The mystery of medications linked to suicide

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The mystery of medications linked to suicide

As number of drug warnings rise, investigators search for reasons why

By Fran Kritz

Special to msnbc.com

updated 8:55 a.m. ET, Wed., May. 7, 2008

The FDA has issued advisories that the following drugs or drug

classes may have a link to suicidal thoughts and/or actions:

— Singulair

— SSRI antidepressants (including Paxil and Prozac)

— Chantix

— Tamiflu

— Accutane

— Epilepsy drugs (including carbamazepine, gabapentin, felbamate,

lamotrigine, levetiracetam, oxcarbazepine, pregabalin and valproate)

When Kate of Queensbury, N.Y., filled a new allergy drug

prescription for her 15-year-old son, Cody, last July, she hoped it

would improve his bothersome allergy symptoms. Now, is

wondering whether a possible side effect of the drug, Singulair,

caused Cody — who she describes as a happy, athletic teenager — to

take his own life about a month later.

isn't alone. Physicians or patients have filed anecdotal

reports with drug companies or the Food and Drug Administration on at

least six drugs or drug classes that may have been linked to episodes

of suicidal thoughts or actions. In just the past few months, the FDA

has released several advisory notices to both doctors and the public

about drugs linked to suicidal thoughts or actions, including

Singulair, epilepsy drugs and the smoking-cessation drug Chantix.

Reports have also been filed on antidepressants, the influenza drug

Tamiflu and the acne medicine Accutane.

It's a medical quandary that has doctors, drugmakers, federal health

officials and patients confused and understandably concerned. Are the

links between these medications and the risk of suicide real? And if

so, how can drugs that are intended to help people instead

potentially prompt them to end their lives?

Experts say there aren't many clear answers but medication links to

suicide, if in fact real, could possibly result from the drug itself,

an underlying disease or condition that predisposes someone to

depression, or a combination of factors.

" The brain is a complex organ, and most of the drugs are complex as

well,'' says Dr. Laughren, head of the division of psychiatric

products at the FDA. " It's not unreasonable to think that a drug that

gets into the brain may have effects other than you hope they would

have … but in some cases, it's just a background event. That's why

it's so important to follow up with an analysis of the clinical

trials.''

After concerns were first raised about possible links between

antidepressants and suicide about four years ago, the FDA

commissioned researcher Posner, the principal investigator at

the Center for Suicide Risk Assessment at Columbia University in New

York, to help determine any suicidal risk posed by medications. Her

quantitative tools and questionnaires to assess suicide risk are

being applied to drugs already on the market and those still in

testing.

" We know that whether or not these drugs actually cause suicidal

thought or action is a question we have to answer, but up until now,

none of the clinical trials for the drugs were set up to address the

question,'' says Posner. " Either way we have to get the right

answers. It's critical to know about drugs that pose risk, but

debunking false notions of risk is equally important to the public

health.''

Finding a link can present other issues. This became evident when the

FDA, based on a review of antidepressant clinical trials, found a

slight increase in suicidal thinking among children and young adults

taking antidepressants such as Paxil and Prozac. The rate in those

taking antidepressants was 4 percent, twice the rate of those taking

a placebo. The information was added to the label of antidepressants

within the last few years, pushing many doctors to stop prescribing

the drugs for many of their patients.

" Use of antidepressants went down, and the suicide rate went up,''

says Dr. a Clayton, medical director of the American Foundation

for Suicide Prevention in New York.

The drug? The diagnosis? Neither?

Laughren says the FDA hopes that by using Posner's methods, they may

be able to find categories of people who might be at risk for suicide

on a particular drug and more carefully determine who should stay

clear of the drug and in whom it can safely be prescribed.

At least in theory, there are some possible explanations for why some

of the drugs in question might be associated with suicidal thoughts

or action, says Noel, director of clinical pharmacy services at

Rosewood Center in Owings Mills, Md., a residential facility for

people with developmental disabilities. Singulair, for example, has a

similar chemical pathway to steroids, which are drugs that can affect

behavior and mood.

The FDA is conducting a safety review of Singulair, which is also

used to treat asthma, that is expected to take about another eight

months. Last week, Kate and her husband, , met with FDA

officials in the office of Congresswoman Kirsten Gillibrand (D-N.Y.),

who is pushing to help find answers on Singulair and other drugs that

have been linked to suicide.

In the meantime, says Ron , a spokesperson for Merck, which

makes the drug, a cause-and-effect link between Singulair and suicide

has not been proven, and patients on the drug who are worried should

consult their doctors. " If patients have any concerns about

Singulair, the most appropriate course of action to take is to speak

with their physician, not to stop taking their medicine, " he

says. " Each patient's doctor is in the best position to determine

whether or not a person should continue to take the medicine.''

Regarding antidepressants, Laughren and other experts say one

possible explanation for the link may be that fatigue is one of the

symptoms of depression and that the initial benefit of an

antidepressant is increased energy. Improving depression symptoms can

take a few weeks, but in the meantime, some patients may use their

extra energy to act on their suicidal thoughts.

While some patients can take a drug and have no risk of suicide, in

others, chemical factors in the drug combined with specific factors

in the patient, or an underlying disease they have, may combine to

influence depression or suicidal thinking or behavior, Noel says.

Suicidal thoughts in patients taking epilepsy drugs, for example,

have been reported in patients on the drugs for epilepsy, depression

or other psychiatric conditions, but generally not in patients taking

the drug for migraine headaches, for which they are sometimes also

prescribed, says Noel.

" In some cases, the conditions being treated, even asthma, can be its

own risk factor for suicidal thinking — confounding the impact a drug

may have, " says Posner. Asthma symptoms can impair daily living, such

as being unable to walk far because of difficulty breathing, or

having to cart oxygen around. Having your life hampered in this way

can make some people with asthma think about suicide, experts say.

When it comes to Chantix, one theory is that the smoking-cessation

drug, which works to block the pleasure pathways in the brain that

make nicotine so satisfying, also suppresses other types of pleasure

and happiness, leading to depression. But at the same time, stopping

smoking, the goal for patients taking Chantix, can itself be a risk

factor for depression, says Posner, and smoking itself is a risk

factor for suicide.

A spokesperson for Pfizer, the maker of Chantix, says the company is

continuing to investigate the association between the drug and

suicide risk, and urges patients considering Chantix to talk frankly

with a doctor about what to expect when getting off cigarettes.

A representative of the Pharmaceutical Research and Manufacturers of

America in Washington, D.C., says the trade group is hoping for more

answers soon.

" We looked at this with SSRIs [antidepressants] and the other drugs

that have received warnings, " says Alan Goldhammer, deputy vice

president of scientific and regulatory affairs. " We're keenly

interested to move forward and better understand what is the number

being observed in the case of true suicides and how does that relate

to the age group and population at large.''

'A common background event'

Adding to the confusion of how to determine the possibility that a

drug can cause suicidal thinking or action is the fact that suicide

and suicidal thinking is, sadly, fairly common in the United States.

Suicide is the fourth leading cause of death for adults between the

ages of 18 and 65, according to the most recent data from the

National Center for Health Statistics, accounting for about 26,500

deaths in that age group in 2005. For those ages 15 to 24, suicide is

the third leading cause of death.

For all ages, suicide rates increased just under 1 percent between

2000 and 2005, but children and young adults ages 10 to 24

experienced an 8 percent increase between 2000 and 2004, following a

decrease in the 15 years prior to 2000, according to the Centers for

Disease Control and Prevention in Atlanta. Ileana Arias, head of the

CDC's National Center for Injury Prevention and Control, says the

agency doesn't have an explanation for the increase.

" What makes this so difficult is that suicidal thinking is a common

background event,'' says Laughren, citing data from the CDC which

found that one out of five young adults ages 13 to 19 admits to

thinking about suicide.

Experts say recent increases in the reporting of medication side

effects may be bringing attention to the issue of drugs possibly

linked to suicide, but that doesn't prove a connection.

" Whenever an alert is issued by the FDA, the notice reminds patients

and doctors to report side effects to the agency or drug company, and

so we are getting more reports, which are then dispatched to health

care professionals and consumers. That's a good thing, but it doesn't

tell us enough,'' says Cohen, head of the Institute for Safe

Medication Practices in Horsham, Pa. " It's only after the reports

have been investigated, which takes time, that we can know for sure

if a reported side effect is actually related to the drug.''

When a suicide occurs, says Clayton, families and friends look for

answers, and because prescription medications are so prevalent, they

may well find that their friend or loved one was taking one or more

medications and often make the connection. " But that doesn't mean

that the drug was a factor in the death,'' Clayton says.

Clayton and other psychiatric experts worry about listing suicidal

thinking as a possible side effect on medications because,

understandably, patients or their families are likely to see that and

decide not to take a drug that could be beneficial for a medical

condition.

Insufficient information

While investigators try to sort out the data and reports, family

members of people who have committed suicide have said they didn't

have enough information when choosing a drug to determine whether it

was a safe choice.

Although Cody had no history of depression or suicidal

thinking, his mother says that if she had known that Singulair was

linked to feelings of sadness, she might not have let him take the

drug.

In fact, Merck voluntarily added depression to the drug's label in

April 2007, three months before Cody's doctor prescribed the drug,

because a number of doctors and patients reported the side effect to

the company or the FDA. But says her doctor did not tell them

the drug could cause depression, nor was depression listed as a side

effect of the drug on the company Web site, which she checked when

the drug was first prescribed, and wasn't in the information that

came stapled to the prescription from the pharmacy.

Insufficient patient and doctor information on side effects of

prescription drugs is hardly a new issue. At a 2002 Congressional

hearing, Congressman Bart Stupak (D-Mich.) reported a similar lack of

information on the acne drug Accutane that his teenage son B.J. was

taking. B.J. killed himself in 1999, after several months on

Accutane, and his parents have linked his death with the drug.

At the hearing, Stupak said that in 1998 the FDA publicly noted

reports of depression, psychosis and suicidal thoughts and actions

with the drug, but a year later when B.J. got the drug their doctor

had not informed them of the risk, and the patient information that

came with the medication did not include it. A spokesman for Stupak

says the congressman is looking into current drugs that have been

linked to suicidal thoughts and actions.

Consumer advocacy groups such as Public Citizen in Washington, D.C.,

say there can be lags in getting information to consumers about new

warnings on drugs. Refill prescriptions don't necessarily highlight

new information, and patient information that pharmacies staple to

the prescription bag don't always include all necessary information,

says Ray Bullman, head of the National Council on Patient Information

and Education in Bethesda, Md., which educates consumers and health

professionals on safe medication use.

The FDA is looking into the quality and timeliness of the information

consumers receive with their prescription drugs, and Congresswoman

Gillibrand would like to see a mechanism put in place by the FDA to

alert physicians directly whenever a serious drug side effect is

announced.

Ask questions, follow up

Medication experts including Cohen, of the Institute for Safe

Medication Practices, says that asking whether any medication might

cause suicidal thinking or action is a reasonable question when a

drug is prescribed, and if the answer is yes, that should be weighed,

with your doctors, against the benefits of the drug.

Posner and other experts say a drug should not be dismissed out of

hand because it has suicidal thinking and/or behavior as a side

effect, without thoroughly discussing the risk-benefit profile of the

drug.

Cohen urges family members to monitor children and young adults for

behavior changes when any new drug is started and to contact the

doctor immediately if they are concerned. He suggests that adults who

are taking a drug that has been linked to behavior changes let a

friend or family know about the prescription and ask them to stay

attuned to any changes.

" Suicide ideation is incredibly common, and is addressable, if

needed,'' says Posner. " In almost all cases when you measure the risk

against the benefit, it almost always favors treatment with the drug

in question for conditions ranging from asthma to depression. "

Fran Kritz is a freelance healthcare reporter in Silver Spring, Md.,

who also writes for the Washington Post and Los Angeles Times.

© 2008 MSNBC Interactive

While pharmacies and doctors may have a lag in finding out and

telling patients about new drug warnings, patients can get that

information quickly on their own.

Ray Bullman of the National Council on Patient Information and

Education in Bethesda, Md., suggests consumers check a new site

called DailyMed, a project of the National Library of Medicine, which

lists the updated labels produced by drug companies.

And the Food and Drug Administration recently began an e-mail service

that alerts consumers whenever a significant change is made to a

medication or device. Consumers can choose from different categories

for e-mail alerts (such as drugs or medical devices).