Dr. Bob's Psychopharmacology Tips

Refractory psychosis

From: shakti@penn.com
Date: Thu, 8 Feb 1996 11:54:16 -0500
Subject: Partial response to clozapine

I treat at my job several very refractory patients with long standing diagnoses of schizophrenia, schizoaffective disorder, and refractory psychotic bipolar disorder. A very large portion of my service (> 90%) is on clozapine. I am running into a problem again and again and would appreciate some feedback. What have people tried as adjuncts to clozapine treatment of psychosis when the patient shows a partial response but continues to be delusional?

A short listing of what I have considered/tried:

• Lithium: hit or miss in my opinion.

• Methylphenidate.

• Glycine: I am trying to get the pharmacy here to suspend disbelief and procure it for me--they're still smarting from tryptophan (health food stuff, you understand!).

• Cyproheptadine: low dose, medium dose, high dose, no effect in my hands.

• Ondansetron: couldn't get medicaid to okay it for non chemotherapy use.

• Valproate: some patients are also on it. however it doesn't seem to make much difference.

From: MKomrad@aol.com
Date: Mon, 12 Feb 1996 21:46:03 -0800
Subject: Partial response to clozapine

I too have extensive experience with clozapine. A few approaches we use at Sheppard Pratt for partial responders:

• Very often partial response becomes full response if you wait long enough (up to 6 months).

• We use clozapine blood levels and make sure that we have a blood level of at least 350. You can get nor-clozapine levels but we haven't found those particularly useful clinically.

• Vigorously look for depression; sometimes addition of SSRI can really help if the phenomenology is there. You noted little value to valproate -- but I think this does make a significant difference if there is a clear cut hx of cycling or manic sx.

• Rarely addition of a second, conventional, neuroleptic (often Haldol or Prolixin) can bring the patient farther than either one alone.

• Your criteria for partial response is persistent delusions. I have seen many patients on clozapine have dramatic improvements in ability to function in their community, care for themselves, and socialize, despite persistent delusions. Many of these patients simply develop a harder encapsulation around persistent delusions and don't bring them up as easily unless the "delusional abscess" is penetrated. So, look to other variables on the BPRS besides "unusual thought content" to gauge clozapine response.

From: MKomrad@aol.com
Date: Sat, 19 Oct 1996 13:39:15 -0400
Subject: ECT for schizophrenia

We use ECT for schizophrenia when there is some affective component. Usually we use biltateral treatment. Typically it takes 10-15 treatments for significant improvement, and we then followup with neuroleptic, often clozapine. In some cases, we continue with maintaince ECT treatment weekly and try to taper it off. I have a few cases where tapering was not possible without relapse and we have continued weekly ECT for 2 yrs in one case and 4 yrs in another. It's the only thing that kept those two patients in the community after each had years of recurrent longterm hospitalizations.

Date: Sat, 19 Oct 1996 21:18:36 -0400 (EDT)
From: Donald Franklin Klein <dfk2@columbia.edu>
Subject: ECT for schizophrenia

I agree that an affective component is overriding but have seen two other odd indications in schizophrenia:

1. Oscillating thought disorder. The sentence starts fine and the last clauses are word salad, but they come back and repeat. I've seen this in chronic catatonia (more or less -- it gets messy) with remarkable results.
2. Chronic distressing but non-delusional ideas of reference and observation. This can be a life saver.

From: "George Nasra" <nasdoc@netacc.net>
Date: Mon, 3 Mar 1997 22:17:44 +0000
Subject: Clozapine and ECT for refractory psychosis

Clozapine and ECT have been used safely as a combination treatment for refractory cases of psychosis. I refer you to the article below.

Combined Clozapine and Electroconvulsive Therapy for the Treatment of Drug-Induced Psychosis in Parkinson's Disease, Stewart A. Factor, D.O., Eric S. Molho, M.D., Diane L. Brown, R.N., The Journal of Neuropsychiatry and Clinical Neurosciences 1995; 7: 304-307.

From: MKomrad@aol.com
Date: Mon, 3 Mar 1997 23:36:11 -0500 (EST)
Subject: Clozapine and ECT for refractory psychosis

I have had a few patients who had a very mild response to clozapine, and then ECT was added, the patients responded, the clozapine was continued after ECT, and they stayed well.

From: KONICKI.P+_ERIC@CLEVELAND.VA.GOV
Subject: Refractory psychosis
Date: 06 Mar 97 17:59 EST

As a psychiatrist in VA hospital ... I have had some success with the following:

• Clozapine alone, average daily dose = 450 mg.

• Clozapine + typical antipsychotic, average daily dose = 450 mg + 500 mg CPZ equivalent.

• For patients with significant negative symptoms, clozapine + methylphenidate, average daily dose = 450 mg + 10 mg.

• Olanzapine 10 to 15 mg. Animal data suggests that there are cataleptogenic effects from olanzapine at higher doses, arguing that there are D2 properties when higher doses of olanzapine are used. This would argue against adding a typical antipsychotic to higher (even ordinary?) doses of olanzapine.

In terms of efficacy, my clinical impresion is as follows:

clozapine > olanzapine > risperidone > haloperidol.

Therefore, I would suggest the following strategy for patients who are refractory to typical antipsychotics:

1. A three month trial of risperidone (4 to 6 mg/day unless 8 mg is tolerated without significant EPS). If ratings and/or clinical indices show no significant improvement (eg, 20% reduction in BPRS score or reduction in clinical target symptoms such as polydipsia or assaultive behavior), then:

2. A three month trial of olanzapine (10 to 20 mg/day). If no response (same criteria as for risperidone), then:

3. A three to six month trial of clozapine. I am not convinced that there is any additional benefit above 400 to 450 mg per day (in most patients) but there is a highly increased rate of seizures (20% in my hands). If no response, then:

4. Addition of either a typical antipsychotic or risperidone if positive symptoms predominate or methylphenidate if negative symptoms predominate. If no response to any of these pharmacological trials, then:

5. Consideration of ECT. I have seen several treatment refractory schizophrenic patients respond to ECT. However, in this case, ECT will need to be continued on a maintenance basis. I have had one case where ECT induced a remission and clozapine maintained the remission.

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

Adding olanzapine to a pre-existing neuroleptic has worked for outpatients to help the negative symptoms somewhat better, and combinations of olanzapine plus conventional neuroleptic do seem to be better for both positive and negative symptoms.

Date: Tue, 27 May 1997 10:32:53 -0400 (EDT)
From: "Cenk Tek, M.D." <ctek@umabnet.ab.umd.edu>
Subject: Refractory psychosis

2 weeks ago I saw a poster by Dr. R. R. Conley of the Maryland Psychiatric Research Center, a double blind comparison of olanzapine vs chlorpromazine in treatment resistant schizophrenia. Olanzapine did not look better than chlorpromazine regarding treatment resistant positive symptoms (as opposed to side effect profile and negative symptoms). I do not remember the details so I guess we need to wait it to be published.

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