what tachyphylaxis is, what causes it, and how to fix it



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1.  What is SSRI & SNRI Poop-Out / Tachyphylaxis

Serotonin-Selective Reuptake Inhibitor Antidepressant Tachyphylaxis, in fancy doctor-speak, better known as SSRI poop-out, is when an SSRI that has been working for you, suddenly stops working and still doesn’t work no matter how much more you take. While this can happen to any medication, crazy or not, reuptake inhibitors in general and serotonin-selective reuptake inhibitors in particular, as a class are more susceptible to it; although individual drugs like Remeron or Gabitril might be failing as frequently as, if not more often than SSRIs.1 It also happens with Serotonin & Norepinephrine Reuptake Inhibitors (SNRIs), but nowhere near as often. I’ve included them here because SNRIs are often a good substitute for SSRIs, especially if SSRIs work well for someone but keep pooping out.

2.  Will it Happen to Me?

That depends. Let’s look at some numbers:

RESULTS: For the 103 subjects, there were 171 maintenance treatment intervals in which a subject received maintenance pharmacotherapy after having recovered from an episode of major depressive disorder. The median duration of maintenance treatment was 20 weeks. Tachyphylaxis occurred during 43 (25%) of these 171 maintenance treatment intervals. The subtype of melancholic (endogenous) major depressive disorder significantly elevated the risk of tachyphylaxis during the subsequent maintenance treatment interval. CONCLUSIONS: Despite the use of maintenance pharmacotherapy, major depression recurs in a considerable number of patients. Improved prophylaxis for these patients requires other treatment strategies based upon a greater understanding of recurrence. --Tachyphylaxis in unipolar major depressive disorder

That doesn’t mean that 25% of the people had it, it just happened 25% of the time.

The numbers from the literature are all over the map. Stahl estimated it at 20–30%. Based on everything I’ve read and all the anecdotal evidence I’ve found there is, at most, a ten percent chance of an SSRI/SNRI suddenly failing for no apparent reason for everyone, but 20–30% seems about right as soon as you’ve tried your second med no matter why the first one didn’t work for you.

And it’s not just people with unipolar depression:

OBJECTIVE: Tachyphylaxis often refers to the loss of antidepressant efficacy during long-term treatment. However, it may also refer to the gradual loss of efficacy after repeated antidepressant exposures over time. The aim of this study was to examine the phenomenon of tachyphylaxis in patients with Bipolar II major depression treated with either venlafaxine or lithium. --Does tachyphylaxis occur after repeated antidepressant exposure in patients with Bipolar II major depressive episode?

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3.  What Causes SSRI & SNRI Poop-Out / Tachyphylaxis

3.1  It’s All Your Fault

Now that most doctors admit poop-out exists, the researchers think it has more to do with the person than the med. I’m not sure which is the more likely cause, but I’m leaning towards the person, in that SSRI tachyphylaxis effect is usually due to a combination of genetics and behavior. This study pretty much nails it. They found that poop-out is usually due to one or more of a bunch of things, including genetics, non-compliance and trying to find a perfect drug in an imperfect world:

Residual symptoms are common among patients treated for MDD who do not achieve full remission. Incomplete remission is associated with increased risk of relapse, suicide, functional impairment, and higher use of health care resources. Several factors, including “downstream” neurochemical mechanisms and clinical factors such as lack of adherence, contribute to the high prevalence of residual symptoms. Various clinical strategies, including switching and substitution antidepressant therapies, are used to address unresolved depressive symptoms. Individual differences in therapeutic response contribute to inadequate treatment and are linked to numerous clinical and neurobiological factors, including noncompliance, underdosing, intolerance, disturbances in neural circuitry, and genetic variability in neurotransmitters. --Clinical Evidence and Potential Neurobiological Underpinnings of Unresolved Symptoms of Depression

3.2  It’s Better to Fight than Switch

We’ve written over and over that frequently switching meds for no good reason can lead to being treatment-resistant when one wouldn’t have been otherwise. Tachyphylaxis after Repeated Antidepressant Drug Exposure in Patients with Recurrent Major Depressive Disorder backs us up on that one. Lots of people are going to be treatment-resistant no matter what, and poop-out could be considered a form of treatment-resistance.

Still, you don’t want to be left in a situation where neither Effexor nor lithium do anything for you:

We hypothesized that a greater number of prior antidepressant exposures would result in a reduced response to venlafaxine, but not lithium, therapy.

RESULTS: The mean number of prior antidepressant and mood stabilizer exposures was significantly higher in venlafaxine non-responders versus responders (p=0.02). There was no significant association between response to lithium response and the number of prior antidepressant and mood stabilizer exposures (p=0.38). The odds of responding to venlafaxine or lithium therapy decreased with an increasing number of prior antidepressant exposures (p=0.04). --Does tachyphylaxis occur after repeated antidepressant exposure in patients with Bipolar II major depressive episode?

So if you have taken too many meds you might be stuck with lithium, or something else that doesn’t work as well as it should. Assuming you haven’t failed it because of real intolerable side effects and not just vanity weight gain, hair thinning and the like.



3.3  From Placebo Effect to Nocebo Effect

You know all of those articles and studies on how antidepressants don’t fare that much better than placebos in the clinical trials. Articles like Symptom Reduction and Suicide Risk in Patients Treated With Placebo in Antidepressant Clinical Trials, Efficacy of antidepressants in adults, and Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. So if a lot of people were merely responding to the placebo effect, then it makes sense, in a way, that SSRI poop-out is a spontaneous failure of an over-priced placebo. In How often do SSRIs and other new-generation antidepressants lose their effect during continuation treatment? Evidence suggesting the rate of true tachyphylaxis during continuation treatment is low Dr. Zimmerman et al. found that 24% of people who responded to the placebo experienced poop-out while ‘only’ 7% of those for whom the SSRIs actually worked had the meds fail on them. Why a placebo would poop-out on someone is still a mystery.

Check that. It’s not a mystery at all. A placebo poops out because it never did anything in the first place! In an actual long-term (one and two years) study, and not just a meta-analysis like the one referenced above, the placebo pooped-out for 73% of the people taking it! Placebos don’t work in the long run.2

3.4  Can I Get a Serotonin Refill?

Medication-induced monoamine neurotransmitter (serotonin, norepinephrine, dopamine, and other less common ones) depletion is a controversial hypothesis in the world of psychopharmacology. The idea behind it is fairly straightforward: if a drug interferes with part of the process that literally recycles serotonin (the “reuptake” of “reuptake inhibitor” is the brain juice equivalent of putting something in the recycling bin), it follows that you could wind up with less serotonin to work with; just like soil that was normally flooded by the local river once every few years loses its productivity - despite all the fertilizers pumped into it - after the river is ‘tamed’ and doesn’t flood nearly as often.
Different meds will often work because they working on different receptors (e.g. 5HT1A) and/or in different parts of your brain, where your brain was still recycling serotonin like it was supposed to.
The problem is too many quacks and the antipsychiatry movement have latched onto the idea as proof that SSRIs (and therefore all crazy meds) will permanently prevent you from ever producing another drop of serotonin (or whichever neurotransmitters your meds are working with) ever again. Which is total bullshit. Especially since reuptake inhibitors don’t stop your brain from recycling monoamines, they merely slow down the rate at which your brain juice is recycled.

Based on my own experiences and the anecdotal evidence I’ve collected, my money is on medication-induced neurotransmitter depletion being a real phenomenon. And once you stop taking the meds that depleted the neurotransmitters involved your body will start producing them again. When is going to depend on a lot of stuff, but it is not going to be permanent.3

And if you think about it medication-induced neurotransmitter depletion is relatively easy to fix.

3.5  I Can’t Tolerate Intolerance

Another theory is the different receptors the meds work on in various parts of your brain develop a tolerance (become sensitized) to the extra serotonin and/or the way drug causes it to hang around. Thus switching meds works because you shift the effect around.

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4.  What Can You Do About It

4.1  You Can Haz Refill

The first, and easiest4 thing to try when an SSRI poops-out on you is to get a prescription for pharmaceutical-grade 5-HTP, or find a brand of 5-HTP, or l-Tryptophan (which gets converted to 5-HTP), that you know is pure and consistent in dosage. Then you and your doctor figure out how much you need to take each day. 5-HTP supplements do convert to serotonin and can affect psychiatric disorders. That’s old news. If all you need is a few 5-HTP capsules a day, along with things exercise, fresh air and a better job, you aren’t depressed/anxious/whatever enough to be reading this site in the first place.

What? You want to know how much 5-HTP to take? Because of all those warnings about mixing l-tryptophan/5-HTP and serotonin syndrome, right?
That’s the problem. There is no right answer. The vast majority of studies about the effect of changing dietary tryptophan on serotonin in people with brain cooties are about depletion. Everyone is happy to prove taking serotonin away makes depression worse. Or it doesn’t. But they still have to cover the most obscure situations. I mean really obscure. There are very few out there where people are given l-tryptophan or 5-HTP while taking an SSRI. I’ve found all of two. In L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI researchers gave 50–200mgs of 5-HTP to people taking 20–40mg of Celexa for…nothing. They were professional guinea pigs and the researchers were testing their prolactin and cortisol levels, so it was all about measuring side effects. In the other, Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa it probably doesn’t matter that the abstract doesn’t state who took how much of what because it failed to make a difference. So for now you and your doctor are on your own.
If it helps, I take 1000mg of l-tyrosine every day to augment the norepinephrine reuptake of the TCA I take, as I had Strattera-induced norepinephrine depletion. I can feel the difference if I take too little, or too much.

If the amino acid l-tryptophan/5-HTP doesn’t work the next step is to take a serotonin agonist like BuSpar, with or without the l-tryptophan.

4.2  Once More on the Med-Go-Round

If one SSRI fails on you, and augmenting it with amino acids and/or BuSpar doesn’t work, do you have a future with other SSRIs? Unfortunately the answer is: maybe. If switching meds is the only thing that seems to work, then it gets really crazy.

  • Changing meds all the time is a potential cause of tachyphylaxis.
  • But if a med up and quits on you, and prescription-strength, pharmaceutical grade l-tryptophan/5-HTP, or an add-on serotonin agonist like BuSpar doesn’t work what choice do you have?
  • So you try another SSRI, and as long as that works you’re OK.
  • Until that one stops working.
  • Lather, rinse, repeat.
  • Until you’ve been through every SSRI available.
  • And every SNRI as well.
  • Which could be evidence it’s been the placebo effect all along.
  • If you eventually make your way back around to the first med you tried and it works again, that’s more evidence it was probably the placebo effect.
  • Especially if the first med was Paxil, or you try Paxil again and it works for a few weeks (or how ever long these drugs are working for you), because Paxil often doesn’t work the second time around.
  • Although, if you were hit with SSRI discontinuation syndrome right away, that would indicate some kind of failure in how the medication was absorbed, or that you’re dealing with serotonin depletion. In which case augmenting the SSRI with l-tryptophan/5-HTP or BuSpar should work.
  • Unless the discontinuation syndrome is “all in your head,” as it were.
  • Still, you could have a really messed-up brain and/or liver and/or endocrine system and/or something else they haven’t figured out is involved that causes SSRIs & SNRIs to work for only a limited amount of time.
  • So unless you get into a double-blind clinical trial for a new SSRI or SNRI, get the placebo, and respond positively to it, you’ll never know for sure if this mess has been due to a variant on the placebo effect (and you shouldn’t be taking meds and reading this site) or if you’re an outlier (and one of the people this site was created for).
  • Because if you were born to quickly burnout on SSRIs, it’s possible that starting with a TCA or an SNRI (see below), or going to one of them as drug #3 instead of another SSRI, could have avoided this hassle.
  • But you’re probably hosed now, because after failing six or seven meds, nothing is going to work as well as it could have. Not an SSRI, not an SNRI, not Lamictal, not Abilify, not lithium, nothing.
  • Or maybe you’d be treatment-resistant no matter what you did because of genetics and/or your lifestyle prior to seeking real treatment for psychiatric problems.
  • I’m sorry if you’re not going to sleep for the next year or two because you’ll be ruminating over this night after night after night. Welcome to my world.

4.3  Two Meds are Better than One

Not so much two meds - because taking one med is usually way better than taking two - but meds that work on two neurotransmitters are much less likely to poop-out than those that work on just one.
Dual Reuptake Inhibitors Incur Lower Rates of Tachyphylaxis Than Selective Serotonin Reuptake Inhibitors: A Retrospective Study and Beyond Remission, Rationale, and Design of the Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) Study, a large, two-year long trial sponsored by Wyeth, found that SNRIs and TCAs were less likely to poop-out than SSRIs. As Wyeth makes two SNRIs (Effexor and Pristiq) that part of that result isn’t surprising, that cheap-as-dirt5 TCAs were also proved to be unlikely to poop-out was refreshing to read.

If two SSRIs fail on you, either due to poop-out or they just didn’t work all that well, try a med from another class. That’s just common sense.

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5.  SSRI & SNRI Dosage Equivalents

5.1  The difficulties involved in determining dosage equivalences

Trying to nail down equivalent dosages for SSRIs is a lot harder than you may think. Even though they are all supposed to be serotonin-selective reuptake inhibitors, only Lexapro is truly selective. All the others mess with more than serotonin, although there is no agreement as to any of that being clinically relevant. In a way it is almost like antipsychotics, in that there is one property they all do - D2 antagonism for antipsychotics6 - and that’s good enough to use in order to figure out which is equivalent to which in case you need to switch in an emergency situation.
In addition to being approximates, the equivalences given aren’t something where you can easily double the dosage on one and expect the dosage on the corresponding one to also be twice as much. How they affect those receptors in your in brain - and anywhere else you have receptors they affect - as well as the pharmacokinetics aren’t linear for all of them. This leads to odd things, like Lexapro often being more effective at a lower dosage while Celexa - the drug from which it is derived - is usually more effective at a higher dosage. And how Paxil’s efficacy essentially tops out at 20mg a day, as any dosage above 20mg either won’t make a difference because of diminishing returns, or works due to Paxil’s effect as a norepinephrine reuptake inhibitor, a sigma-1 agonist, and/or as a CYP2D6 inhibitor.
Potency, while important in calculating equivalence, isn’t everything.

There is a frequent misconception that potency refers to the dose of a drug needed to produce an effect. That is wrong. Instead, it refers to the concentration of a drug needed to produce an effect. Two drugs may be able to produce exactly the same effect, but the concentration needed of each drug may be quite different. The drug that requires a lower concentration to achieve the same magnitude of effect is the more potent drug regardless of the dose needed to achieve that concentration. --Dr. Sheldon Preskorn

This is yet another example of the importance of a drug’s pharmacokinetics. Effect is a factor of potency and various bioavailability aspects. Pure, or free base7 paroxetine is 14 times as potent as free base fluoxetine, but because of its screwy pharmacokinetics and the way the salts are absorbed, 10mg of Paxil (paroxetine hydrochloride) is the equivalent of 20mg of Prozac (fluoxetine hydrochloride).8

And effect is not the same as efficacy. Just because two meds are relatively equivalent at how much more serotonin they’re letting your brain soak in, that doesn’t necessarily mean they’ll work the same way for you.
This guide isn’t concerned with efficacy. It’s only purpose is to give you some rough numbers in case you must switch SSRIs immediately, due to a severe allergic reaction, some other equally bad side effect, or sudden tachyphylaxis (poop-out) that has resulted in SSRI discontinuation syndrome, or some other worst-case scenario.9

5.2  Low/Minimum Therapeutic Dosage Equivalents

20mg Celexa (citalopram HBr) = 10mg Lexapro (escitalopram oxalate) = 50mg Luvox (fluvoxamine maleate) = 10mg Paxil (paroxetine HCl)10 = 20mg Prozac (fluoxetine HCl) = 50mg Zoloft (sertraline HCl) = 75mg Effexor (venlafaxine HCl)11 = 50mg Pristiq (desvenlafaxine succinate)12 = 20mg of Cymbalta (duloxetine HCl)

5.3  Sub-Therapeutic Dosage Equivalents

To give you an idea of the effect of non-linear pharmacokinetics, and because it might be useful in some situations.
5mg Celexa (citalopram HBr) = 2.5mg Lexapro (escitalopram oxalate) = 25mg Luvox (fluvoxamine maleate) = 5mg Paxil (paroxetine HCl) = 5mg Prozac (fluoxetine HCl)13 = 10mg Zoloft (sertraline HCl)14 = 6.25mg Effexor (venlafaxine HCl)15 = you can’t get that small with Pristiq and Cymbalta.

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5.4  Raw Power

Here are the averages of the above meds’ Ki values from the NIMH Psychoactive Drug Screening Program’s database. The lower the number, the greater the strength.
Once again: binding potency of the base substance at the serotonin transport (reuptake) sites is just one factor in determining the overall strength (not efficacy) of a drug. It just happens to be the simplest and is usually close enough. Once again I need to stress an important difference: I’m not using the generic names in this table, but the base chemicals that you’re not going to get at a regular pharmacy16. While many drugs, such as most AEDs, are in their base form, for whatever reasons most antidepressants are not. As such I used the active ingredient in the dosage equivalents, which is why the math does not add up.
SERT: Serotonin transport, the mechanism that is being inhibited by a reuptake inhibitor.

Ingredient free baseKi at SERT
citalopram4.04
desvenlafaxine43.75
duloxetine3.07
escitalopram1.80
fluoxetine7.18
fluvoxamine4.54
paroxetine0.50
sertraline1.13
venlafaxine67.41

.

For more data like the above, see the page on TCAs



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SSRI discontinuation syndrome. | SSRI Overview and Topic Index
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6.  References

  1. Stahl, Stephen M. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (Essential Psychopharmacology Series) Third edition Cambridge University Press 2008. ISBN:978–0521673761
  2. Julien, Robert M. Ph.D, Claire D. Advokat, and Joseph Comaty Primer of Drug Action: A comprehensive guide to the actions, uses, and side effects of psychoactive drugs 12th edition Worth Publishers 2011. ISBN:978–1429233439
  3. Stahl, Stephen M. The Prescriber’s Guide (Essential Psychopharmacology Series) Third edition Cambridge University Press 2009. ISBN:978–0521743990
  4. Virani, Adil S., K. Bezchlibnyk-Butler, and J. Jeffries Clinical Handbook of Psychotropic Drugs 18th edition Hogrefe & Huber Publishers 2009. ISBN:978–0889373693
  5. PDR: Physicians’ Desk Reference 2010 64th edition
  6. Essential Psychopharmacology of Depression and Bipolar Disorder Stephen M. Stahl, M.D., Ph. D. © 2001. Published by Cambridge University Press
  7. Sheldon Preskorn’s Applied Clinical Psychopharmacology www.preskorn.com M.D. Chief Executive Officer of the Clincal Research Institute and a Professor in the Department of Psychiatry and Behavioral Sciences at the University of Kansas School of Medicine - Wichita
  8. The PDSP Ki database
  9. PubChem BioActivity Analysis database
  10. Owens, Michael J., W. Neal Morgan, Susan J. Plott, and Charles B. Nemeroff. “Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites.” Journal of Pharmacology and Experimental Therapeutics 283.3 (1997): 1305-1322.
  11. Hinz, Marty, Alvin Stein, and Thomas Uncini “Monoamine depletion by reuptake inhibitors” Drug, Healthcare and Patient Safety 2011:3 69–77.
  12. Best, Janet, H Frederik Nijhout, and Michael Reed “Serotonin synthesis, release and reuptake in terminals: a mathematical model”. Theoretical Biology and Medical Modelling 2010, 7:34
  13. Trivedi, Madhukar H. M.D., Eric Hollander, M.D., David Nutt, M.D., and Pierre Blier, M.D., Ph.D. “Clinical Evidence and Potential Neurobiological Underpinnings of Unresolved Symptoms of Depression” Journal of Clinical Psychiatry 2008;69:246-258
  14. Meyer, Jeffrey H. M.D., Ph.D.; Alan A. Wilson, Ph.D.; Sandra Sagrati, M.Ed.; Doug Hussey, B.Sc.; Anna Carella, B.Sc.; William Z. Potter, M.D.; Nathalie Ginovart, Ph.D.; Edgar P. Spencer, Ph.D.; Andy Cheok, M.D.; and Sylvain Houle, M.D., Ph.D. “Serotonin Transporter Occupancy of Five Selective Serotonin Reuptake Inhibitors at Different Doses: An [11C]DASB Positron Emission Tomography Study” The American Journal of Psychiatry 2004;161:826-835.
  15. Amsterdam, Jay D., David Williams, David Michelson, Lenard A. Adler, David L. Dunner, Andrew A. Nierenberg, Frederick W. Reimherr, and Alan F. Schatzberg. “Tachyphylaxis after repeated antidepressant drug exposure in patients with recurrent major depressive disorder.” Neuropsychobiology 59, no. 4 (2009): 227-233.
  16. Bell, Caroline, Jolane Abrams, and David Nutt “Tryptophan depletion and its implications for psychiatry.” The British Journal of Psychiatry (2001) 178: 399-405
  17. Neumeister A, Nugent AC, Waldeck T, et al. “Neural and Behavioral Responses to Tryptophan Depletion in Unmedicated Patients With Remitted Major Depressive Disorder and Controls”. Arch Gen Psychiatry. 2004;61(8):765-773.
  18. Moore, Moore Ph.D, Hans-Peter Landolt Ph.D, Erich Seifritz MD, Camellia Clark MD, Tahir Bhatti MD, John Kelsoe MD, Mark Rapaport MD, and J Christian Gillin MD “Clinical and Physiological Consequences of Rapid Tryptophan Depletion” Neuropsychopharmacology (2000) 23, 601–622.
  19. Cools, Roshan, Oliver J Robinson, and Barbara Sahakian. “Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction”. Neuropsychopharmacology (2008) 33, 2291–2299; published online 17 October 2007
  20. Justin H. G. Williams, David I. Perrett, Gordon D. Waiter, and Stephen Pechey “Differential effects of tryptophan depletion on emotion processing according to face direction” Soc Cogn Affect Neurosci. Dec 2007; 2(4): 264–273.
  21. Posternak, Michael A., and Mark Zimmerman “Dual reuptake inhibitors incur lower rates of tachyphylaxis than selective serotonin reuptake inhibitors: a retrospective study.” Journal of Clinical Psychiatry 2005, 66(6):705-707
  22. Kornstein, Susan G. “Beyond remission: rationale and design of the Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) Study.” CNS Spectrums 11.12 Suppl 15 (2006): 28-34.
  23. Rothschild, Anthony J., et al. “Assessing rates and predictors of tachyphylaxis during the prevention of recurrent episodes of depression with venlafaxine ER for two years (PREVENT) study.” Psychopharmacology Bulletin 42.3 (2009): 5.

1 I have nothing whatsoever to back this up with, other than lots of people complaining on teh InterWebs.

2 Not that Effexor and Prozac did much better in that study, but for a good reason. The people were taking randomized dosages. The Effexor dosage someone was on could have been anywhere in the range of 75 to 300 mg a day. Anyone who has taken Effexor can tell you that you have to be on the correct amount for it to work. Prozac was the same. That's the nature of double-blind studies. Sometimes they are a lot worse than open label - where everyone knows who is taking what, or single-blind - where only the people taking the drug or placebo are in the dark.

3 Unless, of course, you're that one person in 100,000 who lost the genetic lottery. Fortunately taking an agonist for whichever neurotransmitters involved will correct that. You may have to deal with side effects you really don't like, but that would suck a lot less than no serotonin, norepinephrine, dopamine, whatever action at all.

4 In theory.

5 Except for protriptyline - the one I take - which cost $400 a month when I paid full retail and $100 a month now that I have insurance. Probably because only 99 other people in North America take it.

6 Although some third-generation APs, like Abilify, don't even do that. They're partial D2 agonists and D3 antagonists.

7 Really, that's the term for it. Sometimes the term "freebase tar" is used. Anyone who came across this page trying to find information of illicit drugs will probably have better luck on Wikipedia.

8 Now you might understand why I'm so anal about using the complete chemical name instead of just the base active ingredient in some places, even though I don't know the difference between a hydrochloride and hydrobromide salt.

9 That usually involves no money and plenty of leftovers. Visit Needy Meds* for information on getting free meds from the drug companies. You really, really, really don't want to get in that situation, nor do you want to depend on this site for anything more than a rough idea of how long you can last as you do something to get some meds from a county / free clinic. Bring your leftovers to trade, as that might even get you more of what you need.

10 The dosage should be the same for Pexeva and other brands of paroxetine mesylate. The dosages and titration schedules in the Pexeva PI sheet are identical to Paxil's.

11 I know, Effexor isn't an SSRI, but at these dosages it doesn't do enough norepinephrine reuptake inhibition to make a difference.

12 Pristiq is even less of an SSRI than Effexor, and 25mg would be at lot closer than 50mg, but this is the lowest dosage you can get.

13 You can get this dosage only with the oral solution.

14 You can try splitting a tablet, but using the oral concentrate would be so much easier.

15 You can get this dosage only with the immediate-release form. And good luck quartering a 25mg tablet.

16 I'm not even sure if a compounding pharmacy can make you a pill with pure, unadulterated paroxetine. Although I'm fairly certain I've seen the base ingredient for some SSRI or other antidepressant available outside of the US, so it may be possible to get something made. You need to ask someone else as to why anyone would want to do because I have no clue if it is a good idea or not.

*Needy Meds


Last modified on Wednesday, 27 August, 2014 at 12:45:23 by JerodPoorePage Author Date created 27 November 2010
“SSRI & SNRI Poop-Out/Tachyphylaxis & Dosage Equivalents” by Jerod Poore is copyright © 2010 Jerod Poore Published online 2010/11/27
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with Microdata: <span itemprop='citation'>Poore, Jerod. "SSRI & SNRI Poop-Out/Tachyphylaxis & Dosage Equivalents." <em>crazymeds.us</em>.(2010).</span>
Linked:<a href="http://scholar.google.com/citations?user=5rkux7sAAAAJ&hl=en&oi=sra">Poore, Jerod</a>. <a href='http://www.crazymeds.us/pmwiki/pmwiki.php/MedClass/SSRIPoopOut'>"SSRI & SNRI Poop-Out/Tachyphylaxis & Dosage Equivalents"</a>. <a href="http://www.crazymeds.us/pmwiki/pmwiki.php/Main/HomePage"> <em>crazymeds.us</em></a>. (2010).
with Microdata:<span itemprop='citation'> <a href="http://scholar.google.com/citations?user=5rkux7sAAAAJ&hl=en&oi=sra">Poore, Jerod</a>. <a href='http://www.crazymeds.us/pmwiki/pmwiki.php/MedClass/SSRIPoopOut'>"SSRI & SNRI Poop-Out/Tachyphylaxis & Dosage Equivalents"</a>. <a href="http://www.crazymeds.us/pmwiki/pmwiki.php/Main/HomePage"> <em>crazymeds.us</em></a>. (2010).</span>

All drug names are the trademarks of someone else. Look on the appropriate PI sheets or ask Google who the owners are. The way pharmaceutical companies buy each other and swap products like Monopoly™ real estate, the ownership of any trademarks may have changed without my noticing.





Page design and explanatory material by Jerod Poore, copyright © 2004 - 2014. All rights reserved.
Keep up with Crazymeds and and/or my slow descent into irreparable madness boring life. Pick your preferred social media target(s):

Almost all of the material on this site is by Jerod Poore and is copyright © 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013, and 2014 Jerod Poore. Except, of course, the PI sheets - those are the property of the drug companies who developed the drugs the sheets are about - and any documents that are written by other people which may be posted to this site will remain the property of the original authors. You cannot reproduce this page or any other material on this site outside of the boundaries of fair use copying without the express permission of the copyright holder. That’s usually me, so just ask first. That means if want to print out a few pages to take to your doctor, therapist, counselor, support group, non-understanding family members or something like that - then that’s OK to just do. Go for it! Please. As long as you include this copyright notice and something along the lines of following disclaimer, I’m usually cool with it.



All rights reserved. No warranty is expressed or implied in this information. Consult one or more doctors and/or pharmacists before taking, or changing how you take any neurological and/or psychiatric medication. Your mileage may vary. What happened to us won’t necessarily happen to you. If you still have questions about a medication or condition that were not answered on any of the pages you read, please ask them on Crazy Talk: the Crazymeds Forum.
The information on Crazymeds pertains to and is intended for adults. While some information about children and adolescents is occasionally presented (e.g. US FDA approvals), pediatric-specific data such as dosages, side effects, off-label applications, etc. are rarely included in the articles on drugs or discussed on the forum. If you are looking for information regarding meds for children you’ll have to go somewhere else. Plus we are big pottymouths and talk about S-E-X a lot.
Know your sources!
Nobody on this site is a doctor, a therapist, or a pharmacist. We don’t portray them either here or on TV. Only doctors can diagnose and treat an illness. While it’s not as bad as it used to be, some doctors still get pissed off by patients who know too much about medications, so tread lightly when and where appropriate. Diagnosing yourself from a website is like defending yourself in court, you suddenly have a fool for a doctor. Don’t be a cyberchondriac, thinking you have every disease you see a website about, or that you’ll get every side effect from every medication1. Self-prescribing is as dangerous as buying meds from fraudulent online pharmacies that promise you medications without prescriptions.
All information on this site has been obtained through our personal experience and the experiences family, friends, what people have reported on various reputable sites all over teh intergoogles, the medications’ product information / summary of product characteristic (PI/SPC) sheets, and from sources that are referenced throughout the site. As such the information presented here is not intended as a substitute for real medical advice from your real doctor, just a compliment to it. You should never, ever, replace what a real doctor tells you with something from a website on the Internet. The farthest you should ever take it is getting a second opinion from another real doctor. Educate yourself - always read the PI/SPC sheet or patient information leaflet (PIL) that comes with your medications and never ever throw them away. OK, you can throw away duplicate copies, but keep at least one, as that’s your proof of purchase of having taken a med in case a doctor doubts your medical history. Plus they take up less space than a bottle, although keeping one inside of a pill bottle is even better.
Crazymeds is not responsible for the content of sites we provide links to. We like them, or they’re paid advertisements, or they’re something else we think you should read to help you make an informed decision about a particular med. Sometimes they’re more than one of those things. But what’s on those sites is their business, not ours.
Very little information about visitors to this site is collected or saved. From time to time I look at search terms used and which pages they bring up in an effort to make the information I present more relevant. And the country of origin, just because I’m geeky like that. That’s about it. Depending on how you feel about Schrodinger, our privacy policy should either assuage or exacerbate your paranoia.
Crazymeds is optimized for the browser you’re not using on the platform you wish you had. Between you and me, it all looks a lot cleaner using Safari or Chrome, although more than half of the visitors to this site use either Safari or Internet Explorer, so I’m doing my best to make things look nice for IE as well. I’m using Firefox and running Windows 72. On a computer that sits on top of my desk. With a 23 inch monitor. Hey, at least you can make the text larger or smaller by clicking on the + or - buttons in the upper right hand corner. If you have Java enabled. Like 99% of the websites on the planet, Crazymeds is hosted on domain running an open source operating system with a variety of open source applications, including the software used to display what you’ve been reading. As such Crazymeds is not responsible for whatever weird shit your browser does or does not do when you read this site3.
No neurologists, psychiatrists, therapists or pharmacists were harmed in the production of this website. Use only as directed. Void where prohibited. Contains nuts. Certain restrictions may apply. All data are subject to availability. Not available on all mobile devices, in the 12 Galaxies Guiltied to a Zegnatronic Rocket Society, or in all dimensions of reality. Hail Xenu!

‘Everything is true, nothing is permitted.’ - Jerod Poore


1 While there are plenty of books to help you with hypochondria, for some reason there’s not much in the way of websites. Then again, staying off of the Internet is a large part of curing/managing the disorder.

2 Remember kids, Microsloth operating systems are like TOS Star Trek movies with in that every other one sucks way, way more. With TOS Star Trek movies you don’t want to bother watching the odd-numbered ones. With Microsloth OS you don’t want to buy and install the even-numbered ones. Anyone who remembers ME and Vista knows what I mean.

3 Have I mentioned how open source operating systems for commercial applications is one of the dumbest ideas in the history of dumb ideas? I don’t even need my big-ass rant any more. Heartbleed has made my case for me. And that’s just the one that got all the media attention. The very nature of an open source operating system makes security as much of an illusion of anonymity. Before you flip out too much: the domain Crazymeds is hosted on uses a version of SSL that is not affected by the Heartbleed bug. That’s one of the many reasons why I pay a lot of money and keep this site on Lunarpages.

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