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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/07 18:37:07」(JST)
wiki ja
| IUPAC命名法による物質名 | |
|---|---|
| (RS)-N-メチル-3-フェニル-3-[4-(トリフルオロメチル)フェノキシ]プロパン-1-アミン | |
| 臨床データ | |
| ライセンス | EMA:リンク、US FDA:リンク |
| 胎児危険度分類 |
|
| 法的規制 |
|
| 投与方法 | 経口 |
| 薬物動態的データ | |
| 生物学的利用能 | 72% 6-8時間でピーク |
| 血漿タンパク結合 | 94.5% |
| 代謝 | 肝臓 |
| 半減期 | 1-3日(急性); 4-6日(慢性); 活性代謝物のノルフルオキセチンは4-16 日(急性、慢性) |
| 排泄 | 腎臓80%, 腸15% |
| 識別 | |
| CAS番号 | 54910-89-3 |
| ATCコード | N06AB03 |
| PubChem | CID 3386 |
| DrugBank | APRD00530 |
| ChemSpider | 56589 |
| KEGG | D00326 |
| 化学的データ | |
| 化学式 | C17H18F3NO |
| 分子量 | 309.3 g/mol (345.8 for •HCl) |
フルオキセチンのカプセル剤
フルオキセチン (Fluoxetine) は、SSRI（選択的セロトニン再取り込み阻害薬）の1つである。塩酸塩は商品名プロザック® (Prozac®) としてアメリカのイーライリリー・アンド・カンパニー社からカプセル剤が発売されている。主として、うつ病、依存症、摂食障害等に有効とされている[1]。塩酸フルオキセチンは、月経前症候群にも有効なことから商品名サラフェム (Sarafem) として販売されている。なお、本剤は日本では未承認であり販売されていない。
1988年の発売当初はその効果（重度のうつ病患者には効果が劣るが、軽度から中度の患者には、一般の抗うつ剤と同等またはそれ以上の効果が認められる）から、新世代の抗うつ剤、奇跡の薬とも言われ大変な人気を博した。その後自殺を誘発させる可能性もあるという副作用に関する説や性欲亢進の作用があるという説[2]も出ているが、因果関係は明らかにされていない。主な副作用としては、吐き気 (21.1%)、頭痛 (20.9%)、神経痛 (14.9%) など。
マウスを使った実験で、大脳皮質において神経細胞の再生を促進する例が報告されている[3][4]。
目次
- 1 環境への影響
- 2 脚注
- 3 関連項目
- 4 外部リンク
環境への影響
アメリカ合衆国では抗うつ剤の使用量が増加しており、一般的な下水処理水にも処理し得ない微量のフルオキセチンが含まれている。ポーツマス大学の生物学者、アレックス・フォードは、下水中に含まれる濃度のフルオキセチンがエビ類に与える影響を調査し、行動に変化が生じることを2010年に報告した[5][6]。
脚注
- ^ プロザックの外箱には"For the treatment of Depression（うつ病）, Bulimia Nervosa（過食症） and Obsessive-Compulsive Disorder（強迫性障害）"と書かれている。
- ^ ゲッティスバーグ大学のピーター・フォングは、ヒトと神経系が似ているハマグリにフルオキセチンを与えたところ、何も与えない対象群よりも10倍の繁殖力を示したという実験結果を発表している。なお、この実験によってフォングは、1998年にイグノーベル賞を受賞している。
- ^ Ohira, Koji; Takeuchi, Rika; Shoji, Hirotaka; Miyakawa, Tsuyoshi (2013). "Fluoxetine-Induced Cortical Adult Neurogenesis". Neuropsychopharmacology. accepted article preview 4 January 2013.
- ^ “抗うつ薬、脳細胞生成に効果 藤田保健大、マウスで実験”. 2013年1月6日時点のオリジナルよりアーカイブ。2013年1月6日閲覧。
- ^ Guler, Yasmin; Ford, Alex T. (2010). "Anti-depressants make amphipods see the light". Aquatic Toxicology 99 (3): 397–404. doi:10.1016/j.aquatox.2010.05.019.
- ^ Ravilious, Kate (2010年7月20日). “排水中の抗うつ剤、エビの行動に影響”. ナショナルジオグラフィック ニュース. http://www.nationalgeographic.co.jp/news/news_article.php?file_id=20100720004 2011年2月14日閲覧。
関連項目
- 抗うつ薬
- 選択的セロトニン再取り込み阻害薬 (SSRI)
- セロトニン・ノルアドレナリン再取り込み阻害薬 (SNRI)
外部リンク
- 「Fluoxetine」 - Medpediaにある「フルオキセチン」についての項目。（英語）
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| この項目は、薬学に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています（プロジェクト:薬学／Portal:医学と医療）。 |
wiki en
Not to be confused with Fluvoxamine. "Prozac" redirects here. For other uses, see Prozac (disambiguation).
| Systematic (IUPAC) name | |
|---|---|
| (RS)-N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine | |
| Clinical data | |
| Trade names | Listed below |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a689006 |
| Licence data | US FDA:link |
|
Pregnancy
category |
|
|
Legal status
|
|
|
Dependence
liability |
Physical: Low Psychological: Low |
|
Addiction
liability |
none |
|
Routes of
administration |
Oral |
| Pharmacokinetic data | |
| Bioavailability | 72%[1] |
| Protein binding | 94-95%[1][2][3] |
| Metabolism | Hepatic (mostly CYP2D6-mediated)[1][4] |
| Onset of action | ~2–4 weeks |
| Half-life | 1–3 days (acute) 4–6 days (chronic)[1][4] |
| Excretion | Urine (80%), faeces (15%)[1][4] |
| Identifiers | |
|
CAS Registry Number
|
54910-89-3 Y |
|
ATC code
|
N06AB03 |
| PubChem | CID 3386 |
| IUPHAR ligand | 203 |
| DrugBank | DB00472 Y |
| ChemSpider | 3269 Y |
| UNII | 01K63SUP8D Y |
| KEGG | D00326 N |
| ChEBI | CHEBI:5118 Y |
| ChEMBL | CHEMBL41 Y |
| Chemical data | |
| Formula | C17H18F3NO |
|
Molecular mass
|
309.33 g·mol−1 |
|
SMILES
|
|
|
InChI
|
|
| Physical data | |
| Melting point | 179 to 182 °C (354 to 360 °F) |
| Boiling point | 395 °C (743 °F) |
|
Solubility in water
|
14 mg/mL (20 °C) |
| N (what is this?) (verify) | |
Fluoxetine (also known by the trade names Prozac, and Sarafem, among others) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. Fluoxetine was discovered and developed by scientists from Eli Lilly and Company.[5] It was approved by the U.S. Food and Drug Administration for the treatment of major depressive disorder in December 1987.[6] The U.S. fluoxetine patent expired in August 2001, so generic formulations are now available in the U.S.[7]
Fluoxetine is used for the treatment of major depressive disorder (including pediatric depression), obsessive–compulsive disorder (in both adults and children), bulimia nervosa, panic disorder, and premenstrual dysphoric disorder.[8] In addition, it is used to treat trichotillomania if cognitive behaviour therapy has been unsuccessful.[9]
In 2010, over 24.4 million prescriptions for generic formulations of fluoxetine were filled in the United States,[10] making it the third-most prescribed antidepressant after sertraline and citalopram.[10] In 2011, 6 million prescriptions for fluoxetine were filled in the United Kingdom.[11] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[12]
Contents
- 1 Medical uses
- 1.1 Depression
- 1.2 Obsessive-compulsive disorder
- 1.3 Panic disorder
- 1.4 Bulimia nervosa
- 1.5 Special populations
- 2 Contraindications
- 3 Adverse effects
- 3.1 Sexual dysfunction
- 3.2 Discontinuation syndrome
- 3.3 Suicide
- 4 Overdose
- 5 Interactions
- 6 Pharmacology
- 6.1 Pharmacodynamics
- 6.2 Pharmacokinetics
- 6.2.1 Measurement in body fluids
- 7 History
- 8 Society and culture
- 8.1 Violence
- 8.2 Brand names
- 9 See also
- 10 References
- 11 External links
Medical uses
Fluoxetine 20 mg capsules.
Fluoxetine is frequently used to treat major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder, bulimia nervosa, panic disorder, premenstrual dysphoric disorder, and trichotillomania.[9][13][14][15] It has also been used for cataplexy, obesity, and alcohol dependence,[16] as well as binge eating disorder.[17] It has also been tried as a treatment for autism spectrum disorders with moderate success in adults.[18][19][20][21]
Depression
The effectiveness of fluoxetine and other antidepressants in the treatment of mild-to-moderate depression is controversial. A meta-analysis published by Kirsch in 2008 suggests, in those with mild or moderate symptoms, the efficacy of fluoxetine and other SSRIs is clinically insignificant.[22] A 2009 meta-analysis by Fournier et al., which evaluated patient-level data from six trials of the SSRI paroxetine and the non-SSRI antidepressant imipramine has been further cited as evidence that antidepressants exhibit minimal efficacy in mild to moderate depression.[23] A 2012 meta-analysis using individual patient level-data from 18 randomized controlled clinical trials of fluoxetine for the treatment of depression concluded statistically and clinically significant benefit was seen irrespective of baseline depression severity, and no significant effect was found on baseline severity on observed efficacy.[24]
A 2009 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.[25] Both the NICE and the Fournier analyses concluded greater evidence is seen for the efficacy of antidepressants in the treatment of chronic mild depression (dysthymia) than in recent-onset 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 it 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.[26]
Obsessive-compulsive disorder
The efficacy of fluoxetine in the treatment of obsessive-compulsive disorder was demonstrated in two randomized multicenter phase III clinical trials. The pooled results of these trials demonstrated that 47% of completers treated with the highest dose were "much improved" or "very much improved" after 13 weeks of treatment, compared to 11% in the placebo arm of the trial.[27] SSRIs including fluoxetine should be used as first-line therapy, along with CBT, for the treatment of moderate to severe OCD.[28]
Panic disorder
The efficacy of fluoxetine in the treatment of panic disorder was demonstrated in two 12-week randomized multicenter phase III trials that enrolled patients diagnosed with panic disorder, with or without agoraphobia. In the first trial, 42% of subjects in the fluoxetine-treated arm were free of panic attacks at the end of the study, vs. 28% in the placebo arm. In the second trial, 62% of fluoxetine treated patients were free of panic attacks at the end of the study, vs. 44% in the placebo arm.[27]
Bulimia nervosa
A 2011 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.[29] However, no difference was observed between treatment arms when fluoxetine and psychotherapy were compared to psychotherapy alone.
Special populations
In children and adolescents, fluoxetine is the antidepressant of choice due to tentative evidence favoring its efficacy and tolerability.[30][31] In pregnancy, fluoxetine is considered a category C drug. Evidence supporting an increased risk of major fetal malformations resulting from fluoxetine exposure is limited, although the Medicines and Healthcare Products Regulatory Agency 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.[32][33][34] Furthermore, an association between fluoxetine use during the first trimester and an increased risk of minor fetal malformations was observed in one study.[33]
However, a systematic review and meta-analysis of 21 studies 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." But the study found also 15 cohort studies that evaluated cardiac malformations and yielded an overall odds ratio of 1.6 (95% confidence interval: 1.31 to 1.95).[35]
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.[36] A review recommended against fluoxetine as a first-line SSRI during lactation, stating, "[fluoxetine] should be viewed as a less-preferred SSRI for breastfeeding mothers, particularly with newborn infants, and in those mothers who consumed fluoxetine during gestation."[37] Sertraline is often the preferred SSRI during pregnancy due to the relatively minimal fetal exposure observed and its safety profile while breastfeeding.[38]
Contraindications
Contraindications include prior treatment (within the past two weeks) with MAOIs such as phenelzine and tranylcypromine, due to the potential for serotonin syndrome.[4] Its use should also be avoided in those with known hypersensitivities to fluoxetine or any of the other ingredients in the formulation used.[4] Its use in those concurrently receiving pimozide or Thioridazine is also advised against.[4]
Adverse effects
Side effects observed in fluoxetine-treated persons in clinical trial with an incidence >5% and at least twice as common in fluoxetine-treated persons compared to those who received a sugar pill include abnormal dreams, abnormal ejaculation, anorexia, anxiety, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, impotence, insomnia, decreased libido, nausea, nervousness, pharyngitis, rash, sinusitis, somnolence, sweating, tremor, vasodilatation, and yawning.[39] Fluoxetine is considered the most stimulating of the SSRIs (that is, it is most prone to causing insomnia and agitation).[40][40] It also appears to be the most prone of the SSRIs for producing dermatologic reactions (e.g. urticaria (hives), rash, itchiness, etc.).[33]
Sexual dysfunction
Sexual dysfunction, including loss of libido, anorgasmia, lack of vaginal lubrication, and erectile dysfunction, is one of the most commonly encountered adverse effects of treatment with fluoxetine and other SSRIs. While early clinical trials suggested a relatively low rate of sexual dysfunction, more recent studies in which the investigator actively enquires about sexual problems suggest that the incidence is >70%.[41] Symptoms of sexual dysfunction have been reported to occasionally persist after discontinuing SSRIs.[42][43]
Discontinuation syndrome
Main article: SSRI discontinuation syndrome
The side effects of the fluoxetine discontinuation are uncommon and mild, especially compared to paroxetine, venlafaxine and fluvoxamine, probably due to the relatively long pharmacological half-life of fluoxetine. [44] One of the recommended strategies for the management of discontinuation syndrome with other SSRIs is to substitute fluoxetine for the original agent, in cases where tapering off the dose of the original SSRI is ineffective.[45][46] 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 reinstated, this result being consistent with its slow elimination from the body.
More side effects occurred during the interruption of sertraline (Zoloft) in these studies, and significantly more during the interruption of paroxetine.[47] According to a 2007 summary report of available evidence, fluoxetine has the lowest incidence of discontinuation syndrome among several antidepressants including paroxetine and venlafaxine.[48]
Suicide
The FDA now requires all antidepressants to carry a black box warning stating that antidepressants may increase the risk of suicide in people 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.[49][50][51] 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.[52]
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 295 trials of 11 antidepressants for psychiatric indications to obtain statistically significant results. Considered separately, fluoxetine use in children increased the odds of suicidality by 50%,[53] and in adults decreased the odds of suicidality by approximately 30%.[50][51] 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%.[54][55]
Overdose
In overdose, most frequent adverse effects include:[56]
|
Nervous system effects
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Gastrointestinal effects
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Other effects
|
Interactions
Fluoxetine and norfluoxetine inhibit many isozymes of the cytochrome P450 system that are involved in drug metabolism. Both are potent inhibitors of CYP2D6 (which is also the chief enzyme responsible for their metabolism) and CYP2C19, and mild to moderate inhibitors of CYP2B6 and CYP2C9.[57][58] In vivo, fluoxetine and norfluoxetine do not significantly affect the activity of CYP1A2 and CYP3A4.[57] They also inhibit the activity of P-glycoprotein, a type of membrane transport protein that plays an important role in drug transport and metabolism and hence P-glycoprotein substrates such as loperamide may have their central effects potentiated.[59] This extensive effect on the body's pathways for drug metabolism creates the potential for interactions with many commonly used drugs.[59][60]
Its use should also be avoided in those receiving other serotonergic drugs such as monoamine oxidase inhibitors, tricyclic antidepressants, methamphetamine, MDMA, triptans, buspirone, serotonin-norepinephrine reuptake inhibitors and other SSRIs due to the potential for serotonin syndrome to develop as a result.[4]
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.[4]
Pharmacology
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| †Values for both drugs represents a lower bound |
Pharmacodynamics
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and selective brain steroidogenic stimulant (SBSS) 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 has been shown to induce in a significant increase in synaptic norepinephrine and dopamine.[62][63][64][65] Thus, dopamine and norepinephrine may contribute to the antidepressant action of fluoxetine in humans at supratherapeutic doses (60–80 mg) .[64][66] This effect may be mediated by 5HT2C receptors, which are inhibited by higher concentrations of fluoxetine.[67]
Fluoxetine's effect on neurosteroids is primarily related to an increase in allopregnanolone, a potent GABAA receptor positive allosteric modulator;[65] a reduction in circulating brain (primarily mesocorticolimbic) allopregnanolone has been associated with both depression and anxiety disorders.[65] Improvement in depressive symptoms in medicated individuals is correlated with fluoxetine-induced increases in allopregnanolone levels.[65] Norfluoxetine, a primary active metabolite of fluoxetine, produces a similar effect on allopregnanolone levels in the brain, and has therefore also been characterized as a selective brain steroidogenic stimulant.[65]
In addition, fluoxetine has been found to act as an agonist of the σ1-receptor, with a potency greater than that of citalopram but less than that of fluvoxamine. However, the significance of this property is not fully clear.[68][69] Fluoxetine also functions as a channel blocker of anoctamin 1, a calcium-activated chloride channel.[70][71] In addition, it acts as a positive allosteric modulator of the GABAA receptor at high concentrations, and norfluoxetine does the same but more potently, actions which may be clinically-relevant.[72] A number of other ion channels, including nicotinic acetylcholine receptors and 5-HT3 receptors, are also known to be inhibited at similar concentrations.[72]
Pharmacokinetics
Norfluoxetine, fluoxetine's chief active metabolite.
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 and α1-glycoprotein.[4] Fluoxetine is metabolized in the liver by isoenzymes of the cytochrome P450 system, including CYP2D6.[8] 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. CYP2D6 is responsible for converting fluoxetine to its only active metabolite, norfluoxetine.[73] Both drugs are also potent inhibitors of CYP2D6.[74]
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.[4] Similarly, the half-life of norfluoxetine is longer (16 days) after long-term use.[8][75][76] 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.[77][78] Moreover, the brain concentration of fluoxetine and its metabolites keeps increasing through at least the first five weeks of treatment.[79] 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.[77] 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%,[79] 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.[75]
Measurement in body fluids
Fluoxetine and norfluoxetine may be quantitated in blood, plasma or serum to monitor therapy, confirm a diagnosis of poisoning in hospitalized patients or assist in a medicolegal death investigation. Blood or plasma fluoxetine concentrations are usually in a range of 50–500 μg/L in persons taking the drug for its antidepressant effects, 900–3000 μg/L in survivors of acute overdosage and 1000–7000 μg/L in victims of fatal overdosage. 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.[80][81][82]
History
Number of Americans who received SSDI and SSI for mental illness in 1987 (blue) when Eli Lilly and Company introduced the antidepressive drug Prozac, compared to 2003 (red).
Hoping to find a derivative inhibiting only serotonin reuptake, an Eli Lilly scientist, David T. 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 1972,[83] showed the compound later named fluoxetine to be the most potent and selective inhibitor of serotonin reuptake of the series.[5] Wong published the first article about fluoxetine in 1974.[5] A year later, it was given the official chemical name fluoxetine and the Eli Lilly and Company gave it the trade name Prozac. In February 1977, Dista Products Company, a division of Eli Lilly & Company, file an Investigational New Drug application to the U.S. Food and Drug Administration (FDA) for fluoxetine.[84]
Fluoxetine appeared on the Belgian market in 1986.[85] In the U.S., the FDA gave its final approval in December 1987,[86] and a month later Eli Lilly began marketing Prozac; annual sales in the U.S. reached $350 million within a year.[84]
Eli Lilly's U.S. patent on Prozac (fluoxetine) expired in August 2001,[87] prompting an influx of generic drugs onto the market. Prozac was rebranded "Sarafem" for the treatment of PMDD in an attempt to stem the post-patent decrease in Eli Lilly's sales of fluoxetine.[88]
As of April 2, 2010, fluoxetine is one of four antidepressant drugs that the FAA allows pilots to take. The others are sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro).[89]
There has been research on possible effects of fluoxetine on marine life.[90]
Society and culture
Violence
Neither the American Psychiatric Association,[91] the National Institute for Health and Care Excellence (NICE),[92] nor the American College of Physicians[93] list violence among the potential side effects of treatment with serotonin selective reuptake inhibitors. Similarly, the World Health Organization and the European Psychiatric Association do not list violence among the potential side effects of SSRIs.[94][95]
Psychiatrist David Healy and certain patient activist groups have compiled case reports of violent acts committed by individuals taking fluoxetine or other SSRIs,[96][97] and have argued that these drugs predispose susceptible individuals to commit violent acts.
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.[98] Other studies, including randomized clinical trials and observational studies, have suggested that fluoxetine and other SSRIs may reduce the propensity for violence. 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[99] A second clinical trial performed at the University of Chicago found that fluoxetine reduced aggressive behavior in patients in intermittent aggressive disorder.[100] A clinical trial found that fluoxetine reduced aggressive behavior in patients with borderline personality disorder.[101] These results are indirectly supported by studies demonstrating that other SSRIs can reduce violence and aggressive behavior.[102][103][104][105] A NBER study examining international trends in antidepressant use and crime rates in the 1990s found that increases in antidepressant drug prescriptions were associated with reductions in violent crime.[106]
Brand names
Fluoxetine is available under many brand names internationally. The table below provides a listing of these and the countries they are marketed in.
| Table of brand names for fluoxetine pills[33][107] |
|---|
† indicates discontinued brands
|
In combination with the atypical antipsychotic olanzapine it is known by a few brand names, including:
| Table of brand names for fluoxetine/olanzapine combination pill[33][107] |
|---|
† indicates discontinued brands
|
See also
- Orphenadrine
- Atomoxetine
- Reboxetine
References
- ^ a b c d e Altamura, AC; Moro, AR; Percudani, M (March 1994). "Clinical Pharmacokinetics of Fluoxetine" (PDF). Clinical Pharmacokinetics 26 (3): 201–214. doi:10.2165/00003088-199426030-00004. PMID 8194283.
- ^ "FLUOXETINE HYDROCHLORIDE capsule [Sandoz Inc]". DailyMed. Sandoz Inc. January 2013. Retrieved 23 November 2013.
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External links
| Wikimedia Commons has media related to Fluoxetine. |
- Trouble in Prozac, from Fortune magazine
- Fluoxetine, from the United States National Library of Medicine's Drug Information Portal
- Biographies of inventors:
- David T. Wong, from Nature
- Bryan B. Molloy, from Invent Now
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UpToDate Contents
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- 1. 選択的セロトニン再取り込み阻害剤：薬理学、投与方法、および副作用 selective serotonin reuptake inhibitors pharmacology administration and side effects
- 2. 成人における双極性障害：抗うつ剤による大うつ病エピソードの治療 bipolar disorder in adults treating major depression with antidepressants
- 3. 小児単極性うつ病および薬物療法：薬剤の選択 pediatric unipolar depression and pharmacotherapy choosing a medication
- 4. 選択的セロトニン再取り込み阻害剤中毒 selective serotonin reuptake inhibitor poisoning
- 5. Risks of antidepressants during pregnancy: Selective serotonin reuptake inhibitors (SSRIs)
English Journal
- Maternal exposure to fluoxetine during gestation and lactation affects the DNA methylation programming of rat's offspring: Modulation by folic acid supplementation.
- Toffoli LV1, Rodrigues GM Jr1, Oliveira JF2, Silva AS2, Moreira EG2, Pelosi GG2, Gomes MV3.Author information 1Universidade Norte do Paraná (UNOPAR), Brazil.2Universidade Estadual de Londrina (UEL), Brazil.3Universidade Norte do Paraná (UNOPAR), Brazil. Electronic address: mvmgomes@gmail.com.AbstractFluoxetine is an antidepressant that has been largely used for treatment of depression in pregnancy. In the present study we evaluated the effects of the exposure to fluoxetine during gestation and lactation on DNA methylation of rat brain regions. Female Wistar rats were treated with 5mg/kg of fluoxetine during pregnancy and lactation. In order to assess the effects of fluoxetine in the context of maternal folic acid supplementation we performed an additional combined treatment composed by folic acid (8mg/kg/day) and fluoxetine (5mg/kg/day). On the postnatal day 22, male rats were euthanized and hippocampus, cortex, hypothalamus, and periaqueductal gray area were removed. Global DNA methylation was quantified using a high-throughput ELISA-based method. Neurofunctional changes were addressed using validated behavioral tests: hot plate, elevated plus maze and open field. A decrease in the global DNA methylation profile of hippocampus was associated to the exposure to fluoxetine, whereas an increase in methylation was observed in cortex. The combined treatment induced an increase in the methylation of hippocampus indicating the potential of folic acid to modulate this epigenetic alteration. Increase in the latency to the thermal nociceptive response was observed in animals exposed to fluoxetine whereas this effect was abolished in animals from the combined treatment. In summary we demonstrated that exposure to fluoxetine during gestation and lactation affect the DNA methylation of brain and the nociceptive response of rats. Furthermore our data reveal the potential of folic acid to modulate epigenetic and functional changes induced by early exposure to fluoxetine.
- Behavioural brain research.Behav Brain Res.2014 May 15;265:142-7. doi: 10.1016/j.bbr.2014.02.031. Epub 2014 Feb 28.
- Fluoxetine is an antidepressant that has been largely used for treatment of depression in pregnancy. In the present study we evaluated the effects of the exposure to fluoxetine during gestation and lactation on DNA methylation of rat brain regions. Female Wistar rats were treated with 5mg/kg of fluo
- PMID 24583191
- Molecular basis for selective serotonin reuptake inhibition by the antidepressant agent fluoxetine (prozac).
- Andersen J1, Stuhr-Hansen N, Zachariassen LG, Koldsø H, Schiøtt B, Strømgaard K, Kristensen AS.Author information 1Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark (J.A., N.S.-H., L.G.Z., K.S., A.S.K.); and Center for Insoluble Structures (inSPIN) and Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry, Aarhus University, Aarhus, Denmark (H.K., B.S.).AbstractInhibitors of the serotonin transporter (SERT) are widely used antidepressant agents, but the structural mechanism for inhibitory activity and selectivity over the closely related norepinephrine transporter (NET) is not well understood. Here we use a combination of chemical, biological, and computational methods to decipher the molecular basis for high-affinity recognition in SERT and selectivity over NET for the prototypical antidepressant drug fluoxetine (Prozac; Eli Lilly, Indianapolis, IN). We show that fluoxetine binds within the central substrate site of human SERT, in agreement with recent X-ray crystal structures of LeuBAT, an engineered monoamine-like version of the bacterial amino acid transporter LeuT. However, the binding orientation of fluoxetine is reversed in our experimentally supported model compared with the LeuBAT structures, emphasizing the need for careful experimental verification when extrapolating findings from crystal structures of bacterial transporters to human relatives. We find that the selectivity of fluoxetine and nisoxetine, a NET selective structural congener of fluoxetine, is controlled by residues in different regions of the transporters, indicating a complex mechanism for selective recognition of structurally similar compounds in SERT and NET. Our findings add important new information on the molecular basis for SERT/NET selectivity of antidepressants, and provide the first assessment of the potential of LeuBAT as a model system for antidepressant binding in human transporters, which is essential for future structure-based drug development of antidepressant drugs with fine-tuned transporter selectivity.
- Molecular pharmacology.Mol Pharmacol.2014 May;85(5):703-14. doi: 10.1124/mol.113.091249. Epub 2014 Feb 10.
- Inhibitors of the serotonin transporter (SERT) are widely used antidepressant agents, but the structural mechanism for inhibitory activity and selectivity over the closely related norepinephrine transporter (NET) is not well understood. Here we use a combination of chemical, biological, and computat
- PMID 24516100
- Effects of antidepressant drug exposure on gene expression in the developing cerebral cortex.
- Tsapakis EM1, Fernandes C, Moran-Gates T, Basu A, Sugden K, Aitchison KJ, Tarazi FI.Author information 1MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom; Department of Psychiatry and Neuroscience Program, Harvard Medical School and McLean Hospital, Boston, Massachusetts.AbstractTo clarify the basis of limited responses in children and adolescents to antidepressant treatments considered standard in the treatment of adult major depressive disorder, juvenile Sprague-Dawley rats were subjected to 21-day treatment with dissimilar antidepressant drugs fluoxetine, imipramine, or vehicle control. Total RNA was extracted from brain frontal cortices and hybridized to the Affymetrix 230.2 chip. A total of 18 microarrays were analyzed (i.e., six biological replicates in three treatment groups). Transcripts identified were validated using Taqman real-time quantitative PCR methodology, and the relative expression of each gene was also determined. In both the imipramine- and fluoxetine-treated animals, expression of six genes was down-regulated (ANOVA-filtered gene expression data using dChip [version 2005]): Gpd1; Lrrn3; Sult1A1; Angptl4; Mt1a; Unknown. Furthermore, four genes were over-expressed: P4Ha1; RDG1311476; Rgc32; and SLC25A18-like by both imipramine and fluoxetine. These data demonstrate that antidepressant drugs interfere with the expression of genes involved in cell signaling, survival, and protein metabolism. Our results show that antidepressants regulate the induction of highly specific transcriptional programs in the developing frontal cortex. These findings provide novel insights into the long-term molecular actions of antidepressant drugs in the developing brain. Synapse 68:209-220, 2014. © 2014 Wiley Periodicals, Inc.
- Synapse (New York, N.Y.).Synapse.2014 May;68(5):209-20. doi: 10.1002/syn.21732. Epub 2014 Feb 13.
- To clarify the basis of limited responses in children and adolescents to antidepressant treatments considered standard in the treatment of adult major depressive disorder, juvenile Sprague-Dawley rats were subjected to 21-day treatment with dissimilar antidepressant drugs fluoxetine, imipramine, or
- PMID 24458505
Japanese Journal
- 増進的介入と生命の価値 : 気分操作を例として
- 島薗 進
- 生命倫理 15(1), 19-27, 2005-09-19
- 医学が治療という任務を超えて、心身の能力を増進させたり、性格を変化させたりすることは許されるのか。許されるとしても限度があるとすれば、どのような限度だろうか。増進的介入をめぐるこうした論議の中で重要な意義をもつものに、軽度のうつ気分の改善に効果があるプロザックなどのSSRI(選択的セロトニン取り込み阻害薬)をめぐるものがある。気分操作という面でSSRIが切り開いた新たな医薬の機能を解説し、心理療法 …
- NAID 110006858294
- Inhibition of G protein-activated inwardly rectifying K^+ channels by fluoxetine (Prozac)
- KOBAYASHI T
- Br J Pharmacol 138, 1119-1128, 2003
- NAID 30022966148
- Blockage of 5HT2C serotonin receptors by fluoxetine (Prozac)
- NI YG.
- Proc Natl Acad Sci USA 94, 2036-2040, 1997
- NAID 80009513703
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- Fluoxetine hydrochloride