Monday, September 24, 2007

How to Select an Antidepressant: Part 2

Dinah posted about How Psychiatrists Select Antidepressants, which was a very thoughtful and concise description of the factors we take into consideration. Supremacy Claus commented on Dinah's pragmatic, plain-speaking distillation (talk about plain-speaking pragmatism, check out this legal eagle's excellent blog). Dr Smak (another great blog... she and Dinah should go shoe-shopping together) was surprised to find no mysterious revelations, and "The" Shrink (a great new psychiatrist blog... welcome!) felt doctor preference was a missing element.

I started a comment, but it got so long and non-plain-speaking (sorry, S. Claus) that I moved it here.

Shrink, not so sure about the physician preference part (or maybe I am atypical... ha). I don't have a "favorite" or fall back antidepressant, as I find that when I apply Dinah's list (which is quite comprehensive and a good list), I am usually left with one or a couple drugs, and can still find a reason to pick one over the other (eg, cost). I feel I am quite familiar with the zillions (ok, maybe it's only 15 or 20) and ready to pick whichever seems best.

I do think Dinah's #4, 5, and 6 should be expanded on, and #4 should be split into 2 separate sections (I'm a splitter)... #4a being Other Medical Issues (eg, Seizure -x-> Wellbutrin; Psoriasis -x-> Lithium; Hypertension -x-> Effexor; etc) and #4b being Drug Interactions.

Drug Interactions is a whole 'nother post, and is a BIG factor for me when prescribing. Many of my pts are on multiple meds, so it becomes really important to think about this. Prozac and Paxil, for example, are famous for 2D6 interactions, so I avoid it when folks are on drugs which are solely metabolized by that enzyme. Luvox is a great hs antidepressant, but will muck with 1A2-metabolized drugs. Serzone and 3A4 drugs (though, haven't seen Serzone in years now... too bad, was a great drug to have around, esp if you knew how to use it... great for blocking SSRI-induced sexual side effects).

#5: Target Sx - When I think thru these, I think in terms of receptors (may be a tomato-tomahto thing here). I hear "no appetite" and think "I want histamine antagonism"; I hear "can't concentrate" and think "dopamine agonism"; I hear "no energy" and think "norepinephrine".

#6: Side Effect Profile - This is the one I spend the most time on with a pt. For any given side effect that is either desireable (sleepy, energizing, stimulates appetite, reduces appetite, etc) or undesireable (weight gain, wt loss, sexual, rash, seizure, nausea, etc), I have a pecking order in my head of drugs and their propensity to cause -- or not cause -- the particular side effect (other term is "adverse reaction", though they are only "adverse" when undesireable). The above 3 sections are where a better understanding of psychopharmacogenetics would come in handy.

The above may be where Dr Smak noted the perceived "secret way" in which shrinks pick 'em. What may be different in the way in which psychiatrists and PCPs select antidepressants is just in the way these thought processes get all merged together, or maybe thought about in an explicit way (my receptor-tomahto approach) or an implicit or nonverbal way (Dinah's best guess-tomato approach).

This "gut feeling" about which drug to use is merely the end result of a massive probability calculation which is automatically performed in the brain, based on all the above input about which side effects or target symptoms should take precedence for that specific pt, which drugs are more or less likely to deliver them based on receptor and metabolic profiles and based on literature and personal experience, in addition to the other factors like likelihood for compliance and affordability, all boiled down to a single "I think you should try Effexor". Much of that calculation is not conscious, and I think Dinah belies the complexity under the surface by simply (but honestly) stating "my best guess".


Anonymous said...

Maybe I'll post a post to counter your post you posted about my post.

And I wear the same shoes all the clogs in winter and a couple of pairs of sandals in summer, sneaks for exercise, flip flops to hang, "moon boots" --lands end slippers with cushy soles for cold winter days. I don't do heels, most shoes aren't comfortable, my feet are too wide, I'm not a shoe person but in my next life I'll have size 6.5 feet, and learn to love heels and I'll be one. Sorry Dr. Smak.

Anonymous said...

And furthermore, tomatoes have nothing to do with how I choose medications.

When are you doing your post on Treatment-Resistant Depression? and How mUch money have we made on GoogleAds?

The Shrink said...

I wouldn't disagree with anything you or Dinaah's post suggest on sifting through the options to generate a list of what's sensible to prescribe.

My point was that we tend to have a dozen antidepressants that we use a lot and it's more likely we will prescribe from these e.g. I seldom use tricyclics first line and can't remember the last time I used trimipramine so wouldn't be as likely to prescribe that as I would clomipramine or amitriptyline.

Why does this matter? Because I believe we need to have sufficient experience of drug outcomes to be able to proffer sound counsel to our patients.

"I feel more tired, is it the Rx?" It may be. Or it may be that an alerting Rx has given more drive so, on retiring to bed at night, you've been busier and are more washed out. How likely is it that Rx is contributing to a symptom? Answers gained from reading are at best blunt statistics that don't relate to our specific patient (knowing there's a 7.6% chance of a side effect doesn't help me). Only through experience with many patients can we gain a rich understanding of the idiosyncracies of each drug.

We're using psychotropics, we're expecting a change in symptoms (hopefully for the better). When patients take our Rx and on review generate a different list of experiences, how do we ascribe significance to them without robust knowledge of the drugs?

I'm making heavy work of this when, in fact, it's a very minor factor and Dinah's got the truth of it. Almost all prescribing deliberations involve the points made . . . I was just advocating that it can't be too impersonal and prescriber factors have a valid role too, albeit a very small one! :-)

Anonymous said...

How about a post discussing psychopharmacogenetics more? I'd be really interested in that! From what I've gathered so far, it seems like it's taking the action of a drug and a patient's own DNA into account to give you a better prediction of how well the drug will work and what side effects they will experience. Is this close? What a modern miracle that would be!

jcat said...

Agree with Michelle...more on the psychopharmacogenetics! My p-doc is really rated as a psychoparmacologist - and with TRD BP, that helps me sometimes to feel that if anyone can find an answer he will - and he reckons that the most exciting psych developments are all in this area. That within 10 years or so, the whole meds choice will be refined to an almost exact science. Can't wait...
There were apparently some interesting sessions at the APA congress in San Diego??

Dr. Shock said...

Sorry I favor EBM above "no appetite" and think "I want histamine antagonism"; I hear "can't concentrate" and think "dopamine agonism"; I hear "no energy" and think "norepinephrine". These effects are not EBM, patients respond differently to the same antagonist. So efficacy is the main factor as well as side effects although all antidepressants have them.
But the most important factor is stick with an antidepressant, learn it's side effects interactions etc. Do not switch from one to the other in every patient.
At least that's what I tell my students and that I stick with.
More European, we usually use tricyclic antidepressants with our inpatients on our depression unit in an University Hospital (Anderson 2000). Imipramine is our first choice. Most of them already had SSRIs without effect or partial response.
Treatment resistant depression is a challenge I face everyday at work, see one of my articles on my blog for our algorithm.


Dr Shock

Dr. Smak said...


Don't give up hope.

Shoes are like anti-depressants. Sometimes you need to try several on before you get the right fit.

This coming from a size 10 pes planus.

Dr. Smak

Dinah said...

I'm still thinking about your post and I've moved on from Shoe Shopping Issues.

I decided to leave this as a comment, rather than a third How To Pick An SSRI post.

My thoughts on your thoughts:
Drug interactions are, for me, part of "other medical issues." Drug interactions isn't another post, it's a whole book.

I read your enzyme and receptor stuff and wondered why you are so much smarter than me. Boy does this sound good. Reminds me of when Paxil first came out and the drug reps talked about how it is the most serotonergic drug. I don't care about the most serotonergic. I want to hear it's the bestest, quickest antidepressant with the fewest contraindications and side effects. What do I care from serotonergic. I especially don't care about serotonergic tomatoes.

I, too, will think in terms of side effect profiles (so if your a sleepless, skinny, weight losing depressed person, I too might prescribe remeron and hope). Mostly though, I've found that people get them or they don't and I don't think in terms of
"I want histamine antagonism"... I try meds all the time that someone might object to-- we tend to think that wellbutrin makes people a bit jittery and isn't the best medication if someone's very anxious or agitated-- I use it all the time with these issues, I just warn the patient and say "I can't predict if you will or won't get side effects. If you get more jittery, we'll stop it and it's got a short half life." Lots of people tolerate meds you think wouldn't tolerate. I have plenty of patients on Lithium or Zyprexa or Depakote who haven't gained weight on them. I don't tend to pick prozac as my first choice med -- it's a great anti-depressant but since I'm a bit wishy-washy and 'best guess' about it all, I like the short half-life of other ssri's: when I get it wrong, we can stop the med. You make it sound more predictable than I've found it to be.

I like to differentiate side effects from adverse effects. I did that in my Side Effects post, so I'll avoid repeating myself here.

I've treated people with neurological illnesses and even seizure disorders with Wellbutrin. I warn them, if they say "no way" I respect this, I call their neurologists (...they generally say Fine....but who knows if someone will seize until they do). It's never my first or second choice in a patient with a risk factor for seizures, but I sometimes end up there after plugging for a while.

And I don't use much Effexor, too long to titrate and I like Cymbalta better and there's no 37.5 dose (whose brilliant marketing idea was That!?) But my understanding is that the hypertensive effect is an ideosyncratic thing that happens in 1-2% of people, it happens or it doesn't and pre-existing hypertension is not a contraindication. Am I wrong? No wonder I don't use it much.

To The Shrink: "I'm tired, is it the med?" Basically, if a patient says they're having a side effect to a med, given that I'm not in their skin, I believe them. I once had a woman tell me that serzone was making it look like everything had a sort of tail as she moved her eyes...kind of weird, I didn't get it, thought "Right." Two days later I read in a journal about people seeing "trails" after starting Serzone. Now I listen and only rarely do I question (and then even in my own head) if the patient is "imagining" a side effect.

Dr. Shock: what's EBM ---empiric behavioral medicine?/ I'm lost.

And to the drug rep on the last post:: You may have inspired my next post.

NeoNurseChic said...

Nice one.

So now I'm wondering what you in the prescribing roles do with patients who have migraine or other headache types and use triptans anywhere from once in a blue moon to twice a week or more, and also have depression. Is there any place where SSRIs and triptans can coexist? I said this before, but I haven't read much on this at all, and I'm rather curious about it.... You may be thinking, "don't just ask a question - go read up on it first..." That's what teachers always say, anyway! :-P

Roy, I'm glad you focus so heavily on drug interactions. My psychiatrist is like that, and I wish there were more people like you out there! (I won't rehash my anticholinergic disasters...) Just when you would think the lessons would be learned, I've been prescribed the most anticholinergic of TCAs by a neuro (trusting that it would be remembered my anticholinergic disasters that left me not knowing my own name, and therefore not additionally looking the drug up on my own to make sure) only to learn from my psychiatrist that the true properties of this med make it something I should avoid like the plague. That's more of an "other medical issues" example rather than a drug interaction one, but it's kind of both because the ach stuff came from interactions more than just single meds mixed with my own chemistry. My psychiatrist seems very knowledgeable about pharmacology, and when I am prescribed a med by any other doc I have, no matter what the specialty, I usually run it by him, too, before starting it. I trust that he is truly thinking about my best interests and I know he is very observant and won't forget my history. It's good to hear that there are people out there who really do pay such close attention!

On EBM: Evidenced-Based Medicine?

On Shoes: Dinah - I'm a lot like you with shoes!! I wear my fav flip flops (well, sometimes I wear a couple other pairs) in the summer, sneakers to work and to relax, and I have brown and black clogs that I wear in the winter. I actually have a closet full of about 25 pairs of shoes, and I regularly wear about 3 of them. I also have these "moon boots" slippers - but they are boot slippers filled with down and made by restoration hardware - and the most comfortable, warmest slippers I've ever put on my feet! I'm a size 7.5, and they don't make shoes narrow enough for my feet! There are lots of shoes that I'd like to wear, but can't cuz my feet slide right through them! Crocs? Forget it - I'll walk right out of them! But they do look cute... Yesterday while in Lancaster with Jason, he got a pair of shoes at the Clarks outlet, and I saw a pair I really really really wanted, but couldn't afford to spend about $40 on shoes at the moment so I passed on them! They sure were cute!! I like to get new shoes, but I still have my fave 2-4 pairs that I wear all the time! The rest are just for special occasions... Oh and in all truthfulness, I prefer to go barefoot, so as soon as I'm home, I ditch the shoes! :)

Take care!
Carrie :)

Aqua said...

Yes like Dinah asks, PLEASE!!!!! do a post on Treatment Resistant Depression...Med combo ideas? ECT followed by any particular meds? Therapy ideas? Anything would help...please? Are there any specialists in this area in North America (Canada esp.) that I could see?

When I am asking about TRD depression I mean for many drug trials and years of therapy...not just one or two drugs that haven't worked.

If I sound's because I am...thanks.

Anonymous said...

I have hot pink crocs...does that make me cool or what? And teva flipflops. Can you tell I am a student?

So these posts are giving me PTSD from the pharmacology and pharmacokinetics classes from pharmacy school. I got a D and a D+ respectively. I think I was given the D's because I actually went to class. As you can imagine...I am not living the glorious life as a pharmacist. Although it was cool to have a white coat for a while!

The whole genetic thing is cool...however people still smoke on clozapine...

But seriously, I thought doctors took a good look at peoples prescription coverage and pick the antidepressant with the biggest COPAY!!!!!!!

I spend $40 copay on just my effexor alone! At one time I had a weird dose that I needed two sized caps...and so my copay was $80 a month! Yippee!!!

So about $100 for all of my crazy drugs! And I am a student.
And spend money on stupid things like hot pink crocs!

Dr. Shock said...

EBM=Evidence Based Medicine. Well at least we think it is. A lot of discussion going on about the use of EBM. By the way, some exciting new developments for treatment resistant depression (TRD) like DBS=Deep Brain Stimulation, but until recently I had never heard of magnetic seizure therapy! (MST)? Sorry for all the abbreviations.
Regards Dr Shock

Roy said...

I am shocked... SHOCKED!... to hear that someone with the name of Dr Shock hasn't heard of Magnetic Seizure Therapy.

Just kidding. Great to have your viewpoints here. Thank you. Feel free to become addicted to our blog and push up your rate to 65% (with wife's permission :-)

I think someone already stated this somewhere else, but the problem with EBM is that it lags several years behind current practice. I think it is a great way to confirm things we do in practice.

As for the receptor talk, thinking in these terms is just shorthand in my brain for categorizing drugs into probability curves for a given target symptom or side effect (YMMV). It is not either/or (eg, "antihistamine makes all people sleepy or not"; "clozapine response can be predicted by psychopharmacogenetics [PPG]").

For me, at least, it's like when I play Texas Hold 'em... if I get an unsuited 7 J , I am less likely to stay in because the probability of getting an 8 9 10 is fairly low. However if I get them suited (eg, both spades) I am more likely to stay, because I also get a chance at a flush.

I will write more posts on PPG.
I will write more posts on PPG.
I will write more posts on PPG.

jcat said...

Mmmm - have looked at DBS and TMS and a whole bunch of abbreviations for TRD. Have tried about 40 odd meds over last 3 years, including all sorts of experimental stuff like Ketamine (although Aqua has mentioned a couple of studies on methadone...holding off on that one as too addictive for someone with all sorts of substance-abuse potential/history!!). Would be very keen to see other POV's on this...

NeoNurseChic said...

Personally, I'm waiting for DBS of the hypothalamus for cluster headache and other headache types. I saw a neurosurgeon 3 years ago about getting an occipital nerve stimulator implant, but he felt I wasn't a candidate since the location of my headaches are primarily frontal, and the occipital nerve really doesn't reach all the way to the forehead, even though in theory it does. The neurosurgeon was really a wonderful doctor (with excellent bedside manner, which I was surprised by in a neurosurgeon!), and he said he felt my best hope would be with DBS of the hypothalamus, but it's only been done experimentally in Europe. Only 2 studies have been published to my knowledge, and in one study, 2 people died. (I believe this was a Belgian study.) But when they perfect this surgery, you can bet I will be first in line!

They also are trying magnetic type things for migraine. This link goes to a news story on our local news where they interviewed my neurologist about a new device called the "migraine zapper". I think this is the same as the TMS you all are discussing for depression. I congratulated my neuro on the interview, and he told me that they want to also look into the device as a cluster headache abortive. The trouble with me is I have two different chronic, complex headache types - and they are both so rare that there is little known about them....

And the reason I write all of this is because if something is found for TRD, there is often a link in that it also works for someone's migraine and then can be tried for people like me. DBS and TMS are already being investigated for those with difficult headache types, but it's still so early yet. I haven't tried either one, but I hope to! So many of these diseases have similar underlying pathogenesis in some way. Now if we could just learn how the brain and its chemicals works in a much more thorough and exact fashion, then maybe we could find some cures! I still have some hope for this...

Take care,
Carrie :)

Anonymous said...

I've found occipital nerve stimulators to be an exciting treatment option for migraines. In my research, though, I read that a lot of the times they work great at first, but then over time the leads start to stray and they don't function as well. It's a problem they haven't been able to fix yet without another expensive surgery.

neonursechic--Have you ever tried using 100% medical oxygen as an abortive for your clusters?

Anonymous said...

Wow! You see Dr Young?? He's tops! He co-wrote an excellent book on migraines and other headaches with Dr Silberstein. :)

NeoNurseChic said...

Michelle - Yes to all of the above. I have an oxygen tank sitting about 6 feet from me right now. Need to get the tanks refilled though. I have been going to the headache center at Jefferson since December 2001 (I got my New Daily Persistent Headache in January 2001). I saw another neuro there who I got along with great, but he moved out of the country in 2003, and I started seeing Dr. Young in the fall of that year. We didn't click as well at first, but now we get along great. Generally, I see a nurse practitioner (Rachel), whom I love, but I see Dr. Young when things start to get more difficult and Rachel and I have tried some early treatment changes. I am seeing Dr. Young next month specifically because I'm in a rut and having a LOT of issues with it right now, making it difficult for me to work and exist. I might get through work, but then my days off are spent lying in bed because I dont' want to take triptans every day, and I need them when I work.

I've been in the hospital for headaches about 8 times and have done outpatient IV infusions maybe 5 times. Unfortunately, my NDPH has responded to next to nothing, and my clusters are chronic and have not been prevented by typical means. I've tried over 100 different medications and in various combinations, but have had no success. I've also been the experimental dummy for treatments such as IV propofol, continuous IV lidocaine, mexiletine, and some other things. The story is rather long and complicated!

So depression is a factor for me. I believe I've had depression prior to ever having such severe headache problems, but I've never taken meds specifically to treat depression. Depression is definitely made worse by severity of pain and disability from the headaches and other problems I have been diagnosed with since getting the headaches, too. I've got a bone disease (avascular necrosis) from too many steroid tapers/IV steroids in the hosp, and several other things - but I was desperate for relief, and I don't regret what I tried. The psychologist at Jefferson Headache Center is always talking about how depression and migraine work through the same chemicals so that when one is bad, it worsens the other - and I note the connection. In terms of psych dx, I also have ADD and anxiety. I was not put on meds for ADD until topamax screwed up my brain and I had severe memory/concentration problems and almost failed out of school. I've been off topamax since January 2004, but I have been unable to come off the ADD meds. C'est la vie!

I own the book "Migraine and Other Headaches" and I believe it is the best book written for the layperson on migraine and headaches in existance. The chapter of that book on NDPH is excellent, too. I am a trainee member of the American Headache Society and spent some time working in headache research. I still do education sessions from time to time, and I usually bring that book with me to recommend.

I've friends who have had the ONSI placed for both chronic migraine and chronic clusters. Nobody has gotten 100% relief with it - some have gotten some relief but others have gotten no relief, unfortunately. I appreciated the honesty of the neurosurgeon when he said he didn't think I was a good candidate for it!

Where do you live? Do you go to a major headache center? Earlier today I thought of actually calling in to see if I could get to outpatient infusions, but that involves missing work, and I'm also going away this weekend to visit my gran. The head has just been pretty bad lately, and that always makes my quality of life kinda crappy...

Sorry to hijack the thread here!! MIchelle, you can always email me at LizzPiano (at) gmail (dot) com if you want!

Take care!
Carrie :)

Anonymous said...

Off topic - but I don't know how to contact Shrink Rap off the blog. I just checked in to see what's up, and found that Google is now placing ads on your site - not a problem with that, for me - BUT one of the ads is a link to a site where you can obtain drugs without a prescription - not sure that is what you would choose to have on your site.

Fat Doctor said...

Here's a fun memory:

I had a patient, age 36, with premature ejaculation.

I prescribed paroxetine for its side effect profile of delayed ejaculation but forgot to mention it is also used as an antidepressant.

On followup, he admitted he is having better sex, and "the craziest thing, I actually feel happier, and I don't think it's just the sex."

Anonymous said...

One of the ads is for a site that lists every scary really awful freaky side effect of lexapro that anyone has ever encountered, might possibly encounter... and then you can click to get scary info on every other drug. It is less educational than propaganda.

Anonymous said...

Hi Roy!
Loved both the posts. I actually started somebody on Serzone recently (don't tell my malpractice company!)
Reading both posts, though, made me think of that book, Blink (I forget the author), which is a wonderful treatise on decision-making, and how some decisions, while appearing like gut decisions, are actually based on years of experience and training, and are actually are often the best decisions. When I read the book, I really felt that it applied to psychiatry. You're not always sure why you make particular decisions, after listening carefully to a patient, but there is method to it.
See you soon! Camel

Roy said...

Thanks, Camel. Blink is one of my gotta-make-time-to-read-it books.

Fat Doc, So does this mean that you actually listened to a podcast for the first time? Ours? Re:Paxil and PE... I came up with the idea of dissolving Paxil in saline and making a nasal spray to see if it would work as an on-demand treatment for premature ejaculation. Never got around to trying it.

and Miss Mouse and Anon, thank you for your comments about the ads. I added a link below it where you can leave a comment that includes the ad's URL. If I have that I can block objectionable content (raises the question: should we block stuff like Interesting ethical/free speech/censorship issues here.

Rach said...

Blink is by Malcolm Gladwell, who writes for the New Yorker. Yes, I think much of what he writes about in the book (and to a lesser extent, in The Tipping Point ) applies to Medicine.

BTW, Roy, Blink is an easy book to get through. I actually had to read both of Gladwell's books for a seminar I took in undergrad, and read both in a weekend. He has an interesting writing style, one which I find enjoyable - not unlike the way you, Dinah and Clink write your blog posts, actually!

S said...

Regarding doctor preference, and only a couple years late: Having been inpatient several times, and having friends who've also been hospitalized, it's pretty well-known that some psychiatrists have their "pet drugs".

We patients talk. One hospital stay, we found that every single one of us on the ward who was seeing Dr. F was on Zyprexa -- one for mania, one for auditory hallucinations, one for anxiety, one for being old or something, and me ostensibly for depression (though after pulling my chart i found that he suspected schizoaffective disorder -- wtf? -- though he never actually mentioned it to my face). More recently, in a different hospital, there was Dr. A, who puts everyone on Lamictal and diagnoses everyone (myself included, another wtf) as bipolar.

Now, i'm sure you don't do this. I think this style of practice must require a significant lack of self-reflection, and i don't think the doctors i speak of are floating around in the blog world at all.

A cynical person might say they're receiving kickbacks. For the record, i don't think that at all. I suspect confirmation bias, and i suspect that could be a particular danger with hospital shrinks, because of course all their patients improve enough to get discharged, and then they don't see most of 'em again... but then again, i kind of feel like a jerk for suggesting this, because of course confirmation bias must be something that psychiatrists are acutely aware of. Right? Whereas i'm just a manual laborer with no particular insight. Anyway. It concerns me.

S said...

Oh, well, i hadn't read the posts directly above mine. I don't have anything in particular to say about shoes.