Duloxetine (Cymbalta)

Duloxetine

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Not to be confused with dapoxetine.

Duloxetine

Systematic (IUPAC) name
(+)-(S)-N-Methyl-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propan-1-amine
Identifiers
CAS number	116539-59-4 (free base) 136434-34-9 (hydrochloride)
ATC code	N06AX21
PubChem	CID 60835
IUPHAR ligand ID	202
DrugBank	APRD00060
ChemSpider	54822
Chemical data
Formula	C18H19NOS
Mol. mass	297.41456 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	~ 50% (32% to 80%)
Protein binding	~ 95%
Metabolism	Liver, two P450 isozymes, CYP2D6 and CYP1A2
Half-life	12.1 hours
Excretion	70% in urine, 20% in feces
Therapeutic considerations
Licence data	EU EMA:Link, US FDA:link
Pregnancy cat.	C(US)
Legal status	℞-only (US)
Routes	Oral

Duloxetine (Cymbalta, Ariclaim, Xeristar, Yentreve) is a serotonin-norepinephrine reuptake inhibitor manufactured and marketed by Eli Lilly. It is effective for major depressive disorder and has been shown to be as effective as venlafaxine for generalized anxiety disorder (GAD). Duloxetine failed the US approval for stress urinary incontinence amidst concerns over liver toxicity and suicidal events; however, it was approved for this indication in Europe. Duloxetine alleviates pain associated with diabetic neuropathy and fibromyalgia. Its efficacy relative to established treatments such as anticonvulsants and tricyclic antidepressants has not yet been studied.
The role of duloxetine in the treatment of various conditions has led to divergent opinions. Owing to a large number of side effects and lack of clear advantage over existing medications, some reviews have concluded that duloxetine "should not be used" for stress urinary incontinence^[1] and "currently has no place in the treatment of depression or diabetic neuropathy."^[2][3] At the same time, some professional guidelines recommend duloxetine in chronic neuropathic pain, especially diabetic polyneuropathy for which it is first-line treatment, and as an add-on medication in stress urinary incontinence instead of surgery.^[4][5]

Contents [show] 1 History 2 Indications 2.1 Major depressive disorder 2.2 Stress urinary incontinence 2.3 Diabetic peripheral neuropathy 2.4 Generalized anxiety disorder 2.5 Fibromyalgia 2.6 Chronic fatigue syndrome 2.7 Interstitial Cystitis 2.8 Musculoskeletal Pain 3 Contraindications 4 Adverse effects 4.1 Postmarketing spontaneous reports 4.2 Discontinuation syndrome 4.3 Suicidality 5 Pharmacology 5.1 Pharmacodynamics 5.2 Pharmacokinetics 6 References 7 External links

[edit] History

Cymbalta 60mg

Duloxetine was created by Lilly researchers. David Robertson, David Wong, a co-discoverer of fluoxetine, and Joseph Krushinski are listed as inventors on the patent application filed in 1986 and granted in 1990.^[6] The first publication on the discovery of the racemic form of duloxetine known as LY227942, was made in 1988.^[7] The (+)-enantiomer of LY227942, assigned LY248686, was chosen for further studies, because it inhibited serotonin reuptake in rat synaptosomes two times more potently than (–)-enantiomer. This molecule was subsequently named duloxetine.^[8]
Initial trials conducted in patients using regimens of 20 mg/day or less did not convincingly demonstrate its efficacy^[9] and the dose was increased to as high as 120 mg in subsequent clinical trials.^[10]
In 2001 Lilly filed a New Drug Application (NDA) for duloxetine with the US Food and Drug Administration (FDA). However, in 2003 the FDA "recommended this application as not approvable from the manufacturing and control standpoint" because of "significant cGMP (current Good Manufacturing Practice) violations at the finished product manufacturing facility" of Eli Lilly in Indianapolis. Additionally, "potential liver toxicity" and QTc interval prolongation appeared as a concern. The FDA experts concluded that "Duloxetine can cause hepatotoxicity in the form of transaminase elevations. It may also be a factor in causing more severe liver injury, but there are no cases in the NDA database that clearly demonstrate this. Use of duloxetine in the presence of ethanol may potentiate the deleterious effect of ethanol on the liver." The FDA also recommended "routine blood pressure monitoring" at the new highest recommended dose of 120 mg, "where 24% patients had one or more [blood pressure] readings of 140/90 vs. 9% of placebo patients."^[11]
After the manufacturing issues were resolved, the liver toxicity warning included in the prescribing information, and the follow-up studies showed that duloxetine does not cause QTc interval prolongation, duloxetine was approved by the FDA for depression and diabetic neuropathy in 2004.^[12] In 2007 Health Canada approved duloxetine for the treatment of depression and diabetic peripheral neuropathic pain.^[13]
Duloxetine was approved for use of stress urinary incontinence (SUI) in the EU in 2004. In 2005, Lilly withdrew the duloxetine application for stress urinary incontinence (SUI) in the U.S., stating that discussions with the FDA indicated "the agency is not prepared at this time to grant approval ... based on the data package submitted." A year later Lilly abandoned the pursuit of this indication in the U.S. market.^{[14] [15]}
The FDA approved duloxetine for the treatment of GAD in February 2007.^[16]

[edit] Indications

The main uses of duloxetine are in major depressive disorder, general anxiety disorder, stress urinary incontinence, painful peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain associated with osteoarthritis and chronic lower back pain. It is being studied for various other indications.

[edit] Major depressive disorder

Duloxetine has demonstrated efficacy for the treatment of major depressive disorder. In three out of six well-designed properly controlled pre-marketing trials duloxetine performed better than placebo; the three other trials were inconclusive.^[17] Recently, duloxetine was shown to be effective in elderly with recurrent major depressive disorder where it improved cognition, depression, and some pain measures.^[18] A meta-analysis of these trials indicated that the effect size of duloxetine as compared with placebo was weak-to-moderate, and similar to other 11 antidepressants studied.^[19] The rationale behind the development of duloxetine was that inhibition of the reuptake of both serotonin and norepinephrine would make it work better than selective serotonin reuptake inhibitors (SSRIs), which inhibit only the reuptake of serotonin. However, in a comparative meta-analysis of clinical trials duloxetine appeared to be insignificantly less effective than SSRIs.^[20] A head-to-head comparison of duloxetine with an SSRI escitalopram (Lexapro) found duloxetine to be both less tolerable and less effective.^[21] Another analysis of the comparative efficacy of modern antidepressants found duloxetine to be significantly, by 30-40%, less efficacious than mirtazapine (Remeron), escitalopram, venlafaxine (Effexor) and sertraline (Zoloft). Duloxetine was similar to fluoxetine (Prozac), fluvoxamine (Luvox) and paroxetine (Paxil). The tolerability of duloxetine was significantly worse than the tolerability of escitalopram and sertraline.^[22]

A review in Prescrire International summarizing the existing evidence noted that duloxetine has limited efficacy in depression and no advantages over other antidepressants. Prescribers observed that, taking into account the risk of hepatic disorders and drug interactions, there is no reason to choose duloxetine when so many other options are available.^[2] Similar analysis was presented by Drug and Therapeutics Bulletin, which is a part of the respected BMJ Group.^[23]

[edit] Stress urinary incontinence

Duloxetine was first reported to improve outcomes in stress urinary incontinence (SUI) in 1998.^[24] Systematic reviews with meta-analysis, conducted in 2005 by Cochrane Collaboration^[25] and in 2008 by University of Minnesota,^[26] concluded that duloxetine failed to cure SUI better than placebo. According to the Cochrane review, some studies showed that episodes of incontinence were reduced by about 50%. This was associated with an improvement in quality of life measurements.^[25] According to the University of Minnesota review, duloxetine performed worse than oxybutynin (Ditropan) or tolterodine (Detrol) that cured 18% of the cases, or than pelvic floor muscle training + bladder training, which cured 13% of the cases. In terms of "improvement", that is incomplete cure, duloxetine showed improvement in 11% of patients while pelvic floor muscle training + bladder training showed improvement in 36% of the cases.^[26] Significant side effects were common with duloxetine; they were reported as acceptable and about a fifth had to discontinue the medication because of poor tolerance.^[25]
In addition, the full report prepared by Minnesota Evidence-based Practice Center for the US government, on which the University of Minnesota review is based, notes that weight reduction would result in improved SUI in 990 adults per 1,000 treated.^[27] In the light of the cited data, the report does not mention duloxetine in its policy recommendations. The only recommended interventions are early behavioral changes in weight, physical activity, and pelvic floor muscle training.^[27]
The only clinical trial, which directly compared duloxetine with the gold standard of the SUI treatment pelvic floor muscle training (PFMT) was conducted by Eli Lilly and gave mixed results. The incontinence episode frequency in duloxetine group decreased by 57% vs. 35% in the PFTM group. However, the differences in the pad use and quality of life were not statistically significant. To the contrary, 65% patients doing PFTM reported feeling better vs 54% of the patients on duloxetine. 31% of the patients on duloxetine discontinued the trial due to the side effects during the first 12 weeks.^[28] In the continuation of this trial more than 91% of the patients on duloxetine experienced side effects.^[29]
Summing up the existing evidence, a review in Prescrire International recommends pelvic floor exercises, which are "risk-free and effective in two-thirds to three-quarters of cases", as the first line treatment of SUI. Duloxetine use reduced the frequency of stress incontinence by one episode a day as compared with placebo. "The tangible effect of duloxetine on the quality of life is doubtful, with a maximum gain of five points on a 100-point scale." The review notes that, at best, duloxetine efficacy is "modest and transient, while its adverse effects are numerous and potentially severe."^[1]

[edit] Diabetic peripheral neuropathy

Duloxetine was approved for the pain associated with diabetic peripheral neuropathy (DPN) based on the positive results of two clinical trials. The average daily pain was measured using 11-point scale, and duloxetine treatment resulted in an additional 1–1.7 points decrease of pain as compared with placebo.^[30][31][32] At least 50% pain relieve was achieved in 40–45% of the duloxetine patients vs. 20–22% of placebo patients. The pain almost completely disappeared, decreasing by more than 90%, in 9–14% of duloxetine patients vs. 2–4% of placebo patients. Most of the response was achieved in the first two weeks on the medication. Duloxetine slightly increased the fasting serum glucose; however this effect was deemed to be of "minimal clinical significance".^[30]
Duloxetine was not effective for the numbness or tingling, nor for the other complications of diabetes. It reduced the pain without treating the underlying nerve damage.^[33] Only tight glycemic control was unequivocally demonstrated to slow the progression of neuropathy.^[34][35] Benfotiamine, alpha-lipoic acid and ranirestat have also shown some promise.^[35]
The comparative efficacy of duloxetine and established pain-relief medications for DPN is unclear. An independent systematic review in BMJ noted that tricyclic antidepressants (imimpramine and amitriptyline), traditional anticonvulsants and opioids have better efficacy than duloxetine. Duloxetine, tricyclic antidepressants and anticonvulsants have similar tolerability while the opioids caused more side effects.^[34] A review in Drug and Therapeutic Bulletin saw no place for duloxetine in the treatment of DPN, based on its high cost and insufficient evidence of the comparative efficacy with tricyclic antidepressants.^[3] Another independent review in Prescrire International, considered the moderate pain relief achieved with duloxetine to be clinically insignificant and the results of the clinical trials—unconvincing. The reviewer saw no reason to prescribe duloxetine in practice.^[2] The comparative data collected by reviewers in BMC Neurology indicated that amitriptyline, other tricyclic antidepressants and venlafaxine may be more effective. However, the authors noted that the evidence in favor of duloxetine is much more solid.^[36]

[edit] Generalized anxiety disorder

Duloxetine is just as effective as venlafaxine in the treatment of generalized anxiety disorder with demonstrated improvements in function and quality of life for sufferers. Long-term use of duloxetine prevents relapse of generalized anxiety disorder. According to researchers linked to Eli Lilly, clinical trials have demonstrated that duloxetine is well tolerated both in the short term and the long-term.^[37] Other Eli Lilly dependent researchers suggested that duloxetine should be considered a first line treatment for generalized anxiety disorder.^[38][39] Although this view was repeated in a recent independent review,^[40] the major guidelines such as Maudsley Prescribing Guidelines^[41], Mayo Clinic Health Information^[42] and Canadian Psychiatric Association Guidelines^[43] do not mention duloxetine among the recommended treatment options.

[edit] Fibromyalgia

On October 19, 2006, Eli Lilly issued a press release saying they had done trials which found that Cymbalta (duloxetine), at 60 mg once or twice daily, significantly reduced pain in more than half of women treated for fibromyalgia (FM), with and without major depression, according to 12-week data presented at the annual meeting of the American College of Rheumatology. Eli Lilly is in Phase III of its FM trials and is expected to submit a sNDA to the FDA for approval of Cymbalta for FM within the next 12 months. Eli Lilly hopes Cymbalta will be the first FDA approved medication for FM and had been promoting Cymbalta for FM since 2004.^[44]
Duloxetine is superior to many other medications for the treatment of fibromyalgia due to its freedom from muscarinic, histaminergic and adrenergic adverse reactions. Its effectiveness in pain relief is believed to be due to its modulation of the nociception system. A meta-analysis of clinical trials has confirmed its pain relief, fatigue reducing properties as well as its effectiveness in improving physical and mental performance.^[45]
In the study testing the efficacy of Cymbalta for FM, participants completed several questionnaires to measure the amount of pain and discomfort the disease caused them at the beginning of the study, and then at the end of each of the first two weeks and every second week for the remaining 12 weeks of the study. Researchers also tested the participants for depression.^[44]
Women who took Cymbalta had significantly less pain and discomfort than those who took the placebo. For men, who made up only 11% of the study, there was no effect from taking the medication compared with a placebo. Reportedly, depression played no part in whether or not the drug worked to control pain. The change in the level of women's pain was particularly pronounced after a month of taking the drug, then leveled off a bit before dropping again near the end of the study.^[44]
However, in one of the primary measures of pain there was no significant difference between the two groups at the end of the 12-week trial. Also, because the trial lasted only 12 weeks, it is impossible to tell how well the drug would control treatment for a longer period of time.^[44]
The Food and Drug Administration regulators approved the drug for the treatment of fibromyalgia in June 2008.^[46]

[edit] Chronic fatigue syndrome

As of January 11, 2007, Eli Lilly is currently enrolling patients for double blind Phase II and Phase III trials of Cymbalta for the use of chronic fatigue syndrome (CFS) in conjunction with the University of Cincinnati.^[47] CFS is characterized by severe disabling fatigue of at least six months' duration which cannot be fully explained by an identifiable medical condition.

[edit] Interstitial Cystitis

There is a U.S. Patent 6150396 for the use of duloxetine for treatment of Interstitial Cystitis although one study found positive outcomes in only a small proportion of cases ^[48]. Interstitial Cystitis is a bladder and urinary tract disorder which presents as chronic pelvic and perineal pain. It is speculated that duloxetine suppresses neural impulses related to pain below a threshhold level sufficient to alleviate some or all neurological pain symptoms.

[edit] Musculoskeletal Pain

On November 4, 2010, the U.S. Food and Drug Administration approved Cymbalta to treat chronic musculoskeletal pain, including discomfort from osteoarthritis and chronic lower back pain.

[edit] Contraindications

The following contraindications are listed by the manufacturer:^[49]

• Hypersensitivity - duloxetine is contraindicated in patients with a known hypersensitivity to duloxetine or any of the inactive ingredients.
• MAOIs - concomitant use in patients taking MAOIs is contraindicated.
• Uncontrolled narrow-angle glaucoma - in clinical trials, Cymbalta use was associated with an increased risk of mydriasis (dilation of the pupil); therefore, its use should be avoided in patients with uncontrolled narrow-angle glaucoma, in which mydriasis can cause sudden worsening.
• CNS acting drugs - given the primary central nervous system (CNS) effects of duloxetine, it should be used with caution when it is taken in combination with or substituted for other centrally acting drugs, including those with a similar mechanism of action.
• Cymbalta and thioridazine should not be co-administered.

[edit] Adverse effects

Nausea, somnolence, insomnia, and dizziness are the main side effects, reported by about 10% to 20% of patients.^[50]
In a trial for mild major depressive disorder (MDD), the most commonly reported treatment-emergent adverse events among duloxetine-treated patients were nausea (34.7%), dry mouth (22.7%), headache (20.0%) and dizziness (18.7%), and except for headache, these were reported significantly more often than in the placebo group:^[51]
Duloxetine and SSRIs have been shown to cause sexual side effects in some patients, both males and females. Although usually reversible, these sexual side effects can sometimes last for months, or years, even after the drug has been completely withdrawn. This disorder is known as post-SSRI sexual dysfunction.^{[citation needed]}

[edit] Postmarketing spontaneous reports

Reported adverse events which were temporally correlated to Cymbalta therapy include rash, reported rarely, and the following adverse events, reported very rarely: alanine aminotransferase increased, alkaline phosphatase increased, anaphylactic reaction, angioneurotic edema, aspartate aminotransferase increased, bilirubin increased, glaucoma, hepatitis, hyponatremia, jaundice, orthostatic hypotension (especially at the initiation of treatment), Stevens-Johnson syndrome, syncope (especially at initiation of treatment), and urticaria.^[52]

[edit] Discontinuation syndrome

Further information: SSRI discontinuation syndrome

During marketing of other SSRIs and SNRIs, there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomia, hypomania, tinnitus, and seizures. Although these events are generally self-limiting, some have been reported to be severe. The withdrawal syndrome from duloxetine resembles the SSRI discontinuation syndrome.
When discontinuing treatment with Cymbalta, the manufacturer recommends a gradual reduction in the dose, rather than abrupt cessation, whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate. The use a liquid form of the drug may facilitate more gradual tapering."^[53]
In MDD placebo-controlled clinical trials of up to nine weeks' duration, systematically evaluating discontinuation symptoms in patients taking duloxetine following abrupt discontinuation found the following symptoms occurring at a rate greater than or equal to 2% and at a significantly higher rate in Cymbalta-treated patients compared to those discontinuing from placebo: dizziness, nausea, headache, paresthesia, vomiting, irritability, and nightmare.^[54]

[edit] Suicidality

The FDA requires all antidepressants, including duloxetine, to carry a black box warning stating that antidepressants may increase the risk of suicide in persons younger than 25. This warning is based on statistical analyses conducted by two independent groups of the FDA experts that found a 2-fold increase of the suicidal ideation and behavior in children and adolescents, and 1.5-fold increase of suicidality in the 18–24 age group.^[55][56][57]
To obtain statistically significant results the FDA had to combine the results of 295 trials of 11 antidepressants for psychiatric indications. As suicidal ideation and behavior in clinical trials are rare, the results for any drug taken separately usually do not reach statistical significance. In line with the general results, duloxetine use in depressed adults insignificantly decreased the odds of suicidality by 12%^[56] or 20%^[57] depending of the statistical technique used. However, in the subgroup of young adults (18–24 years old) duloxetine increased the odds of suicidality 5-fold, close to statistical significance.^[56] There have been no trials of duloxetine in minors.
Several commentators noted that the data FDA used in their analysis of duloxetine-associated suicidality may have been incomplete. According to Arif Khan, the Summary Basis of Approval used by the FDA to approve duloxetine for depression contained only the mention of two completed suicides out of 3490 patients, and the rest of the data was not sufficient to "conduct any meaningful analysis."^[58] Jeanne Lenzer wrote in The Independent and Slate Magazine, and this fact was also confirmed by a Lilly spokesman, that another two completed suicides, which occurred in the depression studies ran by the Lilly's Japanese partner Shionogi, have not been reported to the FDA.^[59][60] According to Lenzer, four completed suicides also occurred in the trials of duloxetine for stress urinary incontinence (SUI). As these trials failed, the FDA initially insisted that any information about them is a commercial secret and cannot be released.^[60] Later, in a short statement the FDA acknowledged that in SUI trials eleven suicide attempts occurred in persons taking duloxetine vs none in the placebo group.^[61]
A series of four cases of duloxetine-associated suicidality has been reported. In all four cases depressed patients began having suicidal thoughts after starting on duloxetine or increasing its dose. These thoughts stopped, and the patients returned to normal after duloxetine was discontinued, and they were switched to another antidepressant.^[62]
A suicide of 19-year-old Traci Johnson, a healthy volunteer in a duloxetine clinical pharmacology study, was highly publicized. For about a month she had been given high doses of duloxetine, and then she was switched to placebo. Four days after the switch, she hanged herself with her scarf from a shower rod in the bathroom of Lilly Laboratory for Clinical Research.^[63][64] The New York Times article mentioned a withdrawal syndrome as a possible reason for this suicide.^[64]

[edit] Pharmacology

[edit] Pharmacodynamics

Although the exact mechanisms of the antidepressant and central pain inhibitory action of duloxetine in humans are unknown, they are believed to be related to its potentiation of serotonergic and noradrenergic activity in the central nervous system. Preclinical studies demonstrate that duloxetine potently inhibits neuronal serotonin and norepinephrine reuptake,^[65] and it has been demonstrated that this inhibition is balanced throughout the dosing range (when compared to venlafaxine in which the inhibition of noradrenaline is low at low doses and raises as the dose escalates).
It is also considered a less potent inhibitor of dopamine reuptake. However, duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors and can therefore be considered to be a selective reuptake inhibitor at the 5-HT and NA transporters. Duloxetine undergoes extensive metabolism, but the major circulating metabolites do not contribute significantly to the pharmacologic activity.

[edit] Pharmacokinetics

Duloxetine has an elimination half-life of about 12 hours (range 8 to 17 hours) and its pharmacokinetics are dose proportional over the therapeutic range. Steady-state is usually achieved after 3 days.
Elimination of duloxetine is mainly through hepatic metabolism involving two P450 isozymes, CYP2D6 and CYP1A2.
When orally administered it is well absorbed. There is an average 2-hour lag until absorption begins with maximum plasma concentrations occurring about 6 hours post dose. Food does not affect the C_max of duloxetine, but delays the time to reach peak concentration from 6 to 10 hours. Duloxetine is highly bound (>90%) to proteins in human plasma, binding primarily to albumin and α1-acid glycoprotein.
Metabolism and Elimination — Only trace amounts (<1%) of unchanged duloxetine are present in the urine and most of the dose (aprox 70%) appears in the urine as metabolites of duloxetine with about 20% excreted in the feces.

[edit] References

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27. ^ ^{a b} http://www.ahrq.gov/downloads/pub/evidence/pdf/fuiad/fuiad.pdf
28. ^ "Trial 2615a Efficacy and Safety of Duloxetine compared with Placebo, Pelvic Floor Muscle Training, and Combined Duloxetine/Pelvic Floor Muscle Training in Subjects with Moderate to Severe Stress Urinary Incontinence" (PDF). www.clinicalstudyresults.org. http://www.clinicalstudyresults.org/drugdetails/viewfile.php?study_name=Trial+2615a++Efficacy+and+Safety+of+Duloxetine+compared+with+Placebo%2C+Pelvic+Floor+Muscle+Training%2C+and+Combined+Duloxetine%2FPelvic+Floor+Muscle+Training+in+Subjects+with+Moderate+to+Severe+Stress+Urinary+Incontinence&file=http%3A%2F%2Fpdf.clinicalstudyresults.org%2Fdocuments%2Fcompany-study_4001_0.pdf. Retrieved 02-03-09. 
29. ^ "Trial 2615b. Efficacy and Safety of Duloxetine compared with Placebo, Pelvic Floor Muscle Training, and Combined Duloxetine/Pelvic Floor Muscle Training in Subjects with Moderate to Severe Stress Urinary Incontinence" (PDF). www.clinicalstudyresults.org. http://www.clinicalstudyresults.org/drugdetails/viewfile.php?study_name=Trial+2615b+Efficacy+and+Safety+of+Duloxetine+compared+with+Placebo%2C+Pelvic+Floor+Muscle+Training%2C+and+Combined+Duloxetine%2FPelvic+Floor+Muscle+Training+in+Subjects+with+Moderate+to+Severe+Stress+Urinary+Incontinence&file=http%3A%2F%2Fpdf.clinicalstudyresults.org%2Fdocuments%2Fcompany-study_2356_0.pdf. Retrieved 02-03-09. 
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32. ^ Raskin J, Pritchett YL, Wang F, et al. (2005). "A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain". Pain Med 6 (5): 346–56. doi:10.1111/j.1526-4637.2005.00061.x. PMID 16266355. 
33. ^ Essential Science Indicators
34. ^ ^{a b} Wong MC, Chung JW, Wong TK (July 2007). "Effects of treatments for symptoms of painful diabetic neuropathy: systematic review". BMJ 335 (7610): 87. doi:10.1136/bmj.39213.565972.AE. PMID 17562735. 
35. ^ ^{a b} Várkonyi T, Kempler P (February 2008). "Diabetic neuropathy: new strategies for treatment". Diabetes Obes Metab 10 (2): 99–108. doi:10.1111/j.1463-1326.2007.00741.x. PMID 17593238. 
36. ^ Sultan A, Gaskell H, Derry S, Moore RA (2008). "Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials". BMC Neurol 8: 29. doi:10.1186/1471-2377-8-29. PMID 18673529. 
37. ^ One of the authors, HJ Möller "has participated in speakers bureau for Eli Lilly, has been a member of advisory board for Eli Lilly and has received grant/research support from Eli Lilly [2]Müller N, Schennach R, Riedel M, Möller HJ (April 2008). "Duloxetine in the treatment of major psychiatric and neuropathic disorders". Expert Rev Neurother 8 (4): 527–36. doi:10.1586/14737175.8.4.527. PMID 18416656. 
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39. ^ Disclosure information for Susan Kornstein, see: Wohlreich MM, Wiltse CG, Desaiah D, et al. (2007). "Duloxetine in Practice-Based Clinical Settings: Assessing Effects on the Emotional and Physical Symptoms of Depression in an Open-Label, Multicenter Study". Prim Care Companion J Clin Psychiatry 9 (4): 271–279. PMID 17934551. PMC 2018841. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2018841/. 
40. ^ Carter NJ, McCormack PL (2009). "Duloxetine: a review of its use in the treatment of generalized anxiety disorder". CNS Drugs 23 (6): 523–41. doi:10.2165/00023210-200923060-00006. PMID 19480470. 
41. ^ Kerwin, Robert; Taylor, David H.; Carol Paton (2007). Maudsley Prescribing Guidelines. Informa Healthcare. pp. 254. ISBN 0-415-42416-X. 
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[edit] External links

• Manufacturer website
• Eli Lilly Cymbalta Prescribing Guide
• U.S. National Library of Medicine: Drug Information Portal - Duloxetine

[show] v • d • e Antidepressants (N06A) [show]   Specific reuptake inhibitors (RIs), enhancers (REs), and releasing agents (RAs) Selective serotonin reuptake inhibitors (SSRIs) Alaproclate · Citalopram · Escitalopram · Femoxetine · Fluoxetine · Fluvoxamine · Indalpine · Ifoxetine · Litoxetine · Lubazodone · Panuramine · Paroxetine · Pirandamine · Seproxetine · Sertraline · Vilazodone · Zimelidine Serotonin-norepinephrine reuptake inhibitors (SNRIs) Bicifadine · Clovoxamine · Desvenlafaxine · Duloxetine · Levomilnacipran · Eclanamine · Milnacipran · Sibutramine · Venlafaxine Serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs) Brasofensine · BTS-74,398 · Cocaine · Diclofensine · DOV-21,947 · DOV-102,677 · DOV-216,303 · EXP-561 · Fezolamine · JNJ-7,925,476 · NS-2359 · PRC200-SS · Pridefrine · SEP-225,289 · SEP-227,162 · Tesofensine Norepinephrine reuptake inhibitors (NRIs) Amedalin · Atomoxetine/Tomoxetine · Binedaline · Ciclazindol · Daledalin · Esreboxetine · Lortalamine · Mazindol · Nisoxetine · Reboxetine · Talopram · Talsupram · Tandamine · Viloxazine Dopamine reuptake inhibitors (DRIs) Medifoxamine · Vanoxerine Norepinephrine-dopamine reuptake inhibitors (NDRIs) Amineptine · Bupropion/Amfebutamone · Cilobamine · Manifaxine · Methylphenidate · Nomifensine · Radafaxine · Tametraline Norepinephrine-dopamine releasing agents (NDRAs) Amphetamine · Befuraline · Lisdexamfetamine · Methamphetamine · Phenethylamine · Piberaline · Tranylcypromine Serotonin-norepinephrine-dopamine releasing agents (SNDRAs) 4-Methyl-αMT · αET/Etryptamine · αMT/Metryptamine Selective serotonin reuptake enhancers (SSREs) Tianeptine Others Indeloxazine · Tramadol · Viqualine [show]   Receptor antagonists and/or reuptake inhibitors Serotonin antagonists and reuptake inhibitors (SARIs) Etoperidone · Nefazodone · Trazodone Noradrenergic and specific serotonergic antidepressants (NaSSAs) Aptazapine · Esmirtazapine · Mianserin · Mirtazapine · Setiptiline/Teciptiline Norepinephrine-dopamine disinhibitors (NDDIs) Agomelatine Serotonin modulators and stimulators (SMSs) Lu AA21004 [show]   Tricyclic and tetracyclic antidepressants (TCAs/TeCAs) Tricyclics: Amezepine · Amineptine · Amitriptyline · Amitriptylinoxide · Azepindole · Butriptyline · Cianopramine · Clomipramine · Cotriptyline · Cyanodothiepin · Demexiptiline · Depramine/Balipramine · Desipramine · Dibenzepine · Dimetacrine · Dosulepin/Dothiepin · Doxepin · Enprazepine · Fluotracen · Hepzidine · Homopipramol · Imipramine · Imipraminoxide · Intriptyline · Iprindole · Ketipramine · Litracen · Lofepramine · Losindole · Mariptiline · Melitracen · Metapramine · Mezepine · Naranol · Nitroxazepine · Nortriptyline · Noxiptiline · Octriptyline · Opipramol · Pipofezine · Propizepine · Protriptyline · Quinupramine · Tampramine · Tianeptine · Tienopramine · Trimipramine; Tetracyclics: 7-OH-Amoxapine · Amoxapine · Aptazapine · Azipramine · Ciclazindol · Ciclopramine · Esmirtazapine · Loxapine · Maprotiline · Mazindol · Mianserin · Mirtazapine · Oxaprotiline · Setiptiline/Teciptiline [show]   Monoamine oxidase inhibitors (MAOIs) Nonselective: Irreversible: Benmoxin · Echinopsidine · Iproclozide · Iproniazid · Isocarboxazid · Mebanazine · Metfendrazine · Nialamide · Octamoxin · Phenelzine · Pheniprazine · Phenoxypropazine · Pivalylbenzhydrazine · Safrazine · Tranylcypromine; Reversible: Caroxazone · Paraxazone; MAOA-Selective: Irreversible: Clorgyline; Reversible: Amiflamine · Bazinaprine · Befloxatone · Befol · Brofaromine · Cimoxatone · Esuperone · Harmala Alkaloids (Harmine, Harmaline, Tetrahydroharmine, Harman, Norharman, etc) · Methylene Blue · Metralindole · Minaprine · Moclobemide · Pirlindole · Sercloremine · Tetrindole · Toloxatone · Tyrima; MAOB-Selective: Irreversible: Ladostigil · Mofegiline · Pargyline · Rasagiline · Selegiline; Reversible: Lazabemide · Milacemide [show]   Azapirones and other 5-HT1A receptor agonists Alnespirone · Aripiprazole · Befiradol · Buspirone · Eptapirone · Flesinoxan · Flibanserin · Gepirone · Ipsapirone · Oxaflozane · Tandospirone · Vilazodone · Zalospirone [show]   Dietary supplements (vitamins, minerals, amino acids, etc) Ascorbic acid (Vitamin C) · Fish oil · Folic acid (Vitamin B9) · L-5-HTP (Oxitriptan) · L-DOPA (Levodopa) · L-Methionine · L-Phenylalanine · L-Tryptophan · L-Tyrosine · Lithium · Magnesium · Melatonin · Niacin/Niacinamide (Vitamin B3) · Omega-3 fatty acids · Pyridoxine (Vitamin B6) · Rubidium · SAMe · Zinc [show]   Research compounds and miscellaneous agents 5-HT4R agonists RS-67,333 · SL65.0155 5-HT7R antagonists Amisulpride α2δ-VDCC blockers Gabapentin · Pregabalin β3-Adrenoceptor agonists Amibegron · Solabegron σ1R agonists Opipramol CB1R agonists Nabilone · Tetrahydrocannabinol/Dronabinol COMT inhibitors Entacapone · Tolcapone CRF1R antagonists Antalarmin · CP-154,526 · Pexacerfont · Pivagabine D2/D3AR antagonists Amisulpride · Sulpiride D2/D3/D4R agonists Piribedil · Pramipexole · Ropinirole · Rotigotine · Roxindole DOR agonists BU-48 · Buprenorphine · BW373U86 · DPI-287 · Heroin · Kratom · SNC-80 Enkephalinase inhibitors D-Phenylalanine · RB-101 FAAH inhibitors Acetaminophen/Paracetamol · AM-404 · URB-597 KOR antagonists 5-GNTI · Buprenorphine · JDTic · Norbinaltorphimine MOR agonists Buprenorphine · Codeine · Dextropropoxyphene · Dihydrocodeine · Fentanyl · Heroin · Hydrocodone · Hydromorphone · Kratom · Methadone · Morphine · Opium · Oxycodone · Oxymorphone · Pethidine/Meperidine · Tapentadol · Tramadol MT1/MT2R agonists Agomelatine · Melatonin · Ramelteon · Tasimelteon NK1R antagonists Aprepitant · Casopitant · Fosaprepitant · L-733,060 · Maropitant · Vestipitant NMDAR antagonists Dextromethorphan · Ketamine · Magnesium · Memantine · Zinc PDE4 inhibitors Mesembrine (Kanna) · Rolipram TRPC6 activators Adhyperforin (St. John's Wort) · Hyperforin (St. John's Wort) M: PSO/PSI mepr dsrd (o, p, m, p, a, d, s), sysi/epon, spvo proc, drug(N5A/5B/5C/6A/6B/6D)

[show] v • d • e Serotonergics [show]   5-HT1 receptor ligands 5-HT1A Agonists: Azapirones: Alnespirone • Binospirone • Buspirone • Enilospirone • Eptapirone • Gepirone • Ipsapirone • Perospirone • Revospirone • Tandospirone • Tiospirone • Umespirone • Zalospirone; Antidepressants: Etoperidone • Nefazodone • Trazodone; Antipsychotics: Aripiprazole • Asenapine • Clozapine • Quetiapine • Ziprasidone; Ergolines: Dihydroergotamine • Ergotamine • Lisuride • Methysergide • LSD; Tryptamines: 5-CT • 5-MeO-DMT • 5-MT • Bufotenin • DMT • Psilocin • Psilocybin; Others: 8-OH-DPAT • Adatanserin • Befiradol • BMY-14802 • Cannabidiol • Dimemebfe • Ebalzotan • Eltoprazine • F-11,461 • F-12,826 • F-13,714 • F-14,679 • F-15,063 • F-15,599 • Flesinoxan • Flibanserin • Lesopitron • Lu AA21004 • LY-293,284 • LY-301,317 • MKC-242 • NBUMP • Osemozotan • Oxaflozane • Pardoprunox • Piclozotan • Rauwolscine • Repinotan • Roxindole • RU-24,969 • S 14,506 • S-14,671 • S-15,535 • Sarizotan • SSR-181,507 • Sunepitron • U-92016A • Urapidil • Vilazodone • Xaliproden • Yohimbine Antagonists: Antipsychotics: Iloperidone • Risperidone • Sertindole; Beta blockers: Alprenolol • Cyanopindolol • Iodocyanopindolol • Oxprenolol • Pindobind • Pindolol • Propranolol • Tertatolol; Others: AV965 • BMY-7378 • CSP-2503 • Dotarizine • Flopropione • GR-46611 • Isamoltane • Lecozotan • Metitepine/Methiothepin • MPPF • NAN-190 • PRX-00023 • Robalzotan • S-15535 • SB-649915 • SDZ 216-525 • Spiperone • Spiramide • Spiroxatrine • UH-301 • WAY-100,135 • WAY-100,635 • Xylamidine 5-HT1B Agonists: Lysergamides: Dihydroergotamine • Ergotamine • Methysergide; Piperazines: Eltoprazine • TFMPP; Triptans: Avitriptan • Eletriptan • Sumatriptan • Zolmitriptan; Tryptamines: 5-CT • 5-MT; Others: CGS-12066A • CP-93,129 • CP-94,253 • CP-135,807 • RU-24969 Antagonists: Lysergamides: Metergoline; Others: AR-A000002 • Elzasonan • GR-127,935 • Isamoltane • Metitepine/Methiothepin • SB-216,641 • SB-224,289 • SB-236,057 • Yohimbine 5-HT1D Agonists: Lysergamides: Dihydroergotamine • Methysergide; Triptans: Almotriptan • Avitriptan • Eletriptan • Frovatriptan • Naratriptan • Rizatriptan • Sumatriptan • Zolmitriptan; Tryptamines: 5-CT • 5-MT; Others: CP-135,807 • CP-286,601 • GR-46611 • L-694,247 • L-772,405 • PNU-109,291 • PNU-142,633 Antagonists: Lysergamides: Metergoline; Others: Alniditan • BRL-15572 • Elzasonan • GR-127,935 • Ketanserin • LY-310,762 • LY-367,642 • LY-456,219 • LY-456,220 • Metitepine/Methiothepin • Ritanserin • Yohimbine • Ziprasidone 5-HT1E Agonists: Lysergamides: Methysergide; Triptans: Eletriptan; Tryptamines: BRL-54443 • Tryptamine Antagonists: Metitepine/Methiothepin 5-HT1F Agonists: Triptans: Eletriptan • Naratriptan • Sumatriptan; Tryptamines: 5-MT; Others: BRL-54443 • Lasmiditan • LY-334,370 Antagonists: Metitepine/Methiothepin [show]   5-HT2 receptor ligands 5-HT2A Agonists: Lysergamides: ALD-52 • Ergonovine • Lisuride • LA-SS-Az • LSD • LSD-Pip • Lysergic acid 2-butyl amide • Methysergide; Phenethylamines: 25I-NBMD • 25I-NBOH • 25I-NBOMe • 2C-B • 2C-B-FLY • 2CB-Ind • 2C-E • 2C-I • 2C-T-2 • 2C-T-7 • 2C-T-21 • 2CBCB-NBOMe • 2CBFly-NBOMe • Bromo-DragonFLY • DOB • DOC • DOI • DOM • MDA • MDMA • Mescaline • TCB-2 • TFMFly; Piperazines: BZP • Quipazine • TFMPP; Tryptamines: 5-CT • 5-MeO-α-ET • 5-MeO-α-MT • 5-MeO-DET • 5-MeO-DiPT • 5-MeO-DMT • 5-MeO-DPT • 5-MT • α-ET • α-Methyl-5-HT • α-MT • Bufotenin • DET • DiPT • DMT • DPT • Psilocin • Psilocybin; Others: AL-34662 • AL-37350A • Dimemebfe • Medifoxamine • Oxaflozane • PNU-22394 • RH-34 Antagonists: Atypical antipsychotics: Amperozide • Aripiprazole • Carpipramine • Clocapramine • Clozapine • Gevotroline • Iloperidone • Melperone • Mosapramine • Olanzapine • Paliperidone • Pimozide • Quetiapine • Risperidone • Sertindole • Ziprasidone • Zotepine; Typical antipsychotics: Loxapine • Pipamperone; Antidepressants: Amitriptyline • Amoxapine • Aptazapine • Etoperidone • Mianserin • Mirtazapine • Nefazodone • Trazodone; Others: 5-I-R91150 • AC-90179 • Adatanserin • Altanserin • AMDA • APD-215 • Blonanserin • Cinanserin • CSP-2503 • Cyproheptadine • Deramciclane • Dotarizine • Eplivanserin • Esmirtazapine • Fananserin • Flibanserin • Ketanserin • KML-010 • Lubazodone • Mepiprazole • Metitepine/Methiothepin • Nantenine • Pimavanserin • Pizotifen • Pruvanserin • Rauwolscine • Ritanserin • S-14,671 • Sarpogrelate • Setoperone • Spiperone • Spiramide • SR-46349B • Volinanserin • Xylamidine • Yohimbine 5-HT2B Agonists: Oxazolines: 4-Methylaminorex • Aminorex; Phenethylamines: Chlorphentermine • Cloforex • DOB • DOC • DOI • DOM • Fenfluramine • MDA • MDMA • Norfenfluramine; Tryptamines: 5-CT • 5-MT • α-Methyl-5-HT; Others: BW-723C86 • Cabergoline • mCPP • Pergolide • PNU-22394 • Ro60-0175 Antagonists: Agomelatine • Asenapine • EGIS-7625 • Ketanserin • Lisuride • LY-272,015 • Metitepine/Methiothepin • Rauwolscine • Ritanserin • RS-127,445 • Sarpogrelate • SB-200,646 • SB-204,741 • SB-206,553 • SB-215,505 • SB-221,284 • SB-228,357 • SDZ SER-082 • Tegaserod • Yohimbine 5-HT2C Agonists: Phenethylamines: 2C-B • 2C-E • 2C-I • 2C-T-2 • 2C-T-7 • 2C-T-21 • DOB • DOC • DOI • DOM • MDA • MDMA • Mescaline; Piperazines: Aripiprazole • mCPP • TFMPP; Tryptamines: 5-CT • 5-MeO-α-ET • 5-MeO-α-MT • 5-MeO-DET • 5-MeO-DiPT • 5-MeO-DMT • 5-MeO-DPT • 5-MT • α-ET • α-Methyl-5-HT • α-MT • Bufotenin • DET • DiPT • DMT • DPT • Psilocin • Psilocybin; Others: A-372,159 • AL-38022A • CP-809,101 • Dimemebfe • Lorcaserin• Medifoxamine • MK-212 • ORG-37,684 • Oxaflozane • PNU-22394 • Ro60-0175 • Vabicaserin • WAY-629 • WAY-161,503 • YM-348 Antagonists: Atypical antipsychotics: Clozapine • Iloperidone • Melperone • Olanzapine • Paliperidone • Pimozide • Quetiapine • Risperidone • Sertindole • Ziprasidone • Zotepine; Typical antipsychotics: Chlorpromazine • Loxapine • Pipamperone; Antidepressants: Agomelatine • Amitriptyline • Amoxapine • Aptazapine • Etoperidone • Fluoxetine • Mianserin • Mirtazapine • Nefazodone • Nortriptyline • Trazodone; Others: Adatanserin • Cinanserin • Cyproheptadine • Deramciclane • Dotarizine • Eltoprazine • Esmirtazapine • FR-260,010 • Ketanserin • Ketotifen • Latrepirdine • Lu AA24530 • Metitepine/Methiothepin • Methysergide • Pizotifen • Ritanserin • RS-102,221 • S-14,671 • SB-200,646 • SB-206,553 • SB-221,284 • SB-228,357 • SB-242,084 • SB-243,213 • SDZ SER-082 • Xylamidine [show]   5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7 ligands 5-HT3 Agonists: Piperazines: BZP • Quipazine; Tryptamines: 2-Methyl-5-HT • 5-CT; Others: Chlorophenylbiguanide • Butanol • Ethanol • Halothane • Isoflurane • RS-56812 • SR-57,227 • SR-57,227-A • Toluene • Trichloroethane • Trichloroethanol • Trichloroethylene • YM-31636 Antagonists: Antiemetics: AS-8112 • Alosetron • Azasetron • Batanopride • Bemesetron • Cilansetron • Dazopride • Dolasetron • Granisetron • Lerisetron • Ondansetron • Palonosetron • Ramosetron • Renzapride • Tropisetron • Zacopride • Zatosetron; Atypical antipsychotics: Clozapine • Olanzapine • Quetiapine; Tetracyclic antidepressants: Amoxapine • Mianserin • Mirtazapine; Others: CSP-2503 • ICS-205,930 • Lu AA21004 • Lu AA24530 • MDL-72,222 • Memantine • Nitrous Oxide • Ricasetron • Sevoflurane • Thujone  • Xenon 5-HT4 Agonists: Gastroprokinetic Agents: Cinitapride • Cisapride • Dazopride • Metoclopramide • Mosapride • Prucalopride • Renzapride • Tegaserod • Zacopride; Others: 5-MT • BIMU-8 • CJ-033,466 • PRX-03140 • RS-67333 • RS-67506 • SL65.0155 • TD-5108 Antagonists: GR-113,808 • GR-125,487 • L-Lysine • Piboserod • RS-39604 • RS-67532 • SB-203,186 5-HT5A Agonists: Lysergamides: Ergotamine • LSD; Tryptamines: 5-CT; Others: Valerenic Acid Antagonists: Asenapine • Latrepirdine • Metitepine/Methiothepin • Ritanserin • SB-699,551 * Note that the 5-HT5B receptor is not functional in humans. 5-HT6 Agonists: Lysergamides: Dihydroergotamine • Ergotamine • Lisuride • LSD • Mesulergine • Metergoline • Methysergide; Tryptamines: 2-Methyl-5-HT • 5-BT • 5-CT • 5-MT • Bufotenin • E-6801 • E-6837 • EMD-386,088 • EMDT • LY-586,713 • N-Methyl-5-HT • Tryptamine; Others: WAY-181,187 • WAY-208,466 Antagonists: Antidepressants: Amitriptyline • Amoxapine • Clomipramine • Doxepin • Mianserin • Nortriptyline; Atypical antipsychotics: Aripiprazole • Asenapine • Clozapine • Fluperlapine • Iloperidone • Olanzapine • Tiospirone; Typical antipsychotics: Chlorpromazine • Loxapine; Others: BGC20-760 • BVT-5182 • BVT-74316 • EGIS-12233 • GW-742,457 • Ketanserin • Latrepirdine • Lu AE58054 • Metitepine/Methiothepin • MS-245 • PRX-07034 • Ritanserin • Ro 04-6790 • Ro 63-0563 • SB-258,585 • SB-271,046 • SB-357,134 • SB-399,885 • SB-742,457 5-HT7 Agonists: Lysergamides: LSD; Tryptamines: 5-CT • 5-MT • Bufotenin; Others: 8-OH-DPAT • AS-19 • Bifeprunox • LP-12 • LP-44 • RU-24,969 • Sarizotan Antagonists: Lysergamides: 2-Bromo-LSD • Bromocriptine • Dihydroergotamine • Ergotamine • Mesulergine • Metergoline • Methysergide; Antidepressants: Amitriptyline • Amoxapine • Clomipramine • Imipramine • Maprotiline • Mianserin; Atypical antipsychotics: Amisulpride • Aripiprazole • Clozapine • Olanzapine • Risperidone • Sertindole • Tiospirone • Ziprasidone • Zotepine; Typical antipsychotics: Chlorpromazine • Loxapine; Others: Butaclamol • EGIS-12233 • Ketanserin • LY-215,840 • Metitepine/Methiothepin • Pimozide • Ritanserin • SB-258,719 • SB-258,741 • SB-269,970 • SB-656,104 • SB-656,104-A • SB-691,673 • SLV-313 • SLV-314 • Spiperone • SSR-181,507 [show]   Reuptake inhibitors SERT Selective serotonin reuptake inhibitors (SSRIs): Alaproclate • Citalopram • Dapoxetine • Desmethylcitalopram • Desmethylsertraline • Escitalopram • Femoxetine • Fluoxetine • Fluvoxamine • Indalpine • Ifoxetine • Litoxetine • Lu AA21004 • Lubazodone • Panuramine • Paroxetine • Pirandamine • RTI-353 • Seproxetine • Sertraline • Vilazodone • Zimelidine; Serotonin-norepinephrine reuptake inhibitors (SNRIs): Bicifadine • Desvenlafaxine • Duloxetine • Eclanamine • Levomilnacipran • Milnacipran • Sibutramine • Venlafaxine; Serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs): Brasofensine • Diclofensine • DOV-102,677 • DOV-21,947 • DOV-216,303 • NS-2359 • SEP-225,289 • SEP-227,162 • Tesofensine; Tricyclic antidepressants (TCAs): Amitriptyline • Butriptyline • Cianopramine • Clomipramine • Desipramine • Dosulepin • Doxepin • Imipramine • Lofepramine • Nortriptyline • Pipofezine • Protriptyline • Trimipramine; Tetracyclic antidepressants (TeCAs): Amoxapine; Piperazines: Nefazodone • Trazodone; Antihistamines: Brompheniramine • Chlorpheniramine • Diphenhydramine • Mepyramine/Pyrilamine • Pheniramine • Tripelennamine; Opioids: Meperidine (Pethidine) • Methadone • Propoxyphene; Others: Cocaine • CP-39,332 • Cyclobenzaprine • Dextromethorphan • Dextrorphan • EXP-561 • Fezolamine • Mesembrine • Nefopam • PIM-35 • Pridefrine • Roxindole • SB-649,915 • Ziprasidone VMAT Ibogaine • Reserpine • Tetrabenazine [show]   Releasing agents Aminoindanes: 5-IAI • ETAI • MDAI • MDMAI • MMAI • TAI; Aminotetralins: 6-CAT • 8-OH-DPAT • MDAT • MDMAT; Oxazolines: 4-Methylaminorex • Aminorex • Clominorex • Fluminorex; Phenethylamines (also Amphetamines, Cathinones, Phentermines, etc): 2-Methyl-MDA • 4-CAB • 4-FA • 4-FMA • 4-HA • 4-MTA • 5-APDB • 5-Methyl-MDA • 6-APDB • 6-Methyl-MDA • Amiflamine • BDB • BOH • Brephedrone • Butylone • Chlorphentermine • Cloforex • Diethylcathinone • Dimethylcathinone • DMA • DMMA • EBDB • EDMA • Ethylone • Etolorex • Fenfluramine (Dexfenfluramine) • Flephedrone • IAP • IMP • Lophophine • MBDB • MDA • MDEA • MDHMA • MDMA • MDMPEA • MDOH • MDPEA • Mephedrone • Methedrone • Methylone • MMA • MMDA • MMDMA • NAP • Norfenfluramine • pBA • pCA • pIA • PMA • PMEA • PMMA • TAP; Piperazines: 2C-B-BZP • BZP • MBZP • mCPP • MDBZP • MeOPP • Mepiprazole • pFPP • TFMPP; Tryptamines: 4-Methyl-αET • 4-Methyl-αMT • 5-CT • 5-MeO-αET • 5-MeO-αMT • 5-MT • αET • αMT • DMT • Tryptamine (itself); Others: Indeloxazine • Tramadol • Viqualine [show]   Enzyme inhibitors Anabolism TPH AGN-2979 • Fenclonine AAAD Benserazide • Carbidopa • Genistein • Methyldopa Catabolism MAO Nonselective: Benmoxin • Caroxazone • Echinopsidine • Furazolidone • Hydralazine • Indantadol • Iproclozide • Iproniazid • Isocarboxazid • Isoniazid • Linezolid • Mebanazine • Metfendrazine • Nialamide • Octamoxin • Paraxazone • Phenelzine • Pheniprazine • Phenoxypropazine • Pivalylbenzhydrazine • Procarbazine • Safrazine • Tranylcypromine; MAO-A Selective: Amiflamine • Bazinaprine • Befloxatone • Befol • Brofaromine • Cimoxatone • Clorgiline • Esuprone • Harmala alkaloids (Harmine, Harmaline, Tetrahydroharmine, Harman, Norharman, etc) • Methylene Blue • Metralindole • Minaprine • Moclobemide • Pirlindole • Sercloremine • Tetrindole • Toloxatone • Tyrima [show]   Others Precursors L-Tryptophan → 5-HTP Cofactors Ferrous iron (Fe2+) • Magnesium (Mg2+) • Tetrahydrobiopterin • Vitamin B3 (Niacin, Nicotinamide → NADPH) • Vitamin B6 (Pyridoxine, Pyridoxamine, Pyridoxal → Pyridoxal phosphate) • Vitamin B9 (Folic Acid → Tetrahydrofolic acid) • Vitamin C (Ascorbic acid) • Zinc (Zn2+) Others Activity enhancers: BPAP • PPAP; Reuptake enhancers: Tianeptine

Retrieved from "http://en.wikipedia.org/wiki/Duloxetine"

Categories: Serotonin-norepinephrine reuptake inhibitors | Eli Lilly and Company | Thiophenes | Naphthalenes | Phenol ethers | Amines

Hidden categories: All articles with dead external links | Articles with dead external links from November 2010 | Articles with broken citations | Articles containing unverified chemical infoboxes | All articles with unsourced statements | Articles with unsourced statements from September 2007

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