Dr. Bob's Psychopharmacology Tips

Antidepressant effects of antipsychotics

Subject: Antipsychotics to augment antidepressants
Date: Sat, 17 Feb 1996 12:50:11 -0500 (EST)
From: "Jeffrey R. Stenzel" <jstenzel@polar.Bowdoin.EDU>

I primarily practice in an inpatient setting and we often get very depressed people, not frankly psychotic, but constantly ruminating. If benzodiazepines don't sufficiently relieve their distress, I often prescribe low-dose antipsychotics, after a complete explanation to the patient, on a "you tell me if you feel better after 1 to 2 doses" basis. Most seriously depressed people with constant ruminations improve and continue use of the antipsychotics for 2 to 4 weeks and then discontinue without further need.

From: LJGROLD@aol.com (L.James Grold M.D.)
Date: Sun, 18 Feb 1996 00:55:13 -0500
Subject: Antipsychotics to augment antidepressants

I also have found that small doses of trifluoperazine works well in combo with an antidepressant. Years ago the thinking was that the antipsychotic merely raised the blood level of the antidepressant. I don't believe that is the only effect in non-psychotic treatment-resistant patients. I have used trifluoperazine for some patients for years watching carefully for any sx of tardive dyskinesia. I have in the past few years tried unsuccessfully to substitue risperidone for it. It doesn't seem to have the same mood-stabilizing effect in the low doses I have tried.

From: RMRich1@aol.com (Roberta M. Richardson, M.D.)
Date: Sun, 18 Feb 1996 23:28:40 -0500
Subject: Antipsychotics to augment antidepressants

That intense rumination may represent actual psychosis that hasn't quite been ferreted out. More careful questioning regarding the "worries" may reveal delusional thinking that warrents, indeed, requires, the addition of an antipsychotic.

The "classic" in the geriatric inpatients I work with is rumination over bowel function. Closer questioning may reveal that the patient believes she isn't having bowel movements when she actually is, that the quality of the stool is perceived as meaningful in some way that really doesn't make sense, that she is eating poorly because she believes the food will have nowhere to go since her bowels are not moving well, etc. Sometimes the family is able to provide these details when the patient doesn't tell you either because of embarrassment, not talking much, or whatever.

Given the well-documented data regarding poor response of psychotic depression to antidepressant alone, I think that if the rumination is so intense as to be not amenable to reason, there is probably an underlying psychosis and adding an antipsychotic, if feasible, is appropriate.

From: rdb@icu.com (Richard David Brand, MD)
Date: Mon, 19 Feb 1996 09:00:17 -0500
Subject: Antipsychotics to augment antidepressants

The ruminations may involve some SSRI responsive obsessional/depressive diathesis. I like your thinking. I have seen several patients who appeared blocked by a pervasive thinking pattern (rumination), and I also have found this responsive to short term, low dose antipsychotics, leaving sadness in its wake.

Date: Mon, 19 Feb 1996 19:43:21 -0500
From: "Paul Luisada, M.D." <pvl2@cornell.edu>
Subject: Antipsychotics to augment antidepressants

I don't think you need to invoke psychosis or elevated antidepressant blood levels to explain the empirical observation that small doses of some neuroleptics (eg: perphenazine 2-4 mg/day) for a short (2-4 week) period appear to substantially enhance the antidepressant response in some of these anxiously depressed individuals.

I often use Dr. Stenzel's "if it works in a day or two, stay on it" approach with adjunctive neuroleptics, usually with outpatients. My experience is that if the effect is not seen at tiny neuroleptic doses, higher ones are usually not worth pursuing. Like Dr. Stenzel, I've not been able to get this effect with risperidone, but this may be a question of dosage, as even breaking a 1-mg tablet in half still delivers a hefty antipsychotic dose.

There is no psychosis I can detect in these patients, although their anxiety is sometimes high enough to be considered at a psychotic level.

Date: Thu, 22 Feb 1996 07:06:37 +0900
From: fukuda@med.teikyo-u.ac.jp (Rimmei Fukuda)
Subject: Antipsychotics to augment antidepressants

For neurotic or mildly depressed patients with excessive "worrying" or rumination which is not apparently psychotic, I often use sulpiride (Dogmatyl) at a low dose (100-300 mg/d) in addition to a benzodiazepine. I guess this is a kind of common practice in our country (Japan).

This combo will often work without any excessive thought-dulling effect and preserve patients' social functioning, although sometimes intolerable side effects may occur.

One of the "pros" of this combo is that the comedicated benzodiazepine may reduce EPS.

From: JoelSHoffm@aol.com (Joel S Hoffman)
Date: Sun, 24 Nov 1996 16:24:38 -0500
Subject: Antidepressant effects of antipsychotics

Thoughtful clinicians 20 years ago sometimes used low dose standard neuroleptics to antidepressant effect, particularly thioridazine (e.g., 10 mg), trifluoperazine (e.g,. 1 mg), perphenazine (e.g., 2 mg), and even haloperidol (e.g., 0.5 mg). There were some good results here and there, albeit scarcely a reliable treatment. The late Nathan Kline used clozapine from Europe at a dosage of 25 mg with frequent benefit in treatment resistant depression.

I have found olanzapine a wonderful addition to the armamentarium for complex and treatment resistant illness with marked affective symptomatology. In effectiveness I would rate clozapine > olanzapine > risperidone. But of course olanzapine has a much easier side-effect profile than clozapine. One has to be careful because even though some patients have more symptom relief with olanzapine than clozapine, an occasional patient will do much worse as one makes a gradual transition from clozapine to olanzapine (I taper clozapine only after starting olanzapine).

Date: Tue, 14 Jan 1997 08:05:02 -0500 (EST)
From: Bill Boyer <wboyer@emory.edu>
Subject: Antidepressant effects of olanzapine

For what it's worth: in 2/2 very rapid cyclers I have found olanzapine to have apparent mood-stabilizing and antidepressant properties. I am suspicious they are somewhat hypomanic as a result, but it is mild and (knock on wood) by no means disabling. I have seen much worse manic reactions with risperidone.

Date: Tue, 14 Jan 1997 08:10:33 -0800 (PST)
From: Joseph Barrett <jbarrett@u.washington.edu>
Subject: Activating effects of olanzapine

My experience with olanzapine has been that it does cause activation and potentially hypomania in bipolar and schizoaffective patients. This often comes as a relief to patients mired in clozapine sedation, but it has possible risks of worsening cycles.

Date: Tue, 14 Jan 1997 19:59:51 -0600
From: "John M. Talmadge, M.D." <talmadge@onramp.net>
Subject: Activating effects of olanzapine

I have seen both sedation (more commonly) and a couple of cases of apparent activation, the latter characterized by insomnia and restlessness. My total number of patients on this new medication is fewer than two dozen, however, and my experience has generally been quite positive.

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

There are anecdotal reports (many members of the Lilly Advisory Board for Zyprexa concur) suggesting some activation of bipolar patients if mood stabilizers are not coadministered.

Date: Thu, 22 May 1997 19:07:48 -0400
From: Eric Fier <efier+@pitt.edu>
Subject: Mood-stabilizing effects of olanzapine

I've seen a surprising number of patients with bad bipolar 1 disorder do remarkably well on olanzapine (Zyprexa) monotherapy; several of them previously required multiple mood stabilizers plus haloperidol or perphenazine to hold them. A good amount of research is being done now at the Western Psychiatric Institute on the use of olanzapine in bipolar disorder.

Date: Thu, 22 May 1997 21:01:46 -0400 (EDT)
From: David Tobolowsky <dmtmd@dc.seflin.org>
Subject: Mood-stabilizing effects of olanzapine

My patient with psychotic bipolar disorder plus Crohn's disease plus short bowel syndrome continues to do well for over five months on 5 mg of olanzapine alone.

From: LJGROLD@aol.com (L. James Grold M.D.)
Date: Fri, 23 May 1997 00:06:08 -0400 (EDT)
Subject: Mood-stabilizing effects of olanzapine

I have found olanzapine an excellent mood stabilizer especially in the recalcitrant depressed group of patients who may be bipolar but are not obviously so. It has turned several treatment failures into successes. A couple of patients describe it as a life-saver. I have added it to one or another antidepressant plus one of the standard mood stabilizers.

Date: Thu, 22 May 1997 21:41:40 -0700
From: Eduardo Dunayevich <dunayev@jane.penn.com>
Subject: Mood-stabilizing effects of olanzapine

I had a bipolar female with psychotic mania who responded nicely to olanzapine monotherapy.

Date: Sat, 24 May 1997 18:29:52 +1200
From: Felicity Plunkett <felicity@iprolink.co.nz>
Subject: Mood-stabilizing effects of olanzapine

There have always been bipolar patients who were well for years on small doses of an antipsychotic. Here in NZ generally some GP keeps them on a little trifluoperazine or thioridazine for 15 years (not so much as a definitive plan but more from forgetfulness), then someone refers the patient to a psychiatry clinic, we go "tut, tut, this patient has a mood disorder & should be on a mood stabiliser" and put them on lithium, etc., & they promptly start relapsing & are hell to stabilise again!

Anyway, my point is that we know antipsychotic meds do act as prophylaxis in bipolar patients -- probably best in those that mostly get the manic phases. The new antipsychotics like clozapine & olanzapine, with their different receptor actions, tend to be less "anhedonic" in action, so patients perk up a bit & feel brighter & less blunted. They're thus also good in bipolar patients who get depressions as well. Is it a specific antidepressant effect? -- probably not, but who knows? Does olanzapine cut the mustard like clozapine regarding efficacy? -- the jury's still out on that one too.

From: MKomrad@aol.com
Date: Tue, 27 May 1997 00:30:53 -0400 (EDT)
Subject: Mood-stabilizing effects of olanzapine

So far, I have not found olanzapine useful for mood stabilization in the way that clozapine has been.

Date: Tue, 27 May 1997 10:40:21 +0200
From: "William Boyer, M.D." <wboyer@emory.edu>
Subject: Mood-stabilizing effects of olanzapine

I am also using olanzapine as part of the regimen for difficult bipolars. A couple of caveats, though:

One patient (probably schizoaffective) reports his auditory hallucinations got louder, "like through a loudspeaker", on both occasions that his dose got up to 15 mg/day. We have also seen at least one patient become non-psychotically manic (but perhaps he might have anyway).

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