Do SSRI's Even Work? And if so, How?

Just in case you feel like reading Sunday's New York Times Magazine before it come out, over on "Post-Prozac Nation: The Science and History of Depression," Siddhartha Mukherjee will be writing about the history and efficacy of antidepressants.  Dr. Mukherjee writes:


Fast forward to 2012 and the same antidepressants that inspired such enthusiasm have become the new villains of modern psychopharmacology — overhyped, overprescribed chemicals, symptomatic of a pill-happy culture searching for quick fixes for complex mental problems. In “The Emperor’s New Drugs,” the psychologist Irving Kirsch asserted that antidepressants work no better than sugar pills and that the clinical effectiveness of the drugs is, largely, a myth. If the lodestone book of the 1990s was Peter Kramer’s near-ecstatic testimonial, “Listening to Prozac,” then the book of the 2000s is David Healy’s “Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression.”


He talks about depressed people in the 1950's being cured as a side effect of their treatment for tuberculosis (isoniazid was one of the first medicines to elevate mood in the depressed) and hyptertensive patients becoming depressed on Raudixin.


Mukherjee goes on:

In 2011, Hen and his colleagues repeated these studies with depressed primates. In monkeys, chronic stress produces a syndrome with symptoms remarkably similar to some forms of human depression. Even more strikingly than mice, stressed monkeys lose interest in pleasure and become lethargic. When Hen measured neuron birth in the hippocampi in depressed monkeys, it was low. When he gave the monkeys antidepressants, the depressed symptoms abated and neuron birth resumed. Blocking the growth of nerve cells made Prozac ineffective.

Hen’s experiments have profound implications for psychiatry and psychology. Antidepressants like Prozac and Zoloft, Hen suggested, may transiently increase serotonin in the brain, but their effect is seen only when new neurons are born. Might depression be precipitated by the death of neurons in certain parts of the brain?


He finishes off with the ideas:

The differences in responses to these drugs could also be due to variations in biological pathways. In some people, neurotransmitters other than serotonin may be involved; in yet others, there may be alterations in the brain caused by biological factors that are not neurotransmitters; in yet others, there may be no identifiable chemical or biological factors at all. The depression associated with Parkinson’s disease, for instance, seems to have little to do with serotonin. Postpartum depression is such a distinct syndrome that it is hard to imagine that neurotransmitters or hippocampal neurogenesis play a primary role in it. 

Nor does the theory explain why “talk therapies” work in some patients and not in others, and why the combination of talk and antidepressants seems to work consistently better than either alone. It is very unlikely that we can “talk” our brains into growing cells. But perhaps talking alters the way that nerve death is registered by the conscious parts of the brain. Or talking could release other chemicals, opening up parallel pathways of nerve-cell growth. 

But the most profound implications have to do with how to understand the link between the growth of neurons, the changes in mood and the alteration of behavior. Perhaps antidepressants like Prozac and Paxil primarily alter behavioral circuits in the brain — particularly the circuits deep in the hippocampus where memories and learned behaviors are stored and organized — and consequently change mood.

Ketamine, Special K, and Depression

I just wrote a post over on Clinical Psychiatry News about the experimental use of ketamine (aka, rave drug "Special K") for instant relief of depression and suicidal ideation.

Please go over there to read it (link above), and feel free to comment there (sorry, registration is required but it's free) or here. I'd like to hear about providers who have used ketamine for their patients and from people who themselves have used it for depression.

Edit: find a list of clinical trials using ketamine for depression on clinicaltrials.gov.

No Better Than a Sugar Pill?

We're only a few minutes in to "today" but here's a link to an article in the New York Times by Peter Kramer-- In Defense of Antidepressants.  Kramer writes:


Could this be true? Could drugs that are ingested by one in 10 Americans each year, drugs that have changed the way that mental illness is treated, really be a hoax, a mistake or a concept gone wrong?
This supposition is worrisome. Antidepressants work — ordinarily well, on a par with other medications doctors prescribe. Yes, certain researchers have questioned their efficacy in particular areas — sometimes, I believe, on the basis of shaky data. And yet, the notion that they aren’t effective in general is influencing treatment. 

Kramer goes on to discuss issues in the research that may have biased studies that deem anti-depressants to be no better than placebo.  Do read it if you get the chance.

Podcast #58: I Need a New Drug and Happy Five Years of Shrink Rap and Still Blogging

(Belated) Happy Blogiversary to Us!

Five Years and Still Blogging

Shrink Rap quietly turned Five on April 21st. We chatter about this while we podcast. We kept it short again and talked about some new medications. Roy mentioned a new antidepressant, Viibryd that's a bit like a combo of an SSRI + buspirone. Dinah talked about a conference she went to on psychopharm update and she read some of the slides that were presented by Dr. Neil Sandson. This led us to talk about some other new medications, including long-acting antipsychotic medications that are administered by injection.

We then talked about Silenor, a sleep medication which is the re-packaging of an older medication, Doxepin, in a lower dose. A phone call to the pharmacy revealed some interesting information about the cost of these medications, but you'll have to listen, or call the pharmacy yourself, if you want the answer.

This all led us to a discussion of the combination medication for the treatment of obesity, Contrave, that did not get FDA approval, and Steve's post on his psychiatry blog, Thought Broadcast, on Contrave compared to Swiffer floor cleaning system. Huh? Oh, listen and maybe we make sense.


Thank you for listening.
We invite you to go to iTunes and write a review.

And our Shrink Rap book should be available in the next few weeks: our review copies have arrived. Our next line will be "Go To Amazon and write a review!"

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This podcast is available on iTunes or as an RSS feed or Feedburner feed. You can also listen to or download the mp3 or the MPEG-4 file from mythreeshrinks.com. Thank you for listening. Send your questions and comments to: mythreeshrinks@gmail.com.

Is This Fish Happy or Toxic?

Thank you to Anon who sent us a clip to this interesting article in the Montreal Gazette about all the fish in the St. Lawrence River who are being exposed to anti-depressants though human waste.

William Marsden writes in "Antidepressants Found in Fish":

"It's very hard," Sauve said. "The question itself is quite interesting. You can't ask a fish whether it is happier or not. One of things they can do is use cameras to look at the male behaviour. Will it have the same behaviour in mating or feeding? Then you have to go back and look at its normal behaviour. It's quite tedious work and difficult."

Quebecers purchase about 555 million antidepressants a year. That works out to about one in four Quebecers taking one pill a day. That does not include the amount prescribed by psychiatric hospitals.

Hmm... I'm not sure what to say. Should we be more alarmed about what the meds are doing to the fish (and just how happy should a fish be?) or the idea that Quebecers average a one in four rate of taking anti-depressants?

Antidepressants on Kevin.MD

Dheeraj Raina is a psychiatrist who has a blog post on KevinMD called "How an Antidepressant Can Hurt Your Patient."

The post is directed at primary care docs and talks about the danger and downside of prescribing anti-depressants. Too much use as 'feel good' drugs without careful consideration of the diagnosis, appropriate treatment with adjunctive psychotherapy, and the risk of manic induction and suicide.

It's probably not likely that every patient with anxiety and depression will end up seeing a psychiatrist. Obviously, we at Shrink Rap don't think antidepressants should be doled out mindlessly--- if primary care docs are going to prescribe them, they should--

Know how to diagnose depression.
Know how to use the medications. This is not as easy as it might sound: Antidepressants take time to work and the dosing requires titration. Sometimes they need to be changed, increased, augmented. If the first try at a standard dose works, you can call it a day---but this is why the meds have the rap for being only as good as placebo. They don't work if you don't know how to use them and one size doesn't fit all.
There are risks, side effects, adverse reactions, and contraindications.
With psychotherapy, time, and support, there are people who won't need treatment with medications and those options get bypassed when a script gets written in a quick visit.

PS. I agree with Dr. Raina that this can't be done in a 15 minute office visit.

My Three Shrinks Podcast 52: The Friendly Skies

In Dinah's post Fly Those Friendly Skies she talks about the new FAA policy regarding pilots on antidepressant medication. We found out something about pilot life span. Retired pilots live five years longer than their non-flying peers.

We talk about the New York Times article In Therapy: Cell Phones Ring True. The article discusses what therapists learn about their patients through their cell phone conversations and pictures.

Roy introduced us to the Lanny-yap blog, where we found a picture of Roy's dog, Eddie. This blog has a reference to a Scientific American article on anisomycin, an experimental medication that has been used in rats to wipe out fearful memories. Shades of Eternal Sunshine of the Spotless Mind (2004)!

Finally, we talk about a prospective study of 16,000 adults who started college and tried to guess which psychiatric diagnoses were most associated with failure to complete college. The full study can be found in the April edition of Psychiatric Services.

Once again, we talk about our upcoming book. We still need a title we can all agree on. Help us out by sending ideas to mythreeshrinksATgmail.com!

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This podcast is available oniTunes or as an RSS feed orFeedburner feed. You can also listen to or download the .mp3or the MPEG-4 file from mythreeshrinks.com.

Thank you for listening

Send your questions and comments to: mythreeshrinksATgmailDOTcom

Fly Those Friendly Skies

We've talked before about whether having the diagnosis of a mental illness should prevent a person from pursuing certain careers. We've also mentioned that pilots, in particular, can not be on psychotropic medications. One concern is that a depressed pilot might not seek treatment because s/he fears losing her job. Is it better to have a pilot with untreated mental illness, or one on medication?

In The Wall Street Journal, Shirley S. Wang and Melanie Trottman write that the FAA has reconsidered this policy and will allow pilots to fly if they are being treated with Zoloft, Celexa, Lexapro, or Prozac. They write:

The new policy doesn't mean pilots who want to begin taking one of the medications can get in the cockpit right away. Before being granted a waiver by a physician certified by the FAA, a pilot must be considered "satisfactorily treated" for 12 months; in the meantime, he or she will be grounded.

For pilots who have been secretly taking antidepressants, the FAA is offering a grace period. The agency said it wouldn't take action against such pilots if they come forward within six months. However, pilots with a recent case of depression or who want to begin a new medication regimen will be subject to the one-year waiting period, according to FAA spokeswoman Alison Duquette. "We're really looking for stability," she said.

Grounded for 12 months? Seems like a long time. What do grounded pilots do? Do they get paid? Is this really destigmatization?

Why Can't We Be Sad?

Today's New York Times Magazine has a really interesting article by Jonah Lehrer called "Depression's Upside." Mr. Lehrer talks about a possible evolutionary purpose for Major Depression.

Mr. Lehrer writes:

The persistence of this affliction — and the fact that it seemed to be heritable — posed a serious challenge to Darwin’s new evolutionary theory. If depression was a disorder, then evolution had made a tragic mistake, allowing an illness that impedes reproduction — it leads people to stop having sex and consider suicide — to spread throughout the population. For some unknown reason, the modern human mind is tilted toward sadness and, as we’ve now come to think, needs drugs to rescue itself.

The alternative, of course, is that depression has a secret purpose and our medical interventions are making a bad situation even worse. Like a fever that helps the immune system fight off infection — increased body temperature sends white blood cells into overdrive — depression might be an unpleasant yet adaptive response to affliction. Maybe Darwin was right. We suffer — we suffer terribly — but we don’t suffer in vain.

So I didn't like the article at the beginning; it relied on anecdotes--the woman who felt so much better with antidepressants that she'd grown complacent in a bad marriage, for example. It doesn't capture all the patients I see, and any way you dice it, if you end up dead from suicide, your productivity comes to a halt. It seems to me that there are some people who suffer in ways that these anecdotes don't explain. I suppose, however, even if we assume that depression is an unproductive, tormenting state, when it ends, is there something to be gained from having gone through it. Lehrer tells us, "Wisdom isn't cheap, and we pay for it with pain." I, personally, think there remains a differentiation between pain and major depression, and that perhaps one can grow through all sorts of suffering, and I'm all in favor of finding my own personal path to wisdom in ways that might not entail so much suffering. Just a thought.

But I ultimately, I liked the article because Lehrer, while clearly a proponent of the "don't mess with evolution, less drugs, please," school of thought, presents a balanced view. He gives Peter Kramer (Listening to Prozac) a voice, and talks about the objections to the viewpoint he puts forth. He describes a theory that depression is evolutionarily helpful because of the ruminative nature of the illness. He also cues us in that this is just one explanatory theory which remains unproven, and there are others. Lehrer continues:

Other scientists, including Randolph Nesse at the University of Michigan, say that complex psychiatric disorders like depression rarely have simple evolutionary explanations. In fact, the analytic-rumination hypothesis is merely the latest attempt to explain the prevalence of depression. There is, for example, the “plea for help” theory, which suggests that depression is a way of eliciting assistance from loved ones. There’s also the “signal of defeat” hypothesis, which argues that feelings of despair after a loss in social status help prevent unnecessary attacks; we’re too busy sulking to fight back. And then there’s “depressive realism”: several studies have found that people with depression have a more accurate view of reality and are better at predicting future outcomes. While each of these speculations has scientific support, none are sufficient to explain an illness that afflicts so many people. The moral, Nesse says, is that sadness, like happiness, has many functions.

The article finishes off with the idea that people in depressive states are better thinkers, they notice more, they work better. He talks about a study that shows that on gloomy days with dismal music playing, shoppers notice more trinkets by the cash register. Gloomy weather and oppressive music might set a low mood tone, but this seems a far cry from an episode of major depression, and not something that is generalizable to anything more than clouds and music and trinkets. There's a second study mentioned of undergrads doing an abstract reasoning test that shows people with a "negative mood" perform or focus better; again, it falls short of being a comparison for major depression. The shrinks among us find it hard to imagine that 'negative moods' and Major Depression are all that linked. Everyone has negative moods. Not everyone has major depression.

What about the studies that link mood disorders and creative tendencies? This does seem likely, and we're left to wonder (my own thoughts, not the article) if the intense experience of an episode of mood disturbance either fuels creativity by feeding it material or requiring a release, or if the genetics are wired such that mood disorders and artistic talents might be coded near one another.

You thoughts?

Shrink Rap: Grand Rounds is up at CRZEGRL (Veteran's Day theme)

The theme for crzegrl's Grand Rounds this week is Veteran's Day.

The shrinky links:

• doctors & mistakes (Medicine & Technology)
• pharma ads & claims on twitter (HealthBlawg) ... also follow #FDAsm on Thur & Fri for coverage of the FDA's anticipated hearing on social media and Web2.0 (links for live streaming on HITshrink)
• antidepressants for chronic pain (How to Cope with Pain)
• love in the recovery room (Anesthesioboist) ... not really shrinky, just beautiful

Rethinking Antidepressants

Thanks to Henry for sending this link.

On cnet news, Elizabeth Armstrong Moore writes about research presented at this month's Neuroscience conference in Chicago:

Depression researcher Eva Redei presented research at the Neuroscience 2009 conference in Chicago this week that calls into question two tenets of depression science: that stressful life events are a major cause of depression, and that an imbalance in neurotransmitters triggers depressive symptoms.

Armstrong goes on to report that the research looks at the overlap of genes in RATS (not peeps) and notes that antidepressants work better for stress then depression and the genetic overlap between the two is minimal (--oh, why isn't Roy writing this, he's so much more eloquent than I am about the genetic stuff).
Armstrong goes on to say:

To test the long-held belief that stress is a major cause of depression, Redei looked for similarities between these two sets of genes. Out of more than 30,000 genes on the microarray, 254 were related to stress and 1,275 to depression. Only 5 were found in both samples.

"This finding is clear evidence that at least in an animal model, chronic stress does not cause the same molecular changes that depression does," Redei says. She is now looking at the genes that differ in the depressed rats so that she can narrow down targets for drug development.

Antidepressants are also often ineffective, Redei says, because they aim to boost the neurotransmitters serotonin, norepinephrine, and dopamine, whose reduced levels have been associated with depression. But this strategy is now also being called into question.

It's sort of news to me that we thought stress "causes" depression. I guess I thought extreme stressors (as opposed to general 'stress') can precipitate depression in those inclined to become depressed. Many people suffer extreme distress without getting major depression and many people with histories of major depression weather severe storms without a recurrence. What is nice about this research is that it challenges us to think in new ways, and I think sometimes research gets hooked around theories that aren't definitely proven and creativity gets stifled. Anything that nudges that can't be bad....

Can Black Box Warnings Kill?

I'm going to write about a story I saw on-line about a depressed mother who poisoned her small child. It's a terribly tragic story, and please keep in mind that I only know what I read in the article Here, and I've never examined anyone involved. The question being asked at the trial is that of whether the mother, who was depressed, was legally sane and knew it was wrong to kill her child, and that's not what I'm going to write about. I didn't pick a graphic to go with this blog post, because I couldn't think of any photo that would be appropriate to such an angst-ridden topic.

I'm pulling a few sentences from the newspaper article to use as a springboard for discussion:

They said Sparrow told a nurse practitioner she was considering using sedatives to kill herself, her daughter and her dog, but that medical professional did not contact the authorities or otherwise try to get Sparrow committed to a psychiatric hospital.

After hearing Sparrow had just stopped taking the antidepressant Prozac for fear it was causing the suicidal thoughts, the nurse practitioner let her go home with the instruction to come back if she didn't feel better...

I was struck by two things in the recounting of the story as I read it: that both the patient and the nurse practitioner thought her suicidal thoughts came from the Prozac (and both, perhaps, trusted they would stop with the cessation of the medicine--- obviously I don't know that's what they thought, but it's implied in this particular recounting of the story), and that a homicidal mother was apparently allowed to leave a clinic without being evaluated by a psychiatrist, I think. So my comments are general, because I don't trust a press account to be all-inclusive, and perhaps things transpired that didn't make it in to print.

When Prozac first came on the market, there were some concerns that it made people suicidal, and these concerns were dismissed. With years (oh, more than a decade) researchers revisited this idea and concluded that people under the age of 26 have a low incidence (1-2%) of violent thoughts caused by anti-depressants, and so we have the Black Box Warning about such thoughts. Does all the publicity about how the possibility of suicidal thoughts can arise from the medications narrow peoples' thinking? If we think a medication has caused a suicidal idea, does this prevent people from exploring other options? Perhaps the medication isn't working, or perhaps the depression has gotten worse and has broken through. Perhaps something else has transpired that increases risk. And if the medication is the culprit, what do we know about how long one has to be off it before such violent thoughts stop and the risk is gone? I think the answer is that we don't know.

I don't know if the woman described above saw a doctor the day she was in the clinic, or what exactly she said to the nurse practitioner. I don't know if the outcome would have been any different if she'd been committed to a psychiatric facility. What I do know is that when any story has a tragic ending, it's hard to wonder if more couldn't have been done.

We pass so-called scope-of-practice laws--- should psychologists prescribe? Should nurse-practitioners practice essentially independently? The fuss goes into the legislative battles before-the-fact, one fought primarily by legislators and lobbyists, not clinicians. We don't generally look backwards and ask if poor outcomes are more more likely to occur in settings where we've dropped our standards and we don't seem to ever ask if we should revoke those decisions. I'm not saying we should--- but perhaps we should ask more questions.

Advertising Works

On the Maryland Psychiatric Society's listserv I recently heard about a newly available (in the US) SNRI, Savella (milnacipran). It came out for fibromyalgia earlier this year but is used for depression in other countries. First I heard it was available. Who knew?

Then, I pick up the June issue of the Psychiatric Times. I usually let this languish in a pile, still wrapped in plastic, for a few months, and then summarily discard it, unread, once it breaks my "3 months rule". (If a throw-away mag/journal is more than 3 months old, toss it.)

I flip through it and discover -- only because of the advertisements -- several other new drugs I am unaware of. Where have I been that I've not been clued in? Twitter #fail!

So here are the other things.

• Fanapt (iloperidone) was approved, for treating schizophrenia. Vanda makes it.
• You can get 225mg of Effexor XR in a *single tablet*! But it's not "Effexor," it's actually a generic brand called Venlafaxine Extended Release (yes, that is the actual brand name). And it's a tablet, not a capsule. Made be Upstate Pharma. Who knew?
• There's also a new brand of bupropion (aka Wellbutrin) out there that puts an extended release formulation of the maximum dose (450mg) all in one pill. I heard about that one in an email from Sanofi, about this new formulation called Azplenzin (though you have to order 522mg to get 450mg). This one's so new, a Google search turns up only 3 hits.

So, I'm just saying that the marketing works to get something new noticed. The more important part is doing the research to determine if it is something that may help you or your patient.

Paxil, anyone?

I ran a poll, not long ago, after reading Peter Kramer's blog post on the relative efficacy of the different SSRI's. Here's what we found:

Which SSRI is the most Effective?

Prozac 15% (22 votes)
Zoloft 14% (21 votes)
Luvox 0% (0 votes)

Paxil 5% (8 votes)
Celexa 7% (10 votes)

Lexapro 19% (28 votes)

Cymbalta (SNRI) 13% (20 votes)

Effexor (SNRI) 18% (27 votes)
Wellbutrin (neither, but it's here anyway) 9% (14 votes)

Total Votes: 150

Which Medicine Causes the Most Side Effects

Prozac 13% (17 votes)
Zoloft 7% (10 votes)
Luvox 5% (7 votes)
Paxil 31% (41 votes)
Celexa 1% (1 votes)

Lexapro 4% (6 votes)
Cymbalta 7% (10 votes)
Effexor 25% (33 votes)

Wellbutrin 7% (9 votes)

Total Votes: 134

Okay, so let's start by talking about how this 'poll' is meaningless. We don't know who took it-- patients, docs, random plumbers surfing through. We don't know what experience these people have had with antidepressants-- so the question has different meaning if it's asked to a doc who has only ever prescribed Prozac and Zoloft, then if it's asked to a patient who has been on a long trial of every medication. There's no real head-to-head here, no measures of efficacy, no controls. And I didn't even specify what the efficacy was for: Depression? Anxiety? OCD? Panic? Halitosis? Slipping behind your ear to hold your glasses in place?

Still, we had a clear loser, and I was surprised: Paxil. Few people voted for it's efficacy, many for it's side effects.

I don't start people on Paxil so much anymore: the lore is that it causes more weight gain then the others, and when I do prescribe it, I tell people to get weighed. It may cause weight gain, as an overall risk to populations, but all I care about is if it causes weight gain to my particular patient, and clearly, some people do not gain weight on it. The more concerning thing about Paxil has been the withdrawal syndrome that some people experience and so far I've found that it's manageable, especially if people come off very slowly. Still, all things being equal, these days I may start with something else.

So why was I surprised: I guess I haven't heard a lot of patients complain about side effects, and I have patients who've been on this medicine for some time. It seems to work particularly well, at least that's my impression, for Anxiety, and it seems to be well tolerated, the 'polls' would say otherwise. And for the uninsured, the generic is on Walmart's $4 list (as is Celexa).
Just my thoughts.

And to those who've read yesterday's post about does Facebook wreck your brain: If you read either the original article or the comments to our post, you'll note that the original piece is simply theories that all this computer time may re-wire people; there were no studies, no proof. And as some of our readers pointed out, On-line interactions may well be a segway into the world of Real Life encounters for people who might otherwise hesitate. I often wonder if my college experience would have been broadened by the world of the internet---

Quote of the Day

I've had a long day and it felt like every one was pretty troubled. I'm trying to decide who to give credit to for the 'quote of the day.' I started by thinking it might go to the person who informed me that I looked good (always nice to hear) and then added that usually I look sick and I've gained some weight. Okay, I'm not sure what to do with that one.

I've decided, instead, that I liked the remark posted by blogging psychiatrist Doug Bremmer in the comment section of my post Tell Your Doctor if You Experience Any of the Following....

He writes:

Doug Bremner (MD) said...

As a "blogging doctor" I am struck by how much anger there is out there about side effects of antidepressant medications, and how much psychiatrists are felt to be to blame for that. Perhaps there has been over-promotion of prescription medications. But there are side effects that we don't know about and only learn about with longer experience. We are not magicians or mind readers.

I do often feel when I read our comments from readers who've had bad experiences with medications or hospitalizations or psychiatrists who say insensitive things, that people feel there is something purposeful about it. It's hard when someone comes in and describes something as a side effect of the medication and I recall that the symptom was there before the medication was even started. With time, we've learned that this can be the case-- if a patient starting an SSRI now says "this medication is making me feel more suicidal," Docs listen. It's still hard when someone says a medicine causes a side effect never described and I don't know what to do with it. Sometimes I try to talk people into staying on their medication if, for example, they complain that a newly added anti-depressant is making them more depressed-- the medicines take time to work, weeks in fact. If a patient continues to complain, eventually I'm left to conclude that this medication either doesn't work or isn't tolerated in this person. Sometimes people complain bitterly about side effects while at the same time they say they feel the medication helps, and then I say: It's up to you. It gets trying when this means that every visit consists of stopping a medication that hasn't been given a fair chance only to begin another medication-- the arsenal of medications available can be run through pretty quickly with this strategy and it doesn't make sense. Okay, I'm rambling.

Are You Chemically Unbalanced?

This will be quick; I'm actually headed off to work.

In his "In Practice" blog, Peter Kramer discusses the issue of whether the concept of a chemical imbalance is still a useful one and he looks at the evidence for and against such a theory, concluding that the concept met a premature death.
"Since 1993, other biochemical contributors to depression have claimed their roles, especially “stress hormones” and factors that influence nerve cell growth. The new overarching biological model of depression (I outline it in Against Depression) integrates all three factors—monoamines, stress, and cell growth—but serotonin dysregulation remains very much on the table as a contributor to depression."

Dr. Kramer talks about PET scans and genes and differential rates of monoamine metabolism, and the stupid little bouncing Zoloft mascot with the smiley face.

For the shrink in the field, so far it doesn't mean much. I can't order a test to find out if someone has too much of one enzyme breaking down any given neurotransmitter and thereby telling me what to prescribe. I'm waiting. In the meantime, what I do have is patients who come in wanting to know what they have. "Do I have a chemical imbalance?" Now what does that even mean? Do you have too much serotonin in some places in your brain and not enough in others? How would I know that? Too much (compared to what?) monamine oxidase breaking down your noradrenergic neurotransmitters? Should we inhibit them and this will make you better? Let me get my probe.

What I do know is that while I don't know what is meant by a "Chemical Imbalance," my patients do. For them it is a term that explains things, that writes the story, that has meaning. There's something socially acceptable about it. "I have poor coping skills" is pejorative and equally unprovable. "I have a chemical imbalance" is somehow explanatory, though still unprovable in a day-by-day psychiatric practice.

So, generally, if a patient with Major Depression asks, "Do I have a Chemical Imbalance?" I simply say "yes." It seems to work.

Why This Shrink Doesn't Prescribe MAOI's

Graham wrote in a question:

OK, so since it was a pretty generic post, I'm going to ask a question of you three that's pretty far off topic. Why do you think MAO inhibitors are so infrequently used in psychiatric practice today? Besides dietary/drug interactions, their safety profile is good. There are masses of studies showing efficacy. Why switch patients from one SSRI/TCA to another to another instead of trying a MAO inhibitor. Do you think MAOI's have a place as second line agents in certain circumstances?

What a great question, I've been thinking about this one for a bit and this is what I've come to. I don't use Monoamine Oxidase Inhibitors (MAOI's) to treat depression or anxiety, though from time to time, I think about it. Why not? It's a really good question, they are really good medications, sometimes helpful when other meds don't work, and lore has it that they are helpful with "rejection sensitivity" in patients with borderline personality disorder.

So Why Don't I use them?

1) They are dangerous in combination with a bunch of foods-- aged cheeses, certain red wines, fava beans, and I'd have to look up the rest of the list. It includes medications, even some over-the-counter medicines. Accidental or purposeful ingestion of these substances in combo with MAOI's can lead to hypertensive crises-- think stroke and death. This makes me a little wary.

2) Pure gut bad association-- at the hospital where I went to medical school, the young daughter of a New York Times editor died-- the combination of MAOI's and prescribed Demerol were thought to play a role in her death.

3) I don't like to give patients medicines that they can easily fatally overdose on.

4) My own naivete. By the time I started residency training in psychiatry, SSRIs were hot. Many patients were on TCA's (tricyclic antidepressants, and you can OD on these, too). I saw two patients in my residency on MAOIs. I've worked in 3 different clinics, each with an active caseload of about 1,000 patients. There was one patient in the first clinic I worked in (1992) on an MAOI. I've never seen the chart of any other patient treated at any of these clinics with an MAOI. Okay, I haven't seen any patient's chart, but the point here is that I'm just not familiar with them, so they aren't my first/second/third/fourth choices for treatment. Should they be?

5) Once you've used an SSRI, you have to wait weeks to use an MAOI, not always an easy prospect for a depressed patient.

Thanks Graham, I'm running my next sidebar poll in your honor!

This is Why You Need A Psychiatrist

From today's Wall Street Journal, an article on how antidepressants aren't all they were cracked up to be: Antidepressants Under Scrutiny Over Efficacy. David Armstrong and Keith Winstein write,

"Since the overwhelming amount of published data on the drugs show they are effective, doctors unaware of the unpublished data are making inappropriate prescribing decisions that aren't in the best interest of their patients, according to researchers led by Erick Turner, a psychiatrist at Oregon Health & Science University. Sales of antidepressants total about $21 billion a year, according to IMS Health."

Actually, the issue at hand is that the pharmaceutical companies don't publish or make public the studies that don't show the results that will sell their meds. It's not a news release that we've suddenly realized that antidepressants don't always work. These are two separate issues. The WSJ article is based on a report in the New England Journal of Medicine, Selective Publication of Antidepressant and Its Influence on Apparent Efficacy, and it uses data on antidepressant studies to make this point. Okay, it's also about how antidepressants aren't as effective as the drug companies say they are, but this just doesn't surprise me. The WSJ article goes on to say,

"There is a view that these drugs are effective all the time," he (Dr. Turner) said. "I would say they only work 40% to 50% of the time," based on his reviews of the research at the FDA, "and they would say, 'What are you talking about? I have never seen a negative study.'" Dr. Turner, said he knew from his time with the agency that there were negative studies that hadn't been published.

There's someone out there who thought antidepressants work all the time? This is why people need psychiatrists, not primary care docs, managing their psych meds:

1) Even at high enough doses given for long enough (6 weeks), any given antidepressant may not work on any given patient. Or it may help with some symptoms and not others.

2) If one antidepressant doesn't work, another might.

3) If one antidepressant doesn't work, augmenting with a second medication may work.

4) As a patient suffering from Bipolar Disorder, depressed, moderate in severity, recurrent, said to me recently, "I think the therapy helps as much as the medicine."

I don't think it's news that a) anyone can write a prescription for Prozac and the patient may not get better, or b) this is complicated stuff.

The issue of the pharmaceutical agencies hiding their negative data is also not news. Personally, I think the legal penalties for withholding this information should be stiff enough to stand as a deterrent. You just don't hear of drug company CEO's in the cell next to Martha Stewart.

My Three Shrinks Podcast 37: Poop-Out

[36] . . . [37] . . . [38] . . . [All]

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Sorry for the delay in getting podcasts out, folks. This one may be a bit confusing, as we recorded it prior to the new sound equipment, so it is not "new and improved". This is actually #37. So, the next one to come out will be #39 (later this week... really! :-).

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December 9, 2007: #37 Poop-Out

Topics include:

• SSRI Poop-out (a.k.a. tachyphylaxis). This is the phenomenon where a drug is working, then seems to wear off or stop working after some period of time. (see also How a Shrink Picks an Antidepressant, Family Intervention Overcomes Poop-Out, and Stassen's article on resilience.) (I also referred to the use of gestures when speaking.) Also discussed placebo response, light therapy, and Dinah's shpiel.
  
  
• Google Ads. We discuss issues about our minimal use of ads on the blog.
  
  
• Q&A from Tony. Refer back to Questions for the Doctor.
  
  
• Clink's Opera Post.
  

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Find show notes with links at: http://mythreeshrinks.com/. The address to send us your Q&A's is there, as well (mythreeshrinksATgmailDOTcom). This podcast is available on iTunes (feel free to post a review) or as an RSS feed. You can also listen to or download the .mp3 or the MPEG-4 file from mythreeshrinks.com. Thank you for listening.

How This Shrink Picks A Sleep Medication

I have more to say about sleep medications. But I have a lot less to say about choosing a sleep medication than I do about choosing an anti-depressant, and my thinking on this is a lot less structured.

Everyone who wants medication to help them sleep gets a talk about the obvious sleep hygiene issues. Here are the basics:
-- Choose a 7 hour period during which you'd like to sleep. Keep it the same everyday, for example, midnight to 7 am, but the exact hours aren't important. The regularity is. Set an alarm.
--Don't nap.
--Don't watch TV or do anything else interesting in bed (sleep and sex, that's it)
--No caffeine after 2 pm. And not much before that. That includes caffeinated soda and iced tea and sadly, chocolate.
--Exercise regularly, preferably 3 hours before you go to bed, but absolutely no closer to bedtime.
--Limit alcohol, and don't drink it near bedtime, it screws up your sleep architecture.
--If you have sleep apnea, use your CPAP machine. Really.

No one follows these recommendations, at least not when I make them.
Linda, the self-proclaimed sleep Nazi, would add: No Screens of any kind after 11 pm for adults and 10 pm for kids-- no computers, TV, video games. Even I'm glad I don't live at her house.

I prescribe sleep medications frequently, insomnia's a common complaint. Sometimes I feel strongly that someone should take a sleep medication-- disturbed sleep goes hand-in-hand with affective (mood) disorders and in patients subject to manic episodes, sleep is really important and I worry that poor sleep habits might either announce or precipitate an episode. Often, though, I feel like it's not the end of the world if every night's sleep is not perfect (great blogging gets done in those wee hours), and that some people are too quick to look to pills to fix problems. I'm probably going to get blasted for that one.

Sleep issues take on a life of their own. People get anxious about not sleeping and it builds on itself. They have all sorts of expectations about how much sleep they need or should have-- one patient was beside herself because she was only sleeping 6 hours a night and felt she needed 8 to 9 hours. Maybe she was right, but when I suggested that maybe she only needed 6 hours and that's why she was waking up, she felt I was dismissive and she found another doc. Another patient said he was greatly relieved when I told him his body was getting rest by just lying there quietly, he stopped worrying so much, and his sleep improved (plus, he turned on his CPAP machine).

All medications have the potential for side effects and adverse effects. Sleep medications are no exception. And many sleep medications are addictive and many patients insist they won't become addicted. And even folks who don't become addicted in an up-the-dose, abuse-the-med kind of way, they get habit-forming, whatever that means, and there are people who will end up taking a pill to sleep every night of their lives and won't hear of even trying to stop the medicine.

So my non-scientific, mostly random method of picking a sleep medication:

If the patient presents with depression, I hope that as the depression resolves, the sleep disturbance will resolve. Some anti-depressants are so sedating (TCAs, Remeron, Serzone, Trazodone) that they are effectively sleeping pills. Other times the anti-depressant, especially SSRIs, cause the sleep disturbance.

Trazodone. It works well in combination with SSRI's. It's cheap. It's not addictive. It's easy to stop. The down side: the fear of priapism and there have been case reports of patients who need surgical intervention. Ouch. The other downside: it doesn't always work, even in escalating doses. Or, it works but patients complain of feeling drugged for hours after waking up. When it's good, it's good.


If trazodone doesn't work or isn't tolerated, and there is no history of substance abuse (particularly of issues with alcohol/benzos), then I try Ambien. This usually works, and it doesn't have a hangover. At least it works for a while, some people get tolerant to it's effects. And some people never want to stop taking it. It's theoretically not very addictive, but it does hit those same benzodiazepine receptors.

If there's a history of substance abuse, I may try visteril. This works only rarely. Once someone has had extended exposure to alcohol or benzodiazepines, it's hard to knock them out.

If visteril doesn't work, I try Rozerem, even though I hate the Abe Lincoln/Beaver advertising campaign, and even though it costs a small fortune, and even though it did terribly on our survey. It does seem to work.

Sometimes I use seroquel or zyprexa. These work, though they have that same effect of leaving some people feeling groggy in the A.M. With all the concern about how these medications are linked with diabetes and lipid disorders, I use low-doses, as needed only for the short-term, and I don't prescribe it as quickly as I used to. Unlike many sleep medications, these are fairly easy to stop.

If there's no history of substance abuse, if the patient is a light social drinker with no history of abuse, then I may try ativan or valium for a short term issue. Restoril works well, though with it's long half-life, it's always a bit surprising that people don't feel groggy on this the next day.

I've never prescribed Sonata, and the first and only patient I gave Lunesta to complained of a horrible taste in her mouth.

With those thoughts, Good Night, Sleep Tight, Don't let the Bed Bugs bite.