reefer madness

“Doctor, I’m afraid I might have ruined my brain.” Mr D’s wide brown eyes bore a pleading expression.  He was a young law student with a cherubic dimple set in his left cheek.  He had had no history of psychiatric issues until six months prior to our appointment.  Then, one Saturday evening during his winter recess from school, he’d celebrated the end of the semester with friends by smoking an enormous amount of marijuana and attending a 3-D movie.  

During the movie, he told me, he had a terrifying experience.  “It was as if I’d lost all of my memories.  I knew nothing.  I was nobody.  I was starting over.” During the course of the movie he gradually regained his memories but retained a feeling of foreboding.  Ever since that time he had been having episodes of déjà vu in which otherwise innocuous situations would give him the sense that he was about to be catapulted back into the memoryless state he had experienced in the movie. 

Simple triggers like buying a cup of coffee at his favorite stand would give him a sudden, horrifying feeling that he had been there before, and that he knew what would happen next: He would be thrown back to the place of no memories.  Or, he was having a dream and he would be forced to relive this same sequence in an endless loop, forever.  The feeling would last a few minutes, and then dissipate as surely as it had come. 

He’d been having experiences like this up to thirty times a day, ever since that night at the movies.  They were interfering with his sleep, his work, and his love life. He hadn’t touched marijuana again since that night.  Still, they weren’t going away.  Finally he decided he needed help.  Could I help him?  He spread his hands nervously on his lap. 

Marijuana use has long been associated with increases in psychotic manifestations.   (For many years it was unclear whether marijuana truly tilted the brain towards psychosis, or whether marijuana was simply more appealing to the psychosis-prone brain.  Earlier this year, the results of a decades-long study of marijuana use and psychosis in 3800 individuals were released (McGrath et al).  They confirmed the results of two other large cohort studies that found the longer people had been using marijuana, the more likely they were to report psychotic symptoms.  In addition, this most recent study analyzed sibling pairs and found that the same relationship held true – weakening the argument that some other, unknown genetic or environmental factor might be stacking the deck.) 

However, Mr D.’s symptoms weren’t the classical psychotic signs of hallucinated voices or paranoid delusions.  The déjà vu reminded me more of neurological oddities such as temporal lobe epilepsy than of any psychiatric syndrome.  But this patient had neither a history of epilepsy nor any risk factors for seizure, and the link to marijuana use was too clear to ignore.  I decided to offer Mr D. an antipsychotic – the very sort of drug we give to people who insist that the aliens are after them, or the CIA has bugged their hospital rooms, or they are the Messiah.              

I made the offer tentatively, worried that the very word ‘antipsychotic’ would set alarm bells ringing in Mr D’s formerly entirely sane and rational young head.  I more than halfway expected him to refuse it.  But to my surprise he accepted it eagerly.  “I’ve been living with this for six months,” he explained.  “I just need it to stop.”            

And stop it did.  Two hours after his first dose, Mr D reported to me the next week, he could feel the grip of his illusions relaxing.  Within a few days he went from having thirty episodes per day to having fewer than ten.  After two weeks on the drug he felt he was his old self.  He discontinued the medication without incident.            

There is much we do not know about the neurobiological effects of marijuana.  The psychoactive ingredients, cannabinoids, come in dozens of varieties whose relative proportions vary from plant to plant, presenting a complexity of Gordian proportions to the would-be researcher.   

Our bodies’ cannabinoid receptors (built to respond to our own endogenous cannabinoids but, happily for college students the world over, also responsive to the herbaceous variety) are found generously distributed throughout the brain (Glass et al.), including the frontal cortical areas that are implicated in psychosis.  They seem to act as local modulators, damping the strength of signals coursing through the brain’s circuits – including the frontal dopamine circuits in which hyperactivity seems to underlie psychotic episodes.  Tire out the endocannabinoid ‘braking system’ by flooding it with ganja, and you have an unchecked river of dopamine signaling leading to hallucinations and paranoia (Fernandez-Espejo et al.). 

Why should this cause psychosis long after the marijuana is gone from the system?  I don’t know the answer, but I do know that for Mr D., the way to fix it was to use a dopamine-blocking antipsychotic.  He’s doing well so far, though perhaps a bit wiser and warier. 

designer brains for all!

So let me say up front that this is a Rant, one inspired by the fifth young go-getter this week to walk across my threshold demanding I diagnose him with AD(H)D and prescribe him Adderall to get him through his dissertation/term paper/research proposal/whatever.

In my (not so) humble opinion, AD(H)D is not so much a disease (in the sense of a physiologic malfunction) as an unfortunate interaction of personality x environment. Certain personality types just don’t do well with being required to sit in a chair for 8 hours a day. A lot of those same people would probably do phenomenally well at running around outside spearing buffalo, (see Kuo and Taylor), but sadly for them, that’s not the environment in which they find themselves.

So, we have medication that can alter these people’s brains so they conform more acceptably to the society where they do find themselves. We could have another very long and involved discussion about whether that’s a good choice or not but my feeling is, if a pill is the difference between good function and borderline or poor function, then please, weigh the pros and cons and make your own decision. It’s your brain. Not my business to dictate whether you ‘need’ it or not.

What I really don’t like is the cultural apparatus that is telling us the suboptimally attentive have a Disease, because the only legitimate reason to take a drug is if you have a Disease, and therefore that these people who take stimulants so they can function more effectively at work or school must have a Disease, because that is the only socially acceptable way that they can take their medication.

And what I really, really don’t like is that as a physician I am being put in the middle of this. I am being told that the only way these people can have their medication is if I diagnose them with a Disease and prescribe them the medication to Treat it. There’s no box to check that says “This could help you do better than you are doing now, and I don’t mind if you take it, so long as you understand the risks and benefits.” There’s only the Disease box and the No-Disease box. And I can’t give out the drug unless I check the right box.

The thing about treating this Disease with stimulants is that, in the right dosage and formulation, they are going to be performance enhancers for *most people.* How many thousands of students and professional writers have used a jot of speed to get them through that important deadline? I’m currently working in our university’s student health center, where I see a lot of people who are coming to me for stimulants so they can make their already excellent function even better. I honestly do not mind if people want to take brain-altering chemicals to help them write their papers – I’m swigging a bolt of caffeine as I write this post – but I do get a squicky feeling when I’m asked to write a doctor’s note about their ‘disease’ and a prescription so that they can ‘treat’ it.

So in my perfect world there would be public recognition of the wide latitude of uses for psychotropic medications, the terribly broad and nonspecific symptom clusters that constitute what we refer to as psychiatric disease , and the many reasons why people might want to take a drug that improves their ability to get their work done (see interesting perspectives on this from Nature and the Guardian) - even if their current abilities are well within the broad range of normal. Will the public accept the availability of a smorgasbord of designer psychotropics for your business and recreational neuroenhancement needs? Maybe, maybe not. But please, let’s stop putting doctors in the middle by maintaining the fiction of a ‘disease’ for which stimulants are the ‘cure.’

family matters

Mrs U first came to my attention some time after the birth of her first child. She was a stately woman, dark and slender, dressed always in brightly colored robes. Her husband brought her to see us because she had stopped speaking. Ever shy, he reported that she'd become gradually more and more taciturn, and at the time of our first meeting she hadn't said a word in several weeks.

At first we were uncertain of the cause. Was she so depressed that she had withdrawn entirely? Did she perhaps have a medical issue, such as insufficient thyroid activity or a vitamin deficiency? Mrs U's thyroid levels, as well as the rest of the blood tests we ran, were entirely normal. We started her on a small amount of an antidepressant, and soon added an antianxiety agent. She started speaking again, though she still had periods of mutism, often when she was stressed or upset.

Around this time, Mrs U and her family took a trip home to Africa, to visit her large and close birth family. They spent several months there. When they returned, Mrs U was a different woman. She smiled pleasantly, laughed at her recollections of her trip, planned eagerly for some classes she intended to take. She remained somewhat shy but the episodes of speechlessness had vanished.
"I could see her getting better by the hour on the plane trip over," Mr U told us. "It was amazing, Doctor. In the airport on this side she seemed anxious, terrified, looking here and there, speaking little. As the hours on the plane passed she began to smile a little. By the time we reached her childhood home she was almost entirely herself again, so that even her own mother could barely notice anything amiss!"

We smiled and nodded, happy to see Mrs U doing so well. She weaned, uneventfully, off her antianxiety medication, though she continued to take the antidepressant. Things remained this way for several months. Then, slowly, she began to deteriorate again.

Her eye contact was the first sign. Though always retiring of manner, when well she met my eyes in conversation, with an occasional frank and open smile. As time passed, though, her eyes began to slide past me even as she answered my questions. They would be fixed on the floor, or out the open window. She maintained our conversation appropriately. Nonetheless she seemed to be elsewhere. I filed that under 'to be kept track of' in my mental cabinet.

Soon after that I began to receive concerned calls from Mrs U's husband. She had begun to say strange things. One day she was convinced that she should leave her husband for a stranger she had seen on the street. Another day she became obsessed with a cartoon she had seen on the television, referring to it over and over. She was unable to keep up with her classes and had to drop them. However, she
always said her mood was fine. She didn't seem anxious or sad in the least, only... strange; and increasingly so. She continued to care for her son ably and with great patience, according to her own word and to her husband's observations. Our original diagnoses of depression and anxiety seemed less and less satisfying.

Ultimately things came to a head when Mrs U began to have frank hallucinations, horrible ones of vermin in her mouth and people under the stairs. That sealed her diagnosis as a psychosis of some form. We started her on an antipsychotic and slowly, things started to improve.

After a couple of weeks of treatment the floodgates opened. Though she'd never before put more than ten words together in my presence, she was fluently talkative. She revealed that she'd been having horrific religiously themed nightmares for a year. Voices of people in her house. A chip implanted in her head. CIA cameras hidden all around her. All very, very classic psychotic symptoms.

I felt silly that I hadn't recognized this before. Mrs A, in her early twenties, was the right age for a first psychotic break. It's very common for schizophrenic patients in the throes of their illness to withdraw completely from the world, unable to give voice to the phantasmagoria in their heads. Easy to recognize after the fact; but since social withdrawal can also reflect depression, anxiety, and other common woes, things are not always clear in the moment.

She did reasonably well on her antipsychotic, though she was still somewhat odd. She would laugh at inappropriate moments and stare vacantly through the window when you talked to her. Her husband was frustrated with our inability to return his wife to her old self. We were frustrated with it as well.

Shortly after starting the antipsychotic, Mrs U took another long trip to her home country. Once again, her symptoms improved. Although she was not able to wean off her medication, she appeared to recover a good deal of her old personality. She was able to interact normally with her family and friends and handled her domestic duties without difficulty. Ultimately her husband decided that his family was best served by staying in their home country. As of this writing Mrs U remains well.

Mental health and mental disease are defined largely by functional capacity. If a person can live, love, and work, we consider him well. But the level of function required for love and work may differ radically from society to society. The 'basic capacities' required to live among secure and supportive extended family, and perhaps do some simple labor under supervision as necessary, are quite different from the 'basic capacities' required to live alone, maintain employment, and manage personal finances complete with lines of credit and other pitfalls.

Schizophrenic patients exist at all levels of functioning, ranging from those who require ongoing institutionalization to extremely high-functioning and high-achieving individuals. The differences among them may be partly due to severity of disease and to innate psychological reserve, but are also strongly dependent on the environment surrounding each.

Over the past six decades, the increasing availability of medication for psychiatric illness, along with factors such as social change and cost concerns, have led to the deinstitutionalization of the mentally ill. In the US, where strong and supportive extended families are not the rule, this has often led to the need for a sort of wraparound care, where a cadre of social workers and psychiatrists helps to guide each patient through the complexities of daily life. In the crudest sense they are functioning as a paid family - much as we in the US have outsourced other former family domains such as child care and elder care. This outsourced domestic work then counts as part of the GDP, and to the economic might of the nation. What isn't clear to me is whether - acknowledging such clear improvements as the reduction in social stigma that attaches to mental illness - such a solution is a gain overall for the mentally ill themselves.

Prozac for the unhappy marriage?

(The characters sketched in this piece are composites of several individuals I’ve encountered in my training and my life. They contain elements of real patients and acquaintances but do not represent strictly true accounts of specific people.)

The couple who walked into my office for a consultation the other week seemed, at first, similar to many of the South Asian immigrants I've met. He, confidently dressed in Western clothing, entered and spoke first. She, slim and even-featured in a brightly colored sari, had a diffident smile and walked a step or two behind her husband.

They'd come, he (and she) said, because she was depressed. She seemed sad, a bit withdrawn, wasn't sleeping well. Could I help?

The husband graciously offered to leave the room so I could talk privately with the patient. She remained vague about her concerns. She reiterated that she felt a bit down, but then said that really she was feeling all right. She admitted to waking frequently at night but then said really she felt well rested enough. She agreed she'd lost some weight, but then volunteered that she'd been about this weight before the birth of her first child so that seemed all right to her. And her marriage? Well, yes, perhaps there were some problems in her marriage. What problems? Oh, nothing. Well, maybe something. Maybe nothing important.

I probed gently, cautiously. The marriage was an arranged one. I nodded, unsurprised. At twenty years of age, this woman had married a man she'd known only a couple of weeks and then followed him to the farthest corner on the globe from her family and his. Since then they'd had two children together, and made a place and a life for themselves in a local community of similar immigrants. On the surface, things were fine.

And beneath that? Well, perhaps their sex life wasn't... what she would wish. She was resolutely vague on this matter, absolutely unwilling to offer up any detail or clarification.

We made no headway until the patient's husband returned and revealed the room's elephant: He was gay. He had had several homosexual encounters with men over the course of the marriage. He understood this was contributing to his wife's pain. He wondered whether I would be willing to help her out. With an antidepressant.

In truth, I was stunned. Evidently the man did not see his homosexuality as any significant barrier to maintaining his marriage. I glanced at the woman. She had turned her face entirely away from both of us and was staring resolutely at the door. Every tendon in her taut pose said I want out of here.

Open homosexuality in India is, frequently, tantamount to social suicide. The term 'gay' is used as an insult, indicating unmanliness or cowardice. Avowed homosexuals are often treated as outcasts from mainstream society. Nonetheless, since the decriminalization there of homosexual intercourse in 2009, gay social scenes have blossomed cautiously in the larger cities. Yet in a nation in which three-quarters of the population lives in rural areas, this is still a drop in the bucket. Indian society is structured around the extended family unit. A single person past the age of marriage generally loses social status and suffers gossip and stigma. Marry one must then, and present one's parents with healthy and studious heirs.

Any wonder, then, that many of India's gay population simply bow to the cultural expectation of marriage? No need to suffer the singles scene; marriage to someone suitable can be arranged swiftly enough to avoid tripping the gaydar of the lucky bride (or groom). If s(he) has any. One can easily be married in India far younger than the age when many gay Westerners discover their own true sexual orientations.

And then what?

Escape to the West offers some slippage of the knot. Far from the watchful eyes of family and neighbors, hairline cracks in the marriage eggshell are not so visible. If one spends a lot of time with male friends, if one's wife seems saddened and distracted, who is to notice really? And if one can grit one's teeth and think of England enough times to produce a male heir, then none will be the wiser.

But with freedom comes peril. Divorce is not so taboo here. In India, a divorcee can expect social opprobrium and little chance of remarriage. The cost associated with leaving an unsuitable husband may thus be far greater than the benefit. (Divorced men have more hope of a second chance.) But in the West, that calculus can be reversed.

What to do with the couple before me? An antidepressant seemed unlikely to improve the situation. The wife had no past history of any mood disorder, and antidepressants don't fix trying life circumstances. Counseling seemed in order, but I wasn't culturally equipped to provide it. What would be the goal? To maintain the marriage? To dissolve it? The husband's wishes seemed clear but I wasn't sure the wife would ever say enough to me for us figure out what it was she wanted.

Ultimately I told them I'd ask my colleagues to see if I could find them a referral to a South Asian psychiatrist who, I felt, might have a better chance of helping them. Neither of them seemed particularly happy with that - after all, there is also a stigma against mental illness among Indians that presents a strong barrier to either consulting a psychiatrist or becoming one. It had probably taken a good deal of courage and need for them to come to me in the first place, and here I was passing the buck to somebody else. I felt sorry for these two people, yoked sadly in an arrangement that fulfilled neither. But the pills and workbooks in my arsenal were not designed for such a situation. What they seemed to need, I thought, was the answer to Reinhold Niebuhr's Serenity Prayer: serenity to accept the things one cannot change, courage to change the things one can, and the wisdom always to know the difference.

(A little note about my extended absence: After a promising start, I let this blog go by the wayside just about a year ago, shortly before I had my first baby. I find being a parent is absolutely fantastic and also supremely absorbing and time-intensive. My daughter is now ten months old and I'm just starting to recover my interest in the world around me. It seems like a good time to revive the blog.)

Now that I spend three days a week at home with my daughter, I'm listening to a lot of talk radio to get my grownup time.

Yesterday morning while supervising the gleeful mashing of banana into hair, I heard a fascinating NPR interview with Barbara Strauch.


She's the science editor for the New York Times who recently wrote a book called "The Secret Life Of The Grownup Brain."

I've yet to read it (though it's now on my list!), but based on the interview Ms Strauch's book is an exploration, not of the decline and fall of the aging brain, but the changes - some for ill but some for good - that come to cognition with middle age. The young brain may be better at rapid calculation and short-term memory, but the aging one seems to be better at recognizing where information fits into existing patterns.

"We are better at getting the gist of arguments," she says. "We are better at recognizing categories. And we're much better at sizing up situations. We're better at things like making financial decisions, which reaches a peak in our 60s. Social expertise -- in other words, judging whether someone's a crook or not a crook, improves and peaks in middle age."

Now this doesn't quite fit with the common perception that the brain just gets mushier and mushier with age. Interviewer Terry Gross was posing questions from the point of view that the brain goes into a smartness free-fall after somewhere around age 25. As evidence, she pointed out that synapses - the electrical connections between nerve cells - decrease in number over time. She assumed this meant a parallel decline in cognitive capacity, as if synapse number were equivalent to 'smartness dose.' More connections mean more braininess, right?

Well, it may be a little more complicated than this.

One might think that you'd gain synapses as you learn things; but actually, the brain has the most synapses at a time when it knows the least. Synapses are overproduced in childhood and then reduced as the brain matures. As you grow and learn, some existing connections are strengthened and new synapses are formed - but more are weakened and pruned away.

J Comp Neurol. 1997 Oct 20;387(2):167-78.
Regional differences in synaptogenesis in human cerebral cortex.
Huttenlocher PR, Dabholkar AS.


This pruning isn't simply the death of brain tissue and reduction in cognitive capacities. It is more like specialization: as a sculptor carves away excess marble to reveal his intended form, so the brain prunes away excess connections to reveal a latticework of meaning. We are still pretty far from understanding exactly how this works, but here is a really nice paper from a few years ago that proposes a model of how changes in the strengths of nerve cell connections might underlie learning:

Fusi, S., Drew, P. and Abbott, L.F. (2005) Cascade Models of Synaptically Stored Memories. Neuron 45:599-611.


So Strauch's thesis, that the middle-aged brain is better at putting things into context, parallels the common understanding that as we gain life experience, we are more able to assimilate new information in terms of the many things we already know. It's called wisdom, and older people in traditional cultures around the world are revered for it. Funny that we should require all the power of modern neuroscience to remind us of this!

Market competition is not going to fix US health care

Imagine you are getting your car serviced. You bring it to the shop, you get an estimate. When the work is done the shop presents you with a bill. It may be a little more or less than the estimate was, but either way that's what you'll be paying. Now imagine that instead of paying the bill as it's presented, you tell the shop: No, I don't think your work is worth this much. In fact I think it's only worth half this much, and that's what I'll pay. You pay half the bill and walk out, leaving the mechanic with his mouth open.

Sound out of line? This is exactly what happens every day to health care providers across the country. I recently made two visits to a specialty practice group at a large public academic hospital. Here are the services I received:

2 ultrasounds: ~40 minutes of time with each of 2 ultrasound techs and ~20 minutes of time with an attending radiologist (+resident but she was just observing)
~20 minutes of counseling with a pediatric surgeon
~20 minutes of counseling with a high-risk OB

Don't forget all the overhead costs and behind-the-scenes work like maintaining the ultrasound, scheduling the appointments, dictating and transcribing the reports, discussing the case, etc.

The cost for all of this work was $994. I have to say this doesn't sound unreasonable to me, though perhaps others' views may differ.

The insurance company, however, decided the work was worth only $477.12. That left the hospital $516.88 in the hole. But since they have an agreement with my insurance company, I'm not being held responsible for the difference. The hospital is presumably going to eat the cost. (I'm planning to call the practice group and offer to pay the difference, because I got excellent service, I was treated incredibly well, and I feel terrible that my insurance company is screwing over the hospital like that. But that's a side issue.)

In any other line of business you'd be stuck paying the sticker price, regardless of what you thought was fair. Only in health care does a third party get to decide what a provider's services are worth. The doctor or hospital can say ahead of time, we will work with Insurance Company A or we won't; but once they agree to work with that insurance company they are bound to accept whatever the insurance company decides is fair reimbursement.

Surprised at the cost of your health care? Remember that if you or your health insurance company pays in full, you're subsidizing all the people who don't have health insurance, or whose insurance (like mine, or like MediCare) doesn't pay the full cost of the services provided.

This is just one of the many ways that the insurance system divorces the health care system from the competitive forces of the free market.

Here's another one to wrap your brain around: Basic market principles imply a cost for a product or service. The better your product or service, the more you can charge for it and (in a perfect world) the more money you make. Right? Not down the rabbit hole of health insurance. Insurance companies make money by *refusing* the service they ostensibly provide - payment for health care. The more claims they deny, the bigger their profit margin. This completely subverts the competition principles of the free market. It also results in insurance companies spending a lot of money to pay people who figure out how to deny claims. Hence (among other, more complex reasons) why private insurers in the US have three times the overhead of MediCare, which doesn't waste effort figuring out how to deny people's claims.

Check out also this comparison of overhead costs in the privatized US system versus the centralized Canadian system (Woolhandler et al., NEJM 349:768-775):

And hence why placing blind trust in the power of the free market is, at least in this instance, a terrible idea.


In fact, not only is the health insurance system divorced from the principles that make free markets successful, it's divorced from its own founding principle of spreading the risk.

The whole point of insurance is that you have a large number of people at risk for an adverse event. These people all pay into a pool that will cover the small number who actually experience the adverse event. Somehow insurers decided it was OK to start divvying people up into risk pools, so that people who are less at-risk pay less, and people who are more at-risk pay more (or are blocked from getting insurance entirely). Sounds reasonable at first, but it's a slippery slope. As we find out more about ways to predict risk, we can charge sick (or risky) people more and more and healthy (or low-risk) people less and less. Soon you have a system where all the sick people are blocked from participating, or are paying the costs of their own health care with no participation from the healthy community. That's not spreading the risk. You might as well just pull out your checkbook and pay your doctor his fee. Except then you wouldn't be generating profits for the insurance companies.

The only way health insurance is going to work is if we go back to the basics:
If you want to use a risk-spreading model, everybody needs to participate. Young, old, sick, well. No excluding people and no basing premiums on expensively-generated risk profiles. Practically, the only way I can see to do this is a single-payer system. Whether the government wants to do the job itself or contract out to a private company is its own business; but however it's done, everybody (or almost everybody) has got to be enrolled to make it work.

This is why the Obama-Biden health care plan is not going to work.

Obama wants to let people opt out of the national program if they like their own insurance - or if they are simply healthy and don't want to participate. In fact, with a guaranteed-issue plan available there is no reason to buy insurance until *after* you get sick. This would result in healthy people refusing to buy insurance, and the system cannot remain solvent without that crucial population of people who pay in more than they take out.

If people want to opt into private insurance in addition to the national plan, fine, but they can't be let out of the risk pool of the national plan.

The good news is, if everyone is insured, and health care providers can be assured of getting paid in full every time they perform a service, then they won't need inflated sticker prices to cover all the nonpayers and underpayers.

If people want to yell "Socialist!" when they hear these arguments that's fine, but what are they going to do about maintaining solvency in the health care system? If you want to stick to your capitalist guns then your only viable option is laissez-faire, fee-for-service, truly free-market health care. (And if that's what you want you'd better be prepared to see a lot of poor people dying of treatable diseases.)

Because what we have now is not working, and for the reasons detailed above neither are any of the other half-cocked hybrid attempts to apply competitive market principles to a system that turns them on their heads.

depression that isn't

What do you do with a healthy patient who wants to die?

Ms K was 95. Her face was only softly lined, and her ash-white hair was smooth and silky as a girl's. She was in what one might call quite good health, having survived both a heart attack and a cancer many decades ago. Save a matched pair of titanium hips, her body parts were all factory originals.

By all accounts, her life was still a full one. She was close to her children and their spouses. She had a cadre of friends and neighbors who queued at the door to her hospital unit. She was possessed of an adoring younger husband, a stripling of 89. Indeed, he treated her to an extremely long, lingering kiss with evident tongue, in full view of the medical team as well as of their son (who sighed, "This is like a bad romance movie!" as he edged out the door).

And yet, she was decided on death. Quite decided. One day she declared that she would no longer eat, and that was that. "I'm 95 years old," she said, "and it's time." No coaxing, wheedling, or caviling; no gnashing of teeth and no rending of garments could dissuade her. After a few days of this, her distraught family brought her to the ER. After it was duly determined, via the usual sequences of poking, prodding, and sticking with needles, that she suffered from no medical illness, psychiatry was called.

After much ineffective discussion, Ms K was diagnosed with depression (though she professed no sadness) and brought into the hospital. She lay there for days refusing food and medications, even basic nursing care. Far from the etheral candle flame near snuffing out, Ms K held court from her bed, directing her frantic relatives to fulfill various social obligations and execute a litany of domestic chores.

Stymied, the psychiatry team consulted the hospital ethics board. The ethics board was equally flummoxed. Its concern was to rule out the possibility that Ms K was acting in her right mind, and not out of a reaction to depression or pain. A meeting was held with the physician team, the patient, her husband, and her son and daughter-in-law.

According to the family, this desire for death wasn't like Ms K at all. Generally she was quite life-loving and had never expressed a wish to die. At the same time they admitted that she seemed quite of sound mind otherwise, that her personality was pretty well unchanged and her mind continued to be the steel trap it had always been. They did note that she had always been very pain-averse, that she was at the beginning of a long course of physical therapy to recover from a hip replacement, and that she'd been pretty well exhausted by the physical therapy for the replacement of her *other* hip a few years ago.
Of course the very fact that she'd undergone the second hip surgery - and that her surgeon felt her 95-year-old hip was appropriate for replacement - suggested that both she and the surgeon had expected her to have quite some life left to make use of it.

The best we could figure out was that she'd just decided she would rather die than go through more physical therapy. But that seemed a bit... dramatic, didn't it? Then again, from what her family said, Ms K was nothing if not dramatic.

As an aside, I'm not opposed to the choice of a dignified, peaceful, planned exit when it's the only choice over an imminent and pain-filled one. That doesn't sound like mental illness to me. But that is pretty different from this. It's pretty different when a dying patient chooses the time and the means, versus a healthy - but aged - one choosing to end her life for no clear reason. Especially when she's nested in a network of people who would be devastated by her passing, but unspeakably more so by her *intentional* passing. When you think about it from that perspective, it starts to sound a little bit selfish in a way.

What to do about Ms K? A masterful ethicist managed to convince her that in order to let her have her wish of self-starvation, we would first have to be convinced that she was not depressed. And one way for us to do that would be for Ms K to give us a trial of... eating. And taking an antidepressant. In order to prove that her course of action was entirely voluntary, she'd have to show us she could change it.

Somehow this made sense to Ms K, and she agreed to take the antidepressant - but not to eat. So there she was, dutifully tossing back a Lexapro every morning but steadfastly refusing to eat while her desperate family surrounded her bed, alternately threatening and cajoling her.

Meanwhile, we called in the pain team. Ms K had never really complained of pain to us, but given the recent hip surgery and the trepidation about physical therapy, we wondered if there was more than she was letting on. The pain team came up with an improved regimen for her, and that did seem to improve things.

So how did this all turn out? After a week or so without food but snappy as ever, Ms K realized this undertaking was going to last longer than she'd bargained for. It looked as if starvation was going to be more trouble than it was worth. One day she asked for breakfast, and that was that. I suspect the pain from the hip surgery was the real problem; but Ms K never let on. She just acted as if this was a temporary redirection and she was going to find a better method of suicide sometime soon. But she didn't seem acutely dangerous, and her family promised to keep a close eye on her; so after she'd gotten her electrolytes back in balance we discharged her from the psych unit.

You never really do know what's going on with most patients until you've been with them a while. One of my psychiatry preceptors has said that the reason the patient gives for coming in is almost *never* the real problem. At the time I thought that was exaggerated but I'm starting to come around. I guess if psychiatry were more straightforward it wouldn't be nearly as interesting.

Open Letter of Apology to the Patient I Saw Last Night

You came into the hospital hoping to deliver a baby. In fact you weren't pregnant, but you wouldn't believe that; so the ER called me. We had a pretty nice conversation. I didn't challenge your belief that you were pregnant despite a negative urine pregnancy test and an ultrasound showing a normal nongravid uterus; and in turn you loosened up just a little bit. You were still clearly mistrustful - and who wouldn't be in your situation? as you said you'd been in and out of psychiatric hospitals more often than you could remember - but you were willing to talk. You definitely didn't want to come into the hospital, you said.

I was ready to send you home, really I was. Sure you were delusional, but it was a pretty benign delusion, as delusions go. You weren't suicidal. You weren't homicidal. You had a place to stay and seemed reasonably well groomed and nourished. I wasn't worried about your ability to take a cab back to your apartment, the same way you had come. You even had a psychiatrist, you knew your medications and doses (unlike 95% of the patients who come through the ER), you were carrying the pills in your purse, and you had an appointment in less than a week. There are thousands of people out there with worse delusions than yours - more severe, more pervasive, more dangerous - who manage to survive from day to day and to find a little pleasure in life, which is about all anyone can ask for anyway.

Unfortunately for you, things weren't that easy. Since I'm still a resident, I work under the supervision of an attending physician. At night the attending physician is at home, offering advice by phone; but she bears the ultimate responsibility for the patient care decisions that we make. See where this is going? I made you sound as good as I could - as good as you were - but she wasn't having it. She said you were delusional and wouldn't be safe at home, and that unless we could find someone to come get you at 4 AM, we would have to bring you into the hospital even though you didn't want to come.

But you didn't have anyone who could come get you. Like a lot of mentally ill people, you'd burned your bridges. You weren't close with your family, and the 'friend' you named at first turned out to be someone you hadn't spoken with in ten years. And while I was calling around to area hospitals trying to find a case manager, a psychiatrist, someone - anyone - who knew you and could help you out, or at least vouch for your ability to care for yourself - you decided you'd been waiting around in the ER long enough and it was time to leave.

After that things happened quickly. Four big ER security guys pounced on you to stop you from walking out the door. I heard your screams from the doc-box where I was dialing number after unresponsive number, and my heart sank. By the time I got out there you were already in restraints. At that point I was boxed in, and I had no choice but to write out a legal hold.

It was clear you'd been through this before. Other than telling me you hoped I'd die in a traffic accident, you took it all pretty calmly - much more calmly than I would have in your position. You were evidently familiar with the laws governing this kind of thing. You pointed out that you weren't dangerous to yourself or to others and that the legal basis for me to keep you was pretty thin. There wasn't really anything I could say. I acknowledged that you had a point, apologized to you and thanked you for staying (comparatively) calm. I told you I had no choice but to admit you to the hospital. Then I wrote out some weak excuse for the legal hold, which I knew probably wouldn't stand up to the judicial review that would likely take place in a few days. I hoped someone with more power than I had would let you out before then.

We walk the line between safety and liberty every day. When is it justified to deprive someone of his personal liberty? I think the law has it about right in theory - you should be physically dangerous or unable to assure your own care and safety. Seems straightforward; but in practice the latitude is wide and depends heavily on the judgement of the individuals involved. To me, this case lay far over on one side of the line; to my attending, it was far to the other. This time, the unfortunate patient got caught in the middle.

a science in need of a theory

I've had a number of people wonder why, as someone with a research background, I'd be interested in psychiatry. There's a tendency to view psychiatry as 'fluffy' and not something that would be interesting to a person who has spent years getting down and dirty with cells and proteins.

In my view, psychiatry is truly biomedicine’s last frontier, and no medical specialty could be more fascinating for someone who loves unanswered questions.


Medical science can speak knowledgeably on a molecular and tissue levelabout the causes of diabetes, asthma, and cardiovascular disease. We can trace Type I diabetes from the death of a specific cell type (pancreatic beta-cells) through the loss of their hormone product (insulin) to the immediate result (inability to use and store food energy) to the final result (death, before insulin was widely and cheaply available). We could tell you another good story about heart disease: fatty deposits build up inside the arteries that feed the heart, narrowing their cavities until they can be clogged by small bits of clotted debris, starving the heart of blood and resulting in the death of its muscle tissue - a heart attack. (Yes neither story is so simple, in a nod to the endocrinologists and cardiologists out there - but let's not get bogged down in details.)


However, the DSM-IV lists not one disease for which such a clear pathophysiological chain of events has been established. When faced with depression or schizophrenia, medical science begins to wave its hands, to stutter and mumble vaguely about deficits or excesses of this or that neurotransmitter. In this sense, psychiatry is truly biomedicine’s last frontier.

Sure, we have some vague hypotheses about things. Take for example the 'dopamine hypothesis' of schizophrenia. That's the hypothesis that schizophrenic patients have too much dopamine in the frontal cortex (resulting in positive symptoms like hallucinations and delusions) and not enough in the subcortical areas (resulting in negative symptoms like social isolation and flattened affect). That explains why dopamine-blocking drugs improve the positive symptoms but aren't so great at fixing the negative ones.

That's a nice finding, and it is likely accurate to a degree; but it's not what you would call pathophysiology. That's like saying the problem with my computer is that it's got too much electricity in the hard drive and not enough in the disk drive. The computer doesn't work by bathing its various parts in electricity, and neither does the brain work by bathing its various parts in neurotransmitter soup. The important thing for each of them is the patterns in which the circuits are communicating with each other, and naming the medium of that communication - be it electricity or dopamine - isn't anything like the answer to a question about why the system is broken.

But nonetheless, psychiatry continues to offer explanations like "Too much dopamine!" or "Not enough serotonin!" to questions about why people have various psychiatric illnesses.

Many of these answers are based on reverse-engineering from medication effects. We've got this drug that increases serotonin transmission, and it fixes depression, so therefore depression must be the result of insufficient serotonin. We've got this other drug that blocks dopamine transmission, and it fixes schizophrenia, so therefore schizophrenia must be the result of too much dopamine.

The obvious problem with this reasoning is that a drug isn't a perfect reversal of a disease process. A disease has some complex effects, and a drug has some other complex effects, and some of the drug effects work to cancel out some of the disease effects, but the overlap is in no way perfect and doesn't necessarily offer us any information about the root cause of the disease.

When John Snow removed the handle of the Broad Street pump to halt the 1854 cholera epidemic in London, did that mean that working the pump handle gives a person the cholera? No, and neither does 'fixing' your depression with more serotonin mean that depression is ultimately caused by 'not enough serotonin.' Serotonin is playing a role in there somewhere but a 'serotonin deficit' is overly simplistic as a cause of anything so complex as a psychiatric disorder.

So the drugs do a bunch of things, and symptom relief is only part of the picture. I don't really think they're fixing whatever the underlying problem is, only pushing the brain into a more manageable state (not quite a normal one). Although some schizophrenics are quite pleasant and normal when they're appropriately medicated, lots of others are still evidently off.

So what would a theory of psychiatric disease look like - a real one? Don't look at me, I'm just the critic. But this very interesting and timely article in the New York Times describes a couple of authors who have developed something that's much more along the lines of a Good Theory than any of the other vagueness I've heard. I'm not certain I agree with their lumping of psychosis and mood disorders as fundamentally similar, but I like the way they think.

fear of hell

The screech of my pager jolted me from sleep. A soft-voiced nurse informed me that they were having some trouble with one of the patients and his behavior was very disruptive to the others, so could I come by and see him, please?

I asked for some further details. Apparently he was kneeling on the bathroom floor screaming that Satan was trying to remove his soul through a portal in the back of his head.

Yikes. I quickly pulled up the patient's record for a look. He was a young man in his early twenties with a diagnosis of schizophrenia. History of delusions about the devil. Apparently he had presented voluntarily for help with a chief complaint of "getting schizo again." That sounded like an unusual degree of insight for a severely psychotic patient.

I jogged over to the next building and let myself into the locked unit, jiggling my keys about in apprehension. The unit was quiet. I peered into the empty bathroom on my way to the nursing station.

The nurses greeted me with visible relief. "He's in his room, doctor." I walked down the darkened hall toward a square of fluorescent light spilling across the linoleum. I nodded politely to the patient's silent knife-lipped sitter, and knocked gingerly at the door.

He lay flat on his back in the spare, brightly lit room, arms at his sides. Only his wide, terrified eyes moved to follow me about the room. Pale and trembling in his coat of puppy fat, he looked like a round-cheeked child caught in a nightmare. I asked him what was wrong.

He glanced at me sidelong. "Nausea."

Nausea? "Is that all?" He nodded. "Is it all better now?" Another nod. "Are you sure? Because the nurses told me you were having a lot of trouble a few minutes ago." A third fearful, stiff-necked nod. I paused. "Are you afraid that talking about it is going to make it come back?" A vigorous nod. "Okay," I said. "If you don't want to talk about it, I don't want to make you talk about it. But I might have a better chance of helping you if you could tell me what the problem is."

I'd barely finished my sentence when he burst out, "Satan is talking to me!"

Ah-hah.

"What's he saying?"

The patient shook his head, refusing. Sweat beaded his unlined brow. He looked awful. I took his hand. "Can you tell me what's real?" I asked. He looked at me. "I'm real," I told him. "You're real. The hospital is real. My hand is real." I squeezed his damp chubby hand, and he squeezed back, staring at me, and nodded. "Is Satan real?"

"I can hear him talking right now!"

"Tell him to shut up."

"Shut up!" he screamed vehemently at the empty air to the left of his head, startling the others in the room.

"Good," I coached. "Listen to me. Satan is not real. I know this is frightening. But try to keep reminding yourself that it isn't real. Are you okay?"

He nodded. "Are you okay?"

I was confused. "I'm fine. I want to make sure that you're okay."

"You're all right?" he repeated.

"I'm fine," I reassured him, still unclear about the reason for his concern.

He beamed, for the first time, with relief. "So I can't hurt you with my thoughts?"

I understood. "No, you can't hurt me with your thoughts. That's not real, okay?"

He nodded again. "Sometimes I get confused."

"I know. It's okay. If you get confused you can ask the nurses for help, or you can ask for me to come back. Do you want some medication?"

He nodded again. He was already pushing the limits on antipsychotic dosing for the day but the meds didn't seem to be touching him. "You've already had a lot today," I told him. I'm going to give you something to help you sleep, and just a tiny bit more of something else for the voices. But no more today after that, okay?" He was agreeable. "Is there anything else we can do to make you feel safer?"

"Can someone stay with me?"

"Sure." I gestured toward the implacable sitter at the door. "It's Rose's job to stay here and watch you, and she can help you as well if you get scared again."

"No," he cried, suddenly frightened again. "She's with Satan!"

I looked doubtfully at the sitter, who stared back in frizzy-headed indifference. "No she's not," I reassured the patient. "That's not real, okay? She's here to help you just like everyone else."

"Oh, I'm sorry," he said, addressing himself to the sitter. "I get confused sometimes. I didn't mean to be insulting." She nodded silently.

"It's okay," I offered for her. "Everyone here understands. I'm going to go write for the medication we talked about. Do you need anything else before I go?" He shook his head. "Okay. Just remember to ask for help if things get bad again."

“Thanks,” he said, and I stepped out.

This was definitely not toeing the party line on handling delusions. You’re not supposed to challenge the delusion, or even usually imply that you don’t think it’s real – at least not outside of a structured therapy program. (Cognitive behavioral therapy has been found effective in reducing delusions, but that requires a long-term commitment to treatment and a strong therapist-patient relationship.) Normally what you’re supposed to do in an acute situation like this where you don’t know the patient is simply be supportive and offer medication.


On the other hand, this patient had excellent insight. He knew he was ill, and he found his hallucinations and delusions terribly frightening. My instinct was to offer him assurance that his nightmares weren’t real.

For good or ill, this is the way most working psychiatrists function. They are guided, for the most part, not by the studies and statistics of so-called “evidence-based medicine,” but by their own individual combinations of instinct and experience.

This is true even in the realm of psychopharmacology, which is perfectly amenable to randomized controlled trials; but it is especially and unavoidably true for the doctor-patient interaction. This interaction is important in all fields, but in psychiatry it is an explicit and essential part of the therapy. And it is incredibly difficult to quantify.

Two therapists may use the same method but achieve radically different results. The most important factor in the success of the therapy is the individual therapist – not his degree, not his school of thought, but just his individual character. It’s a bit sobering to think that one’s ability to do this job well is so dependent on innate talent. Why all this education if the job isn’t one that can be learned or taught?

I hope my intervention with the patient in this story was helpful for him. In the long run, one short interaction with an on-call resident isn’t likely to have much of an effect either way. But it’s more than a little unsettling to realize I’ve undertaken such a journey with no compass or road map.

disciplinary medication

Disclaimer: I am not a child psychiatrist and do not speak with professional authority on this subject. These are my own ideas based on various readings and personal experiences.


Everyone loves to hear about someone overcoming obstacles to become a star. This NYT article about Michael Phelps, ADHD-child-turned-Olympian-superstar, caught my eye.

I found most intriguing the bit where Phelps’ mother says that, although he was incapable of sitting still for five minutes in school, he was able to sit patiently at poolside for hours awaiting his chance to swim.

I've heard many stories like this about ADD/ADHD/CD/ODD children: unmanageable under the stringent circumstances of formal schooling (sit still, don't move, don't talk, pay attention), they blossom under circumstances that channel and challenge their natural energy.

In fact, one research team has come up with interesting results suggesting that children with ADHD benefit from exposure to natural settings (Kuo and Taylor).

All this leads me to suspect that this entity which we treat as a disease may actually be a personality trait that lies on the normal spectrum, but that happens to be incompatible with the demands of our technological society.

Human beings evolved to forage, track game, and avoid becoming prey. Those are the tasks for which we were optimally designed. Sitting quietly in school for six to ten hours a day is not in that job description. Humans are amazingly flexible, so most of us can handle it to a greater or lesser degree; but it's not surprising that those out on the high-energy end of the personality spectrum are having some trouble.


So does that mean that we should not diagnose or treat ADHD?  If in another place and time it would have been simply a character trait, does that mean we shouldn't medicate it?  Well, I wouldn’t say that either. Some of the behaviors described for these kids are absolutely beyond the pale of what parents and teachers could be expected to manage by themselves.

Whether these behaviors would be different in a different environment – out on a farm, say, or in a forest – is perhaps irrelevant. We can’t move the kids out of the society they’re in. This is it, for better or worse.

And as always, I’m all for behavioral interventions ahead of pharmacological ones. If the behavior of kids on the milder end of the spectrum can be improved by fixing their diets or letting them tear around outside for a few hours, then that’s an easy decision to make.

But what about kids on the extreme end of the spectrum? The kids who scream, bite, kick, punch, and cannot be coaxed, bribed, threatened, or punished into any semblance of normal behavior?  This is the difficult question faced by parents of ADD/ADHD children: to medicate or not to medicate?

I’m generally extremely wary of giving psychoactive medication to children. The brain is not completely developed until the mid-twenties, and the brains of young children adapt gleefully and abundantly to changing stimuli. If those stimuli include, say, an extended period of dopamine blockade, the brain will adapt by upregulating its sensitivity to dopamine, attempting to restore a more typical balance of dopamine activity.  How long do these effects last? Nobody knows.

Even for the best-studied drugs, there's more information available about gross parameters like height and weight than there is for long-term psychiatric effects.  E.g., Ritalin has been around for a while and is relatively well-studied in children.  At this point it's pretty clear that Ritalin does not have gross effects on children's overall growth and development. I'd be more concerned about subtle long-term changes to their mood and behavior. These things are of course significantly harder to study.  I did find some studies looking at behavior in adult animals who had received psychoactive meds as juveniles.

Here’s a study that shows rats that get Ritalin as adolescents are more sensitive to amphetamines as adults. (Valvassori et al.).  Here's another one that demonstrates the same thing, and also suggests some baseline behavioral changes (Carlezon et al.).  Similar results in this third study (Brandon et al.).

This was later studied in humans and it doesn't look like kids treated with Ritalin are any more likely to become speed addicts as adults than anyone else (less actually), but I'm not aware of any follow-up on, e.g.,  long-term susceptibility to depression or other mental health concerns.

Meanwhile, children are starting to receive medications with much less pediatric data behind them than Ritalin.  For example, the FDA approved the antipsychotic Risperdal for use in children based on three clinical trials that lasted 3, 6, and 8 weeks respectively.

(Risperdal is not approved for use in ADHD specifically but is sometimes prescribed off-label for that indication.)

Huh? Where’s the study that looks at the kids five, ten, or twenty years later? That’s the one I want to see. And barring that (given the difficulties of conducting such extended trials), I’d love to see some more animal studies.

So about those animal studies.  I didn't find many, and what I did find wasn't encouraging. Here’s a study that shows alterations of development, outgrowth, and axonal migration in developing worms receiving antipsychotics (Donohoe et al.).

Unfortunately, the need for behavior control is urgent, and the information just isn’t out there. I think the vast majority of parents are pretty cautious, as they should be, about medicating their kids, and will do so only as a last resort. I also think that’s the right approach; and in the final analysis, if you need it, you need it. Sometimes you have to trade the threat of an unknown outcome in the future for a drop of sanity in the here and now.

But I wouldn’t be soothed into thinking that just because we don’t know about long-term ill effects of childhood medication doesn’t mean they don’t exist. You can only know something is there if you look for it, and that’s something the biomedical research community doesn’t yet appear to have done.

color-by-number

A new patient walked into my psychopharmacology clinic last week. She seemed reasonably typical at first. A line in the chart noted that she was somewhat wary of psychotropic medications, but then many patients are, and I don't tend to mind that attitude myself since I also subscribe to the less-is-more theory of psychiatric meds.

She was on a fraction of the normal dose of a common antidepressant, which, she reported, was her only medication. It seemed unlikely that this small dose was having any effect, positive or negative, on her mental health; but her mood was stable and she was sleeping and eating well. Things looked good. The main points covered, I asked if she had any other concerns.

"Well, I had my brain imaged," she offered. Brain imaging? Did she have a neurological disorder I hadn't known of? I asked which physician had ordered the tests.

"Oh, I did it myself. I saw it on TV and thought it would be a good idea."

Brain imaging advertised on TV, direct-to-consumer?

She handed me a sheaf of papers, of which the first few pages read like Baby's First Book of Neuroanatomy crossed with the New Age Guide to Herbal Remedies. "Prefrontal cortex: Planning ! Attention!... L-tyrosine!... Anterior cingulate: Cooperation! Flexibility!... St John's Wort!" There was then a list of "hyperactive" and "hypoactive" regions in this patient’s brain.

She'd paid out of pocket to have her brain SPECTed at a clinic that advertises on late-night TV.

Where to begin.

Let me just state up front that there is no established role for brain imaging in psychiatry at this time. None. You can't look at a picture of blood flow (or any other parameter) in the brain and make a diagnosis. (SPECT has some utility in distinguishing Alzheimer's from vascular dementia, but that's more neurology than psychiatry.)

To start out with, despite the existence of a number of studies looking at blood flow in depression, there is not a clear consensus on which areas of the brain are most involved.

Then, let me point out that we have no standard against which to judge baseline levels of regional activity. Blood demand fluctuates on a moment-to-moment basis depending on what the brain is doing at any particular time. The variation in demand between individuals and times is not very well described. So my patient's brain regions were over- or underactive compared to what? Somebody else's brain thinking sad thoughts? Her own brain thinking happy thoughts? The average of ten other people's brains doing a crossword puzzle? Any way you slice it, it doesn't sound informative.

Even when looking at more stable and reliable imaging correlates of clinical depression, in which a clear average population difference exists between depressed individuals and normal controls, there is so much overlap between the two groups that you can't usually infer a person's mood from his brain scan alone. Check out this graph from a review by J.H. Meyer, showing MAO-A density in different brain regions.






While there are clear differences between the populations on the whole, it's also just as clear that an isolated brain scan likely won't tell you much about whether that individual is depressed or not. There are just too many people in the overlap region.

As you can tell from these links, science is still in the phase where we use clinical data as the gold standard against which to judge the validity of imaging results. Going the other way round - starting with the scan and inferring the diagnosis - is something that's far away from our current level of understanding.

Consonant with this, the 'interpretation' of this woman's SPECT scan was nothing you couldn't have figured out from talking to her for a few minutes. After citing a number of areas in which 'dysfunction' was discovered by the SPECT scan, it described some related problems she might have, such as "negativity, guilt, blame, irritability." The kinds of things you could diagnose more easily from a cheap interview than from an expensive brain scan.

The recommendations included a number of OTC supplements (without indication of dosage, of course, since these supplements are largely unregulated, little is known about optimal dosing and in any case actual content may vary wildly from what's written on the label). Some of them were items that have some evidence for their utility (e.g., omega-3 fatty acids); others seemed relatively benign (e.g. Coenzyme Q10) but with little available evidence regarding their use in depression; and others (e.g., St John's Wort - see this FDA advisory) can be positively harmful under the wrong circumstances.

My patient was on all of the recommended supplements - some six or seven different pills - despite having declared the Lexapro as her only medication. This is an incredibly frequent error made by patients, who are soothed by the 'supplement' label into thinking the items are somehow safer or less likely to produce side effects than chemically prepared medications. In fact, there are a number of supplements that have produced significant health problems in their users (e.g., ma huang, which was ultimately banned by the FDA), and since their preparation is poorly regulated, both the dose of the medication and the number and identity of the compounds present are pretty much up for grabs. These facts make supplements a rather riskier bet than prescription preparations.

There were some other very general recommendations of the type that any mainstream psychiatric practitioner would typically make: cognitive behavioral psychotherapy, good social and emotional support, exercise, self-relaxation, and a balanced diet without excess use of nicotine and caffeine. All useful advice, none of it requiring the service of gamma ray scans.

I fully expect that brain imaging will one day have a place in psychiatric practice. However, that day is not today, and I find it upsetting when my patients are conned into paying good money for a useless procedure, a dose of radiation, and some occasionally inappropriate advice.

I do find it curious that so many people place deeper trust in the uncharted waters of alternative medicine than they do in the well-documented, frequently evidence-based recommendations of the standard medical establishment. Things aren't always peachy in the world of traditional medicine; doctors have done a lot of harm as well as a lot of good. But I like to think that as a profession we ultimately learn from our mistakes, and I'd submit as evidence the enormous strides modern medicine has made in extending the productive lifespan, reducing infant mortality, etc etc etc. And in a plug for my own specialty of psychiatry, although there are many patients who are beyond our present capacity to help, I know many others who have unquestionably been saved from suicide or from personal and social destruction.

When someone shows me a randomized controlled trial that demonstrates the utility of a supplement, I'll be happy to use it and recommend it. (I already do recommend both fish oil and melatonin under the appropriate circumstances.) Until then, it's just a black box; and that's not something I'm comfortable giving to a patient.

mind control II: yours

I wrote last week about how surprisingly simple it can be to turn around an angry patient. Two small words hold the key to taming the beast: "You're right." Those words are like a magic tonic, a soothing balm. The patient drops his offensive posture, loses his hostile glare. His hackles soften. His ears are open, receptive. Magic.

But it's not enough merely to mouth the two magic words. You need to believe them, to find the grain of truth in the patient's angry accusations and hold it up to the light. Typically that grain of truth contains a failing of your own. That's hard to admit.

In the CBT group I attend we use role-plays as learning tools. We mimic angry patients, throwing harsh words at our colleagues as a challenge to their empathetic skills.
It's curious that even when you are merely acting a role, pretending to be upset, you can feel in yourself the good or bad reaction to the 'therapist's' words. Defensiveness from the therapist provokes further heights of anger. But the crucial initial words "you're right" produce a rush of surprise and disarmament, a shock of pleasure at being understood, a hint of gleeful righteousness, and an intense curiosity and complete willingness to listen to what's coming next.

Rookies never get the task right the first time, or even the first ten times, even after having the strategy thoroughly explained and seeing more experienced members employ it. They simply can't get themselves to say, "You're right; I've failed; you're understandably angry; but tell me more so I can try to fix it." Instead they mouth platitudes like "I hear that you're frustrated," or "Why don't you calm down so we can discuss this," or they get defensive and explain why the patient is wrong to be angry. These strategies are all, of course, bound to escalate the situation.

Never, never on the first try do they plainly acknowledge the patient's anger and the faults of the therapist. I sure didn't, and I've yet to see any other rookies manage it either. It's suspiciously simple, yet incredibly difficult to do.

As I mentioned last week, I've been using this strategy on belligerent colleagues and other assorted meanies as well as on patients. It's been absolutely foolproof so far. But interestingly, when I shared the strategy with some of the psych residents who are not in the seminar, I met stubborn disbelief.

"I don't think it's appropriate to just subdue yourself to the demands of the patient. You have to maintain your own integrity," one woman said.

She'd verbalized the gut resistance to this strategy that comes from your own ego. That's exactly why it's so hard to implement, despite being so simple. Because you have to lose in order to win. You have to cave in order to prevail. You have to drop your ego in the dust and squish it with your toe in order to have any hope of success.

Even in the false environment of the role-play, where your partner flings made-up accusations at you, it's hard to accept and apologize for these acts you didn't commit. In that setting it's really just a script you could recite with no personal involvement whatsoever. "You're right, I did [fall asleep during your session/give you the wrong drug/insert horrific therapeutic sin of your choice], I bet you're feeling really angry right now." That's it, and with minor variations it's pretty much always the same. Yet it takes a long time to be able to do, even under laboratory conditions. How much harder is it when it's truly your own actions that are being assaulted.

Seeing the patient's anger as a threat to your ego integrity is losing sight of the goal of the therapy, which is to help the patient. The goal is not to maintain your own sense of dignity and self-worth; presumably you've already got a healthy dose of those or you haven't any business trying to therapize others. And if you consistently put the goal of preserving your dignity ahead of the goal of helping the patient, you'll have a lot of frustrated patients and that won't be good for your ego as a therapist in the long run anyway.

But we're accustomed to working hard to maintain our dignity and self-worth, because people without them are racked with doubts and insecurities and generally have a difficult time in life. So we're pretty well programmed to protect our egos, which we do in different ways depending on our basic characters, stages in life, and how we frame ourselves to ourselves. But we all do it. When faced with a blow to our egos, we're socialized to parry it, swiftly and surely.

However, it's all too easy to forget that an interaction between a therapist and a patient is not the same as a typical social situation. Your goal is to help the patient support and develop his ego, not to prop up your own. But when faced with a threat, it's instinctive to forget that, and to fall back on the strategies that have always been helpful (defending or rationalizing or denying your actions, deflecting the blame, etc.).

Hence my colleague's assertion that it was important to maintain one's own integrity. But important for what, I'd ask? Important for the patient, I suspect she'd say - to set limits, to teach the patient how to behave calmly and fairly. But the key point here is that there is always a reason for the anger. Truly isolated, reasonless, purely biological anger is a rare thing that occurs with specific brain lesions, typically affecting the hypothalamus. Real humans in the real world have triggers, and if the patient is lashing out at you it's likely that you're at least part of the trigger. It's your job to be the level head and figure out what that part is and what you can do about it. Otherwise your chances of getting the patient to a state where he can be calm and fair are going to be on the slim side of nonexistent.

mind control I: theirs

I'm in a seminar that meets once a week to educate ourselves in the technique of CBT (cognitive-behavioral therapy). This is only one of a plethora of available therapeutic modalities (dialectical behavioral therapy, psychodynamic, psychoanalytic, etc etc etc).

We're learning specific, codified techniques for making our interactions with patients productive. Some of them are very simple; but the results are absolutely amazing.

One of the things that attracted me about psychiatry was how smooth the attendings were about dealing with difficult patients. You'd have an obnoxious patient on the medicine or surgery floors who would have all the docs chewing their stethoscopes with utter frustration. Then the psychiatry consult would walk in and in three minutes he'd have the patient eating out of his hand. Unbelievable. I wondered whether this was a talent they were born with or a result of their education. (Ultimately, as with most things, it's probably a little bit of both.)

It's a bit of a chess game, as one has to think a few moves ahead. If I say this, he'll likely say this. If I don't say this, another chance may not come. If I say it in this particular way, will he react well or badly?

It's perhaps funny to imagine that human interactions could be condensed down into a set of algorithms. One would like to think that individuals are so very different from each other that one size could never fit all. And it's true that one needs to apply one's interpersonal intuition to an extent. But only to an extent. There are definite ways to bring angry or frustrated patients back to a state in which they can engage in rational conversation.

And it doesn't only work in the controlled environment of a hospital or clinic. I've used some of the basic techniques we're learning with other angry, irrational people in my life (mainly frustrated residents from other services) with excellent results. Secret weapons! Psychiatry is incredible.

Next entry: Getting people to be rational is both easier and harder than it seems.

biology vs psychology: false dichotomy?

I was speaking with a very intelligent and insightful patient today who mentioned that he'd felt his problems (depression, some obsessional traits, a mild eating disorder) were all 'psychological' until he found a drug that significantly improved them. From that point on he was convinced they were 'biological,' and embarked upon a quest for the Magic Pill that would solve all his neuroses at a single swallow.

I see references to this sort of split all the time, and not just from patients but also from highly educated physicians and scientists. Somehow they consider that our behavior* arises from two distinct sources: one composed of neurons, synapses, and neurotransmitters, and another composed of experiences, drives, and willpower.

If you buy the biological theory of behavior at all, then it makes little sense to imagine a dividing line between 'biological' and 'non-biological' causes of behavior. Experience alters neurochemistry just as surely as medications do.

Here's a nice (but somewhat technical) piece of work discussing some of the cellular-level changes that have been observed to be triggered by real-world experience (Takahashi, Svoboda and Malinow).

Evidence abounds for the utility of 'talk therapy' in psychiatry. In order to separate the 'biological' from the 'psychological,' one would have to believe that there exists an entirely separate underpinning of human behavior that operates on some ethereal plane, unrelated to the biomechanical world of synapses and neurotransmitters.

If you're going to accept that neurobiology underlies behavior, then there is no clear point at all where you can divide the biological from the psychological. If you accept that experience exerts its effects through alteration of our neuronal activity, and you accept that hearing your therapist is an experience, then there is no room for some nebulous 'non-biological' effect. Your therapist's words tickle your ear neurons, which tickle your brain neurons, which make subtle changes - sticking themselves to some of their neighbor cells, unsticking themselves from other neighbors, changing the rate at which they spit neurotransmitters at each other - and voila! You change your behavior.

That the line between biological and psychological is fuzzy to the point of nonexistence is indeed starting to permeate the general consciousness, at least to a degree. This usually arises in discussions of ethics, where the whole edifice of crime-and-punishment rests on an assumption of free will. This assumption is being radically challenged by evidence that our behavior is heavily determined by factors not under our direct control (genetics and medication in particular).

This opens up another can of worms, because we frequently associate 'biological' with 'beyond our control' and 'psychological' with 'within our control.'  Hence my patient (and many like him) and his Magic Pill search.

But I think the educated world at large is not yet ready to join Steven Pinker in declaring us will-less playthings of our genes and environment. Fine for now, but I'm curious to see what we'll make of coming scientific advances that will no doubt push us even closer to the will-free wall.

*I'm using "behavior" intentionally to encompass all of the workings of the human brain that are manifest to others. I'm doing this very deliberately because the question of whether mind is biological at all is a very sticky wicket and not something I can afford to get into in this limited space.

free will and eating disorders

We've a number of eating-disordered patients on the unit at the moment.  Eating disorders have never been a particular interest of mine; yet as I work more closely with eating-disordered patients, I've come to realize their problems raise a number of interesting philosophical questions.

We've all had the experience of being of two minds.  We want something, yet we do not want it. One experiences this on a regular basis, yet it rarely disturbs the view of oneself as a single, integrated ego, a unified mind.  However, the problem is very severe in the eating-disordered.

How to want to be well but also not want to eat?  How to want one's life back, to know that the eating disorder has wrecked it, to understand that one flirts with death, yet be so petrified of food?  Even my patient Ms. G., weighing just 35 kilos and desperate to regain a normal life, was yet utterly unable to prevent herself from binging, vomiting, and binging again.  "Obviously I have free will," she wailed unprompted, "but somehow I can't stop doing it."

Our medical student was surprised at her intelligence, unable to credit her self-destructive behavior because "but she's so smart!"  But 'smart' has nothing at all to do with it; in fact, quite the opposite: anorexics may have higher than average IQs.

(This may be tied to the well-documented association between anorexia and the need for control.  Besides body weight, academic achievement is another area where due diligence generally yields the desired results, and thus appeals to the controlling anorexic personality.  In fact, Dura et al. note that 'perfectionistic striving' actually yields better academic results for anorexics than would be predicted by their IQs alone.)

 

This makes a degree of sense when one considers that a certain level of complexity is required in order to deny one's own basic drives so severely.  At the most straightforward level of functioning, one merely obeys one's basic drives - hunger, thirst, fear, desire - pursuing the most immediate means of gratification.  At a somewhat more sophisticated level, one may delay instant gratification for a bigger payoff later on, forgoing one candy now for two candies later.  Ultimately, one may come to value successively loftier intangibles above the basics: staying up late to finish that big paper; starving for one's art; giving one's life for one's country.

Well then, how to be cognitively impaired, like our patient Ms. S., and yet have an eating disorder?  Ms. S. had been impaired since birth, and she behaved for all the world like a sweet and coquettish child, grinning impishly at the team, asking for hugs, requesting praise for her accomplishments.

At first I could not believe someone functioning at this simple level was sophisticated enough to have an eating disorder.  I thought she must have an organic illness, a food sensitivity or irritable bowel.  And yet as we weaned her down to the most elemental and gastroenterically benign food supplements it became clear that the problem was not in her bowel, but in her head.  She played all of the typical eating-disorder games: saving food, dumping food, vomiting food, mixing and freezing and thawing and refusing it, drinking gallons of black coffee and diet soda, and on and on and on.  

Ultimately it became clear that at least one of the reasons for Ms. S.' eating patterns had, unsurprisingly, to do with control - a common theme among eating disordered patients.  In Ms. S'. case, though, it was more to do with control over her family than over her body.  Still living with her mother in her forties, Ms. S. yearned to go out and build her own life.  She found that refusing to eat allowed her to exert a measure of control over her large, loving, yet stifling family, all of whom rallied round her and raised a ruckus of attention over her malnourished status.  Which was, evidently, far preferable for Ms. S. than sitting quietly on the couch watching TV all day and being ignored by those with lives of their own.

I hadn't given Ms. S. nearly enough credit for the complex, multilayered psyche she evidently possessed.  Humans are deep creatures, even the simplest of us.  

Not too much can go wrong with a simple machine like an abacus or a bacterium.  But as you add more bits and parts and cogs and circuits and cells and networks, the number of ways things can go wrong explodes.  Ultimately you end up with personal computers and human beings, both of which are endlessly surprising and infuriating in the sheer number of things that can go wrong with them.  Hence computer wizards, and psychiatrists.

chemical love

One of my more interesting recent patients had a problem straight out of a daytime talk show. This was a young gay man in love with his heterosexual roommate. The two of them had a very close relationship, eating dinner together, going to movies as a couple, and generally engaging in very couple-like domestic activities. They also had a surprisingly open relationship. The gay man had confessed his ardor to the roommate, and the roommate, while he did not return the sexual feelings, was mind-bogglingly relaxed about the whole issue and the two of them remained as close as before.



Matters took a turn for the worse when the roommate acquired a girlfriend. Naturally the gay man could not stand the girlfriend and resorted to drinking alone in his room or going for long drives whenever she was around. Ultimately he became so depressed and consumed by the situation that he was unable to work, could not sleep, lost interest in his hobbies, and finally sought psychiatric help.


At first nobody on the treatment team could understand the situation, and in particular the behavior of the roommate. We speculated that perhaps he was a closeted homosexual who unconsciously returned the feelings, or else that he simply couldn't bring himself to give up the incredibly cheap rent offered by his lovesick roommate (who owned the apartment).


The answer turned out to be a bit more complicated. I sat down with both men for a frank discussion of the situation, and found that, at least to casual observation, their relationship appeared as close and open as had been described to me by the gay patient. Together we dissected the timeline of their relationship. It turned out they had been ordinary good friends until they began to use the drug Ecstasy (MDMA). Over the course of a summer they had used the drug weekly together - rarely with anyone else - in the process cementing a bond that ultimately became more like a love relationship than anything else.


It is likely impossible to convey the emotional power of Ecstasy to anyone who has not tried the drug. Roughly, it works by reversing the direction of the reuptake transporter that vacuums leftover serotonin out of the synaptic cleft. This dumps enormous amounts of serotonin into the synaptic cleft - far more than would ever normally be present there at one time. Just as chocolate cake overstimulates the taste receptors that evolved to detect the more mild and nuanced sweetness of fruit, Ecstasy overstimulates circuits designed to underlie the natural pleasures of romantic attachment and sensory experience.


In a stark demonstration that love really is just chemistry, Ecstasy can make you feel a gush of deep affection for just about anyone sharing the experience with you. It's Cupid's Arrow in chemical form.


In this particular case, these two men overstimulated their 'love circuits' together over and over again for an entire summer. It's no wonder the gay one fell in love with his friend. As for the straight roommate, evidently Ecstasy can't alter sexuality (unsuprising, as anyone who's tried it will tell you Ecstasy has little to do with sexual feelings, and in fact often inhibits them). But it did seem to have triggered many of the other hallmarks of romantic love. The man gazed affectionately at his roommate, expressed all manner of deep and abiding emotion for him, was wracked with guilt for the suffering he'd caused. Everything was there but the sexual attraction.


The chemical basis for emotion is nothing new, and at this point carries little shock value. Yet it is still difficult to believe how easily we can manipulate our deepest emotions with a little diddle to the neuropharmacological machinery.


What was the cure for this young man? Fighting fire with fire, I prescribed him Prozac. Prozac works by paralyzing the same reuptake transporter that is reversed by Ecstasy. Instead of being vacuumed back out of the synaptic cleft when their job is done, the serotonin molecules loiter around in the cleft. The simple way to think about this is that more serotonin in the cleft equals more happiness, duh - though in fact the biological effects of SSRIs such as Prozac are somewhat more complicated than that (see Nutt et al for a useful summary).


As one might expect, then, Prozac blocks the effects of Ecstasy. With Prozac in your system paralyzing your reuptake transporters, a nice fat pill of E has no more effect than a sugar tab. That was one little-known side effect I thought might be useful in this particular patient's case.


A more well-documented side effect of SSRIs is inhibition of sexual function, including the ability to orgasm (see Rosen et al. for review). In addition to this, there are some anecdotal reports that SSRIs such as Prozac have adverse effects on romantic love. This is a much mushier and less well-documented realm. I found nothing about it on PubMed, though I did find a bit of schlock in Psychology Today that discusses the phenomenon. If this latter bit did turn out to be true, I would wonder whether the effect were secondary to inhibition of sexual desire or whether it involved a distinct group of neural circuits.





Based on anecdotal reports from people who have used them, it sounds as if SSRIs may in fact dull the capacity for deep emotion. You don't feel sad anymore, you even feel kind of happy, but the happiness is a sort of pleasant zoning out rather than a meaningful joy. Indeed, by some reports the entire spectrum of emotion is flattened out (see, for example, comments posted by readers on this WebMD blog).


Much has been made of the possibility that we are depriving ourselves of essential human experiences by medicating away our emotions (see, for example, this review of Eric Wilson's book Against Happiness). Of course, many others more articulate than I have also argued the opposite side of the story (see this other review of Peter Kramer's Against Depression).


As is often true, I find myself taking a position somewhere in the middle. I don't want my patient to be zoned out forever, but I can't help but think that he's already had more than enough character-building for a while. A little Prozac in this case is probably a good thing.