Seroquel, Weight Gain, And the Pursuit of GAD and Depression Indications

Jim Edwards at BNET dug through the Seroquel documents and found many instances of AZ employees noting that Seroquel causes weight gain. Yet the company seemed bent on keeping this information hidden. As I mentioned last week, this sure seems a lot like Zyprexa redux, except with more sex scandals and perhaps more buried data. I suggest that everyone head over to BNET and see the details.

Despite all the bad news, AZ is pressing onward with its application for FDA approval for Seroquel in both generalized anxiety disorder and depression. Yikes. I broke the story earlier this week about the "scientific literature" claiming that Seroquel worked better than Haldol in the treatment of schizophrenia, yet internal company data showed Haldol as superior to Seroquel in reducing schizophrenia symptoms. Between discrepant data, the apparent hiding of negative clinical trials and trying to keep doctors distracted from data indicating that Seroquel caused weight gain, I think that Seroquel's luck may have ran out -- my bet is that the FDA won't approve the drug for depression or GAD. But I've been wrong before; the FDA did approve Abilify as an add-on treatment for depression based on pretty flimsy evidence.

Son of Risperdal Beats Seroquel

Janssen, manufacturer of Invega (son of Risperdal) funded a study comparing Invega, Seroquel, and placebo in the treatment of schizophrenia. Results were as follows:

"After two weeks, those on Invega had a greater reduction in symptoms as measured by a standard test called Positive and Negative Syndrome Scale for Schizophrenia, or Panss. The test measures symptoms such as disorganized thoughts and uncontrolled hostility. The score for Invega patients declined 23.4 points, 17.1 points for Seroquel and 15 points for placebo, according to J&J."

By the way, note the rather paltry advantage of Seroquel in comparison with placebo. These results fit nicely into a pattern. A study published in the American Journal of Psychiatry in 2006 found that clearly, the best predictor of which antipsychotic would be shown superior in a head-to-head comparison was who funded the study. Also feel free to examine their table in which they point out the biases in these various comparative studies.

Pharma claims to spend bazillions of dollars on research -- but these studies aren't research in the classic sense, which is a scientific endeavor undertaken to gain knowledge. These are exercises in marketing -- set up a study with some sort of bias favoring your drug, then hurry and rush out the drug reps with low cut blouses and fistfuls of reprints of studies showing your drug is superior to the competition. Then, the competition retaliates by setting up a study in which their drug is set up to win due to some sort of biased design. And the cycle goes on and on and on. Pharma then counts these "studies" as research expenditures and waxes on about their dedication to developing lifesaving medications. As if these studies done purely for marketing purposes have anything to do with developing lifesaving medications.

Background on Invega:

• The Creativity Crisis Continues
• Invega: Can You Say 'Patent Extender'?

Zyprexa for Youth: What Marketing Plans?

As reported on Bloomberg, Pharmalot and Furious Seasons, an FDA official has overruled FDA reviewers to put Zyprexa on track for approval for treating adolescent schizophrenia and bipolar disorder.

Lilly claims it has no plans for a major marketing campaign. Yet given the glut of atypical antipsychotics, their frequent use among kids already, and the concerns associated with Zyprexa's side effects, Lilly will have to market aggressively in order to win scripts. Bloomberg also reported that Abilify and Seroquel may win FDA approval for the youth market before long and with Risperdal going generic soon, Lilly will either have to market their drug like hell (i.e., Operation Restore Confidence Part Two?) or accept a minor piece of the market. But perhaps they don't care - maybe the studies were just an attempt to generate good publicity and to extend the patent for six months, which was estimated to be worth a billion dollars in itself.

Danger Kitty

In the world of cat poop and schizophrenia, Stephany at Soulful Sepulcher has a post that is very interesting. Say WHA, you may be thinking, but you'll just have to read her post to find out. I suppose that as a lifelong cat owner, I can thank my lucky stars I didn't develop psychosis. Or something like that.

Grohol Slaps TAC Senselessly Silly

The Treatment Advocacy Center (TAC) recently posted that people with schizophrenia are 10 times more likely to be violent as compared to persons not suffering from schizophrenia. I quickly said "WHA?" That seemed so far detached from reality that I didn't even know where to start. So Marissa Miller had a nice analysis of their figures that pointed out a number of flaws in the analysis. Nice job, Marissa.

Then John Grohol stepped in and (BAM) slapped the TAC analysis silly. Absolutely senselessly silly. I won't even try to steal his thunder. Just go to Psych Central and you'll come away saying, "Those *@!@ at TAC!" Nice job slicing and dicing, Dr. Grohol! I'm always proud when a fellow psychologist throws the BS flag when needed.

Paternal Age, Schizophrenia, and Autism

A good chunk of studies have accumulated over the past few years (e.g., 1, 2, 3, 4, 5) that show a strong link between increasing paternal (father’s) age and risk of schizophrenia in children.

One researcher has described the link as follows:

We found that paternal age explained over a quarter of the risk for schizophrenia in the population. At the time, people were skeptical. But the findings have been replicated many times now, and not a single study has failed to find this strong relationship between father's age and the risk for schizophrenia. And at this point, other explanations for the relationship have been ruled out, including social factors in the family, prenatal care, and parental psychiatric ailments. There simply seems to be a relationship between paternal age and schizophrenia risk.

Wow – one quarter of the risk for schizophrenia explained by paternal age? I’ll admit that these types of studies are not my area of expertise, but from my review of some of these studies, I’m willing to buy that paternal age is a significant risk. These findings have indeed been replicated on numerous occasions.

One of the main researchers in the area, Dolores Malaspina (quoted above), has said that findings such as this should not discourage parents from having children at whatever age they choose. I am not in agreement – older parents should be made aware of the risk and make an informed decision.

Why the effect? Here’s what seems to be a decent explanation…

"Every cell division makes a copy of DNA," [researcher] Gavrilova says. "And the same thing happens with the next division and this final copy is of less quality. This can introduce a slight risk of error in the genetic material of the new sperm. You can call it a kind of copy error.

The longer a man ages, the greater the chance of sperm mutations that could lead to schizophrenia or other problems in offspring.

There is also research linking autism to older fathers. It appears that such information is not widely known. I was certainly not familiar with it until recently. Consider the trends in Western societies – fathers having children at older ages is likely leading to a decent sized increase in rates of schizophrenia, autism, and perhaps other problems as well. While this is excellent news if one is in the antipsychotic business, is this really good news for everyone else?

Shouldn't this information be more widely discussed?

Hat Tip: Just Noticeable Differences.