Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants used for treating depression, anxiety disorder, and pain. Other drugs in this class include milnacipran (Savella), venlafaxine (Effexor), and desvenlafaxine (Pristiq). Duloxetine affects neurotransmitters, the chemicals that nerves within the brain make and release in order to communicate with one another. Neurotransmitters either travel across the space between nerves and attach to receptors on the surface of nearby nerves or they attach to receptors on the surface of the nerves that produced them, to be taken up by the nerve and released again (a process referred to as re-uptake).

Many experts believe that an imbalance among neurotransmitters is the cause of depression as well as other psychiatric disorders. Serotonin and norepinephrine are two neurotransmitters released by nerves in the brain. Duloxetine works by preventing the reuptake of serotonin and epinephrine by nerves after they have been released. Since uptake is an important mechanism for removing released neurotransmitters and terminating their actions on adjacent nerves, the reduced uptake caused by duloxetine increases the effect of serotonin and norepinephrine in the brain. The mechanism responsible for its effectiveness treating pain is not known but also is thought to involve its effects on serotonin and norepinephrine in the brain. Duloxetine was approved by the FDA in August 2004.

Duloxetine is approved for treating the following conditions:

• Major depressive disorder (MDD)
• Generalized anxiety disorder (GAD)
• Diabetic peripheral neuropathic pain
• Fibromyalgia
• Chronic musculoskeletal pain

Duloxetine is used for the treatment of depression, generalized anxiety disorder, pain associated with diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain.

The most common side effects of duloxetine are nausea, dry mouth, constipation, diarrhea, fatigue, difficulty sleeping, and dizziness. Increased blood pressure can occur and should be monitored. Seizures have been reported. Sexual dysfunction (decreased sex drive and delayed orgasm and ejaculation) has been associated with duloxetine.

Some patients may experience withdrawal reactions upon stopping duloxetine. Symptoms of withdrawal include:

• dizziness,
• anxiety,
• nausea,
• vomiting,
• nervousness,
• diarrhea,
• irritability, and
• insomnia.

The dose of duloxetine should be gradually reduced when therapy is discontinued to prevent symptoms of withdrawal.

Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of duloxetine or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be closely observed for clinical worsening, suicidality, or unusual changes in behavior.

The recommended dose for treating depression is 20 or 30 mg twice daily or 60 mg once daily. Patients may be started with 30 mg once daily for one week before the dose is advanced to 60 mg daily.

The recommended dose for anxiety disorder, pain associated with diabetic neuropathy, fibromyalgia, or chronic musculoskeletal pain is 60 mg daily. Starting at 30 mg daily for one week before increasing to 60 mg daily may help patients adjust to the drug. There is no evidence that doses greater than 60 mg/day provide additional benefits. However, the maximum dose for depression or anxiety disorder is 120 mg/day.

• Duloxetine should not be used in combination with a monoamine oxidase inhibitor (MAOI) such as phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), and selegiline (Eldepryl), or within 14 days of discontinuing the MAOI. At least 5 days should be allowed after stopping duloxetine before starting an MAOI. Combinations of SNRIs and MAOIs may lead to serious, sometimes fatal, reactions including very high body temperature, muscle rigidity, rapid fluctuations of heart rate and blood pressure, extreme agitation progressing to delirium, and coma. Similar reactions may occur if duloxetine is combined with antipsychotics, tricyclic antidepressants or other drugs that affect serotonin in the brain. Examples include tryptophan, sumatriptan (Imitrex), lithium, linezolid (Zyvox), tramadol (Ultram), and St. John’s Wort.
• Fluoxetine (Prozac, Serafem), paroxetine (Paxil, Paxil CR, Pexeva), fluvoxamine (Luvox), and quinidine increase blood levels of duloxetine by reducing its metabolism in the liver. Such combinations may increase adverse effects of duloxetine.
• Combining duloxetine with aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), warfarin (Coumadin) or other drugs that are associated with bleeding may increase the risk of bleeding, because duloxetine itself is associated with bleeding.
• Duloxetine has an enteric coating that prevents dissolution until it reaches a segment of the gastrointestinal that has a pH higher than 5.5. In theory, drugs that raise the pH in the gastrointestinal system (for example, Prilosec) may cause duloxetine to be released early while conditions that slow gastric empyting (for example, diabetes) may cause premature breakdown of duloxetine. Nevertheless, aAdministration of duloxetine with an antacid or famotidine (Axid) did not significantly affect the absorption of duloxetine.
• Duloxetine may reduce the breakdown of desipramine (Norpramine), leading to increased blood concentrations of desipramine and potential side effects.

Duloxetine is excreted into the milk of lactating women. Because the safety of duloxetine in infants is not known, breastfeeding while on duloxetine is not recommended.

Do I need a prescirption for duloxetine?

Yes, a presciption is needed.

What brand names are available for duloxetine?

Cymbalta

What preparations of duloxetine are available?

Delayed-release capsules: 20, 30 and 60 mg

How should I keep duloxetine stored?

Capsules should be stored at room temperature, between 15 C to 30 C (59 F to 86 F).