Dr. Bob's Psychopharmacology Tips

Quetiapine

Date: Mon, 2 Jun 1997 13:28:40 -0400 (EDT)
From: hucares@helix.nih.gov (Rona Hu)
Subject: Quetiapine

Seroquel (quetiapine) is an atypical antipsychotic, rumored to be coming out soon. Moderately high affinity for D2 receptors (not as high as haloperidol, comparable to clozapine), low affinity for D1. High affinity (comparable to haldol, clozapine, olanzapine, etc.) for alpha-1 adrenergic receptors. Low affinity (unlike clozapine, risperidone, olanzapine) for 5-HT2C receptors.

Date: Tue, 3 Jun 1997 09:16:34 -0700 (PDT)
From: ferrell@cmgm.stanford.edu (James Ferrell)
Subject: Quetiapine

Dr. Ben Green summarizes the early info on quetiapine in Focus on Quetiapine.

My summary of his summary:

• Efficacy: Works on positive and negative symptoms. "Limited data does not differentiate quetiapine from any other mainstream antipsychotic in a clearly positive way."

• Receptor binding: Higher affinity than clozapine for D1, D2, 5HT1A, 5HT2, muscarinic receptors.

• Side effects: Incidence of EPS lower than haloperidol, comparable to chorpromazine. "No clear tendency to produce or reduce tardive dyskinesia." Tendency to produce weight gain (dose related), to raise liver enzymes. Reduced tendency to raise prolactin levels.

Date: Tue, 03 Jun 1997 09:17:54 -0700
From: William Wilson <wilsonw@ohsu.edu>
Subject: Quetiapine

Quetiapine is the generic name for Seroquel (Zeneca). It is an atypical antipsychotic. There is a good, short review of quetiapine in the Manual of Clinical Psychopharmacology, 3rd ed, Schatzberg, Cole, DeBattista eds, Am Psychiatric Press, 1997, 167-168. Quoting the first paragraph:

Quetiapine is another atypical antipsychotic that is expected to be relaesed in the near futrue. Like clozapine, the drug appears to have low affinity for D1 and D2 receptors but relatively high affiity for D4. Clozapine, olanzapine, and quetiapine all seem to have more pronounced effects on mesolimbic dopaminergic activity than on nigrostriatal pathways, a phenomenon that accounts for their low tendency to produce extrapyramidal symptoms. As with other atypical agents, quetiapine appears to have affinity for 5-HT2 receptors. Quetiapine does not appear to have very significant anticholinergic or antihistaminic effets, but it does block alpha-1-adrenergic receptors to some extent.

From: cprice@mem.po.com (Charles Sowle Price, MD)
Date: Thu, 25 Sep 1997 09:18:23 -0400
Subject: Quetiapine

We were one of the sites in the pre-marketing trial of quetiapine. While I was not directly involved with the testing, the results were not impressive in the few patients that made it to the open label phase of the study. Of course these were refractory schizophrenic patients to start with.

From: cprice@mem.po.com (Charles Sowle Price, MD)
Date: Thu, 25 Sep 1997 20:02:03 -0400
Subject: Quetiapine

Seroquel will be a welcome addition to the atypical antipsychotic armamentarium. It has few side effects, is as effective as typicals, and is not associated with weight gain or sexual dysfunction.

--Charles B. Nemeroff, M.D., Ph.D

Date: Sat, 27 Sep 1997 18:05:40 -0500
From: Larry Ereshefsky <Ereshefsky@uthscsa.edu>
Subject: Quetiapine

It's mechanism of action is very different than other atypicals so it is a welcome addition to the armamentarium. However, on both positive and negative symptoms it is equivalent to haloperidol 12 mg a day.

Date: Mon, 29 Sep 1997 11:09:40 -0500
From: Larry Ereshefsky <Ereshefsky@uthscsa.edu>
Subject: Quetiapine

The multidose study against haloperidol 12 mg/d had the following data (approximately correct numbers; > 50 patients per arm):

BPRS total score (LOCF) Change from Baseline (Least squares mean)
Placebo	+0.05	worsening
Quetiapine 75 mg/d	-0.35	improving, not significantly different than placebo
Quetiapine 150 mg	-0.70	significantly different than placebo
Quetiapine 300 mg	-0.90	"
Quetiapine 600 mg	-0.70	"
Quetiapine 750 mg	-0.58	"
Haloperidol 12 mg	-0.75	"

No differences between quetiapine and haloperidol.

SANS (Scale for Assessment of Negative Symptoms) total score (LOCF) Change from Baseline (Least squares mean)
Placebo	+0.75	worsening
Quetiapine 75 mg/d	-0.60	improving, not significantly different than placebo
Quetiapine 150 mg	-0.75	not significantly different than placebo
Quetiapine 300 mg	-1.60	significantly different from placebo
Quetiapine 600 mg	-0.90	significantly different from placebo
Quetiapine 750 mg	-0.40	not significantly different than placebo
Haloperidol 12 mg	-1.70	significantly different from placebo

Use of Antiparkinsonian meds
14%	Placebo
< 14%	all doses of Quetiapine
~45%	Haloperidol 12 mg/d

All data from 6 week randomized double blind placebo controlled study.

Date: Tue, 30 Sep 1997 13:20:38 -0500
From: Larry Ereshefsky <Ereshefsky@uthscsa.edu>
Subject: Quetiapine

These data are from Zeneca Pharmaceuticals, and some of it has been published.

Date: Fri, 17 Oct 1997 23:04:44 -0400
From: William Braden <braden@brown.edu>
Subject: Quetiapine

The salesman came by with literature:

• Reports of controlled trials comparing it with placebo and haloperidol. It looks as though it's about as effective as haloperidol for both positive and negative symptomatology, but with lower incidence of EPS. Maximum effect obtained around 300 mg/day.

• Package insert. Orthostatic hypotension (syncope in 1%), somnolence (18%). Dogs developed cataracts, humans developed "lens changes during long term treatment"; slit lamp exam "or other appropriately sensitive methods" recommended at initiation of treatment and then every six months. EPS was less on drug than placebo (but 16% of placebo patients had EPS?!).

Date: Sat, 18 Oct 1997 11:27:34 -0700 (MST)
From: "Dr. Alan Gelenberg" <alang@u.arizona.edu>
Subject: Quetiapine

In our hands unimpressive in hard-core chronically mentally ill.

Date: Mon, 20 Oct 1997 09:45:58 -0500
From: Larry Ereshefsky <Ereshefsky@uthscsa.edu>
Subject: Quetiapine

Quetiapine is a very interesting drug from a mechanism of action perspective, e.g, potent effects on serotonin 6, sigma, alpha, and histaminic receptors. Its strength is its weakness... it is different enough that it may not be a broad spectrum antipsychotic. Our success rate in clinical trials with the drug with acutely exacerbated patients was "OK"... not impressive. However, in the refractory schizophrenia study, we had some dramatic responses in "hard-core" patients, though others had negligible effect.

Also, go higher on the dose, e.g., 450 mg is closer to the dose needed in acutely ill folks.

Also, 16% placebo EPS rate is consistent with all of the clinical trials in which washouts are typically about 1 week.

Date: Fri, 31 Oct 1997 16:49:01 -0600
From: Kevin Miller <MillerKB@wpogate.slu.edu>
Subject: Quetiapine

From the clinical trial I was paid by the manufacturer to do for our department:

• Efficacy not exceptional but comparable to others, onset not rapid.

• Significant sedation, requiring careful titration: plus or minus 25 mg. often made a great deal of difference, both in sedation and in effect.

• Target dose usually 300-500 mg.

• No EPS! (None!)

• Seemed effective when given HS only rather than BID as recommended by manufacturer.

Just my impressions. N = 4, I believe.

Date: Fri, 31 Oct 1997 16:17:37 -0800
From: William Wilson <wilsonw@ohsu.edu>
Subject: Quetiapine

We were a site for an industry sponsored one year randomized trial of quetiapine vs "usual care" (any other antipsychotic), N about 13, about 7 on quetiapine.

Our results were similar to Dr. Miller's.

Date: Mon, 3 Nov 1997 08:02:51 -0700 (MST)
From: "Dr. Alan Gelenberg" <alang@u.arizona.edu>
Subject: Quetiapine

Ditto for us.

This topic is indexed under the following subjects:

URL: http://www.dr-bob.org/tips/split/Quetiapine.html
Original tips copyright 1994-97 original authors.
Web page copyright 1995-97 Robert Hsiung.