FDA Approves Depression Drug

Duloxetine won final approval from the Food and Drug Administration (FDA) in August, becoming the latest option for the pharmacological treatment of adults with major depression. The combined selective serotonin-norepinephrine reuptake inhibitor (SSNRI) will be marketed by Eli Lilly and Company under the brand name Cymbalta.

Final approval of the new antidepressant had been expected late last year, but market analysts who follow the pharmaceutical industry cited manufacturing difficulties at a Lilly facility and the ongoing controversy surrounding potential risks of self-harming and suicidal behaviors linked with some antidepressants as contributing to a delay of over six months.

The drug is similar to venlafaxine in its combined action on both serotonin and norepinephrine; however, its action is more balanced between the two neurotransmitters, unlike the heavy weighting of venlafaxine towards action on serotonin levels.

Efficacy of duloxetine was confirmed in four large, randomized, placebo-controlled studies of nearly 6,000 adult patients. Patients taking duloxetine were two to three times as likely to achieve remission than were patients taking placebo.

Efficacy and safety in children have not been studied. In clinical trials, the most common treatment-emergent adverse effects were nausea, dry mouth, constipation, decreased appetite, fatigue, sleepiness, and increased sweating. Similar to venlafaxine, duloxetine may cause increases in both systolic and diastolic blood pressure. It is recommended that blood pressure be monitored prior to starting duloxetine and periodically throughout therapy.

In addition, duloxetine labeling will include the FDA's current cautionary language regarding suicide risk in patients with depression and a reported (but not yet substantiated) possible increase in risk of suicide in those taking antidepressant medications. During clinical trials of duloxetine, at least four patients taking the medication committed suicide; however, the FDA has made no determination yet as to a link between the drug and these patients deaths.

Duloxetine is contraindicated in those taking thioridazine or an MAOI and should be administered with caution in those with hepatic insufficiency, end-stage renal disease, or narrow-angle glaucoma. Use of duloxetine during pregnancy has not been studied in humans, though animal studies indicate that it may be associated with neonatal adverse effects similar to those seen with other SSRIs.

It is recommended that dosing of duloxetine be tapered when therapy is discontinued, rather than abruptly stopping the medication. In clinical trials, duloxetine, similar to SSRIs, was associated with a potential for withdrawal symptoms including dysphoria, agitation, irritability, dizziness, and paresthesias. Duloxetine will be available in 20 mg, 30 mg, and 60 mg capsules. The usual starting dose is recommended to be 60 mg per day. The drug became available last month.

Complete prescribing information on duloxetine is posted online at<www.cymbalta.com>.▪