FDA's proposed "black box" warning for all antidepressants would likely mean an end to television ads for the products.

On Oct. 15, FDA concluded its review of pediatric suicidality associated with antidepressant use by asking all manufacturers to adopt a black box warning and a consumer medication guide explaining the risk.

The warning follows the recommendation of FDA's Psychopharmacological Drugs and Pediatric Advisory Committees (¹ Also see "FDA Will Strengthen Antidepressant Warnings; “Black Box” Not Certain" - Pink Sheet, 20 September, 2004., p. 3).

The most significant commercial impact of the relabeling may be to sharply limit direct-to-consumer advertising of antidepressants.

FDA regulations stipulate that the contents of a boxed warning must be stated exactly in any direct-to-consumer ads. In addition, the regulations stipulate that "reminder ads" cannot be used to promote products with boxed warnings.

Consequently, all information in the black boxes would have to be read as a warning in radio or television ads, virtually prohibiting a typical 30- or 60-second broadcast ad. Print ads would have to include the warning exactly as it is stated in the label.

At least two antidepressants, Pfizer's Zoloft and GlaxoSmithKline's Wellbutrin , have ongoing DTC programs.

Lilly is also in the process of launching the selective serotonin and norepinephrine reuptake inhibitor Cymbalta , and has talked about pursuing a DTC campaign in the future (² Also see "Lilly Cymbalta Launched At Premium Price; Once-Daily Dose Encouraged" - Pink Sheet, 9 August, 2004., p. 3).

FDA is requesting the changes for all 32 approved antidepressant brands, starting with the oldest tricyclics up through Cymbalta.

The request also includes antidepressant ingredients marketed under multiple brands, including Symbyax (fluoxetine in combination with olanzapine for bipolar depression), Sarafem (fluoxetine for pre-menstrual dysphoric disorder) and Zyban (bupropion for smoking cessation).

The request for a consumer medication guide may also have significant commercial ramifications, particularly for the older brands covered by the request.

FDA is asking manufacturers to adopt unit-of-use packaging to ensure that the MedGuide can be physically attached to the prescription given to the patient.

For some manufacturers of older antidepressant products, the added cost of adopting new packaging could pose a significant obstacle.

In addition to the black box warning and MedGuide, FDA proposed a series of additional labeling revisions. The agency has sent a ³ letter to all manufacturers outlining the proposed changes.

FDA also issued a new ⁴ public health advisory Oct. 15 outlining the antidepressant suicidality risk.

The impact of the labeling changes may be to help manufacturers begin to move past the safety issues that have slowed growth in the antidepressant class as a whole.

Questions about the pediatric safety of antidepressants have already been pushed off the front pages by Merck's withdrawal of Vioxx Sept. 30.

The Oct. 15 announcement of the new warnings competed for attention with Pfizer's same-day warning regarding the safety of its COX-2 inhibitor Bextra .

For FDA, however, the change in focus from antidepressants to COX-2 inhibitors does not bring any relief from questions about its internal safety monitoring practices (⁵ Also see "Antidepressant Hearings Offer Starting Point For Vioxx Investigation" - Pink Sheet, 11 October, 2004., p. 3).

During the Oct. 15 press conference announcing the new labeling, FDA's Office of New Drugs was represented by Deputy Director Sandra Kweder, MD. She was introduced as the acting director of the office.

FDA explained that Office of New Drugs Director John Jenkins, MD, is on leave and Kweder is acting as director in his absence. The agency did not offer an expected date for Jenkins' return.

Antidepressant “Black Box” Presents Barrier To DTC Advertising

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