How Zyprexa (olanzapine) Works - The Good, The Bad and The Funny. From People Who Have Taken These Crazy Meds...and SCIENCE!

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Zyprexa Basics Zyprexa Side Effects How To Take Zyprexa Comments Where to Buy Zyprexa / Ratings

Chances Zyprexa Will Work and How Zyprexa Compares to Other Meds: Odds of it working for all forms of schizophrenia - excellent. Even people with refractory / treatment-resistant schizophrenia have a good chance of responding to Zyprexa. Works well and works fast.

Odds of it working for bipolar mania - also excellent. Zyprexa (olanzapine) and Keppra (levetiracetam) are the two best meds for stopping out-of-control mania RIGHT NOW. While I think Zyprexa (olanzapine) is best suited as a crisis med and an add-on for bipolar disorder, I'm not too big on antipsychotics as monotherapy (i.e. the only med you take) for bipolar disorder, it does alone to stabilize a lot of people. If anticonvulsants don't do it for you, Zyprexa can be your med in the long run.

Odds of it working for panic / anxiety disorders - good. Antipsychotics aren't front-line meds for panic / anxiety but they work well for some forms of the disorders. Zyprexa (olanzapine) might be a sledgehammer to a fly approach for panic / anxiety, but only you and your doctor have an idea of how panicked / anxious you are.

Odds of it working for depression - Really good. As a stand-alone med for depression it can work but not very often. But when you mix it with an antidepressant for treatment-resistant major depressive disorder no other atypical antipsychotic works as well as Zyprexa (olanzapine) at pulling people out of the abyss of endless days and nights of laying in a bed of dirty, rumpled sheets staring at the walls and ceiling waiting, waiting, waiting for someone to just come in and kill you to finally put an end to it.

For an explanation of the metrics used in the various studies & trials (e.g. BPRS, CGI, etc.), please see the page on Drug Efficacy.

Now for the details as to how I arrived at the above odds. Mostly it's from anecdotal evidence gathered from various online support groups I monitor, user ratings and comments at Remedy Find, experiences people send to me via e-mail and summaries of efficacy from the books in the references at the end of this page. Additionally there are these trials and studies from the PI sheet and that I found through Pub Med:

For schizophrenia two six-week clinical trials were completed and one 12-month trial was started but not finished. What? Not finished? What's that about? It's about the people in the placebo group getting progressively crazier while the people taking Zyprexa (olanzapine) were getting significantly better, so the trial was halted and everybody got Zyprexa. Anyway, in the two placebo-controlled six-week trials 1mg a day proved to be worthless for schizophrenia, and 15mg a day didn't do much better than 10mg a day. At 10mg a day people started to think more clearly. Here it is in more detail.

In a 6 week, placebo-controlled trial of 149 people involving two fixed Zyprexa (olanzapine) doses of 1 and 10 mg/day taken once a day, Zyprexa (olanzapine) at 10 mg/day (but not at 1 mg/day), was superior to placebo on the PANSS total score (also on the extracted BPRS total), on the BPRS psychosis cluster, on the PANSS Negative subscale, and on CGI Severity. As much as I like lower dosages, I will admit that 1mg a day is pretty useless for schizophrenia according to this trial, as well as the anecdotal evidence of most people in the real world. But it's pretty all or nothing here, either 1mg or 10mg a day. Nothing in between.

In a 6 week, placebo-controlled trial of 253 people involving three fixed dose ranges of Zyprexa (olanzapine), either 2.5 to 7.5mg a day, 7.5 to 12.5mg a day or 12.5mg to 17.5mg a day, all taken once a day regardless of what the dosage was, the two highest Zyprexa (olanzapine dose groups) (actual mean doses of 12 and 16 mg/day, respectively) were superior to placebo on BPRS total score, BPRS psychosis cluster, and CGI severity score; the highest Zyprexa (olanzapine) dose group was superior to placebo on the SANS. There was no clear advantage for the high dose group over the medium dose group. In other words, 10-12.5mg a day works just as well as a higher dosage for many people.

As usual, there are no hard numbers in the PI sheet for what is considered "superior" to placebo on these various tests.

In a longer-term trial, 326 adult outpatients who remained stable on Zyprexa (olanzapine) during open label treatment for at least 8 weeks were randomized to continuation on their current Zyprexa (olanzapine) doses (ranging from 10-20 mg/day) or to placebo. The follow-up period to observe patients for relapse, defined in terms of increases in BPRS positive symptoms or hospitalization, was planned for 12 months, however, criteria were met for stopping the trial early due to an excess of placebo relapses compared to Zyprexa (olanzapine) relapses, and Zyprexa (olanzapine) was superior to placebo on time to relapse, the primary outcome for this study. Thus, Zyprexa (olanzapine) was more effective than placebo at maintaining efficacy in patients stabilized for approximately 8 weeks and followed for an observation period of up to 8 months. So there's definitely no placebo effect over the long run, but really guys, you think you could have given them Haldol or something instead of a placebo so they wouldn't have gone nuts?

I'm not too happy with the bipolar trials. They were smaller (67 and 115 people) and a lot shorter (three and four weeks). So the people in the experimental group took between 5 and 20mg (!) a day and got some vague improvement on the Young Mania Rating Scale . Whoopee shit. You score 0-60 on all of 11 items assessing irritability, disruptive/aggressive behavior, sleep, elevated mood, speech, increased activity, sexual interest, language/thought disorder, thought content, appearance, and insight. Basically if you didn't have the bipolar diagnosis already the test would be fairly pointless in trying to figure out if you bipolar, schizophrenic, obsessive-compulsive, schizoaffective or even ADHD. Even some people in particular parts of the autistic spectrum who aren't bipolar would score well on it. Try taking it during a bout of severe depression, you may not have any self-esteem, sexual interest or least of all elevated mood and activity, but everything else could be really out of whack and you could get hit with a bipolar 2 diagnosis even if you aren't really bipolar 2.

Still, I have absolutely no doubts whatsoever about Zyprexa's effectiveness as an anti-manic. None at all. It's one of the most effective anti-manic meds on the market. I just question the small, short trials using one test to get the high initial dosages they recommend. The other thing is the short duration of the trials. In the short run, all sorts of non-med approaches will actually work to bring someone down from a manic high for a day or a week. That's why Bach Flower Remedies or that Serenity crap appear to work in the short term. It's part of the reason why so many of us fall into the trap of thinking we can deal with our illness without meds, or with dangerously bogus "treatments."

Let's see how Zyprexa (olanzapine) stacks up against other meds. Keep in mind who sponsors the study, as it will tends to make the results more favorable for the med in question (on average 3.6 times more likely, according to a Yale study).

First for schizophrenia:

Zyprexa vs. Geodon. I don't know whose money was behind this study. It doesn't really matter, as they tested as equally effective! Geodon (ziprasadone) just managed to come out ahead because its side effects didn't suck as much. From other published data and anecdotal evidence, I can agree with that. For most people Geodon's side effects do suck less than Zyprexa's.

Zyprexa vs. Solian. Solian (amisulpride) is a standard antipsychotic available in the UK, Europe, and parts of Asia. It is similar in action to Orap (pimozide). It looks like the money for this study was from Lorex-Synthelabo, the manufacturer of Solian. Both meds test as equally effective, but the side effects published in the abstract suck somewhat less for Solian. However, this bit at the end of the abstract is puzzling. "The side-effect profile of the two drugs differed." Well, duh, we expect that. But you leave it out there in a significant way.

Zyprexa vs. Prolixin. Prolixin (fluphenazine) is one of the older standard antipsychotics. This Lilly-conducted test showed Zyprexa to be more effective and the side effects sucked less (really, weight gain vs. EPS and extreme agitation, which sucks less to you?). Against such an old med the results aren't surprising.

Zyprexa vs. Haldol vs. placebo. This Lilly-conducted study pitted the intramuscular injections against each other to see how they worked for people who were really in crisis. The results were that the Haldol (haloperidol) is marginally more effective, but not significantly so, but sucks a hell of a lot more. Despite this being a Lilly study, I don't think there is a better crisis medication on the market than Zyprexa.

Zyprexa vs. Clozaril. This appears to have been an independent study pitting Zyprexa (olanzapine) against Clozaril (clozapine) for treatment-resistant schizophrenia. It looks as if higher than normal dosages of Zyprexa (up to 25mg a day) is just as barely effective as the Clozaril while sucking less. Either way you'll get fat and be subject to diabetes, but you probably won't get EPS or TD with either. Plus with the Zyprexa you need the weekly blood work. I'd just recommend a semi-annual blood panel for liver function at dosages that high.

Zyprexa vs. Haldol. This two-year, independent-looking study has Zyprexa going up against the tried and true standard antipsychotic Haldol (haloperidol) for people who have had their first psychotic episode. Zyprexa tested as more effective and sucking less (more weight gain vs. less EPS, less tremor and less extreme agitation). More importantly the people would stay on Zyprexa more consistently than they would Haldol (haloperidol).

Zyprexa vs. Risperdal. This independent-looking study has Zyprexa testing as superior to Risperdal (risperidone) after 30 weeks. Nothing in the abstract about the dosages used.

Zyprexa vs. Risperdal vs. Clozaril vs. Haldol. This decent sized, 14-week study was sponsored by NIMH (with each of the drug companies chipping in the meds). The results - Zyprexa is the superior atypical antipsychotic, but it all depends on the form of schizophrenia being presented. They're all better than Haldol (haloperidol) as long as you're more concerned about effect and all the non-weight gain side effects.

Zyprexa vs. Risperdal. In this Janssen-sponsored study, 2-6mg a day of Risperdal (risperidone) tests as working as well as (slightly better at some things, not quite as good at others) and sucking less than 5-20mg a day of Zyprexa after only eight weeks. See what I mean about when the manufacturer sponsors the study it often comes out in their favor?

Zyprexa + glycine vs. Risperdal + glycine. This small study indicates that adding high dosages of the amino acid glycine to either Zyprexa (olanzapine) or Risperdal (risperidone) can help with treatment-resistant schizophrenia. It's something to discuss with your doctor before making the switch to Clozaril (clozapine).

ECT + Risperdal or Zyprexa vs. Risperdal or Zyprexa alone for treatment-resistant schizophrenia. Hey, now we're really getting down to what is going to suck less, ECT or Clozaril (clozapine). In this study, ECT combined with either Risperdal (risperidone) or Zyprexa (olanzapine) didn't work that much better and didn't really sucks less. So you'd probably want to try the glycine treatment mentioned above first, but it that pans out, there are treatment options.

Seroquel vs. Zyprexa vs. Risperdal vs. Serdolect vs. Haldol vs. Placebo. Antipsychotic cage match! Five drugs enter, ...and five drugs leave. Unfamiliar to US readers would be Serdolect (sertindole), a European atypical antipsychotic that is unlikely to be introduced to the US market. It's been withdrawn from the UK market and is admitted by Lundbeck to be a med of last resort. Anyway, the results of this analysis of multiple studies involving over 2,400 people with schizophrenia show Risperdal (risperidone) and Zyprexa (olanzapine) to be more effective than Haldol (haloperidol) when it comes to all of schizophrenia's symptoms, while Seroquel (quetiapine fumarate) and Serdolect (sertindole) are just as effective. When it comes to the negative symptoms, though, Seroquel (quetiapine fumarate) tested as less effective Haldol while Risperdal and Zyprexa continue to be more effective. As usual Risperdal had the greatest risk of EPS. Surprisingly the wonder drug Placebo didn't do too badly in some of the studies.

Zyprexa vs. Risperdal vs. Seroquel vs. Clozaril - Straight from the trenches of a state psychiatric hospital in Louisiana, where people get anticonvulsants, antidepressants, benzodiazepines and anything else that makes the real world a messy place to treat the mentally interesting. 100 people staying on average a year in the hospital. The results - Zyprexa (olanzapine) had a slight edge over Risperdal (risperidone). Yet when you came down to the people with hard-core refractory disorders, nothing beat Clozaril (clozapine). Zyprexa was still the better drug to try first, but sometimes you have to just give in to conventional reality and go with the Clozaril.

Now for bipolar disorder:

Zyprexa vs. Depakote. This 47-week, Lilly-conducted study had 251 people take either a flexible dosage of 5-20mg a day of Zyprexa (olanzapine) or whatever their blood levels indicated for Depakote (divalproex sodium) in the range of 500-2,500mg a day. It took an average of only two weeks to calm the hell down for those taking Zyprexa, compared to two months for those taking Depakote (divalproex sodium). Otherwise the Zyprexa was a bit more effective, but sucked a lot more.

Zyprexa vs. Depakote. A smaller, shorter study than the one above had similar results. Zyprexa was somewhat more effective, but sucked a lot more. How much more? One person died due to complications from diabetes. Ouch.

Zyprexa vs. Risperdal vs. lithium. A small, short study sponsored by Janssen for bipolar and schizoaffective disorders. 0.25 to 7mg a day of Risperdal (risperidone) against 7.5 to 17.5mg a day of Zyprexa (olanzapine) against 600 to 900mg a day of lithium. All meds were equally effective and equally sucky during the short period of the study. In 1998 dollars the Risperdal (risperidone) cost half as much as the Zyprexa at the dosages used, and that would still hold true today. I note that one of the doctors conducting the study is Dr. Sanjay Gupta of Olean hospital, not to be confused with CNN's Dr. Sanjay Gupta. This Dr. Gupta is doing some fascinating work, though.

As an add-on for mixed-states and/or ultradian rapid cycling. While Depakote (divalproex sodium) is the best med for either, and Topamax (topiramate) is incredible in its own right for some forms of ultradian rapid cycling, if you don't get along with either, or you experience break-through symptoms while during your normal therapy with either med, Zyprexa (olanzapine) is an awesome emergency add-on medication for mixed states and/or ultradian rapid cycling.

For depression:

Seroquel vs. Risperdal vs. Zyprexa vs. Geodon to augment antidepressants for treatment-resistant depression Another antipsychotic cage match! 49 people who have ridden a total of 76 horsies on the med-go-round. Here are the results - Zyprexa (olanzapine) is the clear winner with a 57% response rate, followed by Risperdal (risperidone) with 50%, Seroquel (quetiapine fumarate) with 33% and bringing up the rear in a real shock to me, Geodon (ziprasidone) with only 10%. So if your doctor wants to try Zyprexa (olanzapine) combined with an antidepressant first to bring you out of the abyss, don't fret the weight thing. Which sucks less, what you're going through now or a few extra pounds?

How Zyprexa Works In Your Brain: Like all Novel / Atypical Antipsychotics, Zyprexa (olanzapine) is a selective antagonist (i.e. it gets in the way of) for key serotonin (5HT_2A/2C Ki=4 and 11 nM), muscarinic (M_1-5 Ki=1.9-25 nM), and dopamine (D_1-4 Ki=11-31 nM), receptors. It also blocks the action of histamine (H₁ Ki=7 nM), and adrenergic (a₁ Ki=19 nM) receptors. It also binds weakly (in that you may or may work this way for you) to GABA_A, BZD, and b adrenergic receptors (Ki >10 Ã‚ÂµM).

So, what does that mean in English? Well excessive dopamine in certain parts of the brain is one popular hypothesis behind the symptoms of schizophrenia. There's also evidence that working on the muscarinic receptors makes a big difference as well. The effects of the other receptors on schizophrenia are less well known. While GABA is currently undergoing a lot of study for schizophrenia, that's the realm of anticonvulsants.

For bipolar disorder, anyone who lives in Bipolarland can tell you about getting manic from having their brain soak in serotonin for too long from an SSRI. Or perhaps the same thing happened from too long of a soak in norepinephrine and dopamine from Wellbutrin. There's even evidence that the muscarinic receptors play a role in bipolar disorder as well.

If my unfortunate and quite accidental experience with a mushroom that had a bit too much muscarine is any indicator, I'll go along with the hypothesis that muscarinic receptors play a big role in bipolar disorder.

Basically Zyprexa (olanzapine) is going to deal with more neurotransmitter receptors than any of the other popular atypical antipsychotics. Only Clozaril (clozapine) deals with more. That's probably why Zyprexa (olanzapine) is effective for things like refractory schizophrenia of all forms and helping to control the nastier aspects of bipolar disorder like mixed states, rapid and sometimes ultradian rapid cycling.

Zyprexa's Half-Life: An average of 30 hours in a range of 21 to 54 hours.

Days to Reach a Steady State: About one week.
When you're fully saturated with the medication and less prone to peaks and valleys of effects. You still might have peaks of effect after taking many meds, but with a lot of the meds you'll have fewer valleys after this point. In theory anyway.

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Otherwise, if you're letting me know about how much you like or hate the site, or need to let me know about medication effects in private, then just drop a note to jerod23 at gmail dot com Honestly, I usually don't have a lot of time to answer e-mail these days. The snide autoresponse message that may or may not hit your mailbox is going to tell you the same thing.
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Dead tree references:

End of books used for this article.

Created Friday, October 08, 2004

Last updated Monday, May 24, 2010

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