Murder Down Under. Supreme Court Justice accepts Zoloft Lustral evidence

[Guest guest]

Murder Down Under

" .....Healy also testified this summer as an expert witness in a

case that resulted in a ruling by a New South Wales, Australia,

Supreme Court judge who determined that a 76-year-old man accused of

strangling his wife of 50 years did so because he was taking

sertraline.

" I am satisfied, " said Australian Supreme Court Justice Barry

O'Keefe, " that but for the Zoloft he had taken, he would not have

strangled his wife. " ................. "

http://pn.psychiatryonline.org/cgi/content/full/36/19/6?

maxtoshow= & HITS=10 & hits=10 & RESULTFORMAT= & searchid=1090095376066_1162 &

stored_search= & FIRSTINDEX=30 & minscore=5000 & journalcode=psychnews

SSRIs Called on Carpet Over Violence Claims

Jim ck

A flurry of recent legal activity has reignited the controversy

surrounding antidepressants' ability to cause aggressive or

violent

behavior. Among the cases is an Australian one in which an SSRI is

blamed for a man's fatal attack on his wife.

Psychoactive medications, and the drug companies that make them,

have been having a bad year in court. In fact, following several

recent legal rulings involving different psychoactive drugs, some

industry analysts are hinting they would not be surprised to see the

drugs' sales—and also their makers' chief

executives—a bit

depressed.

The most recent legal assault against a psychoactive medication came

in August when a Los Angeles law firm filed a complaint against

international drug conglomerate GlaxoKline PLC (GSK), maker of

the SSRI Paxil (paroxetine). The suit contends that not only was GSK

aware of data that indicated that the antidepressant can

be " addictive, " resulting in severe withdrawal reactions, but also

that the company concealed the " evidence, " failing to warn both

physicians and patients about the potential for the reactions.

The lawsuit, which seeks class-action status and unspecified

damages, was filed on behalf of 35 Americans from across the country

who claim that they suffered symptoms ranging from " electric-like

shocks " to suicidal thoughts after they stopped taking the drug. In

asking for damages, the suit alleges " fraud, deceit, negligence,

liability, and breach of warranty " by GSK.

Introduced in the U.S. in 1992, the drug is approved by the FDA for

the treatment of depression, obsessive-compulsive disorder, panic

disorder, and social anxiety disorder.

Wyoming Verdict on Appeal

The drug has been the center of legal controversy before. Earlier

this summer, a jury in U.S. District Court in Wyoming ordered GSK to

pay $6.4 million to the family of a man who killed his wife,

daughter, granddaughter, and then himself after taking two

paroxetine tablets in February 1998.

The wrongful death suit was filed in civil court on behalf of

surviving family members. Attorneys for the family successfully

argued that Schell had told people that he hallucinated when

he had previously taken paroxetine's chemical cousin, fluoxetine

(Eli Lilly and Co.'s Prozac), and that most likely the same had

occurred with the paroxetine he took on the day he shot his family

before turning the gun on himself.

Harvard psychiatrist Maltsberger, M.D., testified that the SSRI

manufacturers should warn prescribing physicians—in particular

family and primary care physicians like the one who prescribed

paroxetine for Schell—that SSRIs can cause a vulnerable minority

of

patients to experience akathesia and mania, which, he told the

court, can induce violence and even suicide.

Testimony was also introduced from a psychiatrist and outspoken

critic of SSRIs, Healy, M.D., director of the Sub-Department

of Psychological Medicine at the University of Wales College of

Medicine.

Healy testified that GSK's studies showed that, as early as 1989,

SSRIs (including paroxetine) can cause 1 in 4 healthy volunteers to

exhibit moderate to severe agitation, which, he said, could lead to

violent behavior. Healy added that his studies have since shown that

another SSRI, sertraline (Pfizer's Zoloft), when given to healthy

volunteers, made two subjects " acutely and seriously suicidal after

just being on the normal dose for two weeks. "

The drug company's attorneys argued that the medication had not

had

time to work and that it was Schell's out-of-control and

escalating

depression that caused his violent behavior.

The Wyoming civil court jury found that the drug was " 80 percent

responsible " for the deaths, with Schell being 20 percent

responsible, and awarded a total of $8 million in damages. GSK was

ordered to pay 80 percent of that total, or $6.4 million.

Spokespersons for GSK had previously indicated in press releases

that the company intended to appeal the verdict.

Murder Down Under

Healy also testified this summer as an expert witness in a case that

resulted in a ruling by a New South Wales, Australia, Supreme Court

judge who determined that a 76-year-old man accused of strangling

his wife of 50 years did so because he was taking sertraline.

" I am satisfied, " said Australian Supreme Court Justice Barry

O'Keefe, " that but for the Zoloft he had taken, he would not have

strangled his wife. "

The defendant in the Australian murder case, J. Hawkins, pled

guilty to the reduced charge of manslaughter on the grounds of

diminished responsibility. His defense attorney successfully argued

that the retired mechanic would not have killed his wife if he had

not taken 250 mg of sertraline, five times the recommended dose, the

morning of the murder.

The judge agreed, saying in his verbal ruling, " The killing was

totally out of character for the prisoner, inconsistent with the

loving, caring relationship which existed between him and his wife

and with their happy marriage of 50 years. "

In his testimony Hawkins hinted at possible hallucinations,

mirroring the Wyoming accounts. " I was looking at my wife, but I

wasn't seeing her face, " Hawkins told the court, describing the

moments in which he strangled her to death. He then attempted to

kill himself.

Spokespersons for Pfizer Inc. defended the drug, saying there is no

evidence to suggest that it has any side effects of aggression,

aggravation, or delusions. Ketelbey, M.D., senior medical

director for Pfizer in Australia, attempted to reassure both

patients and prescribing physicians of the drug's track record.

" Only one side—the defense—presented any data about the side

effects

of Zoloft, " Ketelbey said in a prepared statement following the

Australian judge's ruling, " and what occurred could hardly be

considered a rigorous examination of all the clinical and medical

data surrounding this medicine. While we are sympathetic to all

parties involved in this tragedy, the public health is best served

by accurate information about both this important medicine and the

dangers of untreated depression. "

A spokesperson for the Australian Therapeutic Goods Administration,

the equivalent of this country's FDA, said that this fall the

agency

would review data on sertraline and violent behavior. She told

Psychiatric News that the administration would consult regulatory

agencies and Pfizer about whether they are aware of other reports

attributing serious criminal behavior to the drug.

Do Data Speak for Themselves?

Anecdotal reports of violent and suicidal behavior have been tied to

fluoxetine, paroxetine, and sertraline for a number of years. At

this point, however, published data do not support the allegations.

Last year Arif Khan, M.D., and his colleagues published a study in

the April issue of Archives of General Psychiatry looking at suicide

risk in antidepressant clinical trials, using the Food and Drug

Administration database.

Khan wanted to know whether it was safe, and ethical, to include

placebos in clinical trials of antidepressants using actively

depressed patients. The review found that among nearly 20,000

participants in clinical trials of SSRIs, a total of 34 had

committed suicide, and 130 had attempted suicide. Khan also found

that the " rates of suicide and attempted suicide did not differ

significantly among the placebo and drug-treated groups. " He and his

colleagues concluded that it was, therefore, safe to include placebo

arms in antidepressant clinical trials.

The University of Wales's Healy has a different point of view.

Healy

has combined the data looked at by Khan with additional data

accessed through the Freedom of Information Act. Healy maintains

that his analysis—which is being prepared for publication—of

the

suicide and suicide attempts shows that a significant number of

events occurred during the placebo washout phase in the clinical

trials; when patients enter that phase, they may have been taking

another antidepressant, which must be washed out of their system

prior to the start of the drug trial. Healy noted that some suicides

or attempts occurred during the washout, as opposed to occurring

when a patient was continuously taking placebo or active trial drug.

" Now, when you strip those out and just look at the true placebo

suicides and suicidality versus the true SSRI suicides and

suicidality, " Healy told Psychiatric News, " there's an absolute

increase in suicides and suicidal acts on the active antidepressants

compared with placebo. "

Although Lilly, Pfizer, and GSK did not return phone calls from

Psychiatric News requesting input for this story, each has publicly

said previously that they believe the data show their products are

safe.

Revising Labeling

Current FDA-approved labeling of all three drugs includes general

warnings about the ability of SSRIs to activate mania and hypomania

and about suicide risk being inherent in depression, particularly

early in treatment.

Critics of the medications believe that the potential of the drugs

to cause violent and/or suicidal behavior is documented well enough

to cause the FDA to require stronger warnings to both physicians and

patients. However, the FDA has said that it sees " no reason to

revise the currently approved labeling at this time. "

The British Medicines Control Agency has indicated it is working

with the companies concerned to strengthen the current language

regarding risks for suicidal thoughts and acts (Psychiatric News,

December 1, 2000).

[Guest guest]

Murder Down Under

" .....Healy also testified this summer as an expert witness in a

case that resulted in a ruling by a New South Wales, Australia,

Supreme Court judge who determined that a 76-year-old man accused of

strangling his wife of 50 years did so because he was taking

sertraline.

" I am satisfied, " said Australian Supreme Court Justice Barry

O'Keefe, " that but for the Zoloft he had taken, he would not have

strangled his wife. " ................. "

http://pn.psychiatryonline.org/cgi/content/full/36/19/6?

maxtoshow= & HITS=10 & hits=10 & RESULTFORMAT= & searchid=1090095376066_1162 &

stored_search= & FIRSTINDEX=30 & minscore=5000 & journalcode=psychnews

SSRIs Called on Carpet Over Violence Claims

Jim ck

A flurry of recent legal activity has reignited the controversy

surrounding antidepressants' ability to cause aggressive or

violent

behavior. Among the cases is an Australian one in which an SSRI is

blamed for a man's fatal attack on his wife.

Psychoactive medications, and the drug companies that make them,

have been having a bad year in court. In fact, following several

recent legal rulings involving different psychoactive drugs, some

industry analysts are hinting they would not be surprised to see the

drugs' sales—and also their makers' chief

executives—a bit

depressed.

The most recent legal assault against a psychoactive medication came

in August when a Los Angeles law firm filed a complaint against

international drug conglomerate GlaxoKline PLC (GSK), maker of

the SSRI Paxil (paroxetine). The suit contends that not only was GSK

aware of data that indicated that the antidepressant can

be " addictive, " resulting in severe withdrawal reactions, but also

that the company concealed the " evidence, " failing to warn both

physicians and patients about the potential for the reactions.

The lawsuit, which seeks class-action status and unspecified

damages, was filed on behalf of 35 Americans from across the country

who claim that they suffered symptoms ranging from " electric-like

shocks " to suicidal thoughts after they stopped taking the drug. In

asking for damages, the suit alleges " fraud, deceit, negligence,

liability, and breach of warranty " by GSK.

Introduced in the U.S. in 1992, the drug is approved by the FDA for

the treatment of depression, obsessive-compulsive disorder, panic

disorder, and social anxiety disorder.

Wyoming Verdict on Appeal

The drug has been the center of legal controversy before. Earlier

this summer, a jury in U.S. District Court in Wyoming ordered GSK to

pay $6.4 million to the family of a man who killed his wife,

daughter, granddaughter, and then himself after taking two

paroxetine tablets in February 1998.

The wrongful death suit was filed in civil court on behalf of

surviving family members. Attorneys for the family successfully

argued that Schell had told people that he hallucinated when

he had previously taken paroxetine's chemical cousin, fluoxetine

(Eli Lilly and Co.'s Prozac), and that most likely the same had

occurred with the paroxetine he took on the day he shot his family

before turning the gun on himself.

Harvard psychiatrist Maltsberger, M.D., testified that the SSRI

manufacturers should warn prescribing physicians—in particular

family and primary care physicians like the one who prescribed

paroxetine for Schell—that SSRIs can cause a vulnerable minority

of

patients to experience akathesia and mania, which, he told the

court, can induce violence and even suicide.

Testimony was also introduced from a psychiatrist and outspoken

critic of SSRIs, Healy, M.D., director of the Sub-Department

of Psychological Medicine at the University of Wales College of

Medicine.

Healy testified that GSK's studies showed that, as early as 1989,

SSRIs (including paroxetine) can cause 1 in 4 healthy volunteers to

exhibit moderate to severe agitation, which, he said, could lead to

violent behavior. Healy added that his studies have since shown that

another SSRI, sertraline (Pfizer's Zoloft), when given to healthy

volunteers, made two subjects " acutely and seriously suicidal after

just being on the normal dose for two weeks. "

The drug company's attorneys argued that the medication had not

had

time to work and that it was Schell's out-of-control and

escalating

depression that caused his violent behavior.

The Wyoming civil court jury found that the drug was " 80 percent

responsible " for the deaths, with Schell being 20 percent

responsible, and awarded a total of $8 million in damages. GSK was

ordered to pay 80 percent of that total, or $6.4 million.

Spokespersons for GSK had previously indicated in press releases

that the company intended to appeal the verdict.

Murder Down Under

Healy also testified this summer as an expert witness in a case that

resulted in a ruling by a New South Wales, Australia, Supreme Court

judge who determined that a 76-year-old man accused of strangling

his wife of 50 years did so because he was taking sertraline.

" I am satisfied, " said Australian Supreme Court Justice Barry

O'Keefe, " that but for the Zoloft he had taken, he would not have

strangled his wife. "

The defendant in the Australian murder case, J. Hawkins, pled

guilty to the reduced charge of manslaughter on the grounds of

diminished responsibility. His defense attorney successfully argued

that the retired mechanic would not have killed his wife if he had

not taken 250 mg of sertraline, five times the recommended dose, the

morning of the murder.

The judge agreed, saying in his verbal ruling, " The killing was

totally out of character for the prisoner, inconsistent with the

loving, caring relationship which existed between him and his wife

and with their happy marriage of 50 years. "

In his testimony Hawkins hinted at possible hallucinations,

mirroring the Wyoming accounts. " I was looking at my wife, but I

wasn't seeing her face, " Hawkins told the court, describing the

moments in which he strangled her to death. He then attempted to

kill himself.

Spokespersons for Pfizer Inc. defended the drug, saying there is no

evidence to suggest that it has any side effects of aggression,

aggravation, or delusions. Ketelbey, M.D., senior medical

director for Pfizer in Australia, attempted to reassure both

patients and prescribing physicians of the drug's track record.

" Only one side—the defense—presented any data about the side

effects

of Zoloft, " Ketelbey said in a prepared statement following the

Australian judge's ruling, " and what occurred could hardly be

considered a rigorous examination of all the clinical and medical

data surrounding this medicine. While we are sympathetic to all

parties involved in this tragedy, the public health is best served

by accurate information about both this important medicine and the

dangers of untreated depression. "

A spokesperson for the Australian Therapeutic Goods Administration,

the equivalent of this country's FDA, said that this fall the

agency

would review data on sertraline and violent behavior. She told

Psychiatric News that the administration would consult regulatory

agencies and Pfizer about whether they are aware of other reports

attributing serious criminal behavior to the drug.

Do Data Speak for Themselves?

Anecdotal reports of violent and suicidal behavior have been tied to

fluoxetine, paroxetine, and sertraline for a number of years. At

this point, however, published data do not support the allegations.

Last year Arif Khan, M.D., and his colleagues published a study in

the April issue of Archives of General Psychiatry looking at suicide

risk in antidepressant clinical trials, using the Food and Drug

Administration database.

Khan wanted to know whether it was safe, and ethical, to include

placebos in clinical trials of antidepressants using actively

depressed patients. The review found that among nearly 20,000

participants in clinical trials of SSRIs, a total of 34 had

committed suicide, and 130 had attempted suicide. Khan also found

that the " rates of suicide and attempted suicide did not differ

significantly among the placebo and drug-treated groups. " He and his

colleagues concluded that it was, therefore, safe to include placebo

arms in antidepressant clinical trials.

The University of Wales's Healy has a different point of view.

Healy

has combined the data looked at by Khan with additional data

accessed through the Freedom of Information Act. Healy maintains

that his analysis—which is being prepared for publication—of

the

suicide and suicide attempts shows that a significant number of

events occurred during the placebo washout phase in the clinical

trials; when patients enter that phase, they may have been taking

another antidepressant, which must be washed out of their system

prior to the start of the drug trial. Healy noted that some suicides

or attempts occurred during the washout, as opposed to occurring

when a patient was continuously taking placebo or active trial drug.

" Now, when you strip those out and just look at the true placebo

suicides and suicidality versus the true SSRI suicides and

suicidality, " Healy told Psychiatric News, " there's an absolute

increase in suicides and suicidal acts on the active antidepressants

compared with placebo. "

Although Lilly, Pfizer, and GSK did not return phone calls from

Psychiatric News requesting input for this story, each has publicly

said previously that they believe the data show their products are

safe.

Revising Labeling

Current FDA-approved labeling of all three drugs includes general

warnings about the ability of SSRIs to activate mania and hypomania

and about suicide risk being inherent in depression, particularly

early in treatment.

Critics of the medications believe that the potential of the drugs

to cause violent and/or suicidal behavior is documented well enough

to cause the FDA to require stronger warnings to both physicians and

patients. However, the FDA has said that it sees " no reason to

revise the currently approved labeling at this time. "

The British Medicines Control Agency has indicated it is working

with the companies concerned to strengthen the current language

regarding risks for suicidal thoughts and acts (Psychiatric News,

December 1, 2000).

[Guest guest]

Murder Down Under

" .....Healy also testified this summer as an expert witness in a

case that resulted in a ruling by a New South Wales, Australia,

Supreme Court judge who determined that a 76-year-old man accused of

strangling his wife of 50 years did so because he was taking

sertraline.

" I am satisfied, " said Australian Supreme Court Justice Barry

O'Keefe, " that but for the Zoloft he had taken, he would not have

strangled his wife. " ................. "

http://pn.psychiatryonline.org/cgi/content/full/36/19/6?

maxtoshow= & HITS=10 & hits=10 & RESULTFORMAT= & searchid=1090095376066_1162 &

stored_search= & FIRSTINDEX=30 & minscore=5000 & journalcode=psychnews

SSRIs Called on Carpet Over Violence Claims

Jim ck

A flurry of recent legal activity has reignited the controversy

surrounding antidepressants' ability to cause aggressive or

violent

behavior. Among the cases is an Australian one in which an SSRI is

blamed for a man's fatal attack on his wife.

Psychoactive medications, and the drug companies that make them,

have been having a bad year in court. In fact, following several

recent legal rulings involving different psychoactive drugs, some

industry analysts are hinting they would not be surprised to see the

drugs' sales—and also their makers' chief

executives—a bit

depressed.

The most recent legal assault against a psychoactive medication came

in August when a Los Angeles law firm filed a complaint against

international drug conglomerate GlaxoKline PLC (GSK), maker of

the SSRI Paxil (paroxetine). The suit contends that not only was GSK

aware of data that indicated that the antidepressant can

be " addictive, " resulting in severe withdrawal reactions, but also

that the company concealed the " evidence, " failing to warn both

physicians and patients about the potential for the reactions.

The lawsuit, which seeks class-action status and unspecified

damages, was filed on behalf of 35 Americans from across the country

who claim that they suffered symptoms ranging from " electric-like

shocks " to suicidal thoughts after they stopped taking the drug. In

asking for damages, the suit alleges " fraud, deceit, negligence,

liability, and breach of warranty " by GSK.

Introduced in the U.S. in 1992, the drug is approved by the FDA for

the treatment of depression, obsessive-compulsive disorder, panic

disorder, and social anxiety disorder.

Wyoming Verdict on Appeal

The drug has been the center of legal controversy before. Earlier

this summer, a jury in U.S. District Court in Wyoming ordered GSK to

pay $6.4 million to the family of a man who killed his wife,

daughter, granddaughter, and then himself after taking two

paroxetine tablets in February 1998.

The wrongful death suit was filed in civil court on behalf of

surviving family members. Attorneys for the family successfully

argued that Schell had told people that he hallucinated when

he had previously taken paroxetine's chemical cousin, fluoxetine

(Eli Lilly and Co.'s Prozac), and that most likely the same had

occurred with the paroxetine he took on the day he shot his family

before turning the gun on himself.

Harvard psychiatrist Maltsberger, M.D., testified that the SSRI

manufacturers should warn prescribing physicians—in particular

family and primary care physicians like the one who prescribed

paroxetine for Schell—that SSRIs can cause a vulnerable minority

of

patients to experience akathesia and mania, which, he told the

court, can induce violence and even suicide.

Testimony was also introduced from a psychiatrist and outspoken

critic of SSRIs, Healy, M.D., director of the Sub-Department

of Psychological Medicine at the University of Wales College of

Medicine.

Healy testified that GSK's studies showed that, as early as 1989,

SSRIs (including paroxetine) can cause 1 in 4 healthy volunteers to

exhibit moderate to severe agitation, which, he said, could lead to

violent behavior. Healy added that his studies have since shown that

another SSRI, sertraline (Pfizer's Zoloft), when given to healthy

volunteers, made two subjects " acutely and seriously suicidal after

just being on the normal dose for two weeks. "

The drug company's attorneys argued that the medication had not

had

time to work and that it was Schell's out-of-control and

escalating

depression that caused his violent behavior.

The Wyoming civil court jury found that the drug was " 80 percent

responsible " for the deaths, with Schell being 20 percent

responsible, and awarded a total of $8 million in damages. GSK was

ordered to pay 80 percent of that total, or $6.4 million.

Spokespersons for GSK had previously indicated in press releases

that the company intended to appeal the verdict.

Murder Down Under

Healy also testified this summer as an expert witness in a case that

resulted in a ruling by a New South Wales, Australia, Supreme Court

judge who determined that a 76-year-old man accused of strangling

his wife of 50 years did so because he was taking sertraline.

" I am satisfied, " said Australian Supreme Court Justice Barry

O'Keefe, " that but for the Zoloft he had taken, he would not have

strangled his wife. "

The defendant in the Australian murder case, J. Hawkins, pled

guilty to the reduced charge of manslaughter on the grounds of

diminished responsibility. His defense attorney successfully argued

that the retired mechanic would not have killed his wife if he had

not taken 250 mg of sertraline, five times the recommended dose, the

morning of the murder.

The judge agreed, saying in his verbal ruling, " The killing was

totally out of character for the prisoner, inconsistent with the

loving, caring relationship which existed between him and his wife

and with their happy marriage of 50 years. "

In his testimony Hawkins hinted at possible hallucinations,

mirroring the Wyoming accounts. " I was looking at my wife, but I

wasn't seeing her face, " Hawkins told the court, describing the

moments in which he strangled her to death. He then attempted to

kill himself.

Spokespersons for Pfizer Inc. defended the drug, saying there is no

evidence to suggest that it has any side effects of aggression,

aggravation, or delusions. Ketelbey, M.D., senior medical

director for Pfizer in Australia, attempted to reassure both

patients and prescribing physicians of the drug's track record.

" Only one side—the defense—presented any data about the side

effects

of Zoloft, " Ketelbey said in a prepared statement following the

Australian judge's ruling, " and what occurred could hardly be

considered a rigorous examination of all the clinical and medical

data surrounding this medicine. While we are sympathetic to all

parties involved in this tragedy, the public health is best served

by accurate information about both this important medicine and the

dangers of untreated depression. "

A spokesperson for the Australian Therapeutic Goods Administration,

the equivalent of this country's FDA, said that this fall the

agency

would review data on sertraline and violent behavior. She told

Psychiatric News that the administration would consult regulatory

agencies and Pfizer about whether they are aware of other reports

attributing serious criminal behavior to the drug.

Do Data Speak for Themselves?

Anecdotal reports of violent and suicidal behavior have been tied to

fluoxetine, paroxetine, and sertraline for a number of years. At

this point, however, published data do not support the allegations.

Last year Arif Khan, M.D., and his colleagues published a study in

the April issue of Archives of General Psychiatry looking at suicide

risk in antidepressant clinical trials, using the Food and Drug

Administration database.

Khan wanted to know whether it was safe, and ethical, to include

placebos in clinical trials of antidepressants using actively

depressed patients. The review found that among nearly 20,000

participants in clinical trials of SSRIs, a total of 34 had

committed suicide, and 130 had attempted suicide. Khan also found

that the " rates of suicide and attempted suicide did not differ

significantly among the placebo and drug-treated groups. " He and his

colleagues concluded that it was, therefore, safe to include placebo

arms in antidepressant clinical trials.

The University of Wales's Healy has a different point of view.

Healy

has combined the data looked at by Khan with additional data

accessed through the Freedom of Information Act. Healy maintains

that his analysis—which is being prepared for publication—of

the

suicide and suicide attempts shows that a significant number of

events occurred during the placebo washout phase in the clinical

trials; when patients enter that phase, they may have been taking

another antidepressant, which must be washed out of their system

prior to the start of the drug trial. Healy noted that some suicides

or attempts occurred during the washout, as opposed to occurring

when a patient was continuously taking placebo or active trial drug.

" Now, when you strip those out and just look at the true placebo

suicides and suicidality versus the true SSRI suicides and

suicidality, " Healy told Psychiatric News, " there's an absolute

increase in suicides and suicidal acts on the active antidepressants

compared with placebo. "

Although Lilly, Pfizer, and GSK did not return phone calls from

Psychiatric News requesting input for this story, each has publicly

said previously that they believe the data show their products are

safe.

Revising Labeling

Current FDA-approved labeling of all three drugs includes general

warnings about the ability of SSRIs to activate mania and hypomania

and about suicide risk being inherent in depression, particularly

early in treatment.

Critics of the medications believe that the potential of the drugs

to cause violent and/or suicidal behavior is documented well enough

to cause the FDA to require stronger warnings to both physicians and

patients. However, the FDA has said that it sees " no reason to

revise the currently approved labeling at this time. "

The British Medicines Control Agency has indicated it is working

with the companies concerned to strengthen the current language

regarding risks for suicidal thoughts and acts (Psychiatric News,

December 1, 2000).

[Guest guest]

Murder Down Under

" .....Healy also testified this summer as an expert witness in a

case that resulted in a ruling by a New South Wales, Australia,

Supreme Court judge who determined that a 76-year-old man accused of

strangling his wife of 50 years did so because he was taking

sertraline.

" I am satisfied, " said Australian Supreme Court Justice Barry

O'Keefe, " that but for the Zoloft he had taken, he would not have

strangled his wife. " ................. "

http://pn.psychiatryonline.org/cgi/content/full/36/19/6?

maxtoshow= & HITS=10 & hits=10 & RESULTFORMAT= & searchid=1090095376066_1162 &

stored_search= & FIRSTINDEX=30 & minscore=5000 & journalcode=psychnews

SSRIs Called on Carpet Over Violence Claims

Jim ck

A flurry of recent legal activity has reignited the controversy

surrounding antidepressants' ability to cause aggressive or

violent

behavior. Among the cases is an Australian one in which an SSRI is

blamed for a man's fatal attack on his wife.

Psychoactive medications, and the drug companies that make them,

have been having a bad year in court. In fact, following several

recent legal rulings involving different psychoactive drugs, some

industry analysts are hinting they would not be surprised to see the

drugs' sales—and also their makers' chief

executives—a bit

depressed.

The most recent legal assault against a psychoactive medication came

in August when a Los Angeles law firm filed a complaint against

international drug conglomerate GlaxoKline PLC (GSK), maker of

the SSRI Paxil (paroxetine). The suit contends that not only was GSK

aware of data that indicated that the antidepressant can

be " addictive, " resulting in severe withdrawal reactions, but also

that the company concealed the " evidence, " failing to warn both

physicians and patients about the potential for the reactions.

The lawsuit, which seeks class-action status and unspecified

damages, was filed on behalf of 35 Americans from across the country

who claim that they suffered symptoms ranging from " electric-like

shocks " to suicidal thoughts after they stopped taking the drug. In

asking for damages, the suit alleges " fraud, deceit, negligence,

liability, and breach of warranty " by GSK.

Introduced in the U.S. in 1992, the drug is approved by the FDA for

the treatment of depression, obsessive-compulsive disorder, panic

disorder, and social anxiety disorder.

Wyoming Verdict on Appeal

The drug has been the center of legal controversy before. Earlier

this summer, a jury in U.S. District Court in Wyoming ordered GSK to

pay $6.4 million to the family of a man who killed his wife,

daughter, granddaughter, and then himself after taking two

paroxetine tablets in February 1998.

The wrongful death suit was filed in civil court on behalf of

surviving family members. Attorneys for the family successfully

argued that Schell had told people that he hallucinated when

he had previously taken paroxetine's chemical cousin, fluoxetine

(Eli Lilly and Co.'s Prozac), and that most likely the same had

occurred with the paroxetine he took on the day he shot his family

before turning the gun on himself.

Harvard psychiatrist Maltsberger, M.D., testified that the SSRI

manufacturers should warn prescribing physicians—in particular

family and primary care physicians like the one who prescribed

paroxetine for Schell—that SSRIs can cause a vulnerable minority

of

patients to experience akathesia and mania, which, he told the

court, can induce violence and even suicide.

Testimony was also introduced from a psychiatrist and outspoken

critic of SSRIs, Healy, M.D., director of the Sub-Department

of Psychological Medicine at the University of Wales College of

Medicine.

Healy testified that GSK's studies showed that, as early as 1989,

SSRIs (including paroxetine) can cause 1 in 4 healthy volunteers to

exhibit moderate to severe agitation, which, he said, could lead to

violent behavior. Healy added that his studies have since shown that

another SSRI, sertraline (Pfizer's Zoloft), when given to healthy

volunteers, made two subjects " acutely and seriously suicidal after

just being on the normal dose for two weeks. "

The drug company's attorneys argued that the medication had not

had

time to work and that it was Schell's out-of-control and

escalating

depression that caused his violent behavior.

The Wyoming civil court jury found that the drug was " 80 percent

responsible " for the deaths, with Schell being 20 percent

responsible, and awarded a total of $8 million in damages. GSK was

ordered to pay 80 percent of that total, or $6.4 million.

Spokespersons for GSK had previously indicated in press releases

that the company intended to appeal the verdict.

Murder Down Under

Healy also testified this summer as an expert witness in a case that

resulted in a ruling by a New South Wales, Australia, Supreme Court

judge who determined that a 76-year-old man accused of strangling

his wife of 50 years did so because he was taking sertraline.

" I am satisfied, " said Australian Supreme Court Justice Barry

O'Keefe, " that but for the Zoloft he had taken, he would not have

strangled his wife. "

The defendant in the Australian murder case, J. Hawkins, pled

guilty to the reduced charge of manslaughter on the grounds of

diminished responsibility. His defense attorney successfully argued

that the retired mechanic would not have killed his wife if he had

not taken 250 mg of sertraline, five times the recommended dose, the

morning of the murder.

The judge agreed, saying in his verbal ruling, " The killing was

totally out of character for the prisoner, inconsistent with the

loving, caring relationship which existed between him and his wife

and with their happy marriage of 50 years. "

In his testimony Hawkins hinted at possible hallucinations,

mirroring the Wyoming accounts. " I was looking at my wife, but I

wasn't seeing her face, " Hawkins told the court, describing the

moments in which he strangled her to death. He then attempted to

kill himself.

Spokespersons for Pfizer Inc. defended the drug, saying there is no

evidence to suggest that it has any side effects of aggression,

aggravation, or delusions. Ketelbey, M.D., senior medical

director for Pfizer in Australia, attempted to reassure both

patients and prescribing physicians of the drug's track record.

" Only one side—the defense—presented any data about the side

effects

of Zoloft, " Ketelbey said in a prepared statement following the

Australian judge's ruling, " and what occurred could hardly be

considered a rigorous examination of all the clinical and medical

data surrounding this medicine. While we are sympathetic to all

parties involved in this tragedy, the public health is best served

by accurate information about both this important medicine and the

dangers of untreated depression. "

A spokesperson for the Australian Therapeutic Goods Administration,

the equivalent of this country's FDA, said that this fall the

agency

would review data on sertraline and violent behavior. She told

Psychiatric News that the administration would consult regulatory

agencies and Pfizer about whether they are aware of other reports

attributing serious criminal behavior to the drug.

Do Data Speak for Themselves?

Anecdotal reports of violent and suicidal behavior have been tied to

fluoxetine, paroxetine, and sertraline for a number of years. At

this point, however, published data do not support the allegations.

Last year Arif Khan, M.D., and his colleagues published a study in

the April issue of Archives of General Psychiatry looking at suicide

risk in antidepressant clinical trials, using the Food and Drug

Administration database.

Khan wanted to know whether it was safe, and ethical, to include

placebos in clinical trials of antidepressants using actively

depressed patients. The review found that among nearly 20,000

participants in clinical trials of SSRIs, a total of 34 had

committed suicide, and 130 had attempted suicide. Khan also found

that the " rates of suicide and attempted suicide did not differ

significantly among the placebo and drug-treated groups. " He and his

colleagues concluded that it was, therefore, safe to include placebo

arms in antidepressant clinical trials.

The University of Wales's Healy has a different point of view.

Healy

has combined the data looked at by Khan with additional data

accessed through the Freedom of Information Act. Healy maintains

that his analysis—which is being prepared for publication—of

the

suicide and suicide attempts shows that a significant number of

events occurred during the placebo washout phase in the clinical

trials; when patients enter that phase, they may have been taking

another antidepressant, which must be washed out of their system

prior to the start of the drug trial. Healy noted that some suicides

or attempts occurred during the washout, as opposed to occurring

when a patient was continuously taking placebo or active trial drug.

" Now, when you strip those out and just look at the true placebo

suicides and suicidality versus the true SSRI suicides and

suicidality, " Healy told Psychiatric News, " there's an absolute

increase in suicides and suicidal acts on the active antidepressants

compared with placebo. "

Although Lilly, Pfizer, and GSK did not return phone calls from

Psychiatric News requesting input for this story, each has publicly

said previously that they believe the data show their products are

safe.

Revising Labeling

Current FDA-approved labeling of all three drugs includes general

warnings about the ability of SSRIs to activate mania and hypomania

and about suicide risk being inherent in depression, particularly

early in treatment.

Critics of the medications believe that the potential of the drugs

to cause violent and/or suicidal behavior is documented well enough

to cause the FDA to require stronger warnings to both physicians and

patients. However, the FDA has said that it sees " no reason to

revise the currently approved labeling at this time. "

The British Medicines Control Agency has indicated it is working

with the companies concerned to strengthen the current language

regarding risks for suicidal thoughts and acts (Psychiatric News,

December 1, 2000).