Atypical Antipsychotics: Patient Safety Information

Study shows atypical antipsychotics pose a higher risk for cardiac arrest

The New York Times has reported that a recent study found atypical antipsychotics, which include the friendly family of Clozaril, Abilify, Risperdal, Zyprexa, and Seroquel (maybe Saphris soon), can increase a patient’s risk of dying from cardiac arrest twofold.

The study published in The New England Journal of Medicine also concluded that the risk of death from the psychotropic medications isn’t high. However, an editorial also published in the same issue “urged doctors to limit their prescribing of antipsychotic drugs, especially to children and elderly patients, who can be highly susceptible to the drugs’ side effects.”

A U.S. News & World Report article linked to the FDA’s atypical antipsychotics page for further patient information. If you’re on an atypical, I’d recommend reading each word in the patient safety info that applies to you. Proofreaders like me shouldn’t be the only ones tortured with reading all the fine print. *winks*

FDA: No link between Singulair and suicidal behavior

On Tuesday, the FDA announced that an investigation into Merck’s clinical trial data did not discover a link between Singulair (montelukast) and suicidal behavior. The investigation, which began 9 months ago, was prompted by a number of reported suicides, especially that of 15-year-old Cody Miller who took the drug and appeared to have no history of mood or behavioral problems. (It is worth noting here that Singulair “is the top-selling drug for people under 17 years old” and Merck’s biggest seller with annual sales of close to $4.5 billion.)

In attempt to assess Merck’s data better, the FDA also investigated AstraZeneca’s Accolate (zafirlukast) and Cornerstone Therapeutics’s Zyflo (zileuton). Although the FDA did imply that “the data were inadequate to draw a firm conclusion” and said that the clinical trials were not set up to observe any psychiatric behavior. Here are the data the FDA discovered during their review of these trials:

SingulairSingulair: 41 placebo-controlled trials that included 9,929 patients

  • Reports of suicidal thoughts: 1 (treated with Singulair)
  • Attempted suicides: None reported
  • Completed suicides: None reported

AccolateAccolate: 45 placebo-controlled trials that included 7,540 patients

  • Reports of suicidal thoughts: 1 (placebo group)
  • Attempted suicides: 1 (placebo group)
  • Completed suicides: None reported

ZyfloZyflo: 11 placebo-controlled trials (number of patients unknown)

  • Reports of suicidal thoughts: None reported
  • Attempted suicides: None reported
  • Completed suicides: None reported

Forgive me for being cynical but the data sounds fishy. I can’t pinpoint why but it does. The suicide numbers and patient involvement data seem to deviate some from the numbers listed in Merck’s PR issued last March. (I’m seeing 11,000+ patients vs. 9,929 patients.) Regardless of the clinical trial data, it appears that the FDA as of yet have not reviewed post-marketing data.

Scott Korn, a senior safety surveillance executive for Merck said in an article for Reuters:

“‘At the time we did not believe, and we still don’t think a link has been established’ between Singulair and the suicides.”

In the same article, Sanford Berstein analyst Tim Anderson had this to say about the possibility of the FDA finding a link:

“If the… safety review leads to a stern warning about behavioral changes in the Singulair label, this could frighten users of the drug or their parents and give Merck’s competitors ammunition to attack the brand.”

The Washington Post has Dr. David Weldon, director of the Allergy and Pulmonary Lab Services at Scott & White in College Station, Texas, on record saying that he had not “seen any increase in psychiatric problems with the drug but that some patients had complained of nightmares after starting on Singulair.” (Note: It appears that the closest conflict of interest Weldon would have here is that he served as a consultant and is honoraria for AstraZeneca.)

Dr. Rauno Joks, head of the SUNY Downstate division of allergy and immunology, made an interesting point in the Washington Post article:

“The physician really needs to review whether there are symptoms that have developed since patients started taking the medication, if there’s an underlying depression that was there before medication started.

Also, seasonal allergies in and of themselves can cause fatigue and lethargy, which makes it harder to assess, because those are some of the symptoms you have with depression.”

The FDA says they’ve completed analyses of submitted clinical trial data but their “safety review will continue” for several more months before they come to a concrete conclusion. For customer testimonials, check out medications.com that has over 2,300 people reporting side effects and askapatient.com that has an average 2.3 rating from 524 reviewers. The most commonly reported mood-related side effect on both of the sites is irritability.

Pittman, Zoloft, and akathisia revisited

Christopher PittmanI’ve written about Christopher Pittman, now 19, who confessed to shooting and killing his grandparents when he was on psych meds at the age of 12. He appealed for a Supreme Court hearing but was denied, CNN reported today. He — and his defenders — appealed on the grounds that his 30-year sentence was “excessive for someone that age” and that the dosage of his antidepressants at the time (200 mg) “sent his mind spinning out of control.” Pittman was tried as an adult and, his lawyers argue, “no other inmate in the United States is serving so severe a sentence for a crime committed at such an early age.”

In previous posts here and here, I’ve questioned the link between Zoloft and violence/rage. Pittman, in 2001, had been switched to Zoloft a few days before the murder of his grandparents. However, it sounds like there had been some emotional problems in Pittman’s life that may have given prosecutors a solid case:

At the time of the crime, the boy had bounced around homes for years, experiencing a half dozen family splits and divorces after his mother had twice abandoned him as a child. She has not been in Pittman’s life for years.

Joe Pittman, the boy’s father, raised Christopher Pittman and his sister for much of their lives, but the relationship between father and son deteriorated. A state psychologist later testified this was a “young man who’d had difficulty with the adults in his life.”

On November 28, 2001, Pittman was sent home early for fighting in school and sent to bed by the grandparents. The boy claimed his “Pop-Pop” also beat him with a belt as punishment.

South Carolina prosecutors may easily have set Pittman up as a disturbed young man, which he very well may have been. But there are indications that this disturbance transcended his emotional state into his mental health:

After threatening to harm himself and suffering other emotional incidents, the boy was diagnosed as clinically depressed. His lawyers said Pittman was then given Paxil, a mild antidepressant no longer recommended for those under 18.

Just days before [shooting his grandparents], a doctor had begun prescribing Zoloft, another antidepressant. The family contends the abrupt substitution of drugs caused a bad chemical reaction, triggering violent outbursts.

At trial, a parade of psychiatrists offered conflicting testimony on whether the boy’s emotional problems excused his criminal behavior. Prosecutors called the Zoloft defense a “smokescreen.”

Juror Steven Platt later told CNN the crime appeared deliberate. “It always seemed like the defense was grasping at straws,” he said. “Just because you take prescription medicine doesn’t mean you can’t be held accountable for your actions.”

Read the rest of this entry »

Brief update on Singulair-suicide link

Merck issued a press release today responding to the FDA’s investigation. Along with the standard "we didn’t know about this problem until after it the market" disclaimer, the PR mentioned:

In a cumulative analysis recently provided to the FDA of Merck’s randomized, double-blind, placebo-controlled clinical trials, which included over 11,000 adults and children in over 40 studies who were treated with SINGULAIR, there were no reports of suicidal thoughts or actions and no completed suicides in the patients who received SINGULAIR.

Additionally, in a cumulative analysis recently provided to the FDA of Merck’s randomized, double-blind, clinical trials that compared SINGULAIR with other active agents to treat asthma (which included over 3,900 adults and children who were treated with SINGULAIR and over 3,400 who were treated with other asthma therapies), there was 1 patient who attempted suicide who received SINGULAIR, and there were 3 patients who attempted suicide who received other asthma therapies (including inhaled corticosteroids and long-acting beta-agonists).  These studies were not designed to compare the rate of suicide in patients taking SINGULAIR with the rate of suicide in patients taking these other asthma agents.

Did Merck report that one suicidal attempt when compared to "other active agents to treat asthma"? It doesn’t say anything in their patient safety or prescribing information when I checked. Perhaps someone can find out whether they reported this in their clinical trials?

In the meantime, the Singulair section of medications.com is ablaze with parents who are now expressing concern over their children’s well-being on the drug. Apparently, issues have cropped up with the drug even before the FDA announced their investigation.

"Quetiapine comes from the root word 'quiet'"

[UPDATE: I had some funky issues with my table. It should be fixed now. Sorry about that.]

The first time I visited my psychiatrist for my initial evaluation, he gave me the option of choosing one of three medications: Seroquel, Lithium, or Lamictal. He handed me information about Seroquel and Lamictal. I did some research on both meds (lithium was out of the question because I don’t have time to get my blood checked constantly) and Lamictal sounded like a way better deal than Seroquel. I found mental health blog Furious Seasons (probably via The Trouble With Spikol) and read numerous posts on Seroquel’s adverse effects and all the good stuff AstraZeneca doesn’t tell anyone. From Philip Dawdy’s “Seroquel, The Bipolar Pill?” post, here’s what stood out to me:

“He told her that he didn’t think Seroquel worked benignly for patients and that the increased blood-sugar levels and cholesterol levels associated with its use were unacceptable to him. She broke out a recent paper which claimed that there were no metabolic syndrome problems with Seroquel.”

The post got me thinking. One of the materials I received from my psychiatrist was an article on how Seroquel seems to help the depressive part of bipolar disorder. He had a stack of these articles. My guess is not that he’s an overzealous reader of various newspapers but received the glowing article from – you got it! – a pharma rep. The article was taken from the August 2005 issue of Clinical Psychiatry News. (NOTE: I received the article in November 2006.)

Clinical Psychiatry News’ publication goals:

“Clinical Psychiatry News is an independent newspaper that provides the practicing psychiatrist with timely and relevant news and commentary about clinical developments in the field and about the impact of health care policy on the specialty and the physician’s practice.”

Good thing they didn’t say objectively.

I don’t know much about ClinPsych’s reputation and whether they are generally a good paper that reports things objectively. However, the article, “Atypical Quetiapine Appears Effective for Bipolar Depression,” reads like a press release. I’m not happy about receiving (practically) PR material from my doctor when trying to make an unbiased decision.

The article’s lede:

“The atypical antipsychotic quetiapine led to significantly greater reductions in bipolar depression than did placebo within the first week of treatment and throughout an 8-week randomized, controlled study of 511 patients, Andrew J. Cutler, M.D., said.”

Dr. Andrew CutlerDr. Cutler? Who IS Dr. Cutler? No research necessary; look no further than the article itself:

“The differences between the placebo group and each quetiapine group were significant at each weekly assessment, said Dr. Cutler of the University of South Florida, Tampa. He is a speaker and consultant for, and has received research grants from, the company that makes quetiapine: AstraZeneca.”

At least they disclosed his financial affiliations.

It is also worth noting that Dr. Cutler also founded a clinical research company, CORE Research, which runs many of the clinical trials that he’s involved in. CORE Research’s background details:

“CORE Research, Inc. is a private research company with three offices in the Central Florida area. CORE specializes in pharmaceutical research and psychopharmacology for mental illnesses such as Bipolar Disorder, Depression, Anxiety, Schizophrenia, Attention Deficit Disorder, and Insomnia.”

Private + Pharmaceutical research + Psychopharmacology = Funding from Big Pharma Companies

I sound like I’m touting some grand conspiracy theory. (OK, maybe I am.) CORE’s background bio makes the company sound objective and unaffiliated, which isn’t the case. If Dr. Cutler has “received research grants from” not only AstraZeneca, but other companies, it’s in his best interest to make sure that their pharmaceutical products turn out OK. Namely in the interest of AZ – remember: he’s a consultant for them.

How can I expect to make a decision about which medication to take (remember it’s between Lamictal and Seroquel now) based on promotional materials from pharm companies and – oh – an article touting the benefits of Seroquel with quotes only from the study’s lead author who is paid to say good things about the company’s products?

I didn’t.

Then how did I decide on Lamictal over Seroquel? Wikipedia‘s outline of each medication’s side effects, of course, in addition to other materials. (Don’t EVER overlook the Patient Safety Information of any medication. Unless you’re reading about the molecular structure – ignore that.)

Lamictal (lamotrigine) side effects Seroquel (quetiapine) side effects
Headaches Sedation
Insomnia Agitation
Insomnia Constipation
Major weight loss Memory problems (i.e. anterograde amnesia)
Blurred/double vision Headaches
Muscle aches Abnormal liver tests
Lack of coordination Dizziness
Sleepiness Upset stomach
Nausea Substantial weight gain
Vomiting Stuffy nose feeling
Rash (Stevens-Johnson syndrome) [uncommon in adults] Neuroleptic malignant syndrome [rare]
Binds to melanin-containing tissues (i.e. iris of the eye) Tardive dyskinesia [rare]
Diabetes [unclear]
Cataracts [possible]

Not that Lamictal’s side effects looked like a walk in the park, but considering that I’d already had awful trouble with weight gain on Paxil and Lexapro – nearly 50 lbs. – Seroquel was a serious no-go on my part. That and I don’t mind major weight loss from Lamictal. (Although I have been told Lamictal has no effect on weight.) Below is a copy of the article I received from my psychiatrist or you can just go and read the archived full text at Clinical Psychiatry News.

Quetiapine article