Duloxetine Uses in Fibromyalgia Pain Relief and Treatment Of Major Depressive Disorder

Duloxetine which is marketed under the brand names Cymbalta and Yentreve is effective for major depressive disorder and it is as effective as venlafaxine in generalized anxiety disorder.It is a serotonin-norepinephrine reuptake inhibitor manufactured and marketed by Eli Lilly.
Duloxetine failed the US approval for stress urinary incontinence amidst the concerns about liver toxicity and suicidal events. It was however approved for this indication in Europe. Duloxetine alleviates pain associated with diabetic neuropathy and fibromyalgia. However, its efficacy relative to the established treatments, such as anticonvulsants and tricyclic antidepressants, has not been studied. The FDA approved duloxetine for the treatment of GAD in February 2007.

Indications

The main uses of duloxetine are in major depressive disorder, general anxiety disorder, stress urinary incontinence, painful peripheral neuropathy and fibromyalgia. In addition, it is being studied for various other indications.

Use of Duloxetine In The Treatment Of 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.Recently, duloxetine was shown to be effective in elderly with recurrent major depressive disorder where it improved cognition, depression, and some pain measures.
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.
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.
A head-to-head comparison of duloxetine with an SSRI escitalopram (Lexapro) found duloxetine to be both less tolerable and less effective. 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.

Fibromyalgia Pain Relief Using Using Cymbalta

Eli Lilly issued a press release saying they had done trials which found that Cymbalta, 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.
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.
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.

Duloxetine - Contraindications

The following contraindications are listed by the manufacturer:
1.Hypersensitivity - duloxetine is contraindicated in patients with a known hypersensitivity to duloxetine or any of the inactive ingredients.
2. MAOIs - concomitant use in patients taking MAOIs is contraindicated.
3.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.
4.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.
5.Cymbalta and thioridazine should not be co-administered.

Side effects of Duloxetine

Nausea, somnolence, insomnia, and dizziness are the main side effects, reported by about 10% to 20% of patients.

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:
The Other side-effects include the following

  • Orthostatic hypotension
  • Fatigue
  • Vivid nightmares
  • Increased sweating
  • Decreased appetite and weight loss
  • Blurred vision
  • Paresthesia
  • Disturbances of the gastrointestinal tract, such as nausea, constipation, diarrhea, indigestion, vomiting and profuse bleeding
  • Tremor
  • Anxiety, nervousness, agitation
  • Palpitations
  • Decreased sex drive or difficulty achieving orgasm
  • Impotence or delayed ejaculation
  • Hot flashes
  • Taste disturbances
  • Difficulty passing urine
  • Increase in blood pressure or heart rate
  • Cold hands or feet
  • Jaundice
  • Inflammation of the liver or hepatitis leading to cirrhosis if left unchecked.
  • Depersonalization
  • Hypomania
  • Clenching of teeth and the jaw muscles

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, years, or longer, even after the drug has been completely withdrawn. This disorder is known as post-SSRI sexual dysfunction.

 

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. 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 Cmax of duloxetine, but delays the time to reach peak concentration from 6 to 10 hours.

Duloxetine Dosage

Cymbalta (Duloxetine) should generally be taken orally once daily. For the treatment of Major Depressive Disorder (MDD) The starting dosage is 40 mg/day to 60 mg/day. For Acute Treatment the dosage is 40 mg/day (20 mg twice daily) to 60 mg/day (once daily or as 30 mg twice daily)

Availability And Packaging

Duloxetine is available in the form of Cymbalta capsules in 20, 30, 40 and 60 mg variants.

Generic Versions And Brand names of Duloxetine

Duloxetine which is marketed under the brand names Cymbalta, Duvanta and Yentreve

Additional Information

Manufacturers pamphlet: Eli Lilly - Prescribing information



Considerable portions of the text here is from http://en.wikipedia.org/wiki/Duloxetine and is reproduced here under the Creative Commons Attribution-ShareAlike License