Suicide Prevention Cake

Okay, I know.  It's supposed to read Suicide Prevention Week.  I had a post all written, an attempt at a thoughtful response to an exerpt from Nancy Rappaport's book, In Her Wake: A Child Psychologist Explores the Mystery of Her Mother's Suicide.  I found it on Knowledge is Necessity, one of my favorite blogs to follow.

But before I ever heard about Suicide Prevention Week, I gave the topic a whole month just last June.  And I do recommend that you look at those posts, especially the ones that refer to David L. Conroy, "Suicide is not a choice.  It happens when pain exceeds resources for coping with pain."  Those two sentences open his book, Out from the Nightmare, help to make sense of a topic that people would rather hold at a distance, and give a simple program for suicide prevention.  Reduce pain and/or increase resources.

So after I did my best at one more profundity, I thought again, really, how should one mark Suicide Prevention Week?  It occurred to me, why not celebrate it?  According to Conroy, "Five million people [in the United States] now alive will die by suicide. Twenty-five million more are, or will become, suicide attempters. Suicide has been, or will be, seriously considered by more than 50 million people." [Out of the Nightmare, p. 280.]

But think about it.  In other words, 45,000,000 people now living in the United States are or will at some point be at risk of suicide, and yet their suicides will be prevented.  For the most part, by the people at risk, themselves.  We will keep asking for help until we find somebody who isn't too freaked out to give it to us.  We will take our problems apart, examine them one piece at a time, fix what can be fixed, and either learn to live with or leave behind what cannot be fixed.  We will interrupt a negative thought.  We will get a dog.  We will volunteer.  We will take our meds.  We will stop taking the meds that are making us worse.  We will find a therapist, join a group, speak out against ignorance.  Oh, it's a long list with more ideas here for how to reduce pain, increase resources and remove barriers between.

I propose one more item for the list. We will celebrate our success.  It has been some years since I went to my favorite sushi restaurant for what I thought would be the last time.  So I will go there this week to celebrate how many times I have gone there since and will again in the future. I will bake a cake for a friend to celebrate the number of times that she has prevented her potential suicide.  I will take another friend to coffee to celebrate the number of times that she checked herself into the hospital instead.

Anybody with me on this one? How will you celebrate?  And how will you give yourself cause to celebrate next year?

Costa Rica and Depression

This is my breakfast view on the left.  It is called patita, a vine on the edge of my porch.  I planted the seeds myself.  A stranger gave them to me when I admired it in his yard.

If I look to the right, I see "bird of paradise," outside my neighbor's door.

Some friends invited us for drinks and this view at sunset. 

 

Why the hell would anybody be depressed in Costa Rica?

I prepare my answer for friends back in Iowa.  Most of my friends already know the answer, or else are too discrete to ask.  I really just ask myself.  Why the hell am I depressed in Costa Rica.

Five years into studying this disease, it still baffles me.  I know the answer, too, and yet it baffles me.  There are psychiatrists in Costa Rica.  There are psych wards in Costa Rica.  I have seen the boxes of Effexor on the shelf of the pharmacy where I go to buy contact lens solution.  There is even Electro-Convulsive Therapy in Costa Rica.  I have read the brochure.

So there must be depression in Costa Rica.  I am simply one of the people who have it.  There is something about the way that my brain works, as there is something about the way that other people's brains work, that give us this condition that is found across the planet, in every culture, even in a place where plants grow that are called "bird of paradise."

If other people have trouble believing that it is real, why should I be surprised?  I still wake up mornings and think, "This is crazy!  Snap out of it!"

When I packed for my latest trip, I didn't pack enough medication.  Oh, I knew I couldn't get nortriptyline here in the formulation and dosage that I take -- a question I had asked in a previous trip.  So even though they aren't as effective as they used to be, I counted those particular pills carefully.  But the Valium that takes the edge off until my psychiatrist and I can find the next solution, or at least decide on the next chemistry experiment -- well, who would need Valium in Costa Rica?

So last week I found myself in the pharmacy again, asking about Valium.  It is one of the drugs for which you have to have a prescription.  (You don't for Prozac, nor for Viagra, if that might influence your travel plans.)  It turns out that the eighteen year old with the ponytail who was talking with the staff is the doctor.  No, he must be older than eighteen, not a blemish on that beautiful skin.  I went to his office yesterday, where he had his prescription pad, and he was very understanding.  Still not wanting to believe that I take Valium, I kept underestimating how many I would need before I got back to Iowa.  But he convinced me that if I truly had enough, then I wouldn't worry about it.  I had  said that at the pharmacy, that I was worried about it.  He heard me, and he remembered.  For an eighteen year old, he is really good at paying attention.

Then I asked about Lunesta.  I don't take it very often.  Insomnia is not a side effect of my current med.  I just need it when I get caught at night reliving a living nightmare.  I wondered if I could find a cheaper source.  No, they don't have that one in Costa Rica.  But that started a conversation about side effects, insomnia, SSRI's and all those things I think about.  He said they have a different attitude in Costa Rica.  These side effects are terrible, he said.  So they don't use these heavy duty meds like Zoloft, except as a last resort.  First they try psychotherapy, then very small doses of tricyclics.

I know that Prozac became so popular because it was supposed to work better and have less side effects than the older meds that they prefer in Costa Rica.  And I realize a lot of people swear by it.  But I don't get it.  Over time, SSRI's and SNRI's have turned out to be no more effective than the TCA's.  As far as side effects go, maybe fewer people have them with the newer meds -- I don't know.  That's what the drug reps say.  But if you have to choose between hard core insomnia (Prozac/SSRI) and dry mouth (Elavil/TCA), between suicidal impulses (Cymbalta/SNRI) and constipation (Pamelor/TCA), I have experienced them all, and I'm going for the Costa Rican approach.

Meanwhile, back in the world of publishing papers, there is a current buzz about an old idea, that depression serves a purpose for the species.  It may surprise you to know, but not every culture and every time has tried to extinguish the Grim when it rears its head.  The approach of the European Middle Ages was to classify it as one of the four humours, melancholia.  It may cause difficulties when the humours are out of balance.  But there is a place in this world for the melancholic.  We are good gardeners, night watchmen, writers.  Paul Andrews and J. Anderson Thompson argue for Depression's Evolutionary Roots, that it exists because it "is not a malfunction, but a mental adaptation that brings certain cognitive advantages," among them the ability to ruminate, to think carefully about complex issues and solve problems.  That is not the way my therapist talked about rumination.

I will keep reading and thinking about these ideas, because that is one of the things I do.  I ruminate.  So you will find out more about rumination in the coming months.  Meanwhile, I have a new determination to treat my depression, my body, my mind gently, to discover what I can do with what I have been given.  I am not quite ready to call it a gift.  But I am disinclined to poison myself in order to get rid of it.

Costa Rica is a gentle place.  

photos by Helen Keefe

OMG!!! That's What They Said! Significant

"Clinical studies of adults with depression showed that adding ABILIFY to an antidepressant helped to significantly improve depressive symptoms compared to adults treated with an antidepressant alone."

Okay, first let me say that this is not "Pick on Abilify Month."  I usually wander the web, (not quite so intentional as surfing), for interesting little tidbits to share with my readers.  But at my last appointment, my doctor gave me a list and told me to do my research and pick one.  So for the last month, I have had a focus.

Abilify has long since been eliminated as the winner of this assignment.  But it is such a good example of so many of my interests, including the use of language (as in this monthly OMG!! feature), marketing and clinical trials, that I can't let it go.  In fact, it gets another post later this month.  Not because I am picking on it, but because, well, stay tuned.

I found the winning quote for the month's OMG contest, "...helped to significantly improve depressive symptoms..." at Abilify.com.  It's the word "significant" that wins the award.  They really should share this award with many contestants, because that's what they all say, "significant."

The passage is found on the page intended for consumers.  So you would think they are speaking in the language that consumers speak.  This is not the case.  "Significant" in this sentence does not mean "significant" in the language that you and I speak.  The authors are referring to clinical trials, where the word "significant" is as significant as "toast," as in, "We are having toast for breakfast."  It is not significant enough to include as a facebook status update.  It is more like a twitter.  Though in FDA Land, it is the magic word, like "Open, Sesame", Sesame meaning big bucks.  So that is significant in the language that you and I do speak.  But I don't have a button for OMG Sesame!

At a University of Berkeley site, you can find the following definition:

Significance, Significance level, Statistical significance:  The significance level of an hypothesis test is the chance that the test erroneously rejects the null hypothesis when the null hypothesis is true.

 

And they wonder why we turn to Wikipedia? -- where it says:

In statistics, a result is called statistically significant if it is unlikely to have occurred by chance.

So here is the deal.  Abilify.com is talking about their clinical trials, where people who were not responding to an SSRI or SNRI, one of the current crop of antidepressants, tried adding Abilify or placebo.  There are many interesting features about how Wyeth conducted these trials, and you will hear about them later.  The point is that they had to demonstrate to the FDA that those who took Abilify along with their antidepressant got better results than those who took the placebo.  If they could demonstrate that, the "effectiveness test," then they are part way toward approval for on-label usage, and a vast expansion of their market share, because there are a lot of us around who don't get better on the current crop of antidepressants, and more of us every day.  They also have to pass the "safety test" -- an issue for another day.

So how much better?  A "significant" amount.  And as I said, that does not mean what most people think it means, as in "I feel significantly better since I added Abilify to my treatment strategy."  Did you think that it did, when they said that "adding ABILIFY to an antidepressant helped to significantly improve depressive symptoms"?  It does not mean that at all.

So what does it mean?  There are several tests that researchers use to measure levels of depression.  One is the Montgomery Asberg Depression Rating Scale (MADRS).  This is a ten item scale that lets an evaluator rank your symptoms on a scale of 0 to 6, 0 meaning no symptoms, 6 meaning whale shit on the bottom of the ocean, to quote crazymeds.  Items include feelings of sadness, appearance of sadness, appetite, sleep, suicidal thoughts, etc.  Theoretically, you could get a total of 60 points, but that would put you out of the reach of clinical trials.  They don't let people that sick into clinical trials. They want to pass their clinical trials. So they go for a crowd that is easier to impress.

There were three clinical trials done for Abilify.  The results were consistent from one to the other.  So I will use just one as an example, the third, published in April, 2009.  172 people took a placebo along with their antidepressant.  They had a range of MADRS scores, and the middle score (the "mean") was 27.1, which is moderately depressed.  177 took Abilify with their antidepressant.  They also had a range of MADRS scores, with the middle score of 26.6, also moderately depressed.  There are a variety of small differences between these two groups.  In each case, those receiving the placebo were a lttle bit sicker, but as far as I know, not "significantly" sicker.  After six weeks, both groups had lower MADRS scores, meaning that both had reduced their depressive symptoms.  That is good news for both groups, from the patient's perspective.

Since the placebo group improved as well as the Abilify group, you could infer that some of the improvement came from the experience of being in a clinical trial itself, or maybe just from the passage of time, because people with depression do get better.  But the $64,000 question for Wyeth is whether there was a "significant" difference between the two.  And the answer -- ding,ding,ding -- is yes.  The placebo group reduced its score by 6.4 points, and the Abilify group by 10.1.  So the difference between the two was 3.7.  In the language of statistics, the probability that this difference of 3.7 points was due to chance is .1% -- one in a thousand.  If you get that score for two clinical trials, that's good enough for the FDA.  And they got it for three.

So isn't that significant?  Yes, if you are a statistician.  If you are a patient, if you are weighing the risks and benefits, then maybe yes, maybe not so much.  In a test with a possible score of 60, the difference between the two groups was less than four, or two questions that were answered just a little differently.  3.7 points on the MADRS scale means going from "looks miserable all of the time" to "appears sad and unhappy most of the time," and from "slightly reduced appetite" to "normal appetite."  Do you consider those two differences to be significant?  Is that what you expected when you read Abilify.com, "adding ABILIFY to an antidepressant helped to significantly improve depressive symptoms"?

I have clinpsych.blogspot.com to thank for helping me find the original research report.  In the next stage of the Abilify story, I will explore why these results, significant or not, did NOT impress the people who actually took the medication. 

The Chemistry Experiment -- Placebo

Wouldn't you know.  I take a few days off before my placebo post, and wired.com 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." -- thefreedictionary.com.  

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.

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.

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.

Skunk!

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.