Dr. Bob's Psychopharmacology Tips

Olanzapine effects

From: shakti@penn.com
Date: Mon, 5 Feb 1996 13:47:40 -0500
Subject: Olanzapine effects

Olanzapine probably will be released by December 96 or early 97. Phase 3 trials are completed (heard on the grapevine). The center where I trained used it in phase 2 trials and was not very impressed. However a certain someone from CA who has conducted phase 3 trials and who I heard talk about it was very enthusiastic. Also very encouraging data was presented, I believe, at this year's ACNP in Puerto Rico.

From: "Steven L. Dubovsky" <Steven.Dubovsky@UCHSC.edu>
Date: Tue, 6 Feb 1996 08:00:57 MST
Subject: Olanzapine effects

In Colorado, we have had good luck with this medication in mildly but not severely ill schizophrenic patients. It was well tolerated and effective but didn't do much for severe chronic illness.

Date: Fri, 13 Dec 1996 21:45:17 -0800
From: drrx@ix.netcom.com (Kathleen Schilli)
Subject: Olanzapine effects

I find that olanzapine is quite effective, however getting my docs to exercise patience with this drug is not! Too often many of our psychiatrists forget that this is a drug with a mean time to steady state of 5 to 7 days and want to increase doses every 2 to 3 days! Even though Lilly maintains that the drug can be used acutely, it doesn't seem to work well in that setting.

Date: Tue, 14 Jan 1997 21:45:32 -0800
From: Eduardo Dunayevich <dunayev@penn.com>
Subject: Olanzapine effects

My limited N of 4 pts on olanzapine initially got well at doses of 15 mg/day, then had exacerbations of symptoms and needed increases in dose. It did not seem to be related to sedation, but to a true wearing off of the antipsychotic effect. One patient, whose dose I have increased to 25 mg, is doing better so far with some recapturing of response.

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

It has been our experience at San Antonio State Hospital and the general experience of those on the Lilly Advisory Board for Zyprexa (meeting last week) that the dose of olanzapine can need to be greater than 20 mg/day in selected patients. However, there are also great success stories with 5 mg/day in those very sensitive to neuroleptics, some first break patients, the elderly, etc. Nonetheless the consensus was to start at 10 mg/day in most patients.

Women generally require lower doses than do men, due to differences in CYP1A2 enzyme activity, and there is a study with Japanese subjects showing that lower doses (about 33% less drug) are needed to achieve typical plasma levels. There are no studies evaluating plasma concentration vs. response to date with olanzapine.

Also, cigarette smoking definitely increases drug metabolism and should be factored in to your dosing plan, with about a 50% drop in blood levels in heavy smokers.

Date: Thu, 16 Jan 1997 20:48:16 -0500
From: anjan chatterjee <shakti@penn.com>
Subject: Olanzapine effects

I have treated approximately 15 patients with olanzapine. Here is what I see:

1. Psychotic patients who have never been (successfully) treated with traditional antipsychotics respond well to olanzapine.
2. Treatment refractory patients seem not to do as well as on say risperidone (which is pretty poor in my opinion).
3. Young men who smoke need higher doses (25 mg or more).
4. Old women who don't smoke need lower doses (10-20 mg).
5. Patients on mood stabilisers such as valproate, lamotrigine and carbamazepine need higher doses.

Date: Wed, 22 Jan 1997 20:17:29 -0500 (EST)
From: David Tobolowsky <dmtmd@dc.seflin.org>
Subject: Indications for olanzapine

IMHO, olanzapine is indicated:

1. After intolerance or non-response to two typical neuroleptics.
2. In patients who remain symptomatic on clozapine, to see if it will be at least equally effective without the need for phlebotomy.
3. In patients who develop tardive dyskinesia on typical neuroleptics which does not respond to vitamin E.
4. Once it becomes available more cheaply, as an alternative first-line antischizophrenic agent.

From: cprice@mem.po.com (Charles Sowle Price, MD)
Date: Sat, 1 Mar 1997 13:31:40 -0500
Subject: Olanzapine dosage

You may see clinical improvement for up to 1 or 3 months at the same dose. Most of us can't or won't wait that long at one dose. Perhaps keeping in mind that potential for improvement down the road at a particular dose will encourage a taper back to a lower dose after a patient has been stabilized for several months at a dose that may be in the higher range.

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

So far, it appears that olanzapine takes a very long time to work. (It may not be the best inpatient drug.) It may take up to 2-3 months to kick in.

We all remember that clozapine had cumulative effects that took up to 6 months to maximize. However, often one would begin to see some value in the first few weeks -- and just expect gradually continuing improvement over the next few months. With olanzapine it may be different, and onset of action may be even more tardy.

Date: Mon, 31 Mar 1997 22:59:22 -0500 (EST)
From: David Tobolowsky <dmtmd@dc.seflin.org>
Subject: Indications for olanzapine

To the short list of situations where I feel olanzapine is indicated that I posted to this list a few months ago, I wish to add two more:

1. Neuroleptic-induced menstrual irregularity. I've now had two young women resume regular menses after switching to olanzapine.
2. Neuroleptic-induced sexual dysfunction. I have one young man who is very happy to be getting erections again after switching to olanzapine.

From: "Catherine A. Leslie" <cal7e@avery.med.virginia.edu>
Subject: Olanzapine effects
Date: Thu, 3 Apr 1997 09:56:41 -0500 (EST)

We have recently seen a number of patients coming in from outside facilities on 30 mg of olanzapine -- it being pushed up because of poor response (or titrated too fast). Shouldn't folk be more rigorous (rating scales or careful documentation) to show that $8000 of olanzapine is better than $200 of Haldol?

Date: Fri, 23 May 1997 23:33:52 -0230
From: jamie@nfld.com (Dr. James Karagianis)
Subject: Olanzapine effects

I have had approximately twelve patients with schizophrenia and schizoaffective disorders, mostly chronic, on it. About half are, to people who know them, the best they have ever been.

One patient in particular has changed from an irritating non-compliant verbally abusive troublemaker (how is that for countertransference?) to a pleasant compliant champion of the drug, recommending it to all of the other psychotic patients on our ward.

This could be, of course, a coincidental string of good luck, but time will tell.

Doses are ranging from 10-25 mg per day; not many are on 10.

Date: Tue, 10 Jun 1997 10:56:43 -0400 (EDT)
From: hucares@helix.nih.gov (Rona Hu)
Subject: Olanzapine effects

I've had some experience with olanzapine. Since clozapine had clearly superior effects in treatment-resistant schizophrenia, on negative as well as positive symptoms, a "son of clozapine" with similar efficacy but without agranulocytosis would be highly desirable. Olanzapine is chemically quite similar to clozapine, although its receptor-binding profile is not identical (higher D2 affinity). It remains to be seen if its efficacy compares to clozapine. I've seen several patients do very well on it.

Date: Tue, 10 Jun 1997 23:19:49 -0230
From: jamie@nfld.com (Dr. James Karagianis)
Subject: Olanzapine effects

I am a believer in olanzapine for schizophrenia. My experience is not big, 14 patients [up from 12], but has been markedly positive. Most of my patients have been tried on at least two other antipsychotics, but would not be classified as severely or chronically treatment resistant. I have two who are relatively treatment naive and are responding reasonably well. I have had three or four patients who have become entirely normal. Several others have become better than they have ever been since their illnesses began. Two are objectively better but not subjectively, and one is worse, having become noncompliant after her dantrolene (dopamine agonist) was increased. Most patients have agreed that it is the best treatment they have ever had, and two have spontaneously reported this to me before I could ask. I have to admit I am impressed with this one more than I have been with any other newly released psychiatric drug since I have been in psychiatry (eleven years).

Mark Komrad will tell you that his experience with a much larger sample of treatment resistant schizophrenics is not nearly as positive.

It is being marketed as an antischizophrenic drug. The studies supporting its use seem to be of good quality. I don't think it will eliminate use of Haldol in acute psychosis. It seems to take a couple of weeks to kick in and does not seem to have much benefit in acute agitated psychotic states, from what I have read on the list. Some people are beginning to use it in psychotic mood disorders, but I have no experience in that area.

Side effects are minimal, that is one main reason why patients like it.

Date: Tue, 10 Jun 1997 20:21:42 -0700
From: ahkalali@uci.edu (Amir Kalali)
Subject: Olanzapine effects

During the clinical trials for this new agent, I was struck by the improved subjective experience of the drug by the patients. We have looked at this formally and have presented data on patient satisfaction and compliance. It is very promising.

One problem with the new antipsychotics is that people try them on their most resistant patients where nothing else has worked and become disillusioned when they do not work. This gives the drug an unfair reputation. The evidence suggests that the new antipsychotics work best in first episode patients. Another reason for bad experiences is drug switches that are too fast.

As far as efficacy is concerned,one study from Israel presented in March showed that 30% of clozapine non-responders responded to olanzapine over 6 months.

However my impression is that clozapine remains the gold standard in terms of efficacy, and there are moves to loosen the blood draw guidelines.

The newer drugs will all have a place. They are all different from each other, with some patients responding to one and not another. Also there is evidence that they are better for affective symptoms. Look for this to be a major marketing issue especially for ziprazidone. One thing that will aid prescribers is that there have been many studies done already using the new drugs in different populations, in combination with other psychotropics, etc., prior to FDA approval. These are beginning to be published. I am certainly looking forward to offering sertindole, quetiapine, and ziprazidone to my non-research patients.

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