WARNINGS REVISED FOR TWO ANTIDEPRESSANTS

The labels of nefazodone and venlafaxine have been changed.

The labels of two antidepressants in the class of drugs known as serotonin and norepinephrine reuptake inhibitors (SNRIs) have been revised to include a new warning that patients being treated with any antidepressant should be monitored closely for the worsening of depression and suicidality, especially at the beginning of drug therapy and whenever the dose is changed either upward or downward.

Although an association has not been firmly established clinically, providers should alert patients being treated with nefazodone (Serzone) and venlafaxine (Effexor) and their family members and caregivers to the necessity of monitoring for agitation, irritability, anxiety, panic, insomnia, hostility, impulsivity, akathisia, hypomania, and mania, symptoms that may be linked to a greater risk of worsening depression or suicidal ideation. Additionally, as a reminder, the label of each product now includes the information that the drug has not been approved for use in children.

The Food and Drug Administration (FDA) requested that manufacturers of antidepressants revise the labeling of the drugs in a way that reflects its concern with the increase in anecdotal evidence indicating that some children and adolescents taking the drugs have committed suicide. (See AJN Reports, August, for a fuller discussion of this issue.) The FDA is expected to soon release additional recommendations and guidelines regarding the use of antidepressants in children after a thorough reexamination of the data of clinical trials and case reports, and it is anticipated that the labeling of other antidepressants will be revised accordingly.

In addition to these new warnings, there are other revisions to the warnings and precautions section of the venlafaxine and nefazodone labels. The venlafaxine labeling now gives the precautionary information that some neonates who had been exposed to the drug late in the third trimester of pregnancy developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding. Reported clinical findings include respiratory distress, cyanosis, apnea, seizures, temperature instability, difficulty in feeding, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitters, irritability, and continual crying. The risks to the infant and the potential benefit to the mother presented by the drug should be weighed carefully before venlafaxine is prescribed for use by pregnant women, and lowering the dose during the third trimester should be considered in all who use it.

While the labeling of nefazodone has always included the warning that the drug presents the risk of hepatic failure, a revision to it strengthens the warnings. It now states that the prescriber must consider the risk of hepatic failure, and that this consideration, in many cases, will lead to prescribing another antidepressant. The "Dosage and Administration" section of the label again states that hepatic failure is possible and refers the reader to a black box warning section that details the increased risk of death from hepatic failure.

Nurses should be aware of these revised warnings and precautions, in order to appropriately monitor patients who are taking the drugs. They should also bear in mind that the question of whether or not antidepressants contribute to the risk of suicide in children has not yet been fully answered. Additional information that will help nurses to provide to patients and their families the most accurate and helpful education in the risks and benefits of drug therapy should be forthcoming.

Bender K. FDA deliberates suicidality in children on antidepressants. Psychiatric Times 2004;21(6).Bristol-Meyers Squibb Company. Dear healthcare provider. 2004. http://www.fda.gov/medwatch/safety/2004/serzone_hcp.pdf.Wyeth. Dear healthcare provider. 2004. http://www.fda.gov/medwatch/safety/2004/effexor_dear_hcp_june.pdf.