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What is the fastest route to remission in uncomplicated MDD (aside from ECT)?

Discussion in 'Psychiatry' started by firedoor, Aug 5, 2011.

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  2. Encephalopathy

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  3. whopper

    whopper Former jolly good fellow
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    It'd likely make the person worse in the future. Cocaine?

    When I prescribe antidepressants, I usually have the person raise the dose on their own before they see me again after being on it for a week. Why? Studies show that at the lower dosages, antidepressants pretty much don't do anything. I figure if the person gets better and doesn't need as high a dose, we could always lower it later on. Better to relieve their depression first.

    I've seen docs only raise the dosage after the lowest rung dosage (e.g. Zoloft at 25 mg Qdaily, Citalopram at 10 mg Qdaily), has been tried for over 1 month. If you go on that track, by the time you've given an antidepressant a proper trial (max dose for at least one month), you'd have wait about 6 months, and the med not even work at all.

    The way I do it, I have a patient by the max dosage within 6 weeks. I'm willing to get the patient to the max dose faster (4 weeks) if after explaining the pros and cons, they want me to push it.
     
  4. nitemagi

    nitemagi Senior Member
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    I dunno Whopper, some evidence says ketamine effects last up to 2 weeks. Could be long enough to get going on an SSRI.

    How about a stimulant?
     
  5. Encephalopathy

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    With all due respect, Whopper, do you have any evidence to back up that assertion? Ketamine and cocaine may both have abuse potential but work by completely different mechanisms of action, and ketamine simply does not have the same withdrawal syndrome as cocaine.

    The discovery of ketamine's rapid antidepressant effects 5 years ago has largely been ignored by clinicians because it is often dismissed out of hand as a drug of abuse, it is associated with perceptual disturbances, the delivery method is IV, and there is no pharmaceutical support for an unpatentable medication.

    Nevertheless, we are doing our patients and our field a disservice if we don't look past our initial biases to take an objective view of the evidence base and utilize the most effective clinical interventions for our patients.

    -----

    Mechanism of action of ketamine: Li N, Lee B, Liu RJ, et al. mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists. Science. 2010;329(5994):959–964.

    Average of 19 days before relapse, 1 pt in remission > 3 months: Rot MAH, Collins KA, Murrough JW, et al. Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression. BPS. 2010;67(2):139–145.

    Future of glutamatergic treatment: Zarate C, Machado-Vieira R, Henter I, et al. Glutamatergic modulators: the future of treating mood disorders? Harv Rev Psychiatry. 2010;18(5):293–303.
     
  6. fiatslug

    fiatslug Senior Member
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    Indeed, I think the UCSD Tx-Resistant Depression Clinic is offering IV Ketamine tx for patients who are "running out of options":

    Psychiatric Times Article
     
  7. Sneezing

    Sneezing Even Bears do it!
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    UCSD isn't the only place performing ketamine infusions... It can also be delivered IM, too I believe.
     
  8. ghost dog

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  9. billypilgrim37

    billypilgrim37 Unstuck in Time
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    Maybe the editors of the most prestigious journal in psychiatry know something you don't?
     
  10. whopper

    whopper Former jolly good fellow
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    Hmm, I hope no one seriously thought that I am truly recommending cocaine!?!? If you did, I think the fault is mine because I didn't clarify.

    That's why I mentioned it'd likely make the person worse in the future. So many meds help with depression but aren't worth it because the long-term effects are worse than the short term benefits. E.g. opioids, that at one time were actually used to treat depression. (What? Opioids could cause addiction and dependence?!?!?!)

    I'd be open to using a stimulant but only in extreme cases of depression. E.g. the person is vegetative and appearing almost catatonic. Even then I'd still be hesitant. You're treading on unproven ground.
     
    #10 whopper, Aug 10, 2011
    Last edited: Aug 10, 2011
  11. ghost dog

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    Oh gee, now that's an elegant rebuttal.

    But, I went to Havaaaard.

    Who cares where it was published? Bad science is bad science.
     
  12. billypilgrim37

    billypilgrim37 Unstuck in Time
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    Sorry, I get tired of people griping about important literature because they don't understand its significance. It's a proof of concept trial of a novel antidepressant mechanism. That is huge. The chances of the folks at Archives publishing "bad science" is very small. On average, if you look at an Archives paper and think it is bad, unless you're one of about 50 people in the country, it's probably your problem, not the paper's. Maybe not, but probably.
     
  13. Encephalopathy

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    I'm not sure why you're so exasperated about the length of the trial. They were looking for an acute effect and they found it. It wasn't met to be a stage 3 clinical trial. Follow-up studies are being conducted to determine the length of the effect and the best way to maintain it.

    Whopper, I apologize, I thought you were commenting that ketamine would likely make someone worse and then compared it to cocaine. But now I understand you were just responding to the original question and talking about cocaine, not ketamine. Sorry!
     
  14. alethiologist

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    What about modafinil (temporarily as a short term treatment) and bupropion? If someone's in a catatonic state of depression, why not work on the norepinephrine? And why citalopram and not escitalopram oxalate?
     
  15. whopper

    whopper Former jolly good fellow
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    No need to apologize. Such is what happens on message boards where the other guy might not respond for a few days.

    I made my comment in a somewhat sarcastic sense that may have been lost in the form of written text. The point being that substances of abuse could aid in treating depression. Xanax, cocaine, Heroin, they could all help a patient's depression. I'm sure a HAM-D would show great improvement if you gave the person cocaine.

    But a point being that with things like Ketamine, or cocaine, you just can't think that because scale shows improvement that it's good treatment. Ketamine is a substance of abuse. Such medications (or illicit substances) may have their place with depression augmentation but be very very careful and cautious. Other things have to be taken into consideration such as the risks to the patient. With cocaine, I'd think we'd all agree that the risks outweigh the benefits in the far overwhelming number of cases where someone is depressed.
     
  16. billypilgrim37

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    I think most of the research right now is not so much on how to turn ketamine into a clinically applicable drug (for depression, that is), but how to find/synthesize a molecule that will have the same action without the abuse potential or other drawbacks to ketamine. It's the novel MOA more so than the actual drug that is so exciting.
     
  17. RedPakotaSea

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    I'm a skeptic regarding ketamine's clinical utility, but it's not fair to compare the antidepressant effect of ketamine to that of cocaine. With pleasure-inducing drugs (e.g. opiates, cocaine, amphetamines), there is a short period of euphoria while the drug is in the user's system, which is followed by an abrupt "crash" (moreso with stimulants) that would no doubt exacerbate symptoms of depression.

    However, with ketamine, the antidepressant action starts as the drug is eliminated from the body. At the end of the 40 minute infusion, there is no difference in the HDRS score. It's not until 110 minute mark that ketamine separates from placebo, and by this time the perceptual effects are essentially gone. Additionally, the fact that the antidepressant effects last for a week makes it clear that something very different is going on here.
     
  18. whopper

    whopper Former jolly good fellow
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    Good to know and something I was not aware of.
     
  19. BobA

    BobA Member
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    what's wrong with ECT?
     
  20. ghost dog

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    I still think it would have been a more impressive trial if they followed these patients out for a longer period of time.

    In regards to taking an illicit substance and making it into a pharmaceutical, this has been done (sort of) with THC and nabilone / cesamet. The primary indication for this medication is for post - chemo induced nausea; however, it has been used off label for chronic pain.

    Some patients seem to respond quite nicely to this med. I much prefer scripting this than that of "medical marijuana", which I have yet to do.
     
  21. kugel

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    :clap:

    This was going to be my question.
    Why the dismissal of ECT?
    Perhaps you are so familiar with it's advantages that you didn't feel the need to bore us with them again.
     
  22. WannaSwitchBack

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    OP states " (aside from ECT)"
    What about TCMS? I am too lazy tonight to run a lit search, but the Neurostar folks certainly advocate it.
     
  23. OldPsychDoc

    OldPsychDoc Senior Curmudgeon
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    He also specified "remission"... :rolleyes:
     
  24. whopper

    whopper Former jolly good fellow
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    Speaking of TMS, anyone have their patient on it? Any issues with getting insurance to pay for it?

    I was at the Lindner Institute a few months ago and they showed me the TMS room. I talked to their TMS guy (nuts forgetting his name) who is also a researcher on it. Interesting to say the least.
     
  25. Encephalopathy

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    Exactly!
     
  26. DrGachet

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    [​IMG]
     
  27. WannaSwitchBack

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    Yes, and it really works well. I rotated with a private attending last year and he treated a number of patients successfully. Even treated a few pts with migraines with success. I am currently writing up one of his cases (post thalamic stroke pain which remitted in less than ten TMS sessions). It's pretty awesome.

    They all paid out of pocket. No one was getting reimbursed.
     
  28. cleareyedguy

    cleareyedguy Junior Member
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    Best approach is to do a Hamilton and then hope the patient is on the road to recovery anyway and "responds" within a week with no treatment; it occurs not infrequently and is side effect free.
     
  29. WannaSwitchBack

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    Point taken. Some would argue that the therapeutic interaction along w/hamD & subsequent f/u is a form or treatment...
     

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