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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 schizoaffective disorder. At that point, the positive gains in Strattera should be weighed against possible risks to the patient and the public.
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 schizoaffective disorder. At that point, the positive gains in Strattera should be weighed against possible risks to the patient and the public.


After about 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.{{Fact|date=May 2009}}
After about three years on the market, 10,989 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.{{Fact|date=May 2009}}


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.
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.

Revision as of 19:02, 1 June 2009

Atomoxetine
Clinical data
Pregnancy
category
  • AU: B3
Routes of
administration		Oral (Capsules: 10, 18, 25, 40, and 60 mg; in some countries 80 and 100 mg are also available)
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability63 to 94%
Protein binding40%
MetabolismHepatic, via CYP2D6
Elimination half-life5 hours
ExcretionRenal (>80%) and fecal (<17%)
Identifiers
  • (3R)-N-methyl-3-(2-methylphenoxy)-3-phenyl-propan-1-amine; (R)-N-methyl-3-phenyl-3-(o-tolyloxy)propan-1-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
CompTox Dashboard (EPA)
ECHA InfoCard100.120.306 Edit this at Wikidata
Chemical and physical data
FormulaC17H21NO
Molar mass255.355 g/mol
291.820 g/mol (hydrochloride) g·mol−1
3D model (JSmol)
  • CNCC[C@@H](Oc1ccccc1C)c1ccccc1
Eli Lilly's Strattera capsules.

Atomoxetine is a non-stimulant drug approved for the treatment of attention-deficit hyperactivity disorder (ADHD). It is sold in the form of the hydrochloride salt of atomoxetine, a norepinephrine reuptake inhibitor. This compound is manufactured, marketed and sold in the United States under the brand name Strattera by Eli Lilly and Company, the original patent filing company, and current U.S. patent owner. Generics of atomoxetine are sold in all countries; they are manufactured by Torrent Pharmaceuticals using 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 directly in the United States since it is under patent until 2017[2].

Use

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.[3]

Full therapeutic effects of atomoxetine may take at least a week to be felt. Amoxetine should be taken for 6 – 8 weeks before deciding whether it is effective or not. Many people respond to amoxetine who don't respond to stimulants. Atomoxetine has a low abuse potential. Atomoxetine may be preferred over amphetamine based stimulants in patients with psychiatric disorders, those who cannot tolerate stimulants and those with a substance misuse recurring history. Therapy is usually initiated by gradually increasing the dose to minimize typically minor side effects. As well, some individuals are sensitive to lower doses. If the individual is on stimulants a gradual titration down of the stimulant dose may be prescribed, again to minimize side effects.[4][5] Users who take atomoxetine alone should expect a gradual ramp up of effect over a couple weeks. The system adapts to the drug and the benefits reach their peak over a couple weeks. 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 antidepressant drug; however, in clinical trials, no such benefits could be proven. Since norepinephrine is believed to play a role in ADHD, Strattera was tested—and subsequently approved—as an ADHD treatment.

Nomenclature

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 mass of 291.82. It has a solubility of 27.8 mg/mL in water. Atomoxetine is a white solid that exists as a granular powder inside the capsule, along with pre-gelatinized starch and 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.

Side effects

The side effects include, dry mouth, insomnia, nausea, decreased appetite, constipation, dizziness, sweating, dysuria, sexual problems, weight changes, palpitations, increases in heart rate and blood pressure.[6]

Occasionally after prolonged use some teenagers have experienced slow onset mild depression while using Strattera [citation needed]

Two confirmed cases of liver injury have been reported by Eli Lilly and Company out of approximately two million prescriptions written. In both cases upon discontinuation of atomoxetine, patients' liver functions returned to normal.

Other side effects can include psychosis, mood disorders, depression, abnormal thought patterns, suicidal thoughts or tendecies, and self injury.

Discontinuation adverse effects

Further information: Chemical synapse

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, pharmacodynamic and pharmacokinetic factors contribute to the risk of a withdrawal syndrome.

Psychiatric reactions

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.[7][8] 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 schizoaffective disorder. At that point, the positive gains in Strattera should be weighed against possible risks to the patient and the public.

After about three years on the market, 10,989 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.[citation needed]

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."[9]

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 not 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 cocaine or methamphetamine from 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.

Off-label uses

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.[10][11][12][13]

Experimental uses

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.[14]

A preliminary 12-week, randomized, double-blind, placebo-controlled trial was conducted at Duke University Medical Center which 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.[15]

Overdose

Somnolence is the most common symptom of acute or chronic overdose. Other signs may include Agitation, hyperactivity, abnormal behavior and gastrointestinal symptoms. Mydriasis causing blurred vision, tachycardia and dry mouth occasionally occurs as a result of overdose. Treatment of atomoxetine overdose may include gastric emptying and repeated doses of activated charcoal. Atomoxetine is highly protein bound so dialysis is unlikely to be of benefit.[4]

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "Patent and Exclusivity Search Results". Electronic Orange Book. US Food and Drug Administration. Retrieved 26 April 2009.
  3. ^ Velásquez-Tirado JD, Peña JA (2005). "[Current evidence about atomoxetine. A therapeutic alternative for the treatment of attention deficit hyperactivity disorder]". Rev Neurol (in Spanish; Castilian). 41 (8): 493–500. PMID 16224736.{{cite journal}}: CS1 maint: unrecognized language (link)
  4. ^ a b Unni JC (2006). "Atomoxetine" (PDF). Indian Pediatr. 43 (7): 603–6. PMID 16891679. {{cite journal}}: Unknown parameter |month= ignored (help)
  5. ^ Prasad S, Steer C (2008). "Switching from neurostimulant therapy to atomoxetine in children and adolescents with attention-deficit hyperactivity disorder : clinical approaches and review of current available evidence". Paediatr Drugs. 10 (1): 39–47. doi:10.2165/00148581-200810010-00005. PMID 18162007.
  6. ^ Simpson D, Plosker GL (2004). "Spotlight on atomoxetine in adults with attention-deficit hyperactivity disorder". CNS Drugs. 18 (6): 397–401. doi:10.2165/00023210-200418060-00011. PMID 15089111.
  7. ^ http://www.foxnews.com/story/0,2933,170777,00.html
  8. ^ http://sfgate.com/cgi-bin/article.cgi?f=/n/a/2005/09/29/financial/f092936D43.DTL&hw=Strattera&sn=001&sc=1000
  9. ^ Quoted from STRATTERA (atomoxetine) Risk Benefit Assessment, Preliminary Assessment Report of 9 December 2005 (FOI 06/056 Release by MHRA)
  10. ^ Biederman J, Spencer TJ (2006). "Atomoxetine and adult attention-deficit/hyperactivity disorder: the effects of comorbidity". {{cite journal}}: Cite journal requires |journal= (help); Unknown parameter |month= ignored (help)
  11. ^ Adli M, Pilhatsch MK (2006). "Augmentation with atomoxetine in treatment-resistant depression with psychotic features. A case report". Pharmacopsychiatry. 39: 79. doi:10.1055/s-2006-931547. {{cite journal}}: Unknown parameter |month= ignored (help)
  12. ^ Price LH, Carpenter LL (2005). "Augmentation with open-label atomoxetine for partial or nonresponse to antidepressants". {{cite journal}}: Cite journal requires |journal= (help); Unknown parameter |month= ignored (help)
  13. ^ Biederman, J, Kratochvil CJ (2005). "Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms". {{cite journal}}: Cite journal requires |journal= (help); Unknown parameter |month= ignored (help)
  14. ^ McElroy, Susan (2007), "Atomoxetine in the Treatment of Binge-Eating Disorder: A Randomized Placebo-Controlled Trial" (PDF), Journal of Clinical Psychiatry, 68 (3): 390–398, PMID 17388708
  15. ^ Gadde, K.M. (July 2006), "Atomoxetine for weight reduction in obese women: a preliminary randomised controlled trial", International Journal of Obesity, 30 (7): 1138–1142, doi:10.1038/sj.ijo.0803223, PMID 16418753 {{citation}}: Check date values in: |year= / |date= mismatch (help)
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