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A new study released during the week of October 26, 2009, found that children on widely used psychiatric drugs can quickly gain an alarming amount of weight, with many put on nearly 20 pounds and become obese within just 11 weeks. “Sometimes this stuff just happens like an explosion. You can actually see them grow between appointments,” said Dr. Christopher Varley, a psychiatrist with Seattle Children’s Hospital who called the study “sobering.”

Weight gain is a known possible side effect of the anti-psychotic drugs which are prescribed for bipolar disorder and schizophrenia, but also increasingly for autism, attention deficit disorders and other behavior problems. The new study in mostly older children and teens suggests they may be more vulnerable to weight gain than adults. The study also linked some of these drugs with worrisome increases in blood fats including cholesterol, also seen in adults. Researchers tie these changes to weight gain and worry that both may make children more prone to heart problems in adulthood.

The research is the largest in children who had just started taking these medicines, and provides strong evidence suggesting the drugs, not something else, caused the side effects, said lead author Dr. Christoph Correll of North Shore-Long Island Jewish Health System in Glen Oaks, New York.  But because these drugs can reduce severe psychiatric symptoms in troubled children, “We’re a little bit between a rock and a hard place,” he said.

The authors of the study said their results show that children on the drugs should be closely monitored for weight gain and other side effects, and that when possible, other medicines should be tried first.

The study appears in the Journal of the American Medical Association. It involved 205 New York City-area children from 4 to 19 years old who had recently been prescribed one of the drugs; the average age was 14. Depending on which of four study drugs children used, they gained between about 10 and 20 pounds on average in almost 11 weeks; from 10% to 36%t became obese.

The drugs are Abilify, Risperdal, Seroquel and Zyprexa. Of the four, Seroquel and Zyprexa are not yet approved for children, and they had the worst effects on weight and cholesterol. However, a government advisory panel recently voted in favor of pediatric use for the two drugs, and the Food and Drug Administration often follows its advisers’ recommendations.

The drugs’ makers said these problems are known side effects but emphasized the drugs’ benefits in helping patients cope with serious mental illness.

The four drugs have been considered safer than older anti-psychotic drugs, which can cause sometimes permanent involuntary muscle twitches and tics. That has contributed to widespread use of the newer drugs, including for less severe behavior problems, a JAMA editorial said.

The number of children using these drugs has soared to more than 2 million annually, according to one estimate.

Doctors “should not stretch the boundaries” by prescribing the drugs for conditions they haven’t been proven to treat, said Varley, co-author of the editorial.

Why these drugs cause weight gain is uncertain but there’s some evidence that they increase appetite and they may affect how the body metabolizes sugar, said Jeff Bishop, a psychiatric pharmacist at the University of Illinois at Chicago. The drugs also can have a sedation effect that can make users less active.

During the week of September 7, 2009, Bloomberg.com revealed how Eli Lilly & Co. paid doctors in South Carolina for participating in a speakers’ program in exchange for prescribing the popular antipsychotic Zyprexa, and used golf bets to get more patients on the drug, according to notes by sales representatives.

During a golf game, one doctor agreed to start new patients on Zyprexa for each time a sales representative parred, or put the ball in a hole within a predetermined number of strokes, according to the notes. “I got four pars out of nine holes,” Lilly salesman Vince Sullivan said in a February 2002 note. “I said I wanted my four new patients.”

The notes were made public for the first time in a court hearing in South Carolina in the state’s lawsuit against Lilly over Zyprexa marketing practices. State officials contend Indianapolis-based Lilly marketed the drug for unapproved uses. A trial is set to begin Sept. 14.

South Carolina wants to recoup $200 million it contends it wrongfully spent on Zyprexa prescriptions as a result of Lilly’s push to get doctors to use the medicine, approved only for schizophrenia and bipolar disorder, for other ailments. The state also contends the drug maker withheld information about Zyprexa’s side effects, such as weight gain.

“Call notes are jottings written by sales reps and most reps make hundreds of notes monthly. They are not literal recitations of interactions with physicians,” Marni Lemons, a Lilly spokeswoman, said in telephone interview.

‘Out Of Context’

Lemons said the state’s lawyers took the notes “out of context” and “not one physician employed by the state of South Carolina has testified Lilly promoted off-label to them.”

The notes became public at a hearing in Spartanburg, South Carolina, on Lilly’s motion to have the state’s case thrown out prior to trial.

The state also is seeking a $5,000 fine for each Zyprexa prescription dating back to 1997, according to court filings. That could result in billions of dollars in fines, South Carolina’s lawyers say.

Lilly resolved a marketing investigation over Zyprexa in January with the U.S. Justice Department, promising to pay $1.42 billion, including about $362 million to more than 30 states. South Carolina opted not to join that settlement.

Alaska Settlement

The only trial of a state’s lawsuit ended in March 2008 with an out-of-court settlement in which Lilly agreed to pay Alaska $15 million.

Zyprexa, part of a class of medications called atypical antipsychotics, has been linked to excessive weight gain and diabetes. The lawsuits also claim Lilly failed to properly warn of Zyprexa’s side effects.

Lilly officials have denied the drug maker withheld information about Zyprexa’s side effects or improperly marketed the drug in South Carolina.

Lawyers for the state pointed to a sales note from Sullivan in which he tells another salesman to tie a doctor’s Zyprexa prescriptions to participation in a speakers’ program.

The company paid doctors and psychiatrists to address physician gatherings about the benefits of the antipsychotic. “If his numbers go up, maybe he can talk,” Sullivan said in the August 2001 note.

‘So Much Money’

A year later, Sullivan noted in sales records that he was pressing a doctor to write more Zyprexa prescriptions “because we’re paying him so much money” to participate in the speakers’ program, according to a call note made public.

Lilly also offered other inducements to doctors who prescribed Zyprexa, such as deep-sea fishing trips and Palm- Pilot devices, said John Simmons, a Columbia, South Carolina- based lawyer representing the state.

The sales notes show that many of those prescriptions were for unapproved or so-called off-label, uses, Simmons told Judge Roger Couch.

The FDA regulates what drugs can be used to treat specific ailments. Drug makers can only promote their medicines for FDA-specified illnesses.

Faced with the loss of patent protection for its Prozac antidepressant, Lilly officials pushed salespeople to market Zyprexa for a host of ailments, including depression, agitation and anger, Simmons said. The FDA hadn’t approved the drug for any of those uses, he added.

‘Diamond’

Company officials said in a memo that they were “betting the farm on Zyprexa” to replace Prozac, Simmons said.

In internal memos, Lilly officials used the word “diamond” as a code for talking about their Zyprexa off-label marketing campaign, he said.

He cited notes from visits with doctors in 2000 and 2001 where sales reps reported talking about older patients being treated with Zyprexa for agitation and declining mental acuity.

Simmons noted the drug maker already pleaded guilty to a criminal charge over its off-label promotion of Zyprexa for use with elderly patients.

In that plea, Lilly officials acknowledge that the company illegally pushed the drug’s off-label use by older patients from Sept. 1, 1999, to March 31, 2001.

The company also pushed primary-care physicians to use the antipsychotic medication on children, Simmons said. One of the notes indicated salespeople said the drug is ‘for kids whose parents have to shove the pills down their throat every day.”

‘In His Tea’

Another note shows that one doctor told Lilly he was prescribing Zyprexa for a 13-year-old, whose mother “puts it in his tea.”

Besides illegally marketing its drug, South Carolina officials contend Lilly violated the state’s unfair trade practices law by mishandling Zyprexa and unjustly enriched itself at the state’s expense.

Recent trail data from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer’s disease (CATIE-AD), reveals that elderly patients with Alzheimer’s disease who are treated with second-generation antipsychotics should be monitored closely for weight gain and lipid abnormalities.

The 36-week trial included 421 outpatients with Alzheimer’s disease who were treated for delusions and aggression. The average patient age was 78 years and 56 % were female. The findings are reported in the online edition of the American Journal of Psychiatry.

Seventy-two patients had no exposure to the study drugs, while the remaining subjects were assigned to treatment with Zyprexa (generic: olanzapine), Seroquel (generic: quetiapine), and Risperdal (generic: risperidone); and they could switch antipsychotic medication during the trial.

Female subjects gained an average of 0.14 pounds per week and body mass index increased by 0.03 per week, Dr. Lon S. Schneider at the University of Southern California, Los Angeles, and associates report. Changes in weight and BMI among males were not statistically significant.

The duration of antipsychotic use by women was significantly associated with weight gain. “The prevalence of significant weight gain was 10 percent, 17 percent, and 20 percent among patients with less than 12 weeks, 12 to 24 weeks, and greater than 24 weeks of use compared to 7 percent with no use,” Schneider’s team reports.

The effect on weight was significant for olanzapine and quetiapine, but less so for risperidone. Olanzapine was also significantly associated with increased waist circumference and decreased HDL cholesterol, the “good” cholesterol.

The metabolic changes that correlated with treatment with a second-generation antipsychotic drug were of similar magnitude to those observed in younger people with schizophrenia, the team notes.

The results from a previous analysis of the CATIE-AD data indicated that the drugs did not improve patients’ function and quality of life and did not decrease their need for care.

The worsening cardiac and metabolic risks among these Alzheimer’s patients are “particularly concerning,” they add, and likely explain the increased risk of mortality seen with these drugs.