It is a serotonin–norepinephrine reuptake inhibitor.

It has no significant affinity for dopaminergic, cholinergic, histaminergic, opioid, glutamate, and GABA reuptake transporters, however, and can therefore be considered to be a selective reuptake inhibitor at the 5-HT and NE transporters.

Duloxetine undergoes extensive metabolism, but the major circulating metabolites do not contribute significantly to the pharmacologic activity.

It inhibits the reuptake of serotonin and norepinephrine (NE) in the central nervous system.

It increases dopamine (DA) specifically in the prefrontal cortex.

Brand name Cymbalta.

Mostly used for major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and. neuropathic pain.

It is taken by mouth.

Pregnancy category US: C (Risk not ruled out).

Bioavailability about 50%.

There is an average 2-hour lag until absorption begins with maximum plasma concentrations occurring about 6 hours post dose.

Protein binding about 95%.

Metabolism by the liver, two P450 isozymes, CYP2D6 and CYP1A2.

Circulating metabolites are pharmacologically inactive.

Elimination half-life 12 hours.

Steady-state is usually achieved after 3 days.

Excretion 70% in urine, 20% in feces.

Common side effects include dry mouth, nausea, feeling tired, dizziness, agitation, sexual problems, and increased sweating.

Severe side effects include an increased risk of suicide, serotonin syndrome, mania, and liver problems.

Antidepressant withdrawal syndrome may occur.

Use during the later part of pregnancy can harm the baby.

It is recommended as a first line agent for the treatment of chemotherapy-induced neuropathy, fibromyalgia in the presence of mood disorders

Has demonstrated improvement in depression-related symptoms compared to placebo, but to other antidepressant medications have been less successful.

Has increased side effects and reduced tolerability compared to other antidepressants, and is not recommended as a first line treatment for major depressive disorder.

More effective than placebo in the treatment of generalized anxiety disorder.

Approved for the pain associated with diabetic peripheral neuropathy (DPN), based on the positive results of two clinical trials.

At least 50% pain relief was achieved in 40–45% of the duloxetine patients vs. 20–22% of placebo patients, pain decreased by more than 90%, in 9–14% of duloxetine patients vs. 2–4% of placebo patients.

A systematic review noted that tricyclic antidepressants (imipramine and amitriptyline), traditional anticonvulsants and opioids have better efficacy than duloxetine for pain relief.

The moderate pain relief achieved is clinically insignificant.

It reduces pain and fatigue in fibromyalgia, and improved physical and mental performance compared to placebo.

It may be useful for chronic pain from osteoarthritis.

Contraindications to its use:


Concomitant use in patients taking MAOIs.

Uncontrolled narrow-angle glaucoma:

Associated with an increased risk of mydriasis, and should be avoided in patients with uncontrolled narrow-angle glaucoma.

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.

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.

Main side effects: nausea, somnolence, insomnia, dry mouth, headache and dizziness are the main side effects, reported by about 10% to 20% of patients.

Side effects tended to be mild-to-moderate, and tend to decrease in intensity over time.

On the treatment of major depressive disorder sexual dysfunction occurred significantly more frequently in patients treated with duloxetine than those treated with placebo, and this difference occurred only in men: difficulty becoming aroused, lack of interest in sex, and anorgasmia.

Frequency of treatment-emergent sexual dysfunction are similar for duloxetine and SSRIs when compared in a 6 month observational study in depressed patients.

Upon discontinuation of SSRI drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures.

The withdrawal syndrome from duloxetine resembles the SSRI discontinuation syndrome.

When discontinuing treatment it is recommended a gradual reduction in the dose, rather than abrupt cessation.

Abrupt discontinuation symptoms occurring at a rate 2% or greater: dizziness, nausea, headache, paresthesia, vomiting, irritability, and nightmare.

Carries a black box warning stating that antidepressants may increase the risk of suicide in persons younger than 25.

To obtain such statistically significant results the FDA had to combine the results of 295 trials of 11 antidepressants for psychiatric indications.

An increased rate of suicides have been reported in middle-aged women participating in trials of duloxetine for the treatment of stress urinary incontinence, but no increase in suicidality has been reported in controlled trials for depression or diabetic neuropathic pain.

Rare adverse side effects include:rash elevated LFTs, angioneurotic edema, glaucoma, hepatotoxicity, hyponatremia, jaundice, orthostatic hypotension, Stevens–Johnson syndrome, syncope and urticaria, rash, and orthostatic hypotension.

Major depressive disorder is believed to be due in part to an increase in pro-inflammatory cytokines within the central nervous system.

Antidepressants such as duloxetine, i.e. serotonin metabolism inhibition, cause a decrease in proinflammatory cytokine activity and an increase in anti-inflammatory cytokines.

In the treatment of diabetic neuropathy and central pain syndromes such as fibromyalgia its activities are believed to be due to sodium ion channel blockade.

Cymbalta (duloxetine) 60mg tablets.

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