Dr. Bob's Psychopharmacology Tips

Switching to olanzapine

Date: Mon, 14 Oct 1996 17:27:27 -0500
From: Lauren Marangell MD <laurenm@bcm.tmc.edu>
Subject: Switching to olanzapine from risperidone

Now that Zyprexa (olanzapine) is available in only 5 mg and 10 mg strengths with a mean 1/2 life of 31 hours and no instructions for tapering or switching from other antipsychotic medications, what are some recommendations for switching from Risperdal (risperidone)?

--Mary D. Moller

Date: Wed, 06 Nov 1996 20:59:28 -0500
From: "Jonathan A. Slater, M.D." <jas14@columbia.edu>
Subject: Switching to olanzapine from clozapine

It seems fine to cross-taper from clozapine to olanzapine (Tom Smith ran such a study at the NY Hospital Westchester Division); the drugs do not interact. I successfully did this recently with a teenager who I began on olanzapine 10 mg while I decreased her clozapine from 300 mg to 200 mg. 4 days later I increased her olanzapine to 10 mg bid and lowered the clozapine to 150 mg. Over the next several weeks I lowered the clozapine by 50 mg per week. She initially became more psychotic but now has stabilized. She had some increased sedation as well, but now is almost off clozapine and doing well.

From: MKomrad@aol.com
Date: Sun, 8 Dec 1996 22:33:40 -0500
Subject: Switching to olanzapine from clozapine

We run a service that specializes in more severe, treatment-resistant cases of schizophrenia, often tranfserred from other hospitals. We have seen a series of disasters of patients taken off clozapine (and conventional neuroleptics for that matter) and tried on olanzapine, hoping to get the same effect without weekly blood monitoring. Many of these cases were removed from clozapine very slowly with a lot of overlap with olanzapine, so it's not necessarily a matter of abrupt discontinuation.

Incidentally, this is starting to look identical to the experience we had when risperidone first came out -- it was a flop for most of our chronic, persistantly ill, treatment-resistant patients, and especially for those patients who had done fairly well with clozapine. Risperidone in our well-tried hands at Sheppard Pratt was not "son-of-clozapine." It's starting to look like olanzapine may not be either.

Date: Thu, 2 Jan 1997 20:12:40 -0800
From: drrx@ix.netcom.com (Kathleen Schilli)
Subject: Switching to olanzapine from haloperidol

Although I have not seen a patient here tapered from Clozaril (clozapine) to Zyprexa (olanzapine), we do have patients that are on Haldol (haloperidol) and other high-potency neuroleptics that we attempt a switch-over on. We usually start at 5 or 10 mg of olanzapine while the patient is still on the full dose of neuroleptic, and gradually taper olanzapine up and neuroleptic down.

I am wondering if perhaps half-way thru a taper down of clozapine if starting olanzapine at a smaller than usual dose (say 2.5 mg) with a weekly increase by the same amount and a decrease in clozapine wouldn't work.

Date: Wed, 15 Jan 1997 22:09:26 -0600
From: Ereshefsky@uthscsa.edu (Larry Ereshefsky)
Subject: Aggression on olanzapine

Using benzodiazepines early on, structured milieus, etc., for managing aggression is recommended. Remember, however, that with benzodiazepine + olanzapine there are greater sedative effects than with either given alone.

From: Psybot@aol.com (Serge Botsaris MD)
Date: Sun, 2 Feb 1997 07:44:32 -0500 (EST)
Subject: Switching to olanzapine from clozapine

Go slow on the switch, in the neighborhood of weeks to months. I have seen the results of the olanzapine boom as more chronically psychotic people are admitted to my service with a recurrence in symptoms because their doctor decided to switch abruptly.

I would: add in olanzapine at 5 mg, going up by 5 mg intervals every 2-3 weeks. At the same time, lower the clozapine dose by 20% every week. Stop decreasing the clozapine when any hint of psychotic symptoms returns. Stop increasing the olanzapine when I start noticing any positive improvement (especially in negative symptoms). Usually the dose range I'm seeing is 15-20 mg for those in which it works. For inpatients I go a lot faster due to the pressures of managed care.

From: MKomrad@aol.com
Date: Wed, 5 Mar 1997 23:05:09 -0500 (EST)
Subject: Switching to olanzapine

Long crossover periods from a former neuroleptic to olanzapine may be worthwhile, so as to not pull the rug out from under the patient until the olanzapine kicks in.

From: "Catherine A. Leslie" <cal7e@avery.med.virginia.edu>
Subject: Switching to olanzapine from clozapine
Date: Thu, 13 Mar 1997 10:43:57 -0500 (EST)

Our state hospital recently encouraged docs to switch pts on clozapine to olanzapine. Most didn't. Of the 23 pts who received olanzapine, only 7 were able to come off clozapine completely. About a third were improved, and improvement correlated with olanzapine dose. The average dose for responders was 16 mg per day. There were absolutely no cost savings, in part because of using both clozapine and olanzapine and in part because we needed higher olanzapine doses.

--barbara haskins

From: Simsort@aol.com (Simon Lejeune M.D.)
Date: Mon, 28 Apr 1997 23:13:25 -0400 (EDT)
Subject: Switching to olanzapine

I work on a public sector psych unit in a general hospital. "Switch to olanzapine" -- either a switch from clozapine, after which the patient has become more psychotic, or from standard neuroleptics, which often in schizoaffective patients precipitates a mania -- has become a major reason for inpatient admissions.

Date: Mon, 26 May 1997 23:55:51 -0230
From: jamie@nfld.com (Dr. James Karagianis)
Subject: Switching to olanzapine

At 8:01 PM 5/26/97, Anthony Patterson wrote:

Are you tapering the conventional neuroleptic slowly, rapidly, or not at all?

I have one with refractory positive symptoms who I put back on a little Haldol with the olanzapine. He quit taking the Haldol and kept taking the olanzapine.

Are you finding the change beneficial?

From: MKomrad@aol.com
Date: Tue, 27 May 1997 00:30:53 -0400 (EDT)
Subject: Switching to olanzapine

The Zyprexa reps are suggesting that patients not be pulled off their former neuroleptics for at least a month after starting Zyprexa.

From: MKomrad@aol.com
Date: Tue, 27 May 1997 00:30:55 -0400 (EDT)
Subject: Switching to olanzapine

Our experience is profoundly different than what I have been reading on this list, and I can't figure out why. There's so much positive experience with olanzapine on this list. Maybe our treatment-resistant population is different. Many of our patients have had over 30 hospitalizations or huge numbers of drug trials or exhibited a lot of noncompliance. In this population, we have not found olanzapine very helpful.

Date: Tue, 27 May 1997 08:00:28 -0500
From: Stephen R Saklad <Saklad@uthscsa.edu>
Subject: Switching to olanzapine

I would tend to overlap. While I haven't even attempted a retrospective review of olanzapine response, I have seen *most* patients with agitation or other severe positive symptoms not respond for > 2 weeks (despite having the olanzapine pushed to 30 mg/day in < 2 weeks).

I have been using a 2-week olanzapine (usually 10 mg/day) run in prior to discontinuation of a previous antipsychotic. I believe that olanzapine (Zyprexa) is the first antipsychotic that is not a major tranquilizer. Olanzapine is indeed moderately sedating, particularly in patients with low CYP 1A2 activity like children or someone on an inhibitor. However, olanzapine's sedation is more like that with phenobarbital than the tranquilizing effect seen with a typical antipsychotic like haloperidol (Haldol, which has very little sedation). Benzodiazepines have more of a calming effect with even less sedation than olanzapine.

This is the first *routine* use of combinined antipsychotics that I have found necessary. Of course, if you are not dealing with someone that that is acute and has a GAF score of < 30, then olanzapine might well be successful alone.

It certainly looks like olanzapine is better than typical antipsychotics for negative symptoms over the medium term (several months).

Date: Tue, 27 May 1997 21:51:48 -0230
From: jamie@nfld.com (Dr. James Karagianis)
Subject: Switching to olanzapine

Just to emphasize, I was referring to *non-fragile* cases, ie, those who don't have a history of rapid decompensations to severe psychosis.

I suspect that Mark Komrad's *treatment resistant* population is probably mostly fragile, and I agree with overlapping in such cases. I think Mark has had more experience than me, also, so in general I defer to his superior wisdom. ;-)

Date: Tue, 27 May 1997 22:09:15 -0230
From: jamie@nfld.com (Dr. James Karagianis)
Subject: Switching to olanzapine

My success with olanzapine, looking back, has been in patients who were not particularly agitated, but hallucinating, delusional or thought disordered and with prominent negative symptoms.

Date: Wed, 28 May 1997 23:28:31 -0700 (PDT)
From: "Barry S. Dorfman MD MPH" <bdorfman@slonet.org>
Subject: Switching to olanzapine

My two cents' worth from inside a maximum security forensic hospital (they let me out out night only if I promise to check psycho-pharm!):

My usual protocol is 5 mg the first pm, 10 the next. If there are any problems, I move back to 5 mg for 4-5 days, then proceed with 7.5 for 4-5 days, then 10. We have a pretty difficult to treat group. I used to stop at 10 and wait a month; now I usually go up to 15-20 increasing by 5 every 1-2 weeks.

In my setting I have the advantage of time, so I taper other meds very, very, very, very slowly. First, I don't even start the tapers until reaching 10 mg. I taper clozapine at no more than 25 mg every 4 days, and more usually only 25 mg per week. I taper other meds at a rate no faster than 25% every two weeks. So by the time other meds have been tapered, patients have been on olanzapine 2-3 months or longer.

And perhaps that has played a role in obtaining some good responses. This posting is long already so I won't go into the psychopharmatheology supporting slow tapers and long overlaps except to say it's quite a jolt to any dynamic equilibium to suddenly change anything.

My overall clinical experience has been good. Some patients do as poorly on olanzapine as they did on standard neuroleptics or risperidone. But some clearly are doing better, although an adjuntive prior agent is needed in some, as I've also found with clozapine and risperidone. I've switched only two patients from clozapine to olanzapine. In one case the patient is doing as well and in the other doing definitely better.

So it seems my experience has been more positive than in some other inpatient situations. Go figure!

From: MKomrad@aol.com
Date: Thu, 29 May 1997 00:58:16 -0400 (EDT)
Subject: Switching to olanzapine

I am the psychiatrist for the State of Alaska Department of Corrections. We have a 20 bed psychiatric unit in one of the jails for the severe schizophrenics.

We have switched 3 patients from Clozaril to olanzapine. 2 were very successful, and the third was successful initially but then decompensated in the 4th or 5th month. We took about 3 months to wean off the Clozaril. In each case it was necessary to supplement the olanzapine with Thorazine (chlorpromazine) 300-600 mg per day in order to contain the impulsivity, irritability, and increased affective responses off of Clozaril. Despite the Thorazine the two patients are much more active in their daily treatment activities than they ever were on Clozaril.

We did a drug usage evaluation on 23 patients who were switched from risperidone or other neuroleptics to olanzapine. 13% had dramatic improvement, 52% had significant improvement (usually due to reduced negative symptoms, increased activity level and improved affect), 13% had improvement only because of reduced EPS, and 22% had no improvement. About half of patients needed supplementation with Thorazine at 100-600 mg per day on a regular basis for optimum functioning.

--Bill Worrall MD

Date: Sat, 7 Jun 1997 08:02:39 -0400 (EDT)
From: "Paul Luisada, M.D." <pvl2@cornell.edu>
Subject: Switching to olanzapine

I'd underscore my experience that an overlap period (original dose fluphenazine + target dose olanzapine) of around 2 weeks is safer. In some patients, it may be that olanzapine takes longer to start working than it takes the fluphenazine to wear off.

In at least one patient I was converting, the psychosis reemerged during the overlap period. This problem was easily dealt with by simply stopping the olanzapine. If the fluphenazine dose had been reduced when the relapse began, it would have been attributed to a premature taper. On re-challange with a more cautious increase in olanzapine dose, the patient still experienced trouble.

Date: Mon, 9 Jun 1997 14:13:09 -0400 (EDT)
From: hucares@helix.nih.gov (Rona Hu)
Subject: Switching to olanzapine

I agree that going slower is generally better, if one can do so. Our patients are inpatients with round-the-clock nursing available, so we feel fairly comfortable with a fast taper of the old neuroleptic when going up on the olanzapine by 5 mg to a target 20 mg.

Even if one goes slowly, the switch to olanzapine is faster than the 25 mg-at-a-time creep of switching to clozapine. So far, there have been some good results.

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