Thursday, August 27, 2009

The Chemistry Experiment -- Placebo

Wouldn't you know.  I take a few days off before my placebo post, and scoops me with Placebos are Getting More Effective.  Drug Makers are Desperate to Know Why, by Steve Silberman 08.24.09.  Well, Steve put a lot more into his article than I intended for mine.  It makes for a fascinating read, about the history and current study of the placebo effect, beginning with its discovery during World War II, when an Army nurse lied to a soldier in pain.  They were out of morphine.  So she told him the injection of saline solution was a potent new pain killer.  And the patient's pain was relieved.  

That story is the essence of the placebo effect.  "When referring to medicines, placebo is a preparation which is pharmacologically inert but which may have a therapeutical effect based solely on the power of suggestion." --  

In 1962, the Food, Drug and Cosmetic Act began to require that medications prove their safety and effectiveness against placebos.  One group takes the medication.  Another group takes a placebo, or "sugar pill."  Their rates of improvement and side effects are then compared, to find out whether the medication itself causes the healing, or something else does, like the belief  in the medication, which marshals the body's own healing powers.  

Fast forward to the last decade, when more and more antidepressants have "failed trials," meaning that they perform no better, or not much better than the little sugar pills.  It seems that the new neurological medications are performing just as well as the old ones.  (I think this usually means that within 8-12 weeks, about 30% of people who take them improve their scores on various questionnaires that measure levels of depression.)  But oddly, over time, the placebos are performing better.  Which means the bar that the new meds have to cross to get approved is getting higher.

This is a problem for pharmaceutical companies, who have made a lot of money over a lot of years on neurological medications whose patents keep expiring, at which point the pharmaceutical companies make a lot less money.  They try to get around the patent law, to keep their economic engines turning.  But there are just so many ways you can repackage Celexa/Lexapro and Effexor/EffexorXR/Pristiq, and then you have to come up with a new idea.  And since Prozac seemed to work so well and made so much money, the pharmaceutical companies have been tinkering with the same old idea, not coming up with any new ones, ever since. This is such a problem that the pharmaceutical companies, who are usually very big on their trade secrets, are getting together to figure out what to do.

Why?  Why are placebos getting better?'s article explores some possible explanations.  But myself, I am taking a different tack.  See, I don't think this is a problem.  I think it is very good news, indeed.  Like I have said before, given the side effect issue, and as one who wasn't near so suicidal before I took SSRI's and SNRI's, sign me up for the placebo! 

Given the paucity of new things to try, doctors have been making do with "augmentation."  If you run out of antidepressants to try, how about adding on something else?  Now the possibilities are endless.  And as long as mood stabilizers, anticonvulsants and antipsychotics are on the table, why not add placebos to the mix?  And thus was born last week's post, in which I explored the potentially beneficial synergy between nortriptyline and Peeps.  

I intended to continue the saga this week, with other ideas about antidepressant/placebo combinations that hold promise.  But has led me in another direction.  Forget the antidepressant entirely!  Let's really expand the chemistry experiment, as in The Cure, and  try monotherapy with placebos.  Carefully chosen placebos, depending on your symptom profile, of course.

Remember, I am not a doctor, have no business suggesting that you ever question the wisdom of the FDA and your personal psychiatrist, and am simply tap dancing as fast as I can over a frozen lake in late spring.

That said, let's go at it, starting with the biggest, baddest antidepressant for the deepest, darkest depression, Effexor.  If what you need is for your psychiatrist to swing a baseball bat at the base of your skull, this is the drug for you.  Taper off slowly, because if you have been taking it, you are addicted to it.  Replace it with the biggest baddest basesball bat of another age, Baby Ruth!

Got the idea?  Okay, moving on to Effexor's clone in a velvet glove, Pristiq.  I am vastly amused at the cojones of a pharm company (Wyeth) that would tinker with a medication so little and change its marketing profile so drastically that it seems like a sex change operation.  Replace Pristiq with Godiva.

Now let's give some space to the bipolar spectrum.  Lithium, anyone?  On the left is the formula for lithium citrate.  I think it looks kinda cute.  Monotherapy just isn't going to cut it in the bipolar spectrum, but you can still stay with the same company, pairing Almond Joy with Mounds. Isn't it obvious?  The embedding code is disabled, so I have to simply give you the link to youtube.  Thanks to Helen for finding this for us.

A few years ago, Helen brought home a cd from the hospital.  It said "Zoloft (sertraline HCl)."  I thought, "Cool.  Here is some information about my options."  Nope.  It was music, Vivaldi's Four Seasons -- Summer, Winter, Spring and Fall. On the back it listed Zoloft's four indications: 

  • Major Depressive Disorder 
  • Post Traumatic Stress Disorder 
  • Panic Disorder 
  • Obsessive Compulisve Disorder    

I swear to God, instead of the bullet points, there were musical notes. Evidently, Pfizer finds merit in the seasonal theme.  I figure, with M&M's, you have your options.  You can either choose the season that corresponds with your primary diagnosis.  Or you can keep changing the med to suit the season.  Red and green for winter, pastels for spring, red, white and blue for summer.  In the fall, you can even match your medication to your school's colors! -- black and gold for the Hawkeyes.

Now what about those of you who would be taking Abilify, if you choose not to follow the Placebo Program?  The med that passed its exam because it had a friend who did the ghostwriting, spinning the data so hard that some of it disappeared entirely, and barely passed at that.  Salted Nut Roll.  Enough said.

So what are your ideas for your own meds?  Do you think we could really start a revolution in treating neurological disorders? 

Remember, the Placebo Program is not for everybody.  Talk to your physician about what might work best for you.  Weigh your risks and benefits.  The Placebo Program is contraindicated for those with certain food allergies and/or pancreatic issues.  The good news is that I do not have to be a speed talker to get through the list of side effects in the length of an Abilify commercial.  The primary side effect is weight gain, particularly at higher dosage levels.  But as the man from Lilly says about Zyprexa, "Would you rather have a patient who is happy and fat, or skinny and miserable?" 

Sugar cube photo by Uwe Hermann, licensed under the Creative Commons Sharealike 3.0 License.  Pristiq photo by Tom Varco.  M&M's by Broken Sphere/Wikimedia Commons.  All others in public domain.  Anyone want to send me a picture of a Mounds bar?

Tuesday, August 18, 2009

The Chemistry Experiment -- Augmentation

When I began The Chemistry Experiment, there were about twenty options out there for me to try.  I was a wuss and quit at six.  I said "no" to a fifth SSRI/SNRI, and rejected the whole class of MAOIs (Monoamine Oxidase Inhibitors) -- which were just too tempting to use as a backup plan.  Instead I headed east, and Chinese herbs got me through almost two years.  Later I returned to an antidepressant that hadn't been effective before, but at least it did no harm.  This time it helped.  Was this because I was taking Xiao Yao San as well?  Who knows.  But now it doesn't work any more anyway.

Meanwhile, there is a new strategy called augmentation.  If one med doesn't work, try combining two, an antidepressant with an anti-psychotic, anti-convulsant, mood stabilizer, atypical anti-psychotic.  Suddenly the number of possibilities is up to forty.  That doesn't actually give you 1600 potential combinations, because if you combine MAOIs with most of the others, it'll kill you.  Most days, that doesn't seem like a good thing. Anyway, the number of potential trials has increased exponentially, and I am nowhere near the end of the chemistry experiment.

My doctor gave me five possibilities to augment my current nortriptyline, because she figured I would reject three out of hand.  What is really sad is to be in a such a state that I am giving any of her suggestions serious thought at all.

The National Institute of Mental Health did a major study about five years ago, trying to find the best approach for treating treatment-resistant depression.  All those wonderful success stories you see on tv, the woman skipping on the beach, the man dancing with his wife, are from trials using mild or moderately depressed people who have not been on meds before.  While half of those who take antidepressants achieve remission with their first or second med, and another 10% get at least some relief, the odds fall dramatically after that.  STAR*D (Sequenced Treatment Alternatives to Treat Depression) used six antidepressants and four augmentation strategies, as well as Cognitive Behavioral Therapy, in four sequenced trials for people who had already been treated unsuccessfully with a seventh antidepressant, to try to determine the most effective options.

As it happens, I took four of the six during the same time frame as the study.  And three of my doctor's augmentation suggestions were on the STAR*D list.  So this time, I know the odds.

For example, at the third trial (fourth, counting the unsuccessful med that qualified participants for the study) 15.9% of those who augmented with Lithium achieved remission.  On the other hand, 23.2% had to quit because they couldn't tolerate the side effects.  Lots more had some side effects, but they were intolerable for only a quarter of the participants.  The numbers for T(3), a thyroid medication were 24.7% help and 9.6% intolerable.  So those are my odds for two out of my doctor's five.

A side note: in the fourth trial, comparing an MAOI to an Effexor/Remeron cocktail, remission rates were down to 6.9% and 13.7%.  Withdrawal because of harm rates were 41.4% and 21.6%.  They called those results modest.  My first rule -- if the odds of harm exceed the odds of help, give it a pass.

The results of the STAR*D Study in a nutshell -- the more meds you have to try, the lower your odds of positive results.  They found there is little to recommend one strategy over another, other than by the amount of harm they cause.

There is a major piece of information missing from this $35,000,000 study.  What is the placebo rate?  A few years into a disease that remits without treatment, the rates of remission were low enough to suggest the question -- were the meds preventing remission?  At least the question occurred to me.  To my knowledge, it has not been addressed in the literature.

They didn't use placebos.  So we don't know.  Placebos might have provided clues as to whether the meds made people worse.  But they figured it was unethical not to treat people this sick.  But placebo is a treatment.  I read in The Carlat Psychiatry Report, "in one study that looked at all antidepressant studies submitted to the FDA from 1987 to 1997, the placebo effect was shown to account for 75% of all improvement on active treatment (Khan et al, Arch Gen Psychiatry 2000;57:311-317)."  I, for one, would have volunteered for the placebo!  More on placebos next week...

Remembering The Cure from last week, I have been considering other possibilities, beyond that list of five.  I think Peeps would be a good augmentation for nortriptyline, the simple, well-tested, in and out of microwaves, and much beloved option paired with the plain, old-fashioned tricyclic that comes in generic and never did me any harm.  The starter dose would be the original, your basic yellow chick.  And you wondered when I would get to it, didn't you?!  But Peeps provides other dosage levels, as well, as pictured here.

In fact, like Abilify, Peeps not only increases your blood sugar, but also is a very versatile product.  There are options for comorbidity issues, such as:

-- eating disorders

--personality disorders

-- impulse control disorder

and borderline personality disorder.  I understand this peep may get a new diagnosis in the much debated and eagerly anticipated DSM-V, at which publication, I will have to edit this post.

And then there are your psychotic features.  Oh dear, is Peeps the appropriate medication to treat psychotic features?  Or are psychotic features a side effect of Peeps?  As with most neurological medications, flip a coin.  And while you are at it, expect psychotic features to be a side effect of discontinuation!

flair from

Thursday, August 13, 2009

The Chemistry Experiment -- The Cure

I saw a movie in 1995, The Cure. It was about two boys, eleven year old Dexter and Eric, a little older. When Eric learns that Dexter has AIDS, he decides to find a cure. People find cures all the time in unexpected places. Since Dexter is not allowed to eat candy, Eric thinks that might be why he has AIDS. Keeping track of Dexter's temperature in a notebook, the boys try a lot of candy. After the first trial results were in, finding low efficacy and an unwanted side effect of stomach ache, they switch to plants down by the river, making a series of infusions (tea). This time a stomach ache leads to a hospitalization. When Dexter's mother ends the experiment and Eric's mother tries to end the relationship, the boys head south on a raft to New Orleans, where there will be new plants.

The Chemistry Experiment was something like The Cure, only my doctors didn't monitor as closely as Eric, nor respond as quickly to my side effects. Part way through it, I drew this picture of The Chemistry Experiment. The bottles crossed off were of Prozac, Celexa, Remeron, and Nortriptyline. Cymbalta is the one being added to the test tube, which was my body. I was willing to try no more than three per series, insisting that I wash out the test tube between. I also changed psychiatrists after three, and quit entirely for a while after Effexor.

I saved all my unfinished scrips.
The pills fascinated me. They were the evidence of the violence to my body with which I was collaborating. My therapist really wanted me to throw them away. Eventually I did. But now I wish I still had them. Not to take all at once, that's not my plan. Just for evidence.

It seems that I am not the only one with this fascination. Tom Varco took this series:

.......prozac................... lexapro.................. pristiq.......

Now, I don't know the photographer. I don't know how he chose his subjects, nor
how he obtained them. But what I see here is the impulse to manage the unmanageable through art, to impose a meaning on one's experience. The series makes me wonder if he found more beauty in the meds than I did. I was just fascinated. And awed.

I would be more inclined to put mine in a pile and photograph them all at once, because I don't know how to add pictures to my post easily, and the multiple photos in this post are a real bite.

(The pink ovals here look like Celexa. And the light and dark blue capsules look familiar, but I can't come up with a name. The photo
is in the public domain.)

Here is another example by Lukas Bombach. I get most of my images, by the way, from, where many photos and other media are in the public domain, and others grant use under certain conditions. I can use Tom's photos if I attribute him, and Lukas' if I tell you that it is his and that This file is licensed under the Creative Commons Attribution ShareAlike 2.5. Lukas adds to his photo of seroquel (which is used for schizophrenia and bipolar disorder -- and who knows what else off-label) that the source of this photo is "self-made, yes I'm schizo ;) "

I don't know Lukas either, but I like him.

These little packets of chemicals, we put them in our bodies and hope for the best. My second psychiatrist didn't like it when I called it The Chemistry Experiment. A few minutes later when I asked whether Effexor would work, she said, "We don't know until you try it." It was very expensive and very traumatic to find out that the answer to my question was "no." Jerod says that people who have to quit Effexor also quit their psychiatrists.

The FDA weighs certain factors when it decides whether to allow the general public to participate in the chemistry experiment. Is the medication in question more effective than a placebo? And how much harm does it do along the way? It turns out that in clinical trials of antidepressants, placebos perform very well indeed. The antidepressants now available perform better, but frankly, not by much. The longer the trial the more effective the placebo is, 28% success and up, narrowing the gap, because even untreated, depression does go away. The other thing about placebos, while the people who get the placebos are bothered by side effects, too, they are not bothered nearly so much as those who take the chemicals.

So what I want to know, as I contemplate the next round of the chemistry experiment, why can't I get the placebo?!!!???

Tuesday, August 11, 2009


I have found a new blog to follow, Knowledge is Necessity: Musings on Mental Health by John McManamy. I think we are up to similar enterprises. John also has another website, McMan's Depression and Bipolar Web, which is to mood disorders what Jerod Poore's Crazy Meds is to neurological pharmaceuticals. Read the blog for musings, the others for information.

Meanwhile, here is the link to "Skunk," John's blow by blow of an encounter between the amygdalas of two mammals, a lesson in the amygdala that is more artful than Mother Amygdala from this blog, July 28, 2009. An added feature is the lesson in how to address the presence of this particular mammal in your house. Enjoy!

And thanks to John for his work.

Saturday, August 8, 2009

Depression and the Nobel Prize

It was an irresistible title. I followed the link to the New York Times and found the October 21, 2008 story by Tara Parker-Pope, about Dr. Douglas C. Prasher, a biochemist whose early work contributed to what would later lead to a Nobel Prize -- for somebody else.

Prasher has recurrent major depressive disorder. Today he drives a courtesy van for a car dealer. He says there was more to his departure from science besides his depression, lack of funding, family obligations... But that is part of the story. Depression doesn't help you find funding and meet family obligations. Depression can turn tying your shoes into a challenge. Parker-Pope wrote, "I find Dr. Prasher’s story to be a notable reminder of the toll depression can take on the lives and careers of many brilliant minds."

I told the story to Helen this afternoon, ending in my most dramatic mode, "I coulda had a Nobel Prize!" She didn't let me laugh it off, "Well, you coulda had a PhD. You coulda been bishop of... or rector of..."

She keeps the list in greater detail than I do. I try not to go there. I appreciate Dr. Prasher's response, “There are other people who would have deserved it a whole lot more than me,” he says of the Nobel Prize. “They worked their butts off over their entire lives for science, and I haven’t.” He is smiling in the picture, standing next to the courtesy van. I consider my own checkered resume and think, that's not such a bad job.

Then Helen continues my story, "Instead, you are sitting here, with your afternoon tea and biscuits, surrounded by all this." Surrounded by Costa Rica, our casita, watching the colibri
flit through our papaya, and the ladies holding their umbrellas as they ride their bicycles past our house in the rain.

No moral. It just is.
photo by Helen Keefe, used by permission

Wednesday, August 5, 2009

Crazy Meds

"You have to weigh the costs and benefits," the doctor said, her pen poised over the prescription pad. It sounds logical, doesn't it? And how interesting, that the doctor wants you to take responsibility for this major decision about your own health care, even when you are a mental patient.

Many trips to the doctor, many prescriptions later, I figured out what was wrong with that sentence. Let me put it this way: the cost of a Powerball ticket is $1; the potential benefit this week is $84,000,000. Wow. So millions of people weigh the costs and benefits and then buy their Powerball tickets twice a week. And the report out this week in the New York Times is that in 2005, ten out of every hundred Americans were on antidepressants, an estimated 27,000,000 people. I was one of them. It was logical.

Get it? There is a missing piece of information. What are the odds? Powerball tells you quite frankly. The pharmaceutical companies, not so much.

Responsible health care consumer that you are, notwithstanding your being a mental patient, you go to the internet. You google your doctor's recommendation, and get 8,870,000 hits. (I just tried Zoloft.) They come in three basic flavors:

  • Fear-mongering sites that condemn all neurological medications as tools of the devil with ever-lasting side effects that will cripple or kill you; while the people who prescribe them... members of the global conspiracy. The only solution to your problems is a regimen of vitamins, herbs, exercise, exorcism and bitching about doctors and drugs.
  • Pharmaceutical company sites who offer up their drugs as panaceas... Actual side effects are buried in doctor-speak and no real idea is presented about the chances of their happening, how long they last or if they will go away... The same goes for if the drug will work for you or not.
  • Support group sites that offer tea and sympathy... and far too often will just enable bad choices in not taking your meds or trying to take the wrong drugs for the wrong reasons.
But keep reading. There is a fourth flavor, Crazy Meds: The Good, the Bad and the Funny of Neurological Medications. Click that link, and you will find what I have quoted in italics, above and below, because Jerod says it better than me, which in my opinion means that he says it very well indeed.

Crazy Meds is the fourth flavor because it tells the truth right up front. I know, the meds suck donkey dong. But you know what? When you are mentally ill and you're not taking the right medications, it sucks syphilitic donkey dong while a red-hot poker is being jammed up your ass. That's what it's like without any meds at all, and that's what it's like if you're taking completely inappropriate medications. And that's what its like if you're taking neurological/psychiatric medications when you shouldn't be taking any at all.

You may think his language is extreme. But not if you seriously need the meds, like if you have schizophrenia or epilepsy or bipolar or the depressed-as-fuck form of major depressive disorder. If you do, and if you have been at this game for a while, then you are willing to buy the t-shirt that says exactly what you think. In fact, I encourage you to do so at Straight Jacket T-Shirts and send some bucks to the guy who has done a lot of work for you.

At Crazy Meds you will find straight talk about just how shitty it is to take these things, and why you have to anyway, plus whatever you might be able to do to make it a little less shitty. You will find information about antidepressants in their many varieties, plus antipsychotics, anticonvulsants, mood stabilizers, atypical antipsychotics, stimulants and supplements, and which ones don't play well together, what each is, what it is approved for, what its off label uses are, the pros, the cons, the side effects and their odds, how it works, or how they think it works, what your doctor probably won't tell you, how long it takes to work, how to go off it, and what happens when you do, links to the prescribing information sheets in several countries, typical costs, and access to talk boards. Plus what happens if you are taking it for the wrong ailment. If he can find the odds, he'll tell you.

Jerod is not a doctor or a therapist, and gives you all the appropriate disclaimers, and says he is your fourth source at best, after your psychiatrist, your physician and your pharmacist, none of whom ever gave me anywhere near this amount of useful information. If you check out what he tells you, and he encourages you to do so, you will find it to be solid. This guy has put his manic episodes to good use.

By the way, if you are shopping for my birthday present, I'd like the long sleeve, black (of course) women's size medium. The one that says "bat shit crazy" -- either a translation or a refinement of my diagnosis.