British Ignite Debate in U.S. on Drugs and Suicide...

December 16, 2003

http://www.nytimes.com/2003/12/16/health/psychology/16SUIC.html?ex=1072155600 & en\

=e6d47af77a37a629 & ei=5062 & partner=GOOGLE

December 16, 2003

British Ignite Debate in U.S. on Drugs and Suicide

By ERICA GOODE

Many American psychiatrists were taken by surprise last week when British

drug regulators told doctors to stop writing prescriptions for all but one

of a newer generation of antidepressant drugs to treat depressed children

under 18.

Now the psychiatrists are trying to figure out how to advise the parents of

the young patients who come to them for help. Some parents, the doctors say,

are calling to ask if the drugs their children are taking are really safe.

" The news has certainly generated anxiety, concern and questions, " said Dr.

Flemming Graae, the chief of child and adolescent psychiatry at Westchester

Medical Center in Valhalla, N.Y.

For parents and psychiatrists alike, the issue is not an easy one to sort

out.

The British regulators said that for adults, the benefits of the

antidepressants, most belonging to the class called selective serotonin

reuptake inhibitors or S.S.R.I.'s, clearly outweigh their risks.

But after reviewing 11 studies of the drugs in treating depressed children

and adolescents, the regulators concluded that for most of the medications,

the potential for harmful side effects Ñ including suicidal thoughts and

behavior, as well as hostility Ñ was greater than the evidence for their

effectiveness. Doctors should not prescribe the medications except in

certain circumstances, the regulators said.

The drugs included Paxil, from GlaxoKline; Zoloft, from Pfizer;

Effexor, from Wyeth; Celexa and Lexapro, from Forest Laboratories Inc.; and

Luvox, from Solvay. Prozac, by Eli Lilly, was exempted from the advisory.

(Effexor is a serotonin-norepinephrine inhibitor.)

Few psychiatrists dispute that little is known about how well the drugs work

and how they affect the developing brain: the number of large-scale studies

of S.S.R.I.'s in children is small, many of the findings are less than

impressive, and some drugs have yet to be tested.

And some mental health professionals believe that, given the limited

knowledge, antidepressants are being prescribed too widely and too casually

by doctors, many of them general practitioners rather than psychiatrists.

But medical experts have sharply divergent opinions on whether governments

should intervene in the way that Britain did.

Dr. Harrington, a professor of child and adolescent psychiatry at

the University of Manchester in England, said he thought that, on balance,

the British regulators did the right thing.

" The broad story seems to be that the drugs don't work and they have some

side effects, " Dr. Harrington said. " If we're going to practice

evidence-based medicine and if the basic evidence is negative, then why

prescribe them? "

But some American psychiatrists say the British regulators acted hastily and

went too far.

" Everybody Ñ scientists, parents and advocates Ñ needs an answer to this

question, " said Dr. March, the chief of child and adolescent psychiatry

at Duke University Medical Center. But the British regulators, he said,

" prematurely closed the story. "

Dr. March and other experts argue that the cost of leaving depressed

children and teenagers untreated is high: depression itself can be a lethal

illness. And some psychiatrists say that they have seen " indisputable proof "

in their practices that the drugs help seriously ill children.

Most of the experts said they would continue to use S.S.R.I.'s to treat

children and teenagers. But they added that doctors and parents should

closely monitor children for signs of restlessness, agitation, recklessness,

unusual behavior or thoughts of suicide, especially during the first weeks

of drug treatment and after any increase in dosage. Some anecdotal evidence

suggests that suicidal or aggressive behavior, if it is tied to the drugs,

occurs within the first weeks after the drug treatment is started.

Dr. Graae and others say they start children on very low doses of the

medications and that in some cases a low dose is all that is needed.

Most American experts do not rule out the possibility that in some young

people, the antidepressants may somehow increase the risk of suicidal

thinking or self-harm, though they believe a link remains unproved.

But even if an association were shown, some say, they would favor stronger

warning labels rather than a recommendation that the drugs not be used.

Some researchers said they believed that the Food and Drug Administration,

which is conducting its own intensive review of the drugs and will hold

public hearings on Feb. 2, has taken a more careful and comprehensive

approach to investigating the medications' safety.

Dr. March and other experts said the committee that reviewed the studies for

the British Medicines and Healthcare Products Regulatory Agency, the British

equivalent of the F.D.A., failed to adequately take into account the

complexity of the data and the difficulty of comparing studies done with

varying methodologies and with subjects who suffered from different degrees

of illness. The British agency has posted summaries on its Web site

(www.mhra.gov.uk) of all the studies reviewed.

The British regulators, some experts said, also did not give proper weight

to the high frequency of suicidal thoughts and attempts among depressed

adolescents in general. A study in 2000 by Norwegian researchers of close to

10,000 children ages 12 to 20, for example, found that 30 percent of those

who met criteria for a diagnosis of depression at the beginning of the study

had made a suicide attempt two years later.

Some researchers also questioned the logic of singling out one drug as

better or safer than the others.

Dr. Graham Emslie, a professor of psychiatry at the University of Texas

Southwestern Medical Center and the lead investigator on the studies of

Prozac that the British regulators found convincing, said that because the

studies of different drugs use different measures and are based on

significantly varying numbers of subjects, the discrepancies in their

findings may mean little.

" Any relative difference in effectiveness between S.S.R.I.'s is probably

best explained by methodological differences and not by specific differences

in the medications, " Dr. Emslie said.

The F.D.A., psychiatrists familiar with the agency's investigation said, is

requesting more information from drug companies than was given to the

British drug agency, and has asked outside researchers to trace back and

recode by hand the raw data used in some studies.

The experts said the agency hoped to determine how many of the reports of

suicidal thinking or behavior were real. The F.D.A. also hopes to tell if

the greater incidence of suicidal tendencies found in some studies among

children taking the drugs is meaningful or is simply an artifact of how the

children were assigned to the drug or placebo groups, the experts said. No

suicides were reported in any of the studies.

If a link is found between some of the drugs and suicidal tendencies,

scientists will then have to figure out how many children and adolescents

may be affected Ñ most experts believe the number would be very small Ñ and

how the drugs produce such behavior.

While emphasizing that any attempt to explain what might be going on was

pure speculation, some experts have offered hypotheses. One is that some

children may have a " paradoxical " reaction to the drugs that causes them to

become extremely restless, agitated or impulsive. Dr. Graae said that he had

treated more than 2,000 children with S.S.R.I.'s and had not seen a case

where he thought the drugs produced suicidal thoughts or behavior. But he

said that he had seen cases of children who had shown " a level of

recklessness or risk taking, not necessarily aimed at injuring oneself. "

Another is that the drugs may produce an unstable emotional state in some

children who actually suffer from manic depression that has gone

undiagnosed.

A third idea is that some incidents may occur in children who are taking

their medication irregularly or who have just stopped the drug. Some

S.S.R.I.'s are metabolized by the body very quickly. When they are stopped

abruptly they can produce a variety of reactions, including shifts in mood,

lightheadedness, flulike symptoms and what some patients have described as

" electrical zapping sensations. " Children, experts said, metabolize drugs

more quickly than adults, and may be more susceptible to such reactions. In

three studies of Paxil examined by the British regulators, 20 of 34 events

" possibly related to suicidality " occurred during the 30 days after the

children stopped taking the drug, compared with 8 out of 17 in the placebo

group in the same period.

The British action appears to have already made some American parents more

cautious about starting their children on antidepressants. Dr. Graae said

that one couple he saw decided to postpone their child's treatment with an

S.S.R.I. until they could discuss the issue further.

But for many parents, the pronouncements of government officials has less

impact than their own personal experiences with the drugs.

A woman in Westchester County whose 12-year-old son has taken Zoloft for

several months, for example, said that she resorted to medication only

because she feared her son was on the edge of a serious breakdown.

" I knew my child was in deep trouble, " the mother said. She added that on

the drug her son had improved greatly.

" It's been night and day, " she said.

But Sara Bostock, who says she believes that Paxil caused her 25-year-old

daughter to commit suicide a few weeks after starting the drug, sees the

British action as the first step toward recognizing what she calls the

dangers of S.S.R.I.'s. Ms. Bostock has campaigned for the pharmaceutical

companies to open privately held data to the public.

" I admit to anger and outrage over what I believe was a serious wrong done

to my beloved daughter, " Ms. Bostock said in an e-mail message, " and this

ban does represent some vindication for me. "

In fact, the British regulators stopped short of an outright ban, saying

that for some children, including those who were already doing well on an

S.S.R.I. and those who could not tolerate Prozac, their use might still be

warranted.

What everyone agrees on is that only more research and more detailed

analysis of the studies that exist will be able to provide answers to

parents and clinicians.

" We should let the data tell the story, " Dr. March said.

Corrections | Help | Back to Top

_________________________________________________________________

Don’t worry if your Inbox will max out while you are enjoying the holidays.

Get MSN Extra Storage! http://join.msn.com/?PAGE=features/es

December 16, 2003