IUPAC_name = (3"R")-"N"-methyl-3-(2-methylphenoxy)-3-phenyl-propan-1-amine
width = 150
C=17 | H=21 | N=1 | O=1
molecular_weight = 255.355 g/mol
291.820 g/mol (hydrochloride)
smiles = CNCC [C@@H] (Oc1ccccc1C)c1ccccc1
bioavailability= 63 to 94%
protein_bound = 40%
Hepatic, via CYP2D6
elimination_half-life= 5 hours
excretion =Renal (>80%) and fecal (<17%)
pregnancy_AU = B3
pregnancy_US = C
legal_UK = POM
legal_status = Unscheduled (U.S.)
routes_of_administration= Oral (Capsules: 10, 18, 25, 40, and 60 mg; in some countries 80 and 100 mg are also available)
Atomoxetine is a non-
stimulantdrug approved for the treatment of attention-deficit hyperactivity disorder(ADHD). It is sold in the form of the hydrochloridesalt of atomoxetine. This chemical is manufactured, marketed and sold under the brand name Strattera by Eli Lilly and Company, the original patentfiling company. Generics of atomoxetine are sold into all countries; they are manufactured by Torrent Pharmaceuticalsusing the label Tomoxetin, Ranbaxy Laboratories(through its Division: Solus) using the label Attentin, Sun Pharmaceuticals(through its Division: Milmet Pharmaceuticals), and Intas Biopharmaceuticals. There is currently no generic manufactured within the United Statesdue to patent license manufacturing restrictions chosen by the owner of the US patent Eli Lilly and Company.
Classified as a norepinephrine (noradrenaline) reuptake inhibitor, atomoxetine is approved for use in children, adolescents, and adults. However, its efficacy has not been studied in children under six years old. Its advantage over stimulants for the treatment of ADHD is that it has less abuse potential than stimulants, is not scheduled as a controlled substance and has proven in
clinical trials to offer 24 hour coverage of symptoms associated with ADHD in adults and children.
Although the drug can be "felt" right away, it does not start "working properly" for 3-4 weeks time. Users should expect to feel tired and groggy for a few weeks. Eventually, the system adapts to the drug and the benefits can be felt. Users are recommended to continue taking the drug for at least three weeks before deciding to discontinue its use.
Strattera was originally intended to be a new
antidepressantdrug; however, in clinical trials, no such benefits could be proven. Since norepinephrineis believed to play a role in ADHD, Strattera was tested—and subsequently approved—as an ADHD treatment.
Though approved for ADHD, many doctors prescribe it off-label as an anti-psychotic in cases of certain disorders of thought and less serious mental problems, such as
dyslexia, dyspraxia( clumsiness), and schizoaffective disorder. This is due to its help in 'calming down' and steadying of thought processes, improving symptoms associated with less serious types and degrees of schizophrenia. In this case, atomoxetine has great potential in the treatment of schizophreniaand the Predominantly Inattentive subtype of ADHD (once separately designated Attention-Deficit Disorder (ADD), now often referred to as the subtype ADD-PI). In many cases of the above-mentioned disorders of thought, it is said to work seamlessly better and with less negative side-effects than any of the available (approved) anti-psychotics.
Atomoxetine was originally known as "tomoxetine". However, the U.S.
Food and Drug Administration(FDA) requested the name be changed because, in their opinion, the similarity of "tomoxetine" to " tamoxifen" (a breast cancer drug) could lead to dispensing errors at pharmacies.
Chemistry and composition
Atomoxetine is designated chemically as (-)-"N"-methyl-3-phenyl-3-(o-tolyloxy)-propylamine hydrochloride, and has a
molecular massof 291.82. It has a solubilityof 27.8 mg/mL in water. Atomoxetine is a white solid that exists as a granular powder inside the capsule, along with pre-gelatinized starchand dimethicone. The capsule shells contain gelatin, sodium lauryl sulfate, FD&C Blue No. 2, synthetic yellow iron oxide, titanium dioxide, red iron oxide, edible black ink, and trace amounts of other inactive ingredients.
The most common side effects in children, adolescents, and adults are upset stomach, sporadic nausea, and sudden vomiting. The medication's tendency to decrease appetite may contribute to this problem, as taking Strattera on an empty stomach is usually discouraged; it can also be a problem in itself, in the form of hunger pangs. Consumption of dairy products can cause further upset.
A significant minority of adult male patients taking Strattera suffer minor to severe sexual side effects, including
erectile dysfunction, retrograde ejaculation, painful orgasm, and the decoupling of orgasm from ejaculation, wherein ejaculation takes place up to ten seconds before or after orgasm.
Occasionally after prolonged use some teenagers have experienced slow onset mild depression while using Strattera Fact|date=October 2007
Two confirmed cases of liver injury have been reported by
Eli Lilly and Companyout of approximately two million prescriptions written. In both cases upon discontinuation of atomoxetine, patients' liver functions returned to normal.
Discontinuation adverse effects
The central nervous system (CNS) adapts to the presence of psychoactive drugs. Such adaptation commonly involves the readjustment of neuroreceptors to compensate for the acute pharmacological action of the medication. This adaptation theory also explains why withdrawal symptoms and signs can occur on the discontinuation of such medications as clearance of drug can occur at a rate faster than the brain can readjust to the absence of medication. Hence,
pharmacodynamicand pharmacokineticfactors contribute to the risk of a withdrawal syndrome.
In September 2005, Strattera was determined to increase risk of suicidal thoughts among children and adolescents; one attempted suicide and five cases of suicidal thoughts were reported out of 1,357 young patients taking Strattera, while none was reported out of a control group of 851 taking placebos. [http://www.foxnews.com/story/0,2933,170777,00.html] , [http://sfgate.com/cgi-bin/article.cgi?f=/n/a/2005/09/29/financial/f092936D43.DTL&hw=Strattera&sn=001&sc=1000] . The FDA has required that
black box warnings be placed on all antidepressant medications warning that may result in increased risk of suicidal tendencies in children and adolescents; therefore, Strattera bears such a warning.
For off label use, it is important to monitor the potential increase of paranoia symptoms (since this is a side effect of Strattera) in patients with schizo-affective disorder. At that point, the positive gains in Strattera should be weighed against possible risks to the patient and the public.
In less than three years on the market 10,988 adverse "psychiatric reactions" have been reported to Eli Lilly for the ADHD drug Strattera, according to the British Medicines and Healthcare products Regulatory Agency (MHRA), January 2006.
A FOI Release by the UK Medicines and Healthcare products Regulatory Agency discloses that the administration of Strattera increases risks of suicidal ideation, serious hepatic reactions and seizures in children with ADHD.
:"On 15 September 2005 the MHRA was informed by the Marketing Authorisation Holder for Strattera (Eli Lilly) of an analysis of double blind, randomised, placebo-controlled clinical trial data for atomoxetine which has identified a statistically significant increased risk of suicidal thoughts with atomoxetine compared to placebo in children with Attention Deficit/Hyperactivity Disorder (ADHD)."
:"Strattera (atomoxetine hydrochloride) is authorised through the Mutual Recognition Procedure with the UK as Reference Member State. On discussion with CMS (Germany, the Netherlands and Norway) and subsequently with the Pharmacovigilance Working Party, it was agreed that these new data warranted a full risk:benefit evaluation of atomoxetine in its licensed indications, particularly in light of previous concerns about its safety profile including serious hepatic reactions and seizures. In the interim warnings about the risk of suicidal behaviour with atomoxetine were added via an Urgent Safety Restriction (USR) procedure to allow timely communication of the risk to health professionals and patients." [Quoted from [http://www.psychiater.nu/wp-content/uploads/2008/08/vrijgegeven-documenten-strattera-schandaal.pdf STRATTERA (atomoxetine) Risk Benefit Assessment, Preliminary Assessment Report of 9 December 2005 (FOI 06/056 Release by MHRA)] ]
Potential for abuse
To date, the potential for abuse of Strattera has not been exhaustively researched. The two studies that have been performed suggest that atomoxetine has a low to moderate risk for abuse, since it has a long titration time (meaning that it may have no effect on the user unless they've been taking it regularly for days) and does produce strong stimulating effects like most other ADHD medications (which are usually
dopamine reuptake inhibitors). Monkeys will not self-administer atomoxetine at the doses tested (Gasior et al, Neuropharm 30:758, 2005; Wee & Woolverton, Drug Alcohol Depend 75:271, 2004). However, rats, pigeons and monkeys trained to distinguish cocaineor methamphetaminefrom saline indicate that atomoxetine produces effects indistinguishable from low doses of cocaine or methamphetamine, but not at all like high doses of cocaine (Spealman, JPET 271:53, 1995; Sasaki et al., Psychopharm 120:303, 1995). No place preference studies have been conducted with atomoxetine.
While depression is most commonly associated with the neurotransmitter
serotonin, an imbalance of other neurotransmitters may also result in clinical depression. To that end, atomoxetine, which inhibits the reuptake of norepinephrine, was originally explored by Eli Lilly as a treatment for depression, but did not show a benefit to risk ratio in trials. Failed clinical trials are not submitted to drug regulatory agencies and are considered trade secrets. Subsequently, Lilly then chose to pursue an ADHD treatment route for atomoxetine. Many patients have seen a pronounced anti-depressive effect in conjunction with other antidepressants. More study is needed to understand the full pharmacodynamics. [cite journal | first = Spencer TJ| last = Biederman J| date = March, 2006 | title = Atomoxetine and adult attention-deficit/hyperactivity disorder: the effects of comorbidity| url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16649828&query_hl=2&itool=pubmed_docsum] [cite journal | first = Pilhatsch MK| last = Adli M| date = March, 2006 | title = Augmentation with atomoxetine in treatment-resistant depression with psychotic features. A case report| url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16555170&query_hl=2&itool=pubmed_docsum | doi = 10.1055/s-2006-931547 | journal = Pharmacopsychiatry | volume = 39 | pages = 79] [cite journal | first = Carpenter LL| last = Price LH| date = Oct, 2005 | title = Augmentation with open-label atomoxetine for partial or nonresponse to antidepressants| url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16259536&query_hl=2&itool=pubmed_docsum] [cite journal | first = Kratochvil CJ| last = Biederman, J| date = Sept, 2005 | title = Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms| url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16113620&query_hl=2&itool=pubmed_docsum]
A small (40 people), 10-week, double-blind clinical trial was reported in the "Journal of Clinical Psychiatry" on the effectiveness of atomoxetine for treating
binge eating disorder. The results of the trial was that atomoxetine was "associated with a significantly greater rate of reduction in binge-eating episode frequency, weight, [and] body mass index." The average daily dose given was 106 mg/day. The authors concluded that atomoxetine is effective for short term treatment of binge eating disorder. [Citation
title= Atomoxetine in the Treatment of Binge-Eating Disorder: A Randomized Placebo-Controlled Trial
journal=Journal of Clinical Psychiatry
url = http://www.psychiatrist.com.prxy3.ursus.maine.edu/privatepdf/2007/v68n03/v68n0306.pdf
pmid = 17388708 ]
A preliminary 12-week, randomized, double-blind, placebo-controlled trial was conducted at
Duke University Medical Centerwhich studied the effectiveness of atomoxetine on adult obese women. The study included 30 obese women with an average body mass index of 36.1. Fifteen women were given atomoxetine therapy starting at 25 mg/day with a gradual increase to 100 mg/day over 1 week. Fifteen women were given a placebo with identical dosing. By the end of the trial, the atomoxetine group lost an average of 3.6 kg (3.7% of their body mass) vs a 0.1 kg gain in the placebo group (0.2% gain). Three participants in the atomoxetine group and none in the placebo group lost greater than 5% of their mass. [Citation
date = July 2006
title= Atomoxetine for weight reduction in obese women: a preliminary randomised controlled trial
journal=International Journal of Obesity
pmid = 16418753
doi= 10.1038/sj.ijo.0803223 ]
* [http://www.rxlist.com/cgi/generic3/strattera.htm RxList.com - Strattera]
* [http://www.strattera.com/1_2_taking_strattera/1_2_5_2_available.jsp Strattera Available Dosages]
* [http://medlibrary.org/drugs/other/strattera.html Detailed Strattera Consumer Information: Uses, Precautions, Side Effects]
* [http://www.lillytrials.com/results/by_product/results_strattera.html All Lilly trials]
* [http://www.ehs.lilly.com/msds/msds_atomoxetine_hydrochloride_tablets_and_capsules.html MSDS for Atomoxetine HCl]
* [http://www.druglib.com/druginfo/strattera/abstracts/ Strattera Related Published Studies ]
* [http://online.wsj.com/article/0,,SB108249266648388235,00.html?mod=home%5Fpage%5Fone%5Fus "By learning from failures, Lilly keeps drug pipeline full", The Wall Street Journal, April 21, 2004]
Wikimedia Foundation. 2010.
Look at other dictionaries:
Atomoxétine — Général Nom IUPAC (3R) N m … Wikipédia en Français
atomoxetine — noun A non stimulant drug used for the treatment of ADHD … Wiktionary
atomoxetine hydrochloride — at·om·ox·e·tine hy·dro·chlo·ride (at″ə mokґsə tēn) a selective norepinephrine reuptake inhibitor used in the treatment of attention deficit/hyperactivity disorder, administered orally … Medical dictionary
83015-26-3 — Atomoxétine Atomoxétine Général Nom IUPAC … Wikipédia en Français
C17H21NO — Atomoxétine Atomoxétine Général Nom IUPAC … Wikipédia en Français
Stimulant — Ritalin Slow Release (SR) 20 mg tablets. Stimulants (also referred to as psychostimulants) are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include… … Wikipedia
Norepinephrine transporter — Solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2 Identifiers Symbols SLC6A2; NAT1; NET; NET1; SLC6A5 External IDs … Wikipedia
Treatment of Tourette syndrome — Tourette syndrome (also Tourette s syndrome or TS) is an inherited neurological disorder with onset in childhood, characterized by the presence of motor and phonic tics. Treatment of Tourette syndrome has the goal of managing symptoms to achieve… … Wikipedia
D-161 — Systematic (IUPAC) name 4 ((((3S,6S) 6 benzhydryltetrahydro 2H pyran 3 yl)amino)methyl)phenol Clinical data Pregnancy cat … Wikipedia
Discovery and development of dual serotonin and norepinephrine reuptake inhibitors — Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant drugs used in the treatment of major depressive disorder (MDD). SNRIs are potent inhibitors of serotonin (5 Hydroxytryptamine, 5 HT) and norepinephrine (NE,… … Wikipedia