amphetamine , MDMA , triptans , buspirone , serotonin—norepinephrine reuptake inhibitors and other SSRIs due to the potential for serotonin syndrome to develop as a result. There is also the potential for interaction with highly protein-bound drugs due to the potential for fluoxetine to displace said drugs from the plasma or vice versa hence increasing serum concentrations of either fluoxetine or the offending agent. Fluoxetine is a selective serotonin reuptake inhibitor SSRI and does not appreciably inhibit norepinephrine and dopamine reuptake at therapeutic doses. It does, however, delay the reuptake of serotonin, resulting in serotonin persisting longer when it is released. Large doses in rats have been shown to induce a significant increase in synaptic norepinephrine and dopamine. Fluoxetine increases the concentration of circulating allopregnanolone , a potent GABA A receptor positive allosteric modulator , in the brain. However, the significance of this property is not fully clear. Fluoxetine has been shown to inhibit acid sphingomyelinase , a key regulator of ceramide levels which derives ceramide from sphingomyelin. Fluoxetine elicits antidepressant effect by inhibiting serotonin re-uptake in the synapse by binding to the re-uptake pump on the neuronal membrane \\\\\\\\\\\\[92\\\\\\\\\\\\] to increase its availability and enhance neurotransmission. CYP2D6 is responsible for converting fluoxetine to its only active metabolite, norfluoxetine. The extremely slow elimination of fluoxetine and its active metabolite norfluoxetine from the body distinguishes it from other antidepressants. Fluoxetine and norfluoxetine may be quantitated in blood, plasma or serum to monitor therapy, confirm a diagnosis of poisoning in hospitalized person or assist in a medicolegal death investigation. Norfluoxetine concentrations are approximately equal to those of the parent drug during chronic therapy, but may be substantially less following acute overdosage, since it requires at least 1—2 weeks for the metabolite to achieve equilibrium. In , over The work which eventually led to the discovery of fluoxetine began at Eli Lilly and Company in as a collaboration between Bryan Molloy and Robert Rathbun. It was known at that time that the antihistamine diphenhydramine shows some antidepressant-like properties. Wong , proposed to retest the series for the in vitro reuptake of serotonin, norepinephrine and dopamine. This test, carried out by Jong-Sir Horng in May , \\\\\\\\\\\\[\\\\\\\\\\\\] showed the compound later named fluoxetine to be the most potent and selective inhibitor of serotonin reuptake of the series. Fluoxetine appeared on the Belgian market in Lilly tried several product line extension strategies, including extended release formulations and paying for clinical trials to test the efficacy and safety of fluoxetine in premenstrual dysphoric disorder and rebranding the drug in that indication as 'Sarafem' after it was approved by the FDA in , following the recommendation of an advisory committee in To defend its revenue from fluoxetine, Lilly also fought a five-year, multimillion-dollar battle in court with the generic company Barr Pharmaceuticals to protect its patents on fluoxetine, and lost the cases for its line-extension patents other than those for Sarafem, opening fluoxetine to generic manufacturers starting in Beginning 5 April , fluoxetine became one of four antidepressant drugs that the FAA permitted for pilots with authorization from an aviation medical examiner. The other permitted antidepressants are sertraline Zoloft , citalopram Celexa , and escitalopram Lexapro. Fluoxetine has been detected in aquatic ecosystems, especially in North America. However, a review on the ecotoxicology of fluoxetine concluded that at that time a consensus on the ability of environmental realistic dosages to affect the behaviour of wildlife could not be reached. During the campaign for Governor of Florida , it was disclosed that one of the candidates, Lawton Chiles , had depression and had resumed taking fluoxetine, leading his political opponents to question his fitness to serve as Governor. Neither the American Psychiatric Association, \\\\\\\\\\\\[29\\\\\\\\\\\\] the National Institute for Health and Care Excellence NICE , \\\\\\\\\\\\[\\\\\\\\\\\\] nor the American College of Physicians \\\\\\\\\\\\[\\\\\\\\\\\\] list violence among the potential side effects of treatment with serotonin selective reuptake inhibitors. Serial case report studies of this type have been criticized as being subject to 'confounding by indication', in which effects due to an underlying disease state are mistakenly attributed to the effects of treatment. A randomized clinical trial performed by the US National Institutes for Mental Health found that fluoxetine reduced acts of domestic violence in alcoholics with a history of such behavior \\\\\\\\\\\\[\\\\\\\\\\\\] A second clinical trial performed at the University of Chicago found that fluoxetine reduced aggressive behavior in patients in intermittent aggressive disorder. Despite the above cited evidence, psychiatrist David Healy and certain patient activist groups have compiled case reports of violent acts committed by individuals taking fluoxetine or other SSRIs, \\\\\\\\\\\\[\\\\\\\\\\\\] \\\\\\\\\\\\[\\\\\\\\\\\\] and have argued that these drugs predispose susceptible individuals to commit violent acts. From Wikipedia, the free encyclopedia. For other uses, see Prozac disambiguation. Not to be confused with Fluvoxamine. IUPAC name. Interactive image. See also: Serotonin syndrome. Nervous system effects anxiety nervousness insomnia drowsiness fatigue or asthenia tremor dizziness or lightheadedness Gastrointestinal effects anorexia symptom nausea diarrhea vasodilation dry mouth abnormal vision Other effects abnormal ejaculation rash sweating decreased libido. Substance Abuse in the Mentally and Physically Disabled. CRC Press. Archived from the original on 8 December Retrieved 2 December TGA eBusiness Services. Eli Lilly Australia Pty. Archived from the original on 25 April Retrieved 23 November Archived PDF from the original on 4 March Retrieved 5 April Clinical Pharmacokinetics. Archived from the original on 8 September The most important chemical compounds: a reference guide 1st ed. Westport, Conn. World Health Organization model list of essential medicines: 21st list Geneva: World Health Organization. International Drug Price Indicator Guide. Medford, Massachusetts: Management Sciences for Health. Retrieved 11 April Neurodevelopmental Disorders: Diagnosis and Treatment. Oxford University Press. Dech and Budow were among the first to report the anecdotal use of fluoxetine in a case of PWS to control behavior problems, appetite, and trichotillomania. Pharmaceutical Pr; Archived from the original on 11 April Retrieved 3 April The National Institute of Mental Health. National Institute of Health. Archived from the original on 19 August Retrieved 25 November Harvard Health. Retrieved 15 May The Cochrane Database of Systematic Reviews. Expert Opinion on Pharmacotherapy. PLoS Medicine. Archives of General Psychiatry. A systematic review with meta-analysis and Trial Sequential Analysis'. BMC Psychiatry. National Institute for Health and Care Excellence. Archived from the original on 9 January American Psychiatric Association. The World Journal of Biological Psychiatry. Archived PDF from the original on 1 August Psychotherapy and Psychosomatics. Reproduction, Fertility, and Development. Fluoxetine Hydrochloride. Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 24 November Medicines and Healthcare Products Regulatory Agency. Archived from the original PDF on 2 December Journal of Obstetrics and Gynaecology Canada. Journal of Human Lactation. The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. American Journal of Obstetrics and Gynecology. Applied therapeutics: the clinical use of drugs 10th ed. The Journal of Family Practice. The Journal of Sexual Medicine. Therapeutic Advances in Psychopharmacology. J Psychiatry Neurosci. American Family Physician. Canadian Medical Association Journal. April JAMA Psychiatry. Journal of Perinatology. June The New England Journal of Medicine. Archived from the original on 27 September Retrieved 13 May Archived PDF from the original on 16 March Retrieved 22 September Archived from the original on 28 February Pages 25, Retrieved 6 January Archived PDF from the original on 28 February Retrieved 25 September Current Cardiology Reviews. May Canadian Pharmacists Journal. Retrieved 2 September Retrieved 13 March September Principles and Practice of Psychopharmacotherapy. A 2-week interval is adequate for all of these drugs, with the exception of fluoxetine. With higher daily doses, the interval should be longer. Archived from the original on 14 August Retrieved 3 March Archived from the original on 31 August Clinical Pharmacology and Therapeutics. Pharmacotherapy of Depression. SpringerLink 2nd ed. The Merck Manual Professional. Archived from the original on 3 September Archived from the original on 8 November Retrieved 24 June Biological Psychiatry. Journal of Neural Transmission. Current Opinion in Pharmacology. The Journal of Pharmacology and Experimental Therapeutics. European Journal of Pharmacology. Archived from the original on 10 November Retrieved 10 November July Nature Medicine. Neural Plasticity. Retrieved 28 January A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness'. Archived from the original on 10 April Retrieved 14 April Current Drug Metabolism. Journal of Clinical Psychopharmacology. Archived from the original on 17 April Grup de Recerca en Trastorns Afectius February Journal of Affective Disorders. The Journal of Clinical Psychiatry. Disposition of Toxic Drugs and Chemicals in Man 8th ed. Drug Topics: Voice of the Pharmacist. Archived from the original PDF on 15 December Archived from the original on 11 December In over 43 million prescriptions for antidepressants were handed out in the UK and about 14 per cent or nearly 6 million prescriptions of these were for a drug called fluoxetine, better known as Prozac. Life Sciences. Talking Back to Prozac. Macmillan Publishers. The Indianapolis Star. Archived from the original on 18 August Food and Drug Administration. Archived from the original on 20 August Retrieved 24 May Fortune Magazine. Retrieved 15 June Archived from the original on 5 May International Medical News Group. The New York Times. Archived from the original on 28 September Retrieved 20 July Village Voice. Rights to Lilly Drug'. The Washington Post. Department of Transportation. Archived from the original on 14 January Retrieved 10 February Psychiatric Conditions — Use of Antidepressant Medications'. Guide for Aviation Medical Examiners. Archived from the original on 3 May Bibcode : EnST Aquatic Toxicology. Toxicology Letters. Hot Spot Pollutants: Pharmaceuticals in the Environment. Environmental Pollution. Environmental Toxicology and Chemistry. Archived from the original on 29 June Annals of Internal Medicine. Pharmacological treatment of mental disorders in primary health care PDF. European Psychiatry. Principles of causality in epidemiological research: confounding, effect modification and strength of association'. I: Findings with normal adolescents'. Journal of Abnormal Child Psychology. Psychological Science. Alcoholism, Clinical and Experimental Research. Psycho-pharmaceuticals and crime trends' PDF. Journal of Policy Analysis and Management. Nber Working Paper Series. Archived PDF from the original on 2 December Antidepressants N06A. Atomoxetine Reboxetine Viloxazine. Mianserin Mirtazapine Setiptiline. Etoperidone Nefazodone Trazodone. Vilazodone Vortioxetine. Tricyclic and tetracyclic antidepressants. Amoxapine Maprotiline Mianserin Mirtazapine Setiptiline. Monoamine oxidase inhibitors. Irreversible: Selegiline. Adjunctive therapies. Atypical antipsychotics aripiprazole , brexpiprazole , lurasidone , olanzapine , quetiapine , risperidone Buspirone Lithium lithium carbonate , lithium citrate Thyroid hormones triiodothyronine T 3 , levothyroxine T 4. Anxiolytics N05B. Gabapentin Gabapentin enacarbil Phenibut Pregabalin. SSRIs e. Alpha-1 blockers e. OCD pharmacotherapies. Antiandrogens e. Monoamine reuptake inhibitors. Others: Antihistamines e. Others: A Amoxapine Antihistamines e. Amiodarone Amphetamines e. Serotonin receptor modulators. Antagonists: Atypical antipsychotics e. Antagonists: AR-A Beta blockers e. Agonists: BRL Ergolines e. Antagonists: Metitepine methiothepin. Antagonists: Mianserin Metitepine methiothepin. Agonists: 4-Methylaminorex Aminorex Amphetamines e. Antagonists: Agomelatine Atypical antipsychotics e. Agonists: 2Cs e. Antagonists: Adatanserin Agomelatine Atypical antipsychotics e. Agonists: Alcohols e. Agonists: Ergolines e. Antagonists: ABT Atypical antipsychotics e. Sigma receptor modulators. GABA A receptor positive modulators. Etomidate Metomidate Propoxate. Fospropofol Propofol Thymol. Glutethimide Methyprylon Piperidione Pyrithyldione. Medicine portal. Hidden categories: Webarchive template wayback links CS1: long volume value Pages containing links to subscription-only content Articles with short description Use dmy dates from January Template:drugs. Namespaces Article Talk. Views Read Edit View history. In other projects Wikimedia Commons. By using this site, you agree to the Terms of Use and Privacy Policy. Fluoxetine top , R -fluoxetine center , S -fluoxetine bottom. None \\\\\\\\\\\\[1\\\\\\\\\\\\]. Selective serotonin reuptake inhibitor SSRI \\\\\\\\\\\\[2\\\\\\\\\\\\]. Liver mostly CYP2D6 -mediated \\\\\\\\\\\\[3\\\\\\\\\\\\]. Nervous system effects anxiety nervousness insomnia drowsiness fatigue or asthenia tremor dizziness or lightheadedness. Gastrointestinal effects anorexia symptom nausea diarrhea vasodilation dry mouth abnormal vision. Other effects abnormal ejaculation rash sweating decreased libido. Wikimedia Commons has media related to Fluoxetine. Adjunctive therapies Atypical antipsychotics aripiprazole , brexpiprazole , lurasidone , olanzapine , quetiapine , risperidone Buspirone Lithium lithium carbonate , lithium citrate Thyroid hormones triiodothyronine T 3 , levothyroxine T 4.

Флуоксетин — Википедия

Флуоксетин

Fluoxetine , sold under the brand names Prozac and Sarafem among others, is an antidepressant of the selective serotonin reuptake inhibitor SSRI class. Common side effects include indigestion, trouble sleeping, sexual dysfunction, loss of appetite, dry mouth, rash, and abnormal dreams. Fluoxetine was discovered by Eli Lilly and Company in , and entered medical use in Fluoxetine is frequently used to treat major depressive disorder , obsessive—compulsive disorder OCD , post-traumatic stress disorder PTSD , bulimia nervosa , panic disorder , premenstrual dysphoric disorder , and trichotillomania. The effectiveness of fluoxetine and other antidepressants in the treatment of mild-to-moderate depression is controversial. A systematic review by the National Institute of Care and Clinical Excellence NICE which considered the Kirsch, but not the later meta-analyses concluded strong evidence existed for the efficacy of SSRIs in the treatment of moderate and severe depression, with some evidence for their efficacy in the treatment of mild depression. NICE recommends antidepressant treatment with an SSRI in combination with psychosocial interventions as second-line treatment for short term mild depression, and as a first line treatment for severe and moderate depression, as well as mild depression that is recurrent or long-standing. The American Psychiatric Association includes antidepressant therapy among its first-line options for the treatment of depression, particularly when 'a history of prior positive response to antidepressant medications, the presence of moderate to severe symptoms, significant sleep or appetite disturbances, agitation, patient preference, and anticipation of the need for maintenance therapy' exist. The efficacy of fluoxetine in the treatment of obsessive—compulsive disorder OCD was demonstrated in two randomized multicenter phase III clinical trials. The efficacy of fluoxetine in the treatment of panic disorder was demonstrated in two week randomized multicenter phase III clinical trials that enrolled patients diagnosed with panic disorder, with or without agoraphobia. A systematic review of seven trials which compared fluoxetine to a placebo in the treatment of bulimia nervosa ; six of which found a statistically significant reduction in symptoms such as vomiting and binge eating. Fluoxetine is used to treat premenstrual dysphoric disorder. In children and adolescents, fluoxetine is the antidepressant of choice due to tentative evidence favoring its efficacy and tolerability. Evidence supporting an increased risk of major fetal malformations resulting from fluoxetine exposure is limited, although the Medicines and Healthcare Products Regulatory Agency MHRA of the UK has warned prescribers and patients of the potential for fluoxetine exposure in the first trimester during organogenesis, formation of the fetal organs to cause a slight increase in the risk of congenital cardiac malformations in the newborn. However, a systematic review and meta-analysis of 21 studies — published in the Journal of Obstetrics and Gynaecology Canada — concluded, 'the apparent increased risk of fetal cardiac malformations associated with maternal use of fluoxetine has recently been shown also in depressed women who deferred SSRI therapy in pregnancy, and therefore most probably reflects an ascertainment bias. Overall, women who are treated with fluoxetine during the first trimester of pregnancy do not appear to have an increased risk of major fetal malformations. Per the FDA, infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn. Limited data support this risk, but the FDA recommends physicians consider tapering SSRIs such as fluoxetine during the third trimester. Sexual dysfunction, including loss of libido, anorgasmia , lack of vaginal lubrication, and erectile dysfunction , are some of the most commonly encountered adverse effects of treatment with fluoxetine and other SSRIs. Antidepressant discontinuation syndrome may occur within days or weeks of stopping an antidepressant. Symptoms may include dizziness, disturbance of balance, headache, nausea, insomnia, vivid dreams, sensations of tingling or numbness , irritability, hallucinations , fatigue , depression-like symptoms, and suicide. Antidepressant discontinuation syndrome is often mistaken for recurrent depression, prompting re-administration of the drug. Antidepressant discontinuation syndrome may be reduced or prevented by tapering the medication over several weeks or months. In the FDA required all antidepressants to carry a black box warning stating that antidepressants may increase the risk of suicide in people younger than The suicidality was slightly decreased for those older than 24, and statistically significantly lower in the 65 and older group. There is less data on fluoxetine than on antidepressants as a whole. For the above analysis on the antidepressant level, the FDA had to combine the results of trials of 11 antidepressants for psychiatric indications to obtain statistically significant results. Fluoxetine can affect the electrical currents that heart muscle cells use to coordinate their contraction, specifically the potassium currents I to and I Ks that repolarise the cardiac action potential. When fluoxetine is taken alongside other drugs that prolong the QT interval, or by those with a susceptibility to long QT syndrome , there is a small risk of potentially lethal abnormal heart rhythms such as Torsades de Pointes. In overdose, most frequent adverse effects include: \\\\\\\\\\\\\\[67\\\\\\\\\\\\\\]. Contraindications include prior treatment within the past 5—6 weeks, depending on the dose \\\\\\\\\\\\\\[68\\\\\\\\\\\\\\] \\\\\\\\\\\\\\[69\\\\\\\\\\\\\\] with MAOIs such as phenelzine and tranylcypromine , due to the potential for serotonin syndrome. In some cases, use of dextromethorphan -containing cold and cough medications with fluoxetine is advised against, due to fluoxetine increasing serotonin levels, as well as the fact that fluoxetine is a cytochrome P 2D6 inhibitor, which causes dextromethorphan to not be metabolized at a normal rate, thus increasing the risk of serotonin syndrome and other potential side effects of dextromethorphan. Fluoxetine and norfluoxetine inhibit many isozymes of the cytochrome P system that are involved in drug metabolism. Its use should also be avoided in those receiving other serotonergic drugs such as monoamine oxidase inhibitors , tricyclic antidepressants , methamphetamine , amphetamine , MDMA , triptans , buspirone , serotonin—norepinephrine reuptake inhibitors and other SSRIs due to the potential for serotonin syndrome to develop as a result. There is also the potential for interaction with highly protein-bound drugs due to the potential for fluoxetine to displace said drugs from the plasma or vice versa hence increasing serum concentrations of either fluoxetine or the offending agent. Fluoxetine is a selective serotonin reuptake inhibitor SSRI and does not appreciably inhibit norepinephrine and dopamine reuptake at therapeutic doses. It does, however, delay the reuptake of serotonin, resulting in serotonin persisting longer when it is released. Large doses in rats have been shown to induce a significant increase in synaptic norepinephrine and dopamine. Fluoxetine increases the concentration of circulating allopregnanolone , a potent GABA A receptor positive allosteric modulator , in the brain. However, the significance of this property is not fully clear. Fluoxetine has been shown to inhibit acid sphingomyelinase , a key regulator of ceramide levels which derives ceramide from sphingomyelin. Fluoxetine elicits antidepressant effect by inhibiting serotonin re-uptake in the synapse by binding to the re-uptake pump on the neuronal membrane \\\\\\\\\\\\\\[92\\\\\\\\\\\\\\] to increase its availability and enhance neurotransmission. CYP2D6 is responsible for converting fluoxetine to its only active metabolite, norfluoxetine. The extremely slow elimination of fluoxetine and its active metabolite norfluoxetine from the body distinguishes it from other antidepressants. Fluoxetine and norfluoxetine may be quantitated in blood, plasma or serum to monitor therapy, confirm a diagnosis of poisoning in hospitalized person or assist in a medicolegal death investigation. Norfluoxetine concentrations are approximately equal to those of the parent drug during chronic therapy, but may be substantially less following acute overdosage, since it requires at least 1—2 weeks for the metabolite to achieve equilibrium. In , over The work which eventually led to the discovery of fluoxetine began at Eli Lilly and Company in as a collaboration between Bryan Molloy and Robert Rathbun. It was known at that time that the antihistamine diphenhydramine shows some antidepressant-like properties. Wong , proposed to retest the series for the in vitro reuptake of serotonin, norepinephrine and dopamine. This test, carried out by Jong-Sir Horng in May , \\\\\\\\\\\\\\[\\\\\\\\\\\\\\] showed the compound later named fluoxetine to be the most potent and selective inhibitor of serotonin reuptake of the series. Fluoxetine appeared on the Belgian market in Lilly tried several product line extension strategies, including extended release formulations and paying for clinical trials to test the efficacy and safety of fluoxetine in premenstrual dysphoric disorder and rebranding the drug in that indication as 'Sarafem' after it was approved by the FDA in , following the recommendation of an advisory committee in To defend its revenue from fluoxetine, Lilly also fought a five-year, multimillion-dollar battle in court with the generic company Barr Pharmaceuticals to protect its patents on fluoxetine, and lost the cases for its line-extension patents other than those for Sarafem, opening fluoxetine to generic manufacturers starting in Beginning 5 April , fluoxetine became one of four antidepressant drugs that the FAA permitted for pilots with authorization from an aviation medical examiner. The other permitted antidepressants are sertraline Zoloft , citalopram Celexa , and escitalopram Lexapro. Fluoxetine has been detected in aquatic ecosystems, especially in North America. However, a review on the ecotoxicology of fluoxetine concluded that at that time a consensus on the ability of environmental realistic dosages to affect the behaviour of wildlife could not be reached. During the campaign for Governor of Florida , it was disclosed that one of the candidates, Lawton Chiles , had depression and had resumed taking fluoxetine, leading his political opponents to question his fitness to serve as Governor. Neither the American Psychiatric Association, \\\\\\\\\\\\\\[29\\\\\\\\\\\\\\] the National Institute for Health and Care Excellence NICE , \\\\\\\\\\\\\\[\\\\\\\\\\\\\\] nor the American College of Physicians \\\\\\\\\\\\\\[\\\\\\\\\\\\\\] list violence among the potential side effects of treatment with serotonin selective reuptake inhibitors. Serial case report studies of this type have been criticized as being subject to 'confounding by indication', in which effects due to an underlying disease state are mistakenly attributed to the effects of treatment. A randomized clinical trial performed by the US National Institutes for Mental Health found that fluoxetine reduced acts of domestic violence in alcoholics with a history of such behavior \\\\\\\\\\\\\\[\\\\\\\\\\\\\\] A second clinical trial performed at the University of Chicago found that fluoxetine reduced aggressive behavior in patients in intermittent aggressive disorder. Despite the above cited evidence, psychiatrist David Healy and certain patient activist groups have compiled case reports of violent acts committed by individuals taking fluoxetine or other SSRIs, \\\\\\\\\\\\\\[\\\\\\\\\\\\\\] \\\\\\\\\\\\\\[\\\\\\\\\\\\\\] and have argued that these drugs predispose susceptible individuals to commit violent acts. From Wikipedia, the free encyclopedia. For other uses, see Prozac disambiguation. Not to be confused with Fluvoxamine. IUPAC name. Interactive image. See also: Serotonin syndrome. Nervous system effects anxiety nervousness insomnia drowsiness fatigue or asthenia tremor dizziness or lightheadedness Gastrointestinal effects anorexia symptom nausea diarrhea vasodilation dry mouth abnormal vision Other effects abnormal ejaculation rash sweating decreased libido. Substance Abuse in the Mentally and Physically Disabled. CRC Press. Archived from the original on 8 December Retrieved 2 December TGA eBusiness Services. Eli Lilly Australia Pty. Archived from the original on 25 April Retrieved 23 November Archived PDF from the original on 4 March Retrieved 5 April Clinical Pharmacokinetics. Archived from the original on 8 September The most important chemical compounds: a reference guide 1st ed. Westport, Conn. World Health Organization model list of essential medicines: 21st list Geneva: World Health Organization. International Drug Price Indicator Guide. Medford, Massachusetts: Management Sciences for Health. Retrieved 11 April Neurodevelopmental Disorders: Diagnosis and Treatment. Oxford University Press. Dech and Budow were among the first to report the anecdotal use of fluoxetine in a case of PWS to control behavior problems, appetite, and trichotillomania. Pharmaceutical Pr; Archived from the original on 11 April Retrieved 3 April The National Institute of Mental Health. National Institute of Health. Archived from the original on 19 August Retrieved 25 November Harvard Health. Retrieved 15 May The Cochrane Database of Systematic Reviews. Expert Opinion on Pharmacotherapy. PLoS Medicine. Archives of General Psychiatry. A systematic review with meta-analysis and Trial Sequential Analysis'. BMC Psychiatry. National Institute for Health and Care Excellence. Archived from the original on 9 January American Psychiatric Association. The World Journal of Biological Psychiatry. Archived PDF from the original on 1 August Psychotherapy and Psychosomatics. Reproduction, Fertility, and Development. Fluoxetine Hydrochloride. Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 24 November Medicines and Healthcare Products Regulatory Agency. Archived from the original PDF on 2 December Journal of Obstetrics and Gynaecology Canada. Journal of Human Lactation. The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. American Journal of Obstetrics and Gynecology. Applied therapeutics: the clinical use of drugs 10th ed. The Journal of Family Practice. The Journal of Sexual Medicine. Therapeutic Advances in Psychopharmacology. J Psychiatry Neurosci. American Family Physician. Canadian Medical Association Journal. April JAMA Psychiatry. Journal of Perinatology. June The New England Journal of Medicine. Archived from the original on 27 September Retrieved 13 May Archived PDF from the original on 16 March Retrieved 22 September Archived from the original on 28 February Pages 25, Retrieved 6 January Archived PDF from the original on 28 February Retrieved 25 September Current Cardiology Reviews. May Canadian Pharmacists Journal. Retrieved 2 September Retrieved 13 March September Principles and Practice of Psychopharmacotherapy. A 2-week interval is adequate for all of these drugs, with the exception of fluoxetine. With higher daily doses, the interval should be longer. Archived from the original on 14 August Retrieved 3 March Archived from the original on 31 August Clinical Pharmacology and Therapeutics. Pharmacotherapy of Depression. SpringerLink 2nd ed. The Merck Manual Professional. Archived from the original on 3 September Archived from the original on 8 November Retrieved 24 June Biological Psychiatry. Journal of Neural Transmission. Current Opinion in Pharmacology. The Journal of Pharmacology and Experimental Therapeutics. European Journal of Pharmacology. Archived from the original on 10 November Retrieved 10 November July Nature Medicine. Neural Plasticity. Retrieved 28 January A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness'. Archived from the original on 10 April Retrieved 14 April Current Drug Metabolism. Journal of Clinical Psychopharmacology. Archived from the original on 17 April Grup de Recerca en Trastorns Afectius February Journal of Affective Disorders. The Journal of Clinical Psychiatry. Disposition of Toxic Drugs and Chemicals in Man 8th ed. Drug Topics: Voice of the Pharmacist. Archived from the original PDF on 15 December Archived from the original on 11 December In over 43 million prescriptions for antidepressants were handed out in the UK and about 14 per cent or nearly 6 million prescriptions of these were for a drug called fluoxetine, better known as Prozac. 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Pharmacological treatment of mental disorders in primary health care PDF. European Psychiatry. Principles of causality in epidemiological research: confounding, effect modification and strength of association'. I: Findings with normal adolescents'. Journal of Abnormal Child Psychology. Psychological Science. Alcoholism, Clinical and Experimental Research. Psycho-pharmaceuticals and crime trends' PDF. Journal of Policy Analysis and Management. Nber Working Paper Series. Archived PDF from the original on 2 December Antidepressants N06A. Atomoxetine Reboxetine Viloxazine. Mianserin Mirtazapine Setiptiline. Etoperidone Nefazodone Trazodone. Vilazodone Vortioxetine. Tricyclic and tetracyclic antidepressants. Amoxapine Maprotiline Mianserin Mirtazapine Setiptiline. Monoamine oxidase inhibitors. Irreversible: Selegiline. Adjunctive therapies. Atypical antipsychotics aripiprazole , brexpiprazole , lurasidone , olanzapine , quetiapine , risperidone Buspirone Lithium lithium carbonate , lithium citrate Thyroid hormones triiodothyronine T 3 , levothyroxine T 4. Anxiolytics N05B. Gabapentin Gabapentin enacarbil Phenibut Pregabalin. SSRIs e. Alpha-1 blockers e. OCD pharmacotherapies. Antiandrogens e. Monoamine reuptake inhibitors. Others: Antihistamines e. Others: A Amoxapine Antihistamines e. Amiodarone Amphetamines e. Serotonin receptor modulators. Antagonists: Atypical antipsychotics e. Antagonists: AR-A Beta blockers e. Agonists: BRL Ergolines e. Antagonists: Metitepine methiothepin. Antagonists: Mianserin Metitepine methiothepin. Agonists: 4-Methylaminorex Aminorex Amphetamines e. Antagonists: Agomelatine Atypical antipsychotics e. Agonists: 2Cs e. Antagonists: Adatanserin Agomelatine Atypical antipsychotics e. Agonists: Alcohols e. Agonists: Ergolines e. Antagonists: ABT Atypical antipsychotics e. Sigma receptor modulators. GABA A receptor positive modulators. Etomidate Metomidate Propoxate. Fospropofol Propofol Thymol. Glutethimide Methyprylon Piperidione Pyrithyldione. Medicine portal. Hidden categories: Webarchive template wayback links CS1: long volume value Pages containing links to subscription-only content Articles with short description Use dmy dates from January Template:drugs. Namespaces Article Talk. Views Read Edit View history. In other projects Wikimedia Commons. By using this site, you agree to the Terms of Use and Privacy Policy. Fluoxetine top , R -fluoxetine center , S -fluoxetine bottom. None \\\\\\\\\\\\\\[1\\\\\\\\\\\\\\]. Selective serotonin reuptake inhibitor SSRI \\\\\\\\\\\\\\[2\\\\\\\\\\\\\\]. Liver mostly CYP2D6 -mediated \\\\\\\\\\\\\\[3\\\\\\\\\\\\\\]. Nervous system effects anxiety nervousness insomnia drowsiness fatigue or asthenia tremor dizziness or lightheadedness. Gastrointestinal effects anorexia symptom nausea diarrhea vasodilation dry mouth abnormal vision. Other effects abnormal ejaculation rash sweating decreased libido. Wikimedia Commons has media related to Fluoxetine. Adjunctive therapies Atypical antipsychotics aripiprazole , brexpiprazole , lurasidone , olanzapine , quetiapine , risperidone Buspirone Lithium lithium carbonate , lithium citrate Thyroid hormones triiodothyronine T 3 , levothyroxine T 4.

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