More al-Qaida sleeper cells in U.S.? More wolf calls?

“Government agents have recently uncovered numerous calls from hard-to-track prepaid cell phones, Internet-based phone service, prepaid phone cards and public pay phones in the United States to known al-Qaida locations overseas, federal officials said. The calls are one piece of a growing body of evidence pointing to the presence of suspected members of terrorist sleeper cells operating on U.S. soil, and a growing sophistication on their part to keep their communications secret, the officials said.” MSNBC

A busy summer…

Ruling Roils Death Penalty Cases: “…(T)rying to untangle the consequences of the Supreme Court’s decision in Ring v. Arizona, which said juries rather than judges must make the crucial factual determinations that support the death penalty, (has made for a busy summer for) courts and legislatures in the nine states where juries do not make such findings, or render only advisory verdicts…” NY Times

What They Were Thinking

[City Lights, 1955]

City Lights, 1955. Lawrence Ferlinghetti (on the right, with, from left, Bob Donlin, Neal Cassady, Allen Ginsberg, and Robert LaVigne) recalls, ” When the picture was taken, I was thinking, ‘Are these the best minds of our generation?’ Howl starts with that phrase. I’d say it was a bit of a satirical question. I am the only one in the picture still alive, because I work out all the time. They didn’t work out except raising the elbow or rolling joints. I wasn’t part of the Beat Generation at all. I was really the last bohemian…” NY Times Magazine [Doesn’t it look as if the sign saying “Books” is a thought balloon emanating from LaVigne’s head, by the way? — FmH]

Dispatch from the Frontlines of the Psychopharmaceutical Wars:

FDA Issues Approvable Letter For Abilify. Another new ‘atypical’ antipsychotic medication reaches the marketplace; ‘Abilify’ is its brand name, and aripiprazole its generic moniker. The new generation of ‘atypical’ antipsychotics represents a revolution in increased tolerability and efficacy as compared to the older, ‘typical’ or first-generation antipsychotics. For psychiatrists like myself who treat psychotic illnesses such as schizophrenia, this is as exciting as the explosion in antidepressant development was a decade before. You don’t hear as much about this revolution because there is virtually no public constituency for schizophrenia. However, although you don’t think you have had much contact with the disease because those affected are largely socially shunned and segregated in a manner quite different from depressed patients (no TV ads for antipsychotics forthcoming!), you probably have had at least some indirect contact with its consequences given that it affects 1-3% of the population overall. So I think it’s worth my while wriitng about this development for a general audience of interested souls.

First, there’s its brand name. ‘Abilify’, although mercifully bucking the recent trend for new psychiatric medications to have a ‘z’, a ‘q’ or an ‘x’ in their name, is an extremely silly name, IMHO, and some Bristol-Myers Squibb representatives gearing up to market it to whom I recently spoke agree. [I hope there are no consequences for their disloyalty if any of their corporate superiors read this. — FmH]  We joked about the estimated $1 million fee some agency got to develop a name for this product. I offered the company that, from my vantage point in the psychiatric marketplace [yes, as FmH readers know, you should make no mistake about the fact that it is a marketplace!], I would create advantageous product names for half what they would pay anyone else, but for some reason they haven’t taken me up on my offer.

In any case, from my reading so far, aripiprazole (I try not to use brand names, as a matter of fact) does not seem a massive therapeutic advance over the other ‘atypical’ or ‘second-generation antipsychotics we have available already — clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa &mdash ahhh, there’s that ‘x’ and that ‘z’!), quetiapine (Seroquel) and ziprasidone (Geodon). Predictably, sales efforts will soon begin to jockey for a share of the antipsychotic ‘market’ by spinning the clinical studies (often funded by Bristol-Myers Squibb money) to claim more rapid onset, better response, or improved tolerability. Even the explanations of mechanisms of action for these new molecules are ‘spins’, since the CNS is largely a black box and the molecular actions of these medications are opaque to us. (For those of you who are curious, what I’ve read so far indicates that while, like other atypical antipsychotics, aripiprazole has combined postsynaptic dopamine and serotonin activity, it is also supposed to be a presynaptic dopamine autoreceptor agonist. It remains to see if it is; if that is as distinct from the other atypicals as it is made out to be; and, if it is, how much of a contributor to its effectiveness that might be…)

How useful it is to me and other psychiatrists treating psychotic illnesses, other than those who accept funding from Bristol-Myers Squibb and have already reached their conclusions [grin], will only be clear over time. I may not begin to prescribe it until its track record is better-defined. As a hospital-based psychiatrist who sees patients who have ‘fallen apart’ in the community, I have the following unique opportunity to gauge its efficacy and tolerability quite rapidly, as a matter of fact. Every time a new antipsychotic medication emerges, there is a rush of psychiatrists who adopt it immediately and even take previously stable patients off their existing stabilizing medications in the interest of using the newest and greatest thing. (Being cynical, I assume these are the practitioners who get most of their current ‘continuing medical education’ from manufacturers’ representatives or drug-company-funded symposia, rather than reading independent refereed medical journals and being able to read betwen the lines…) This phenomenon often prompts an epidemic of fresh relapses among patients with major mental illnesses, and the extent to which I start to see admissions of patients who fell apart after being switched to aripiprazole will be one of my indicators of whether it seems to be a worthwhile medication.

The magnitude of that phenomenon when the previous-but-one new antipsychotic, quetiapine (Seroquel), was introduced several years ago has made me avoid that drug in most instances, much to the chagrin of the hardworking manufacturers’ representatives trying to persuade me to use more of it. (The drug companies these days have detailed databases of exactly how many prescriptions of their products, and their competitors’, I prescribe every month. I’d love to find a way to fight a battle about this fact on the privacy front — mine or my patients’…). Quetiapine was a particularly egregious case in point, because it was marketed largely around how superior it is in reducing side effects. True, true; it is much more tolerable, but it is probably in that class of ‘white elephant’ drugs which don’t produce side effects because… well, because they largely don’t produce any effects at all, including therapeutic ones! Actually, quetiapine is a pretty good sedative, but that’s different from having antipsychotic activity. I’m noticing a small number of psychiatrists are starting to notice that ‘the emperor has no clothes’ and question the consensus by writing about its lack of efficacy in major psychotic conditions. The company’s response is to say that they just haven’t been using high enough doses.

What we really need by way of the next advance in antipsychotic psychopharmacology is a long-acting injectible atypical antipsychotic. Many patients who are too disorganized to take daily medication, or who are so dangerous when they are off medication that they are under court compulsion to take it (unwillingly), benefit from receiving their antipsychotic treatment in the form of a deep intramuscular injection of a “depot” preparation of a medication whose effect last between ten and thirty days before another injection is necessary. So far, however, the only medications available in such depot preparations in North America are haloperidol (Haldol) and fluphenazine (Prolixin), both of which are first-generation antipsychotics with the full gamut of undesireable side effects which one would like to spare one’s patients, particularly the uncomprehending ones who have not consented willingly to such a price for their stability. Several European countries have a depot version of risperidone, but it is probably several years off in the US, and olanzapine or ziprasidone would be more preferable still.

Hoping these dispatches from the war zone are of interest; I certainly enjoy venting my spleen about my own profession! So, if anyone is interested, I’ll keep you posted on aripiprazole.