US Brand Name: Symbyax

generic name: olanzapine and fluoxetine HCl

Class: Antidepressants

1.  FDA Approved Uses of Symbyax

Bipolar depression, treatment-resistant depression.

2.  Off-Label Uses of Symbyax

Everything or nothing (see comments).

3.  Symbyax’s pros and cons

3.1  Pros

You get the synergistic effect of an antipsychotic and antidepressant in one pill without your doctor trying to figure out how much of which two to give you. The olanzapine and fluoxetine combination has had the most studies and is a truly potent combination. It’s one pill and prescription instead of two. There’s not as much stigma attached to an antidepressant as there is to an antipsychotic. Even if Symbyax doesn’t work out for someone it introduces the concept of the antipsychotic and antidepressant cocktail - even if it’s not the first AD & AP combo in one pill - as a means to treat bipolar and refractory unipolar depression, and for that reason alone this pill is a huge breakthrough.

3.2  Cons

All the side effects of Prozac (fluoxetine) and Zyprexa (olanzapine), two meds people love to hate. It’s an antidepressant with a good chance of making you fat, tired and celibate, and aren’t you happier already just reading that? Being all wrapped up in one pill makes everything easier, but that also means you’ve got limited options for dosage adjustments, especially with the olanzapine component. Not everyone in Bipolarland takes to SSRIs. Both Prozac and Zyprexa mess with how you deal with dietary sugars, but in different ways, so this drug is probably a total no-no for anyone who is diabetic or has the slightest chance of becoming diabetic.

4.  Side Effects

4.1  Typical Side Effects

The usual for SSRIs and atypical antipsychotics - headache, weight gain, nausea, weight gain, dry mouth, weight gain, sweating, weight gain, sleepiness or insomnia, weight gain, diarrhea or constipation, weight gain, and loss of libido. Did I mention weight gain? Most everything will go away after a week or two, but the sleepiness, weight gain and loss of libido might stick around longer. Or permanently.
Things like weight gain, triglycerides, HDL cholesterol, and blood glucose can all be quantified. Libido, how well you sleep, and how tired you feel all day are subjective. When you’ve been living in the bleak and endless despair of bipolar or treatment-resistant unipolar depression how well do you sleep, how much energy do you have, and how often do you get laid?

4.2  Not So Common Side Effects

Rash, flu-like symptoms, blurry vision, diabetes.

4.3  Freaky Rare Side Effects

Voice alteration, libido increased and aphasia. That’s when you open the world’s weirdest phone sex service.

5.  Interesting Stuff Your Doctor Probably Won’t Tell You

The olanzapine and fluoxetine components of Symbyax have some wildly different pharmacokinetics. How fast they hit you, how long they stick around, and how efficient they work depending upon factors such as ethnicity, gender, age and if you smoke or not - that sort of stuff. They are metabolized by different liver enzymes, so it’s possible that you metabolize one efficiently one the other poorly. On one hand fluoxetine is very egalitarian when it comes to gender and ethnicity, and only a little picky when it comes to age and if you ate anything before taking it. Olanzapine, however, is very picky about your gender, ethnicity, age and if you smoke or not, and couldn’t care less if you ate anything. Thus a young, black, male smoker who takes Zyprexa would need to take four times as much as an older Caucasian in order to get the same benefits from the drug. Eli Lilly said so in Olanzapine. Pharmacokinetic and pharmacodynamic profile. Independent researchers saw the same thing during the CATIE trials and published it in Sex, race, and smoking impact olanzapine exposure.

Symbyax has one of the longest drug-drug interaction lists I’ve seen for a crazy med. As with Luvox, if you take any other meds of any type you need to talk to your pharmacist, read the Drug Interactions section of the PI sheet, and enter everything at Check My Meds� drug-drug and drug-food interaction site to make sure there is no nasty surprise.

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6.  Symbyax’s Dosage and How to Take Symbyax

The dosage and titration is the same for both bipolar and treatment-resistant depression. One 6/25 capsule in the evening. That’s 6mg olanzapine & 25mg fluoxetine. Now that Lilly makes a 3/25 size, starting there would probably be a better idea. Give it a week, preferably two, before going up to 6/25.

If you think it’s working, more or less, and you start getting manic, overly anxious, or exhibit other symptoms that indicate more of an antipsychotic is in order, then moving up to the next highest dosage of olanzapine, either 6/25 or 12/25, would be advised.

If you’re still majorly depressed after at least two weeks at 6/25, you can try the 6/50 for another two weeks. If that doesn’t work then it’s either up to the 12/50 or, if your insurance covers it or you otherwise can afford it, one 6/25 and one 3/25 pill. Symbyax comes in 3/25-, 6/25-, 6/50-, 12/25-, and 12/50 mg sizes, so you and your doctor can figure out all the combinations that might work, as long as you don’t exceed 18mg of olanzapine and 75mg of fluoxetine.

If nothing works by the end of two months, then you should start a discontinuation plan and try another combination of antidepressant and antipsychotic.

7.  How Long Symbyax Takes to Work

The guys at Eli Lilly think it takes about a week.

8.  How to Stop Taking Symbyax

I haven’t figured out the mechanics of discontinuation. Taking an antipsychotic tends to make SSRI discontinuation less of an issue, but in combination? The withdrawal syndrome is mentioned in the PI sheet, but only in the context that it happens to people who suddenly stop taking SSRIs, and fluoxetine is a serotonin-[barely]-selective reuptake inhibitor. You may have to switch to regular Prozac for purposes of discontinuation, and Prozac is the easiest of the SSRIs from which to discontinue. Honestly, it’s highly unlikely you’d get full-on SSRI discontinuation syndrome] if you were to stop taking Symbyax too quickly. If you were taking a 50-75mg a day dosage of fluoxetine and quit taking Symbyax completely without replacing it with an SSRI, [[MedClass/SNRI, or one of the more serotonergic TCAs you’d probably experience discontinuation symptoms.

9.  Symbyax’s Half-Life & Average Time to Clear Out of Your System

30 hours olanzapine component (see Interesting Stuff Your Doctor Probably Won’t Tell You, the range can be 6 to 60 hours) and 9.3 days for the fluoxetine component. Thus you’re clear of the Zyprexa part, on average, in a little over six days. But it takes six weeks to get completely clean of Prozac.

10.  Days to Reach a Steady State

About One week for the olanzapine component and four to five weeks for the fluoxetine component.

11.  Comments

Approved in January 2004, this is was the first med approved only for bipolar disorder (even lithium had prior approvals for other things) and specifically for bipolar depression. Seroquel is now approved for bipolar depression, so its no longer alone in that regard. Symbyax is not really a new med, but a combination of Prozac and Zyprexa, and while the combination of an atypical antipsychotic and a modern antidepressant was getting all the buzz in psychiatric circles in the early-to-mid 2000s - which led to Abilify being approved as an add-on to antidepressants for treatment-resistant depression - it’s not all that new. Etrafon / Triavil is a combination of the tricyclic antidepressant Elavil (amitriptyline) and the standard antipsychotic Trilafon (perphenazine). So there has been a previous version of Symbyax around for about 30 years.

The combination of olanzapine and fluoxetine is the most studied combination of atypical / second-generation antipsychotic and modern antidepressant. The combination of an antidepressant and antipsychotic is a potent way of dealing with depression. The thing is, just because this is the most studied combination doesn’t mean it’s the right one for you. Sure, start here if you have no objections to an SSRI, or either of its component ingredients. Really. This is as good a place as any to begin. Zyprexa is a great med for stomping out breakthrough manias, so while mania is always possible, it’s probably a lot less likely than if you combine Abilify or Geodon with an antidepressant. But if it doesn’t work, don’t give up on the idea of the synergistic effect of an antipsychotic and antidepressant. Each person who requires such a cocktail is different and may require a different combination to achieve psychopharmacological Nirvana. My personal magic combo was Strattera and Risperdal.

As far as off-label applications go, there’s nothing out there. It’s kind of pointless really. Then again, both Prozac and Zyprexa have been tried for a bunch of different brain cooties. As with bipolar and treatment-resistant depression, olanzapine has been used to augment SSRIs to enhance its effects in things like OCD and SSRIs have been added to SGAs to help them. Symbyax is just another option to explore.

12.  Discussion board

Crazy Meds’ Symbyax discussion board

13.  Your Comments About and Experiences with Symbyax

Tell us what you think about Symbyax

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Enter your own Comments & Experiences with Symbyax here.
You must be a registered member of the Crazy Meds Talk forum to post a comment on this page.

14.  Full US PI sheet, Global SPCs & PILs, check for drug-drug interactions

Symbyax Full US Prescribing Information / PI Sheet

Check for drug-drug interactions

15.  Bibliography

Physicians’ Desk Reference Edition 64 � 2010. Published by Medical Economics Company.

Date created 18 Mar 2011 - 15:41 Page Author: Last edited by: JerodPoore

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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 Have I mentioned how open source operating systems for commercial applications is one of the dumbest ideas in the history of dumb ideas?
[begin rant] I rent a dedicated server for Crazy Meds. It’s sitting on a rack somewhere in Southern California along with a bunch of other servers that other people have rented. The hardware is identical, but no two machines have exactly the same operating systems. I don’t even need to see what is on any of the others to know this. If somebody got their server at the exact same time, with the exact same features as I did, I’m confident that there would be noticeable differences in some aspects of the operating systems. So what does this mean? For one thing it means that no two computers in the same office of a single company have the same operating system, and the techs can spend hours figuring out what the fuck the problem could be based on that alone. It also means that application software like IP board that runs the forum here has to have so many fucking user-configurable bells and whistles that even when I read the manual I can’t find every setting, or every location that every flag needs to be set in order for a feature to run the way I want it to run. And in the real world it means you can get an MBA not only with an emphasis on resource planning, but with an emphasis on using SAP - a piece of software so complex there are now college programs on how to use it. You might think, “But don’t people learn how to use Photoshop or Adobe Illustrator in college?” Sure, in order to create stuff. And in a way you’re creating stuff with SAP. But do you get a Bachelor of Fine Arts degree with an emphasis on Photoshop?
Back in the Big Iron Age the operating systems were proprietary, and every computer that took up an entire room with a raised floor and HVAC system, and had less storage and processing power than an iPhone, had the same operating system as every other one, give or take a release level. But when a company bought application software like SAP, they also got the source code, which was usually documented and written in a way to make it easy to modify the hell out of it. Why? Because accounting principles may be the same the world over, and tax laws the same across each country and state, but no two companies have the same format for their reports, invoices, purchase orders and so forth. Standards existed and were universally ignored. If something went wrong it went wrong the same way for everyone, and was easy to track down. People didn’t need to take a college course to learn how to use a piece of software.
I’m not against the open source concept entirely. Back then all the programmers read the same magazines, so we all had the same homebrew utilities. We even had the forerunner to QR Code to scan the longer source code. Software vendors and computer manufacturers sponsored conventions so we could, among other things, swap recipes for such add-ons and utilities. While those things would make our lives easier, they had nothing to do with critical functions of the operating system. Unless badly implemented they would rarely cause key application software to crash and burn. Whereas today, with open source everything, who the hell knows what could be responsible some part of a system failing. [/end rant]