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.

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..."

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.

Mother Amygdala, Have Mercy Upon Us

Once upon a time I wanted to be a neurosurgeon. But I had this idiotic fear of science class -- it was in the water that they gave to girls in the 1950s. So I headed in another direction. Still I am fascinated by the brain, and will keep sharing the stuff that I learn about it. Today's topic is the amygdala.

Ah, the amygdala, the reptilian brain. It is among the oldest parts of the human brain, regulating memory, emotion and fear. The amygdala associates a strong emotional reaction with a piece of information to imprint that information in your memory. You remember best what you associate with strong emotion. If you walk under a tree in the tropics and a poisonous snake falls on top of you, it is highly beneficial from an evolutionary perspective to remember that tree where those poisonous snakes linger. That's when the amygdala is your friend.

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

"The goal of treatment was to maximize the number of patients achieving clinical remission because this would then render them eligible for the mood challenge." [italics added]


The winners of this month's Omgodthat'swhattheysaid Award are Segal, Kennedy, Gemar, Hood, Pedersen, and Buis in "Cognitive Reactivity to Sad Mood Provocation and the Prediction of Depressive Relapse," Archives of General Psychiatry 63:7 July 2006.

They wanted to answer a question I asked in my last post, why does depression come back? Cognitive Behavioral Therapy (CBT) says that automatic negative thoughts cause depression. CBT is designed to make people aware of these thoughts, to interrupt and reframe them. It is often as effective as antidepressants in treating mild and moderate depression, and better in terms of relapse rate. Nevertheless, people treated with CBT do relapse. One explanation is that CBT addresses the cognitive processes that dominate during a depressive episode, but there are underlying and ingrained thought processes that persist even in remission. Give people a list of adjectives, ask them which apply to them, and those who have been depressed but are in remission will nonetheless pick out more negative words than those who have never been depressed.

Suicide Prevention for All of Us

I end this month's focus on suicide with what we can do. Remember, "Suicide is not chosen; it happens when pain exceeds resources for coping with pain." (David L. Conroy, Out of the Nightmare: Recovery from Depression and Suicidal Pain)

So the way out of the nightmare is laid before us: reduce pain and increase resources.   Somewhere below is something you can do for yourself, for those you love and for those whom you have been commanded to love, if you believe in that sort of thing.   These lists are from Conroy, pp. 300-302.  My remarks are in brackets.

Out of the Nightmare: Recovery from Depression and Suicidal Pain

Suicide is not chosen; it happens when pain exceeds resources for coping with pain. 

David L. Conroy had me at the opening sentence.  I read it first at Metanoia.org and knew it came from somebody who had been there.  I recommend the website for help and insight from the insider's perspective.  If you are thinking about suicide, read this first. 

OMG!!! That's What They Said!

First, how did I ever start reading so much about depression, medication and the brain, the topics of Prozac Monologues?  Well, it was after I took two antidepressants that made me crazy and one that made me sad.  Then I was back in a psychiatrist's office, and she said, You have to weigh the costs and benefits.  And I took her seriously. 

But the information she gave me and that I found on the prescription information sheet wasn't very much information at all, not the kind that would have helped me when I was taking the antidepressants that made me crazy.  I knew this because I had read them, and they didn't help me.  I will write more about this some other time. 

The Language Of Doctors And Scientists 

Fact of the Month -- Suicide

It's June, the month with the highest suicide rate for persons with major depressive disorder.  So my posts this month will be on the topic of suicide.  Note to friends: This is not a coded message.  I personally am okay right now.

Today's post introduces the "Fact of the Month" feature.  And today's fact comes from David L. Conroy, Out of the Nightmare, who gets his information from the Statistical Abstract, 1989. 

Statistics -- More Suicides Than Homocides

Cognitive Behavioral Therapy -- aka Cake or Death

Cognitive-Behavioral Therapy (CBT) is a... treatment that focuses on patterns of thinking that are maladaptive and the beliefs that underlie such thinking... In CBT, the individual is encouraged to view such beliefs as hypotheses rather than facts and to test out such beliefs by running experiments. Furthermore, those in distress are encouraged to monitor and log thoughts that pop into their minds (called "automatic thoughts") in order to enable them to determine what patterns of biases in thinking may exist and to develop more adaptive alternatives to their thoughts. -- NAMI.org 

Books on Cognitive Behavioral Therapy

Depression and the Shackles of Shame

There is no blood test for depression, no x-ray nor sonagram.  Depression is the label that is given to a constellation of symptoms.  There are theories about the cause of the symptoms.  But the diagnosis is more like tea leaves. 


Depression Diagnostic Criteria 

· Lasting sad, anxious, or empty mood
· Loss of interest or pleasure in activities once enjoyed, including sex
· Feelings of hopelessness or pessimism
· Feelings of guilt, worthlessness, or helplessness
· Decreased energy, a feeling of fatigue or of being “slowed down”
· Difficulty concentrating, remembering, making decisions
· Restlessness or irritability
· Sleeping too much, or can’t sleep
· Change in appetite and/or unintended weight loss or gain
· Chronic pain or other persistent bodily symptoms without physical cause
· Thoughts of death or suicide, or suicide attempts.

If you have five of the above, including one of the first two, for more than two weeks, and without appropriate reason (like, your mother died) then that's depression. You've got the Grim at the bottom of your teacup. 

Guilt

I have done enough intake interviews that I recognize the differential diagnostic tree when it's coming at me. I used to get nervous when they asked about guilt. No, I don't actually feel guilt, except appropriate guilt for recent misbehavior, not the horrible self-judgment for imagined offenses. I don't feel guilty for my depression. I am not the offender but the offended.

Shame

No, what I feel about my depression, and events that are related, is shame.  And what I really feel shame about is feeling shame.

Thank You For Being My Friends

Try this experiment on yourself.  Imagine that you are standing at the base of the hill.  What do you see, smell, hear?  Put yourself in this picture.  Are you with anybody?  If so, who is it?  What is your relationship like? 

Now, tell me. How steep is the hill?  Really steep?  Sort of steep?  Not so steep? 

Friends And The Perception Of Difficulty 

I Am Not SAD

What month has the highest rate of suicides in the northern hemisphere?  What about the lowest? You will find the answer at the end of this post. 

Seasonal Affective Disorder

Some people get depressed in the winter.  Along about October or November, they start to feel lethargic.  They want to sleep a lot.  They crave carbs and gain weight.  They may lose interest in their normal activities, not want to see people, feel hopeless, think about death.  The deeper the winter, the sadder they feel.  In April, they start to feel better, regain their energy, and even feel giddy by the time May comes round.  It happens almost every year.

This is a specific kind of Major Depressive Disorder called SAD, Seasonal Affective Disorder.  It is no fun.

In The Beginning

In the beginning I went to my doctor for a med check. I had been on Prozac for three months. I was anxious and agitated, irritable, couldn't concentrate and couldn't sleep. I thought I needed a higher dose.

I was wrong. 

As I walked in the door, I had a thought. It was more intrusive than a fantasy, and less welcome. Never mind for now what it was, but it involved a nail file... I didn't tell my doctor about this thought. I just got my higher dose.

That is when things started to get really bizarre. 

The Birth Of Prozac Monologues 

A short while later, while coming off Prozac, I tried to imagine how I could tell people about what it was like to have to come off Prozac. The only medium that seemed appropriate was the stand-up comedy routine.

And that was the birth of Prozac Monologues, with its first chapter, Bizarre.

Someday, Prozac Monologues will be available to the purchasing public. For now, come here to find out about depression and its treatment, drugs and research, the brain and its wonders.

Welcome -- Willa

photo modified from original by Tom Varco

reformatted 11/26/10