bookofjoe

BehindTheMedspeak: Ketamine for depression? Episode 2

Neely Tucker, in her front-page article in today's Washington Post Style section, wrote as good a piece on the subject as you're likely to ever read.

I must admit that I was put off by her first few paragraphs, which seemed far too flighty for a serious story, but once she got down to business, the background and setting for what may be a huge breakthrough in psychiatric treatment was beautifully laid out.

Here's the Post article in its entirety.

Plumbing the Depths Of Depression

Scientists hope a new tool will tap into the source of the blues

Ketamine, sweet ketamine, answer to our glutamatergic dreams. In the long November night of the soul, in the ever-dark downpour of depression, it turns out that there might be a better umbrella than Prozac and Zoloft and Paxil and their serotonin-loving ilk.

Of course, when it comes to antidepressants, nobody really knows anything, anyway, so why not go with ketamine, a mild hallucinogen known to club freaks as Special K?

Yes, yes, break out the male Wistar rats and the injection needles — researchers at the National Institute of Mental Health announced a study recently in which 18 chronically depressed patients infused with low dosages of ketamine improved within two hours. Seventy-one percent improved within a day, and nearly 30 percent were depression-free by that time. In 24 hours! These were people who had been dealing with depression from three to 47 years. They had failed to respond to just about every drug on the market.

Most of them stayed depression-free for up to a week.

Chronic depression, one of the most common, debilitating diseases known to mankind, blown away like a flower petal on a passing breeze.

Is it not the modern nirvana, the utopia of a neurotic generation, the idea that the demons lurking in the nether regions of the cerebral cortex could just.... evaporate? Reigning there in the wet muck of the Freudian dark, the gargoyles of the mind took ketamine like a hit of kryptonite.

Doesn't it make Prozac and friends look like punks? The subsequent news stories focused on the speed — antidepressants generally take two weeks or longer to work — but the true breakthrough, scientists say, is that ketamine seems to do something entirely new. It focuses on glutamate, a chemical neurotransmitter that is involved in electrical flow among brain cells. It has not been targeted by any other antidepressant medication.

Think of depression as a leaky water faucet in the kitchen of the mind. Prozac and friends start working on the problem back at the water plant and, in about half of the cases, eventually find the problem.

In this trial, glutamate (and the "glutamatergic system") was shown to be a wrench-toting plumber who makes house calls. It got right to the problem.

"It's not quite the director of the orchestra, but it's involved with many other systems in the brain than other antidepressants," said Carlos A. Zarate Jr., chief of the mood disorders research unit at NIMH, and lead author of the study.

"It's early, but this is exciting because this gives us a new target, and it's a heck of a first move on it," said J. Raymond DePaulo Jr., chief of the Department of Psychiatry at Johns Hopkins School of Medicine and one of the nation's preeminent researchers on depression. He was not involved in the ketamine trials. "This is working on.... a different set of chemicals. It says the malfunction may be in several different parts of the brain. Ketamine has problems with potential negative effects, but we could create 100 drugs to hit this target of glutamate."

If, you know, that is where the demon actually resides.

Depression: the Jersey dump fire of the mind, being stuck in the urinal of a Charles Bukowski drinking binge, a wet January locked in a closet with Edgar Allan Poe (whose original tombstone read, "Here, at last, he is happy").

It has been documented in various guises — mania, melancholy, schizophrenia, fatalism, despair, suicide — since man first took twig to papyrus. It has been regarded as a moral weakness, a sin, evidence of a flawed mind or the required companion to artistic genius. It uses the normal if unhappy thought patterns of sadness, grief, regret, fear and anxiety to scorch the psyche. It has been found in all cultures in all centuries. You think it is alienation, a postmodern creation of the European industrial age, and then you find out that rural Sri Lanka has the world's highest rate of suicide.

The World Health Organization estimates that 121 million people on the planet currently meet the criteria for clinical depression. These are long-lasting loss of energy, patterns of negative thoughts, inability to concentrate, suicidal ideation, insomnia and so on. There is no test, as there is for diabetes or a brain tumor. There is no clear marker separating, say, natural grief and the medical condition.

It's more of a feeling that goes out of control. It's the difference between waiting for the sun to come up, which is sadness, and the knowledge that the sun will never shine again, which is depression.

Wallace Stevens, "The Plain Sense of Things":

It is difficult even to choose the adjective
For this blank cold, this sadness without cause.
The great structure has become a minor house.
No turban walks across the lessened floors.
The greenhouse never so badly needed paint.

The priest in Ecclesiastes:

"I applied my heart to know wisdom, and to know madness and folly. I perceived that this also was a chasing after wind. For in much wisdom is much grief; and he who increases knowledge increases sorrow."

Playwright Eugene Ionesco:

"No society has been able to abolish human sadness, no political system can deliver us from the pain of living, from our fear of death, our thirst for the absolute. It is the human condition that directs the social condition, not vice versa."

The true genius of the disease, of course, is that it is a cognitive disorder that makes clear thinking impossible — and yet requires insightful self-analysis in order to report the problem to a physician. You have to admit that is pretty ingenious.

Freud revolutionized the psychiatric field and the study of depression with his study of dreams, the taxonomy of id, ego, superego and the unresolved formulations of childhood trauma. Also, sex. You've got Jung, of course, and later the persuasive theory of Aaron T. Beck, the father of cognitive psychotherapy, who argues that depression twists the thinking process into increasingly negative avenues that repeat, over and over again.

And, about the same time as the Beatles, you had scientists voicing the theory that little chemicals ran around in our brains and made us do things that we'd rather not, Freud be damned. This was of great help to the novels of Kurt Vonnegut if nothing else. Brain biology: being utterly unable to get out of bed, running into the yard pronouncing yourself to be the risen Christ or pulling a shotgun out of the hall closet and looking down the barrel. You could take a pill, man. You could still be just as repressed as you ever were, with your mother who had beaten you with a curtain rod, but you just didn't care so much.

Wasn't that great?

It was like pulling a centuries-old dragon into daylight, where you found out it liked fresh hay and a nice barn. The beast could be tamed.

It happened like this: Doctors studying high blood pressure, or tuberculosis, discovered the medications they were using alleviated (or caused) great changes in their patient's moods. One of the main researchers was Rockville's own Julius Axelrod, who spent most of the 1960s learning how a neurotransmitter named noradrenaline works in the brain. (A scientist at the NIH, he won the Nobel Prize in 1970.)

His big idea was something called the catecholamine hypothesis, and it continues to the granddaddy of all psycho-pharmacology.

The thrust of his studies was the role of norepinephrine, a tiny messenger that goes between one neuron in the brain and the next, in depression. It turns out that a lack of that little messenger in the synapses, the spaces between neurons, tends to result in depression, because it can't tell the next neuron to slow down in whatever it is doing. So that neuron has a tiny crash, a little molecular runaway train, and that results in depression.

The first round of medications focused on norepinephrine, and the next generation focused on another messenger called serotonin. That's what Prozac and friends target -- they're called selective serotonin reuptake inhibitors, because they prevent the serotonin from being sucked back ("reuptaking") into the first neuron, and thus keeps them out there in the happy synapses, which results in a sort of mental sunshine.

Got that?

Of course, no one knows why that works, save for a general analogy that when any machine doesn't work well, it starts to fall apart.

Genetics plays a part in depression, too, as it clearly runs in families — but there is no single gene responsible, geneticists say. Exercise alleviates some measures of depression. Light therapy in winter. Reducing stress. Manic depressives — a different category of illness — respond more to lithium. Psychotics, the most severe form of mental illness, respond to still other drugs.

"Everyone is aware that we don't treat depression that well," says Peter D. Kramer, author of "Listening to Prozac" and clinical professor of psychiatry and human behavior at Brown University. "Prozac wasn't effective at more major depressions, but only with more minor forms of mood disorder. I think the field is very much waiting for the next breakthrough. We'd like to have a few more arrows in the quiver."

No kidding, says Cheryl Murphy, a Las Vegas woman who, at 60, has tried to commit suicide five times. She has a daughter and granddaughter who are bipolar. She says she'll be lucky if those two live another 10 years before they succeed in killing themselves. She describes depression, in a telephone interview, as "having your kid's funeral planned in your mind."

Here's her trip through the back aisles of the pharmacy:

"I was on Zoloft first, for years. I was doing fine. Then I decided I was doing so well I didn't need it. When I tried to go back on it, it didn't work. I tried Prozac, and I wanted to kill everybody. It was like drinking tequila. I tried Wellbutrin, Effexor, numerous others. I'm on Neurontin now. It works more for anxiety than it does for the depression, but it keeps me from going off the deep end."

Now there's this target of glutamate, coming in the form of ketamine. It's a cousin of PCP, though, and is mainly used as an anesthetic for pets — hence one of its nicknames, "cat Valium." People sometimes break into vet clinics to get it, for use as a club drug.

So no one thinks your family doc is going to be writing you a script for an orange bottle of ketamine anytime soon, but the research is continuing. Zarate, the NIMH director, said the next step will be to develop counter-medications to mask ketamine's side effects, and then on to other medicines that target glutamate. We're talking about years here.

Kay Redfield Jamison, a Washington-based psychologist and author (whose memoir of her own struggles with bipolar disorder was a national bestseller), thinks the research is exciting because it seems to throw much more light on how depression works in the brain.

"It's hard to put into words how painful severe depression is. It's just awful. It's life-threatening, it threatens work and relationships. When you knock out the ability to think clearly, or the energy to get up and do things, you haven't got much left as a human being.... The exciting thing here is the proof of principle. There is something that can work very quickly."

As the poets tell us, nothing is going to ever dull the pain of human life, or the depth of grief over the death of loved ones, or psychosis, or our sense of existential alienation in the universe.

"It is important to remember how deeply ingrained depression is in human consciousness," Kramer writes in "Against Depression." But, he notes, it seems perverse to describe as normal a condition that "eats away at the brain."

So perhaps it is the struggle against depression that uniquely human, too, in whatever form that might take — prayer, art or a popped pill. Perhaps somewhere in the glutamatergic system or in some other wet corner of the brain there is a medication that can hack the vines away and let terribly ill people see the way to the warmth of love, the hope of redemption or even, as the priest in the Old Testament would have said, the tender mercies of the Deity. All those things are real, or can be felt as real, and all of those things are worth living for.

Even Freud knew that.

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Those who wish to further explore the subject can refer to Episode 1, published here on August 9, 2006; it has numerous links to other related web pages.

Digital Hourglass Timer Stopwatch Clock

Say what?

From the website:

Digital Timer

Timer unites today's precise digital technology with the design of a traditional sand timer.

It's a 100 minute timer and stopwatch.

Flip it over and it becomes a 24-hour clock.

It instantly recalls your last setting.

Digital display shows time of day or elapsed time.

You control it with easy-to-use keypads on either end.

Uses 1 AAA battery (included).

4½"H.

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I got so confused just looking at the picture up top, trying to tell what time it was exactly, that I started getting dizzy.

On the basis of that test, this item is not — repeat, not — TechnoDolt™-approved.

All others — which means almost all of you — proceed without hesitation as you so choose.

$17.95.

'Crossing the Atlantic with a dead engine' — Episode 2: Case Closed

You may recall that on February 19 of last year a British Airways 747 with 351 passengers aboard, Flight 268, had engine number 2 (of 4) burst into flames and then shut down on takeoff from Los Angeles International Airport.

Instead of returning to the airport, the captain decided to try to make it to his planned destination — London, England — on the remaining three engines.

Much discussion (understandably) ensued.

Scott McCartney, in a story in this past Saturday's (September 23) Wall Street Journal, reported that last month the U.S. Federal Aviation Administration, which had originally taken strong exception to the British Airways decision not to abort the flight, decided to drop its attempt to discipline the airline.

In return, British Airways promised not to do it again — in U.S. air space.

Of course, as McCartney wrote, the fact that an investigation of the 2005 incident revealed "that British Airways had flown 747s to distant destinations on three engines 15 times since April 2001" might not be reassuring to those who depend on this carrier.

Here's the September 23, 2006 article.

After Engine Blew, Deciding to Fly On 'As Far as We Can'

Pilot-Tower Tapes Flesh Out 747 Incident That Triggered A Controversy Over Safety

A few seconds after a fully loaded British Airways 747 took off from Los Angeles on its way to London last year, one of its four engines erupted in a spectacular nighttime burst of flame.

The fire burned out quickly, but the controversy has continued to smolder.

An air-traffic controller watching the runways radioed a warning to British Airways Flight 268 and assumed the plane would quickly turn around. To controllers' surprise, the pilots checked with their company and then flew on, hoping to "get as far as we can," as the captain told the control tower. The jumbo jet ultimately traveled more than 5,000 miles with a dead engine before making an emergency landing in Manchester, England, as the crew worried about running out of fuel.

The Los Angeles air-traffic-control tapes, obtained by The Wall Street Journal under the Freedom of Information Act, show that controllers who saw the fiery engine failure with the jet just 296 feet in the air were immediately concerned about the flight and ready to guide it back to the airport. But the decision to return or keep flying rested with the captain and the airline. Ever since, pilots and aviation regulators have debated the decision of the pilots and British Airways. Their questions: Even if the plane was capable of reaching its destination, and perhaps legal to fly, was it smart to try? And was it safe?

The incident also focused renewed attention on an age-old issue in aviation — safety versus economics. An emergency landing would have required dumping $30,000 of fuel, and the airline might have owed $275,000 in compensation to passengers under European Union rules if the flight was more than five hours late. The British Airways pilots' union questioned whether the EU compensation rules, only days old at the time, pressured airlines into pushing flights into risky situations. And in online discussions, pilots wondered if the three pilots might have been pressured into a risky flight to save the airline money.

British Airways says dollars played no role whatever in the decision to keep flying. It points out that the decision was legal under British regulations. A British inquiry ultimately said "no evidence was found to show that the flight continuation posed a significant increase in risk."

Flight 268 also set off a feud between U.S. and United Kingdom regulators over which nation's rules would apply. The U.S. Federal Aviation Administration, taking a different view of the incident than British regulators, opened its own investigation and then an enforcement action, charging British Airways with flying the jet in an "unairworthy condition." The FAA proposed a $25,000 fine. But last month, the FAA quietly dropped the matter rather than fight in court with British Airways and possibly U.K. regulators as well.

While 747s are certified to fly on three engines, doing so leaves much less room for error. They fly a bit slower and can't reach the highest altitudes, where thin air creates less drag, so fuel use increases by about 8%. The real risk is that if the plane should lose a second engine it would have more difficulty flying, especially if two engines on the same side failed -- leaving the thrust all coming from one angle and forcing extensive rudder use to keep flying straight. The plane would then have to fly even lower. Greater fuel consumption might mean the plane would have difficulty reaching an airport if it was over the ocean.

Flight 268's decision clearly surprised Los Angeles air-traffic controllers. The flight took off at about 9:24 p.m. on Feb. 20, 2005. Trouble was soon visible, as evident in radio discussions of "Speedbird 268 heavy." ("Speedbird" is aviation's call sign for British Airways; 268 was the flight number; "heavy" refers to jumbo jets.)

"Speedbird 268 heavy, it appears you have flames coming out of either your No. 1 or No. 2 engine," the tower controller radioed.

"We're shutting it down," replied the captain, already aware of a problem. British investigators later said passengers heard a bang when the engine failed, and some, like the tower, saw flames.

The tower controller alerted a colleague known as a departure controller, whose job was to take over responsibility for the flight as it left the airport.

"Speedbird 268 has got an engine shutdown. He had flames coming out of it. He's coming to you now. We don't know what he wants to do. We know he wants to come back, probably." The departure controller told the crew to climb to 5,000 feet and advise him of their intentions.

Pilot: "Roger standby. Climb and maintain 5,000. We are able. We will advise. We had a surge on takeoff and we're just doing the checks."

Departure controller: "Speedbird 268 heavy roger. Tower said you had flames coming out of the engine and it was shut down. Is that accurate?"

Pilot: "We haven't shut it down. We've throttled it back and we are doing our checklist."

The departure controller asked for the number of people on board — standard procedure in an emergency in case there is a crash. It was 351 passengers plus 18 crew members, the pilot reported.

He next told the controller, "We have now shut down the No. 2 engine. We are going to consult our company and see what they require us to do."

After making four more 90-degree turns, and sending a co-pilot back in the cabin to look out the window at the engine, the captain said: "We just decided we want to set off on our flight-plan route and get as far as we can. So we'd like clearance to, ah, continue our flight plan."

The controller gave the captain clearance to a higher altitude. But when he called other controllers to make arrangements down the line on an internal intercom system, surprise was evident.

"Remember that Speedbird I told you about?" the controller asked a colleague.

"Yeah."

"He's engine-out — No. 2 engine out. He's going to continue to his destination or as far as he can get," the departure controller said.

"OK. I have no flight plan on him." The tapes show the controllers had assumed the pilot wasn't going to London, so they deleted the flight plan from the computer. To reconstruct it, the departure controller called the tower.

"Is he going?" the tower controller who had seen the engine flames asked.

"He's going," was the answer.

"If you would have saw what we saw out the window, you'd be amazed at that," said the tower controller.

As the flight moved east, the departure controller passed the pilot on to another controller. "Thanks for your help. Cheers," the captain said. "Good luck," said the departure controller.

The plane flew across the U.S. at a lower-than-usual 27,000 feet and a speed about 12% slower than normal, according to the British investigation. Hours later, the captain made a final decision about crossing the Atlantic. "Having reached the East Coast of the U.S.A. with no indications of further abnormality and with adequate predicted arrival fuel, the crew decided to continue to the U.K.," said the U.K.'s Air Accident Investigation Branch in a June 2006 report. The AAIB said the casing of a component within the Rolls-Royce engine had worn out, causing a power surge, and high temperatures did severe damage.

Winds were less favorable than anticipated across the Atlantic, causing the jet to burn more fuel than predicted. In addition, the crew became alarmed that they might not be able to access the fuel in one of the four wing tanks. The captain declared an emergency and landed in Manchester. The British investigation later found he would have had enough fuel to make it to London.

After the landing — uneventful but for fire trucks on hand — controversy arose among pilots. U.K. and U.S. agencies both opened investigations. Britain's learned that British Airways had flown 747s to distant destinations on three engines 15 times since April 2001.

Indeed, the same plane, with a different No. 2 engine, lost the use of that replacement in flight two weeks later. This time it was at cruising altitude, en route from Singapore to London. Pilots saw an oil-pressure warning light and shut down the engine, flying for 11 more hours safely.

The U.K.'s AAIB polled seven other airlines that fly 747s. It found that two required pilots to land at the nearest suitable airport if an engine failed before the jet reached cruising altitude; one left it up to the captain; one had no policy; and three had policies similar to that of British Airways. The agency described that policy as telling pilots to fly to their destination or another airport served by British Airways "once certain considerations have been satisfied," such as determining the bad engine was stable and the plane was safe.

British Airways says the practice is safe and prevents disruption for passengers. The AAIB agreed, considering the possibility of a second engine failure extremely remote. The AAIB did recommend that the airline review its three-engine 747 policy, as well as its training for pilots in how to manage fuel supplies in a case where an engine is out. Another British agency, the Civil Aviation Authority, which had approved the "engine-out" policy in British Airways' flight manuals, concluded the airline's decision hadn't violated safety regulations.

British Airways and the CAA both argued that the rules the carrier had to meet were Britain's, not those of the U.S. agency that was accusing the carrier of flying an "unairworthy" plane. "There's a slightly gray area," says Sir Roy McNulty, chairman of the CAA. "It's rare for an issue like this to come up. By and large, the FAA and we are perfectly aligned."

British Airways said even if U.S. rules applied, they were ambiguous. The U.S. rules require pilots who lose an engine to land at the nearest suitable airport, but, British Airways noted, they make an exception for four-engine aircraft if the pilot decides flying onward is "just as safe as landing at the nearest suitable airport." The FAA, however, didn't consider flying across the Atlantic with an engine out to be "just as safe."

In the end, the nations avoided a fight over jurisdiction with a compromise. The U.S. acknowledged that international law gave Britain's CAA oversight of British Airways, and the CAA told the U.S. the airline had agreed to change its procedures for when an engine was out, at least while flying in U.S. air space.

British Airways said it hasn't formally changed procedures but has agreed to take into account "issues that arose from this incident" if a 747 engine fails again. "We have always maintained that we operated this aircraft in strict accordance with the CAA's regulations," it said.

Last month, the FAA told British Airways it was dropping the case based on assurances that airline changes will "preclude the type of extended operation that was the subject of this enforcement action." Says the FAA: "Our goal was to get them to change their procedures, and when we found out they were changing in the U.S., we settled the case."

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I was transfixed listening to the four audio excerpts of radio communications between the controllers and captain of Flight 268, linked in the sidebar (to the left) here.

I say again, the captain's comment after the engine shutdown that "We are going to consult our company" as to how to proceed does not play well with me.

[I am a] Solar Powered Rock

Solar Power Rock

More than just a pretty rock

Spotlight prized plants and greenery with our Solar Power Rock.

This faux stone mimics a regular rock in appearance and texture but is made of lightweight, weather-resistant, UV-protected resin.

The sun provides power for this spotlight to provide dusk-to-dawn light — no wiring needed.

Place in your garden, by a walkway or anywhere outside.

Pre-installed LED bulb lasts over 100,000 hours.

7"L x 6"W x 5"H.

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$21.95 (batteries not included).

Just seeing if you were still awake....

Oh, yeah, I almost forgot — Paul Simon, please call your office: you have a delivery.

Medicine's Greatest Hits — Episode 1: Benadryl — World's Best Sleeping Pill

Hey, a new bookofjoe feature.

I figured why use the old "BehindTheMedspeak" when I could coin this new, much sexier category?

Why is Benadryl (generic name diphenhydramine hydrochloride) the world's best sleeping pill?

1) It works

2) It's cheap

3) It's available without a prescription anywhere in the world

4) It's the least likely of all sleep-inducing drugs to result in catastrophe as a result of an overdose — intentional or accidental

5) It's non-addictive

6) It's got a long track record of safety

So why isn't it the first drug recommended for insomnia?

See number 2 above — there's no profit for Big Pharma there.

Not at $4.99 for 24 tablets (21 cents apiece).

Bonus: even if it takes a while for you to drop off, if you've got a runny nose, itchy throat, watery eyes and find yourself sneezing, Benadryl's intended effects will lessen those symptoms.

FM Radio Pen

From the website:

FM Radio Pen

Here's a ballpoint pen with a built-in FM radio.

Use it anywhere — at work, home or on the go.

It features an automatic scan tuner and high-fidelity stereo ear buds with on/off switch and volume control.

Comes with black and blue ballpoint refills.

Batteries included.

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Not bad for $4.99.

46 Best-Ever Freeware Utilities

Dan Mitchell, in his "What's Online" column in the September 23 New York Times, wrote about this website, the creation of Ian Richards, "a man known as Gizmo."

Lots more computer-related stuff here.

Tricked-Out Prep Trays

From the website:

Prep Trays

The no-mess way to coat your foods

Whether one, two or three coatings, it can now be done with minimal mess and cleanup.

Each 9" x 6" tray connects to the other — side-by-side, end-to-end or at an angle.

Dishwasher-safe.

A set of 3 perfectly matched trays (alas, bereft of ingredients and utensils) is $9.99.