Rx CARE

New agent relieves painful symptoms of depression

The troubling physical symptoms of depression often go unrecognized and/or untreated, although 69% of those with the condition list physical symptoms as the main reason for a visit to their primary care physician. Fortunately, clinicians can now offer their patients with depression an agent that addresses both depressed mood and its common physical symptoms, such as back pain.

The Food & Drug Administration recently approved duloxetine (Cymbalta, Eli Lilly) capsules for the treatment of major depressive disorder. The drug is currently available in pharmacies.

Duloxetine is a potent serotonin and norepinephrine reuptake inhibitor (SNRI), as well as a less potent dopamine reuptake inhibitor, said John Greist, M.D., a clinical professor of psychiatry at the University of Wisconsin-Madison Medical School. The inhibition of serotonin and norepinephrine reuptake is important for the relief of physical symptoms, including those involving pain, he added.

Duloxetine has a greater and balanced inhibition of serotonin and norepinephrine reuptake, and negligible affinity for other receptors, versus older agents, said Lawrence Cohen, Pharm.D., chairman and professor of the department of pharmacotherapy at the University of Washington-Spokane College of Pharmacy. Consequently, its safety profile is significantly better than that of many other antidepressants, he said.

"A significant tolerability issue with the other SNRI available in the United States, venlafaxine (Effexor, Wyeth Pharmaceuticals), is nausea and even vomiting," Cohen said. "I remain optimistic future data will indicate that nausea is not as significant a problem with duloxetine."

In clinical trials, the most commonly observed adverse effects in those treated with duloxetine were nausea, dry mouth, constipation, decreased appetite, fatigue, somnolence, and increased sweating.

Lilly said that duloxetine is contraindicated in those with end-stage renal disease and any hepatic insufficiency. It is classified as pregnancy category C. The company said that clinicians may want to taper the dose of duloxetine in the third trimester of pregnancy. It is not recommended for use in lactating women. The manufacturer also advises against the concomitant use of duloxetine and inhibitors of the cytochrome P450 1A2 and 2D6 systems.

The recommended total dose of duloxetine is 40 mg per day (administered as 20 mg taken twice daily) to 60 mg per day (administered either once daily or as 30 mg taken twice daily). Insufficient evidence exists to determine how long patients should be treated with duloxetine.

Cohen pointed out that these agents are not fully effective for approximately four to six weeks. Pharmacists can make patients and caregivers aware that the medications do not work instantly.

Patients with mood disorders are frequently unaware of any improvement, even though those closest to them recognize that they are doing better, Cohen said. He recommended that pharmacists, families, and caregivers discuss their perceptions of patients' progress. Pharmacists can reassure patients that they are indeed improving.

The labeling for duloxetine contains a boldfaced warning stating that those taking antidepressants should be observed closely for clinical worsening and suicidality.

For its part, the FDA has reminded clinicians, patients, and families that suicidal behavior is part of the illness, and that they should be watchful, Greist said.

Greist and Cohen concurred that the availability of a new therapeutic alternative benefits patients. Cohen predicted that duloxetine will make an excellent alternative to venlafaxine. "Every new agent allows clinicians to treat those who have not responded to anything else, so healthcare professionals should have some optimism about using this drug," Greist concluded.

Charlotte LoBuono

TIPS TO REMEMBER: Cymbalta

• Cymbalta is contraindicated in those with known hypersensitivity to any component of the product.

• Concomitant use of Cymbalta and monoamine oxidase inhibitors is contraindicated. Coadministration of Cymbalta with thioridazine is also contraindicated.

• Use of Cymbalta in those with uncontrolled narrow-angle glaucoma should be avoided.

• Cymbalta should ordinarily not be prescribed to those with substantial alcohol use.

Charlotte LoBuono. New agent relieves painful symptoms of depression.

Drug Topics

Sep. 13, 2004;148:21.