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 GlaxoSmithKline 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.
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 Donald 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 John 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, David 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.
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, David 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. William 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.
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.
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). ▪