Duloxetinesold under the brand name Cymbalta among others,  is a medication mostly used for major depressive disordergeneralized anxiety disorderfibromyalgia and neuropathic pain. It is a thiophene derivative and a selective neurotransmitter reuptake inhibitor for serotonin, norepinephrine, cymbalta and stomach pain to a lesser degree dopamine.
It belongs to a class depression and gabapentin heterocyclic antidepressants known as serotonin—norepinephrine reuptake inhibitors SNRIs. The main uses of duloxetine are in major depressive disordercymbalta and stomach pain, generalized anxiety disorderneuropathic painchronic musculoskeletal painand fibromyalgia. Duloxetine is recommended as a first line agent for the treatment of chemotherapy-induced neuropathy by the American Society of Clinical Oncology as a first-line therapy for fibromyalgia in the presence of mood disorders by the German Interdisciplinary Association for Pain Therapy,  as a Grade B recommendation for the treatment of diabetic neuropathy by the American Association for Neurology  and as a level A recommendation in certain neuropathic states by the European Federation of Neurological Societies.
A Cochrane review concluded that duloxetine is beneficial in the treatment of diabetic neuropathy and fibromyalgia but that more comparative studies with other medicines are needed. Duloxetine was approved for the treatment of major depression in While duloxetine has demonstrated improvement in depression-related symptoms compared to placebocomparisons of duloxetine to other antidepressant medications have been less successful.
Additionally, the review found evidence that duloxetine has increased side effects and reduced tolerability compared to other antidepressants. It thus did not recommend duloxetine as a first line treatment for major depressive disorder, given the then high cost of duloxetine compared to inexpensive off-patent antidepressants and lack of increased efficacy. Duloxetine is more effective than placebo in the treatment of generalized anxiety disorder GAD.
A review from the Annals of Internal Medicine lists duloxetine cymbalta and stomach pain the first line drug treatments, however, along with citalopramescitalopramsertralineparoxetineand venlafaxine. Duloxetine was approved for the pain associated with diabetic peripheral neuropathy DPNbased on the positive results of two clinical trials. The average daily pain was measured using an point scale, and duloxetine treatment resulted in an additional 1—1.
Most of the response was achieved in the first two weeks on the cymbalta and stomach pain. Duloxetine slightly increased the cymbalta and stomach pain serum glucose ; this effect was deemed to be of "minimal clinical significance", cymbalta and stomach pain, however. The comparative efficacy of duloxetine and established pain-relief medications for DPN is unclear. A systematic review noted that tricyclic antidepressants imipramine and amitriptylinetraditional anticonvulsants and opioids have better efficacy than duloxetine.
Duloxetine, tricyclic antidepressants and anticonvulsants have similar tolerability while the opioids caused more side effects. The reviewer saw no reason to prescribe duloxetine in practice.
The authors noted that the evidence in favor of duloxetine is much more solid, however. A review of duloxetine found that it reduced pain and fatigue, and improved physical and mental performance compared to placebo.
It may be useful for chronic pain from osteoarthritis. On November 4,the U. Food and Drug Administration approved duloxetine to treat chronic musculoskeletal pain, including discomfort from osteoarthritis and chronic lower back pain. Duloxetine failed to receive US approval for stress urinary incontinence amid concerns over liver toxicity and suicidal events; it was approved for this use in the UKhowever, where it is recommended as an add-on medication in stress urinary incontinence instead of surgery.
The safety and utility of duloxetine in the treatment of incontinence has been evaluated in a series of meta analyses and practice guidelines. The following contraindications are listed by the manufacturer: In addition, cymbalta and stomach pain, the FDA has reported on life-threatening drug interactions that may be possible when co-administered with triptans and other drugs acting on serotonin pathways leading to increased risk for serotonin syndrome.
In a trial for major depressive disorder MDDthe most commonly reported treatment-emergent cymbalta and stomach pain events among duloxetine-treated patients were nausea Side effects tended to be mild-to-moderate, and tended to decrease in intensity over time.
In 4 clinical trials of duloxetine for the treatment of MDD, sexual dysfunction occurred significantly more frequently in patients treated with duloxetine than those treated with placebo, and this difference occurred only in men.
Loss of or decreased response to sexual stimuli and ejaculatory cymbalta and stomach pain are also reported, cymbalta and stomach pain. 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: The withdrawal syndrome from duloxetine resembles the SSRI discontinuation syndrome, cymbalta and stomach pain.
When discontinuing treatment with duloxetine, 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 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 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. To obtain statistically significant results the FDA had to combine the results of 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 the United States FDA released a public health advisory noting that there had been 11 reports of suicide attempts and 3 reports of suicidality within the mostly middle-aged women participating in the open label extension trials of duloxetine for the treatment of stress urinary incontinence.
The FDA described the potential role of confounding social stressors "unclear". The suicide attempt rate in the SUI study population based on 9, patients was calculated to be perperson years.
This rate is greater than the suicide attempt rate among middle-aged U. In addition, one death from suicide was reported in a Cymbalta cymbalta and stomach pain pharmacology study in a healthy female volunteer without SUI. No increase in suicidality was reported in controlled trials of Cymbalta for depression or diabetic neuropathic pain, cymbalta and stomach pain. Reported adverse events that were temporally correlated to duloxetine therapy include rash, reported rarely, and the following adverse events, reported cymbalta and stomach pain birth control pill and depression Duloxetine inhibits the reuptake of serotonin and norepinephrine NE in the central nervous system.
Duloxetine undergoes extensive metabolismbut the atkins diet plans and weight lifting circulating metabolites do not contribute significantly to the pharmacologic activity. Major depressive disorder is believed to be due in part to an increase in pro-inflammatory cytokines within the central nervous system. Antidepressants including ones with a similar mechanism cymbalta and stomach pain action as duloxetine, i.
The analgesic properties of duloxetine in the treatment of diabetic neuropathy and central pain syndromes such as fibromyalgia are believed to be due to sodium ion channel blockade. Duloxetine is acid labile, and is formulated with enteric coating to prevent degradation in the stomach. Congress and mlb and salary caps 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. Volume of distribution is L. Circulating metabolites are pharmacologically inactive. 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. Duloxetine was created by Lilly researchers. David Robertson; David Wong, a co-discoverer cymbalta and stomach pain fluoxetine ; and Joseph Krushinski are listed as inventors on the patent application filed in and granted in This molecule was subsequently named duloxetine. Inhowever, 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. After the cymbalta and stomach pain 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 The FDA approved duloxetine for the treatment of generalized anxiety disorder in February The first generic duloxetine was marketed by Dr, cymbalta and stomach pain.
From Wikipedia, the free encyclopedia. Not to be confused with dapoxetine. C Risk not ruled out, cymbalta and stomach pain. S4 Prescription only CA: Neuropathic pain — pharmacological management. Treatment of painful diabetic neuropathy: American Society of Clinical Oncology clinical practice guideline".
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Revue Canadienne De Psychiatrie. Annals of Internal Medicine. Medical review s " PDF. Depression and diabetic neuropathy: Food and Drug Administration.
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