US Brand Name: Symbyax
A link here will take you to the official website for the drug.
Other Brand Names:
Generic Name: olanzapine and fluoxetine HCl
Other Forms:Class: Antidepressant, although it’s just a compound of an SSRI and an atypical antipsychotic.
Read up on these sections if you haven’t done so already, because they cover a lot of information about multiple medications that I’m not going to repeat on many pages. I’m just autistic that way about not repeating myself.
FDA Approved Use: Bipolar Depression
Off-Label Uses: Unipolar Depression, Anxiety, PTSD, OCD, Eating Disorders (really, I’m serious)
Pros: You get the synergistic effect of an antipsychotic and antidepressant in one pill without your doctor trying to figure out 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 as a means to treat bipolar and refractory unipolar depression, and for that reason alone this pill is a huge breakthrough.
Cons: All the side effects of Prozac (fluoxetine) and Zyprexa (olanzapine). For an antidepressant this pill is likely to make you fat, tired and celibate, and aren’t you happier already just reading that? The minimum dosage of Zyprexa (olanzapine) is way too high in my opinion. And since it’s all wrapped up in one pill you can’t make any adjustments to either the dosages or the meds. Not everyone in Bipolarland takes to SSRIs. Both Prozac (fluoxetine) and Zyprexa (olanzapine) 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.

Typical Side Effects: The usual for SSRIs and antipsychotics all in one! As this med has just hit the market it’s too soon to tell what is really going to be typical. From the clinical trials we see the expected weight gain, increased appetite and daytime tiredness. We don’t see much in the way of sexual side effects, but I can’t determine if that’s underreporting from the participants because of embarrassment, if the people involved were too depressed to be sexual to start with and Symbyax didn’t make it that much worse, or if the med really didn’t make that much difference. Based on people’s experiences with the component parts, this med is likely to kill your sex drive.

For tips on how to cope with these side effects, please see our side effects page.
These aren’t all the side effects possible, just the most popular ones.

Not So Common Side Effects: Rash, ‘flu-like symptoms. Both Prozac (fluoxetine) and Zyprexa (olanzapine) can make you rashy, and combined they can produce a nasty rash or hives. Also since there is an antipsychotic involved, you have to be on the lookout for Extrapyramidal Symptoms, including Tardive Dyskinesia. Fortunately of the popularly prescribed atypical antipsychotics, Zyprexa (olanzapine) is the either the least likely or second-least likely, depending on which study you read, to produce these effects. I discuss this in more detail in my section on atypical antipsychotics.
These may or may not happen to you don’t, so don’t be surprised one way or the other.

Freaky Rare Side Effects: Voice alteration, libido increased and aphasia. That’s when you open the world’s weirdest phone sex service.
You aren’t going to get these. I promise.

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 Prozac (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. But Zyprexa (olanzapine) is very picky about your gender, ethnicity, age and if you smoke or not, it just doesn’t care if you ate anything. Thus a young, Japanese male smoker who takes Zyprexa would be getting six times the benefit of the drug than an older Caucasian woman taking the same amount. Yeah, if you smoke Zyprexa works better.
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. You may have to switch to regular Prozac (fluoxetine) for purposes of discontinuation. Fortunately Prozac (fluoxetine) is the easiest of the SSRIs from which to discontinue.

Dosage: One 6/25 capsule in the evening. Now, how the hell do you figure out when to move up? Prozac takes forever to reach a steady state, and one study indicates you should give it a full two months before giving up.

If you start getting manic or exhibit other symptoms that indicate more of an antipsychotic is in order, or your existing symptoms that would be helped by the Zyprexa component are being helped but aren’t being helped enough, then moving up to the 12/25 capsules would be advised. But I’d still wait at least two weeks before doing so because I believe in slow titration and you don’t have an option of 9mg of Zyprexa.

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 up to the 12/50. If that doesn’t work by the end of two months, then you should start a discontinuation plan and try another combination of antidepressant and antipsychotic.

Days to Reach a Steady State: One week for the olanzapine component and four to five weeks for the fluoxetine component.
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.

How Long it Takes to Work: Good question! The clinical trials were for two month periods, and Prozac (fluoxetine hydrochloride) a full two months to work. So give it two months before giving up on it.

Half-Life & Average Time to Clear Out of Your System: 30 hours within a range of 21 to 54 hours olanzapine component 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. Thus when discontinuing Symbyax you may need to temporarily switch to 10mg capsules of regular Prozac or even the Prozac liquid after your final Symbyax dose to wean yourself off of Prozac.

If you’ve worked your way up to a particular dosage, it’s usually best to spend this many days at the next lowest dosage before going down the next lowest dosage before that and so forth. This is the least sucky way to avoid problems when stopping any psychiatric medication. Presuming you have the option of slowly tapering off them.

How It Works In Your Brain: Sort of like an SSRI and sort of like an atypical antipsychotic. Yet the combination of the two makes each more effective, and not just because your liver can’t get rid of each component drug as quickly as before. I have my own hypothesis as to why this is, and I’m still working on it.

Odds of Working and How It Compares to Other Meds: If you read the PI sheet you’ll just see something that is very interesting for two reasons. There is a table that gives you hard numbers on just how well Symbyax works to deal with bipolar depression. You don’t see that for antidepressants. They used the Montgomery-Asberg Depression Rating Scale (MADRS), which is one of several such metrics available. On a scale of 0-60 Symbyax changed patient’s depression a mean of 16 and 18 points, which apparently is a BFD. The second thing that is especially telling about the data published on the PI sheet is the drug they used as a control in addition to a placebo. Olanzapine. The atypical antipsychotic component of Symbyax. Why not use Prozac (fluoxetine)? That’s an antidepressant and they were testing for depression after all? Because that would give the game away that SSRIs don’t always test that well when compared to placebo, that’s why.
Comments: Approved in January 2004, this is Lilly’s brand new antidepressant specifically for bipolar depression. It’s not really a new med, but a combination of Prozac and Zyprexa. This is the first fully studied combination of antipsychotic and antidepressant. It has a few studies, another one here. Including several for treatment-resistant unipolar depression; also this one, this one, and this one. As well as studies on anxiety, PTSD, OCD, and even Eating Disorders. Hence my guesses as to what the off-label applications will be.
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. 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 is Strattera and Risperdal. I’ll be writing an article specifically about the antidepressant and antipsychotic cocktail and how to best pick which components would work best for you.

I give this warning to everyone in the bipolar support groups in which I participate and I’ll repeat it here – when combining an antipsychotic and antidepressant, unless you live in the blackest pits of Bipolar 2 despair all of the time, save Geodon as the last antipsychotic to try. Geodon + an antidepressant + bipolar = one-way ticket to Mania City. I still have $6,000 in credit card debt (sitting on a permanent 4.99% rate) from a month-long Geodon & Celexa-inspired mania back in 2001. There have been plenty of other people reporting how Geodon and an antidepressant triggered similar manias. As for those of you with unipolar depression – I’d still reserve Geodon for last unless you had someone print out this page and read it to you because you can do nothing else but stare at the ceiling the few hours a day you’re awake. You don’t have to be bipolar to go nuts by feeling too good with these crazy meds.

As this is is “brand new” med, it will be a few months before I have any more comments on it. Until now just read up what I have on Prozac and Zyprexa.

And while the combination of an atypical antipsychotic and some modern antidepressant is getting all the buzz, 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 over 20 years.

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