According to a survey published by the Commonwealth Fund and Social Science Research Solutions, a third of Americans reported feelings of stress, anxiety, and sadness that difficult to manage on their own. Researchers posit that the lack of universal health care coverage, financial problems, and the government’s pandemic response has impacted the mental health of Americans in a negative manner.

The FDA has approved a nasal spray called Spravato to treat suicidal patients. The drug was approved for those with treatment-resistant depression last year, but has also shown promise to reduce symptoms in suicidal patients in conjunction with therapy and other antidepressants. The drug, while FDA approved, is only administered by a health care provider and is not approved for home use.

Atypical Antipsychotics: Patient Safety Information

These documents are all in PDF form. You will need Adobe Acrobat Reader to view them. Download Adobe Acrobat here.

• Aripiprazole (Abilify)

• Clozapine (Clozaril)

• Olanzapine (Zyprexa)

• Olanzapine-Fluoxetine (Symbyax)

• Quetiapine (Seroquel)

• Risperidone (Risperdal)

• Ziprasidone (Geodon)

If you prefer, you can view the Patient Safety Information in HTML at the official Food & Drug Administration website.

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:

Singulair: 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

Accolate: 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

Zyflo: 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.

FDA: Doctors don't disclose conflicts of interest? We don't really care

According to a NYTimes article, government investigators have reported that the FDA doesn’t seem to care much about the financial disclosure of doctors who participated in clinical trials of medication and diagnostic devices. Then get this:

Moreover, the investigators say, agency officials told them that trying to protect patients from such conflicts was not worth the effort. (Despite the fact that the FDA’s rules require it.)

The article goes on to say that in 42 percent of clinical trials, the FDA did not receive financial disclosure forms that might report conflicts of interest and never followed up on them. In 31 percent of the trials in which the forms were received, “agency reviewers did not document that they looked at the information.” And then, in 20 percent of the cases in which doctors disclosed significant financial conflicts—”neither the FDA nor the sponsoring companies took any action to deal with the conflicts.”

Apparently, the NIH has been investigated for the same thing and government investigators came to the same conclusion as in the FDA case.

Loose Screws Mental Health News

• Postpartum Progress reports that the Melanie Blocker Stokes MOTHERS Act bill did not pass. Spreading lies like this did not help.

• The FDA recently approved Stavzor, a valproic acid delayed release capsule, for the treatment of bipolar disorder, seizures, and migraine headaches. Wow. That’s covering the gamut. The drug looks like it’ll be competing directly with the Depakote brand.

The mastermind behind Stavzor is Noven Pharmaceuticals (in conjunction with Banner Pharmacaps Inc.). The new “small, easy-to-swallow soft gel capsule” is available in three strengths: 125, 250, and 500 mgs. The pills are are “up to 40% smaller than han Depakote® and Depakote ER® tablets at the 500 mg dosage strength.” From Noven’s PR:

Stavzor is approved for the treatment of manic episodes associated with bipolar disorder, as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures, and for prophylaxis of migraine headaches.

The drug will hit the market in mid to late August.

• A recent AP article notes that more than 22,000 veterans contacted the veterans portion of The National Suicide Prevention Lifeline hotline since its inception last July. The government reports that the hotline support has helped to prevent more than 1200 people from committing suicide. The Veterans Administration (VA) estimates that 6500 veterans commit suicide annually. In light of recent news regarding the increase in Marine suicides, the effectiveness of the suicide hotline is offers significant promise.

The hotline receives an average 250 calls each day from veterans that have fought in Iraq, Vietnam, and Afghanistan.

The issue of soldiers with mental illness has recently come to light with studies showing that 1 in 5 soldiers returning from Iraq and Afghanistan have shown symptoms of post-traumatic stress disorder. The issue of the high suicides rate has been a high priority of the VA since mental health director Ira Katz tried to hide the significant number of suicides committed by veterans.

The National Suicide Prevention Lifeline is available 24 hours a day by calling 800-273-TALK (8255); veterans should press “1” after being connected.

• Psychologists are now saying that hitting and yelling at children is causing an increase in mental illness, which has manifested in ages as young as 3 years old. News.com.au reports that 1 in 7 children are affected by a mental disorder.

“We have seen a 60 per cent increase in demand for our child anxiety classes in the past six months,” said [Dr. Kimberley O’Brien, of the Quirky Kids Clinic at Woollahra in Sydney].

It sounds more like the article is speaking of children who are exposed to constant physical and emotional abuse. If that’s the case, shouldn’t there rather be an increase in parenting properly classes?

• Finally, a bit of sad news: police in Connecticut report than 10-year-old killed herself apparently by hanging. Police do not believe that foul play was involved. I can’t imagine being 10 and feeling suicidal. It was tough enough at 14.

John Grohol interviews Wyeth's VP of Medical Affairs on Pristiq

Dr. Grohol interviewed Dr. Phil Ninan, Wyeth’s VP of Medical Affairs on Pristiq, its efficacy, and surrounding issues. It was quite an interesting interview (and long) but here are some highlights that I chose to comment on. I’ll be making some comments in between Dr. Ninan’s answers due to the extensive length. Some parts of the answers have been truncated.

Pittman, Zoloft, and akathisia revisited

I’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.”

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.

Singulair and Suicidal Behavior

In a particularly odd link, the FDA is looking into Singulair, the asthma and allergy drug and its correlation with suicidal behavior. I’ve taken Singulair in the past and not once did it ever occur to me to think about an allergy medication being linked to suicidal behavior. The FDA also says that it could cause mood and behavior changes. The situation that alerted the FDA to this possibility is the story of 15-year-old Cody Miller who killed himself 17 days after switching from allergy medication Allegra to Singulair. Miller’s mother, Kate, approached his medication switch with extreme caution and informed herself of the possible side effects:

She checked the Merck website and the information sheet she got from the pharmacist on Singulair and found no red flags, so they were stumped when Cody started acting out of character.

I have to hand it to Merck: Once the Millers reported Cody’s death, they immediately updated Singulair’s warnings to include suicidal thoughts and actions. However, Cody died on August 4, 2007. Merck updated their information two months later. As of February 29, 2008, the FDA still hadn’t taken any action. Despite the updated warnings, however, doctors and pharmacists were unaware of the new information.

The Singulair website carries the updated side effects, but you have to search it out in the patient information PDF on the fourth of five pages.

If you check with the FDA, you’ll find nothing. That’s because they admit they haven’t updated their website on Singulair since 2001.

According to the FDA’s MedWatch safety information, they have only begun their investigation today. They say it will take 9 months for them to “complete their investigation.” We may not hear of the FDA’s conclusions until early 2009. If this is a single, isolated incident, the FDA may just say the results are inconclusive and allow Merck rip the warning off their patient safety information. It is also important to note, however, that Singulair has also been linked to depression and anxiety.