Why Antidepressants Don't Work

Diagnosing Depression

You go to the doctor complaining that you don't feel like yourself.  You aren't having fun, you are tired, you don't sleep well, you have no appetite and feel pretty worthless about your inability to exercise control over anything in your life.  Sometimes you feel like just ending it all.

Your doc asks whether you have a plan (sometimes you think about how you might do it), if anyone in your family has bipolar (not that you know of) and checks your thyroid and glucose levels.

DSM On Depression -- The Chinese Menu

But before the blood tests come back, your doc has already checked the magic list from the Diagnostic and Statistical Manual of Mental Disorders:

Column A:
1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful).
2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others)
Column B:
3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day.
4. Insomnia or hypersomnia nearly every day
5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)
6. Fatigue or loss of energy nearly every day
7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)
8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)
9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

Ding, ding, ding.  One from Column A, four from Column B. (Your weight loss has been too gradual to count.)  That is all the doc needs to write out a prescription for an antidepressant.  Zoloft is the latest favorite, being the newest.  But if your drug coverage is lousy, you get fluoxetine -- Prozac in its non-generic incarnation.

Depression As A Chemical Imbalance?

You are not sure you want to take an antidepressant.  But your well-educated neighbor assures you that there is no shame in it.  It's not your fault.  Depression is a chemical imbalance in the brain, and antidepressants fix the imbalance.

I call this the chemical stew theory.  Your brain is too bland.  Add some salt and you will be good to go.

What a great marketing technique.  It's simple.  It's morally neutral.  It's even kinda manly, if that's an issue for you -- chemistry, you know.  And your next door neighbor, whose education comes from TV ads, is part of a sales force which has been so effective that one out of every ten people in the United States of America is taking an antidepressant right now.

Too bad it hasn't worked out.

No -- Antidepressants Do Not Fix A Chemical Imbalance

There are a couple reasons (at least) why adding a chemical to the stew does not solve the chemical imbalance.

The first reason is that your brain is not a stew.  If you like the food metaphors (and as you can see, I like the food photos), adding a chemical to your brain is more like adding it to a souffle.  The chemical balance in your brain is finely tuned to a variety of interacting factors.  Changing one of the factors has multiple effects, not all of them intended, and not all of them so good for you.

For example, a souffle has fat in it.  Maybe the problem with your souffle is not enough fat.  But when you mix fat into the egg whites, the whole thing falls flat.

The second reason antidepressants fail to do their intended job is that they do not address the problem at the right location. The theory suggests you can fix the imbalance by increasing the serotonin in your synapses.  But scientists have figured out the problem occurs farther upstream.

Or at least that is what the scientists say who fund their labs with money from the pharmaceutical companies who still want to add a chemical to your brain, just maybe a different chemical than the ones whose patent protections have expired.

The Brain As Machine

The new meds are not going to work either, because they are working with, not a food, but a mechanical metaphor.  So second millennium!

Like this:

If only they can find the right place to change the course of the inevitable falling blade?  I don't think so.  Your brain is not a machine.

The Brain As A Living System

Here we go:

Your brain is a whole world.  Those who would tinker with it need to understand its ecology.

Put the internal combustion machine onto this planet, and the whole rest of it experiences the consequences.

Block serotonin from reentering your neurons, and your tear ducts and intestines dry up.  And your sex life.  Put enough of us on antidepressants and we could become an endangered species.

So if you want to do something about depression, if you have it or love anybody who has it, then you have to pay attention to the ecology.  Your interventions will have complex consequences.

And -- this would be a third reason and most intractable reason why antidepressants don't work -- the planet/body/brain/ecosystem is always working to restore balance to the system.  Up the serotonin in your synapses and eventually another part of the brain adjusts to overcome your interference.  In ecology this phenomenon is called homeostasis.  Psychiatry calls it Prozac Poop-out.

I kept complaining about insomnia, one of my Chinese menu choices that did not go away.  A psychiatrist told me my symptoms were caused by my depression.  Address the underlying depression and eventually the symptoms would be relieved.  Never mind about the symptoms that replace them.  Those symptoms are not on the depression menu, and have nothing to do with the psychiatrist.

A Twenty-First Century Approach To Depression?

But systems theorists tell us that any intervention will move the whole rest of the system.  This works in the environment, the economy, the workplace, the family dinner table.  And in the brain.

So what if we go back to that menu and devise some interventions that are not the equivalent of a chemical sledge hammer?

That brings me back round to last week's post about insomnia, when I promised that the next installment of my sleep series would be:

The Good News About Sleep Deprivation and Suicidality 

The good new is coming next -- implications for treatment of mood disorders and other causes of suicidal thoughts and behavior.

It just took me an extra week to get there.  So what else is new.  It's a Prozac Monologues series.

photo "Loneliness" by  Graur Razvan Ionut, from FreeDigitalPhotos.net 
photo of Chinese menu by Hoicelatina, permission to copy under the terms of the GNU Free Documentation License 
photo of bell by Salvatore Vuono from FreeDigitalPhotos.net 
representation of serotonin in public domain 
 photo of pote asturiano by jlastras and used under the Creative CommonsAttribution 2.0 Generic license 
photo of chocolate souffle by Akovacs.hu at the wikipedia project, who has released it to the public domain
representation of lactic acid in public domain
NASA photo of the Earth in public domain
photo of Anthia goldfish in public domain

More on Sleep and Mental Illness

Last week's post on postpartum depression and sleep led me to a ring of articles about the link between sleep and mood.  So here we go again -- I have stumbled on another series!

My opening shot is piece my son and I used to watch from a Sesame Street bedtime video.  If it inspires you to go take a nap, that's fine by me.  You can read this post later.

Only, one line isn't correct.  It really doesn't matter, don't you know it's so.  'Cuz you sleep in so very many ways.

Sleep Matters

It does matter.  That guy yawning over his book might have pulled an all-nighter.  If he does that often, or stays up late, or changes shifts, he might be sleep-deprived.  Which puts him at risk for depression and suicidal thoughts.


Not to mention that goose egg.

What Is Suicidality

The studies I will be citing refer to suicidality.  So let's start by defining that term.  Actually, the word is used loosely, refering to a range of behaviors, in some places as the intent or attempt to kill oneself, in other places as anything from occasional thoughts to attempts.  Any of which is unpleasant, much of which is terrifying.

Suicidality And Depression

Doctors used to think that only people who were depressed committed suicide.  If somebody with schizophrenia committed suicide, they concluded that the diagnosis had been in error, because people with schizophrenia don't commit suicide.  So the theory went.  Notwithstanding what you have been taught about people who call themselves scientists, even in science it is easier to change your facts than to change your mind.

The general public still tends to accept that idea, suicide=depression.  When somebody they know commits suicide, the assumption is that they missed the signs of depression.

The vast majority of those who commit suicide are depressed.  However, not necessarily so.  People who have other mental disorders, or are in chronic pain, or have been diagnosed with a terminal illness, or have suffered a failure or humiliation, or just too many things and finally one thing too many are all at risk.  As David Conroy explains, Suicide is not chosen; it happens when pain exceeds resources for coping with pain.  Whatever the pain. 

Suicidality As The Tip Of The Iceberg

The Diagnostic and Statistical Manual of Mental Disorders (DSM -- psychiatry's bible) lists suicidal thoughts and behavior as just one symptom in their Chinese menu approach to depression -- one from column A, five from columns A and B.  You don't have to be suicidal to get the diagnosis.  But it is the symptom that really gets their attention.

If you have suicidal thoughts or behavior, then something is going on.  The odds are depression, but at least something.  And obviously, it's not fun.  So it is worth addressing, before it sinks your ship.

Sleep Disturbances And Suicidality

So here is a study that discovered, whatever else is going on in your life -- insomnia more than doubles your risk of suicidal thoughts, planning, action.

It doesn't matter whether you have depression, anxiety disorder or other mood disorders, or chronic medical conditions such as stroke, heart disease, lung disease and cancer.  It doesn't matter whether or not you are abusing drugs or alcohol.  Age, gender, and marital and financial status don't matter.  All of these are risk factors in themselves.  But whatever risk factors you may or may not have, insomnia more than doubles your risk of suicidal thoughts, planning and/or action.

Insomnia comes in three flavors in the medical world: trouble falling asleep, waking in the middle of the night, and waking too early in the morning.  The last has the greatest risk.

Irregular Bedtime And Suicidalality

There are other studies that examine particular applications of the poor sleep/suicidality connection.  Here is one that examines what happens to young adults when they don't go to bed at the same time every night.

The Florida State University Laboratory for the Study of the Psychology and Neurobiology of Mood Disorders, Suicide, and Related Conditions discovered that actively suicidal undergraduates got an average of 6.3 hours of sleep a night -- way not enough sleep.  This we could anticipate.

Then they examined another factor, how much their bedtimes varied -- an average 2.8 hours.  For example, they might go to bed some nights at midnight, other nights at 3 AM.  So they sorted subjects by the second factor, how much bedtime varied.  Regardless of the severity of an individual's depression, the more variable the bedtime, the more suicidal the student became over the course of three weeks.

Get that?  All by itself, how much bedtime varied, all by itself, predicted increasing suicidality.

Varied bedtime also predicted the intensity of mood swings.  Which is significant, because suicide is associated with mania as well as with depression.  Both are indicators of poor cognitive function and poor impulse control.

Not to mention a bad report card.

Adolescent Bedtimes And Suicidality

So here is one more, this one on teenagers.  (Teen do not have the highest suicide rates.  But they do seem to get the most press and the most research dollars.)

James Gangwisch, PhD, of Columbia University studied the sleep habits of 15,659 teens.  He reports that teens whose parents enforced a midnight bedtime were 24% more likely to have depression and 20% more likely to have suicidal thoughts than teens whose parents enforced a 10 PM bedtime.

The 10 o'clockers got an average of eight hours and ten minutes of sleep at night, compared to seven hours and thirty minutes for the midnight crowd.  Both were short of the nine hours that teenagers need, which would account for the general crankiness of most teenagers you know or are.

Oh, and that Nobody else's parents make them... argument?  More than half of parents enforce the 10 PM bedtime.  And 70% of teens comply.

I didn't find a study on the relationship of sleep and report cards.  But some scientists surmise from this and other studies that sleep deprivation may be the real reason for the United States' slip in global competitiveness.

The Good News About Sleep Deprivation and Suicidality

The good new is coming next -- implications for treatment of mood disorders and other causes of suicidal thoughts and behavior.

Now get off the computer and go to bed.

photo of scales from Deutsche Fotothek of the Saxon State Library
 photo of Chinese menu by Hoicelatina, permission to copy under the terms of the GNU Free Documentation License
photomontage of iceberg created by Uwe Kils (iceberg) and User:Wiska Bodo (sky), permission to copy under the terms of the GNU Free Documentation License
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The Insomnia Cure for Postpartum Depression -- AKA Stupid Science Reporting

My niece just gave birth to twins, and friends are bringing home their newborn.  So this report on sleep deprivation is personal.

Last year's Best of Stupid Science Reporting comes from (drumroll, please...) the New York Times: In Sleepless Nights, a Hope for Treating Depression by Terry Sejnowski.

Don't Believe Everything You Read In The New York Times

Evidently, 75 published papers with over 1700 subjects in the last forty years have documented that the depressive symptoms of new mothers are relieved after a sleepless night.  Now let's remember the number one rule of research publishing -- for all we know, the same study may have been published 75 times.

On the other hand, if the author didn't double count studies, that would be an average of 23 participants per study.  Whatever the results, with those numbers, they would not be robust results.  A review of literature cited below examined some of these studies.  One had nine participants.  One had three.  These are not studies.  They are anecdotes.

Sleep Deprivation And Euphoria

Moving on.  Anybody with bipolar disorder or for that matter, any student who has pulled an all-nighter can tell you that sleep deprivation lifts mood.  After we talked until 5 AM my freshman year, the most natural thing to do in the world was to go invade a nearby garden and pick somebody's blackberries. 

Sleep deprivation used as a treatment for depression is efficacious and robust: it works quickly, is relatively easy to administer, inexpensive, relatively safe and it also alleviates other types of clinical depression, Sejnowski reported.

Unfortunately, There Is This Little Problem

But before you throw away your pills, read the but.

Continuing from the article -- First, sleep deprivation is not as convenient as taking a pill.  Actually that's debatable.  No doctor's appointment, no worries about in or out of network, no copay, no trip to the pharmacy, no need to check the formulary...  If that were the only downside, it would have much to commend it.

Second, prolonged sleep deprivation is not exactly a desirable state; it leads to cognitive defects, such as reduced working memory and impaired decision making.  Translation: NOT relatively safe.  I remember when my son was three months old and I had just gone back to work.  I stopped at the stop sign, looked both ways, and then pulled out in front of oncoming traffic.

Finally, depression recurs after the mother, inevitably, succumbs to sleep, even for a short nap.


Wait a minute -- this is the New York Times here.  Read that again.

Sleep deprivation is wonderful cure for depression.  It's quick, cheap and safe.  That's the good news.

The bad news?  A relapse rate of 100% after 15 minutes.

Yes, that would be a difficulty.

There are a few other difficulties with this stupid science report, as well.

Actually, Sleep Deprivation Is Linked To Postpartum Depression

Lori Ross, et al did a review of the literature on this subject.  Against Sejnowski's 75 studies are piles and piles of studies that assert quite the opposite, that sleep deprivation is a significant risk factor for postpartum depression, almost every woman who has postpartum depression is sleep-deprived, and improving mothers' sleep improves their mood.

Sleep Deprivation And Psychosis

The most serious risk of postpartum sleep deprivation would be psychosis.  Studies back over a hundred years, noting that the almost universal early symptom of puerperal [first six weeks after childbirth] cases is loss of sleep (R. Jones, Puerperal Insanity from the British Medical Journal, 1902).

One or two women out of a thousand experience psychosis after giving birth, putting them at risk for suicide and infanticide.  Depending on the study, 42-100% of women with postpartum psychosis also experience insomnia.  Now that is a robust finding.  Furthermore, there is evidence that sleep loss is the last straw that tips women into development of continued bipolar disorder.

Mood is a continuum item.  Depression would be on one end.  Lifting of depression moves in the other direction.  Then comes euphoria, then mania, then psychosis.

Sleep Deprivation And Mania

And speaking of mania, the experience of people with bipolar and college students is well supported in the literature, that sleeplessness can trigger mania.

Sleep For Prevention Of Postpartum Depression

All this stuff is so well known, the Women's Health Concerns Clinic at St. Joseph's Healthcare has developed a preventive intervention that is routinely offered to patients who present with high risk for postpartum depression. Can you imagine a five-day stay in a private room after childbirth?  These and other strategies aimed at improving the sleep of new moms decreased mood disorders and even psychiatric hospitalizations months after childbirth.

Sleep.  That is the REAL cure for postpartum depression.  Forget baby showers.  The kindest gift you can give a new mom is to take care of the kid while mom takes a nap.

Speaking of which,

Aimee -- get off the computer and go to bed!

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OMGThat'sWhatTheySaid: 2010 in Review

Best Of... Worst Of...  The turning of the year is time for evaluation and new direction.  So here is a long ago promised review and ***competition*** for 2010's Readers' Choice Best/Worst/Whatever OMG Award.

The OMGThat'sWhatTheySaid Award was invented when I began reading what scientists say about those of us who have a mental illness.  It expanded to include media contributions to idiocy, offensiveness and outrage exhibited in language about mental illnesses and the people who have them.  The OMG Award allows me to reframe idiocy, offensiveness and outrage into irony -- granting an award for what ought to receive lashes across the backside.

I intended this to be a monthly award.  But, whatever.  I keep going on a tear with some series and lose track. -- I think this blog is charting my major hypomanic cycles?  Many months go by awardless.  So here are not twelve, but just four contenders.  The titles are links to the entire original posts.

September 12, 2010: OMGThat'sWhatTheySaid -- Noncompliance

The doctor tells you to weigh your costs and benefits before you take a medication, because it is your body, your decision.  The prescribing sheet says the doctor already weighed them for you.  If you decide differently than the doctor, then you are noncompliant, you uncooperative mental case, you.

July 23, 2010: OMG!!!That'sWhatTheySaid -- Failed Method/Successful Attempt

If we hang ourselves, or take pills, or jump off a bridge and yet we survive, then we have failed.  If we die, then we were successful.  Feel the love.

March 13, 2010: OMGThat'sWhatTheySaid! -- They

This one is more global.  I gave it to myself, and to any of us who are closeted mental cases, who think, quite accurately as a matter of fact, that if we acknowledge our mental illness, we will lose authority to talk about it.

December 26, 2009: OMGThat'sWhatTheySaid! -- Stigma

I know, this one reaches back to the previous year.  But it is still tragically timely and I am still flummoxed by the good doctor, Paul Steinberg, who thinks that the President should not send letters of condolence to the families of soldiers who commit suicide in a war zone.  (Staff Sgt. David Senft is the most recently reported example.)  Steinberg's reasoning? -- It might take away the stigma of suicide.  And with less stigma, more soldiers with mental illnesses might kill themselves.

So those are the contenders for the 2010 OMG Award.  Vote in the comments.  Feel free to lobby your friends to pad the count.

If you are curious about earlier monthly awards, they include:

November 15, 2009: OMGThat'sWhatTheySaid! -- Language

What they call us and what they call themselves determines the relationship.  The fact that they name the relationship means they have the power, regardless of the words they choose.  Provider/consumer is the new PC relationship, supposedly being more mutual than doctor/patient.  But I disagree.  It does not level the playing field.  It makes one active and the other passive.  What if we called ourselves customers?

September 4, 2009: OMG!!! That's What They Said! Significant

In common usage people think significant difference means a big difference.  Researchers think significant difference means large enough that the difference was not by chance.  (If it was a big difference, they would call it robust.)  Pharmaceutical companies sell a lot of drugs because you don't know the difference.

July 23, 2009: OMG!!! That's What They Said! Relapse

This one was about a research study designed to find out if they could cause relapse in women whose depressive symptoms were in remission.  Again, feel the love.

June 13, 2009: OMG!!! That's What They Said!

Here is the post that inspired the OMG feature, in which I discover a textbook that describes suicide as one of the unfortunate complications of major depressive disorder.

And In Conclusion...

I am always delighted to receive suggestions for new awards.  Let's say it together:

Thanks for reading Prozac Monologues.  Here's hoping I can keep it up in 2011.  You, too.

photo of trophy by Sebcaen and used under the GNU Free Documentation License.
image of whipping girl from La Grande Amie, in  public domain
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