FDA panel urges black box warning for antidepressants, plus Breggin comments.

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BMJ 2004;329:702 (25 September), doi:10.1136/bmj.329.7468.702

 

News roundup

 

FDA panel urges " black box " warning for antidepressants

http://bmj.bmjjournals.com/cgi/content/full/329/7468/702

 

Bethesda, Maryland Jeanne Lenzer

 

 

 

All antidepressants should come with a " black box " label warning

that adolescents treated with the drugs are more likely to become

suicidal, according to an advisory panel to the US Food and Drug

Administration.

 

Black box warnings are among the most stringent cautions issued

by the FDA and are reserved for drugs with very serious or fatal side

effects. The FDA generally follows the recommendations of advisory

committees but is less likely to do so when the vote is split, as it

was in this case (eight of the 23 expert panellists voted against the

warning), said Dr Robert Temple, associate director for medical policy

in the FDA's drug evaluation centre.

 

The surprise vote came after the presentation of new analyses by

the FDA during two days of hearings on 13 and 14 September showing

that children taking the drugs were almost twice as likely to have

suicidal thoughts or to attempt suicide as children receiving placebo.

 

The effects of a black box warning are variable. With some

drugs, it has led to abrupt reductions in prescribing, but with others

the warning seems to have had little effect. According to Joyce

Generali, director of drug information at the Kansas University

Medical Center, 192 drugs carried black box warnings by 14 July. The

largest group with the warning is antineoplastic agents

 

Some panellists expressed concern that a black box warning could

reduce the number of doctors willing to prescribe antidepressants in

children. But Dr Thomas Newman, professor of epidemiology and

paediatrics at the University of California, San Francisco, and a

panellist, said: " We have very strong evidence of harm and not very

strong evidence of efficacy. It wouldn't be a bad thing if the use of

these drugs were diminished. "

 

The panellists decided to place the warning on all

antidepressants rather than single out individual drugs. The only drug

approved by both British and US medical authorities for the treatment

of depression in adolescents, fluoxetine (Prozac), will also carry a

black box warning. Dr Temple said he found it " interesting and

persuasive " that all drugs, including fluoxetine, showed the same

trend toward increased suicidality.

 

But Dr Matthew Rudorfer, assistant chief in the adult and

geriatric section of the US National Institute of Mental Health, said:

" Although antidepressants may cause two to three kids out of every 100

to be involved in a suicide related event, that is outweighed by the

15% of teenagers with untreated depression who commit suicide. "

 

" That's ridiculous, " said Dr Peter Breggin, a psychiatrist and

psychopharmacologist, whose work in the early 1980s led the FDA to

require a new class warning for tardive dyskinesia.

 

" There isn't one stitch of evidence that these drugs decrease

suicidality. Quite the contrary: there is abundant evidence that they

increase the risk. "

 

Dr Breggin adds that Dr Rudorfer's claim is " false " since the

FDA studies showing a 2-3% rise in suicidality was based on " risk

difference " -something that took into account the background rate of

suicidality from depression.

 

Dr Breggin told the BMJ that a black box warning is not the

strongest warning available to the FDA. " They could say the drugs are

contraindicated. But the panellists, with their deep ties to industry,

would never do that, " he said. According to an FDA spokesperson, Jason

Brodsky, 10 of the panellists received waivers because of financial

conflicts of interest.

 

Dr Lawrence Diller, paediatrician and author of the two books on

children and psychotropic drugs, testified in the hearings that

" frontline doctors " are losing trust in researchers-especially when

they learn about " eight negative [antidepressant] studies on children

that were never released to either doctors or the public. Dr Diller

added, " The blame is clear. The money, power, and influence of the

pharmaceutical industry corrupts all. Suppression of negative studies

in the name of protecting stockholder interests, but at the cost of

children's health, highlights the amorality of an unfettered and

unregulated market place. "

 

The advisory panel also recommended that manufacturers should be

required to attach a patient guide to the medicines describing the

increased risk of suicidality in plain language. Dr Temple said the

FDA hopes to reach a decision about the panel's recommendations within

a few months.