Important New Warnings! The Use Of The Antidepressant Venlafaxine (EFFEXOR, EFFEXOR XR) In Children And Adolescents

The manufacturer of the antidepressant venlafaxine (EFFEXOR, EFFEXOR XR), Wyeth Pharmaceuticals, issued a Dear Health Care Professional letter on August 22, 2003 warning of increased reports of suicide-related adverse events such as suicidal ideation and self harm, in addition to hostility, with the use of this drug in children and adolescents.

The new warnings are the result of clinical trials conducted in patients ranging in ages from 6 to 17 years. Venlafaxine was not found to be effective in the treatment of either major depressive disorder or generalized anxiety disorder.

The most common adverse drug reaction leading to stopping venlafaxine in at least one percent of children and adolescents in the major depressive disorder trials was hostility; this was reported in two percent of patients on the active drug compared to less than one percent receiving a placebo. Also, in these trials suicidal ideation was reported in two percent of long-acting venlafaxine patients, whereas there were no reports of suicidal ideation in the placebo group.

In generalized anxiety disorder studies, abnormal/changed behavior was observed in one percent of the children and adolescents given long-acting venlafaxine versus no reports in those receiving the placebo.

There were no deaths in the major depressive disorder or generalized anxiety studies.

The “Precautions” section of the professional product labeling or package insert for venlafaxine has been amended to contain the following two statements:

Usage in Children/Pediatric Use

Safety and effectiveness in pediatric patients (individuals below 18 years of age) have not been established.

In pediatric clinical trials, there were increased reports of hostility and, especially in Major Depressive Disorder, suicide-related adverse events such as suicidal ideation and self-harm.

The warning about venlafaxine follows the FDA’s similar warning about the selective serotonin reuptake inhibitor (SSRI) paroxetine (PAXIL) on June 19, 2003 (see Worst Pills, Best Pills News August 2003).

The paroxetine warning was based on three well controlled clinical trials conducted in children under 18 years of age with major depression, that compared the effectiveness of paroxetine to placebo. These trials found that paroxetine did not work better than placebo in the treatment of major depression. However, suicide-related behaviors, including suicidal thoughts and attempts, were more common in children receiving paroxetine. The risk of these adverse events was about three times greater with paroxetine compared to placebo. There were no deaths in these trials.

The new safety information about the use of these two antidepressants in children appears to be the result of efforts on the part of the government to get drug companies to do clinical trials of drugs that are used in children, such as paroxetine and venlafaxine.

The use of paroxetine and venlafaxine in children was never approved by the FDA and is referred to as an “off-label” use. The new warnings about these antidepressants highlight the potential dangers when drugs are widely prescribed and there is no evidence that they are safe and effective. The root of some of the worst drug disasters in American history is off-label prescribing.

The physician who makes the diagnosis, selects the treatment, and then evaluates that treatment is hardly an objective, unbiased observer, and too many mistakes have been made when prescribing decisions are not predicated on evidence from valid, large-scale studies. Congress recognized over 40 years ago that, in their everyday practice of medicine, physicians could not differentiate between a useful drug and a dangerous one. This is why it passed a law in 1962 requiring drug manufacturers to provide substantial evidence in the form of controlled clinical trials that their drugs would do what they said they would do.

The widespread use of antidepressants in children and adolescents in the absence of adequate research on the safety and effectiveness of these drugs may do more harm than good.

What You Can Do

Parents whose children are taking venlafaxine should consult the prescribing physician immediately.

DO NOT stop venlafaxine treatment immediately. Discontinuation of this drug requires medical supervision.