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Quetiapine
Dosage
in
Bipolar
Disorder
Réunion Ambulatoires SAS, 8.5.2006
Episodes:
A Retrospective Chart Review
1
Khazaal ,
Yasser
1
Zullino
Anne
1
Chatton ,
Martin
2
Preisig ,
Daniele
1Division
of Substance Abuse, University Hospitals of Geneva
2Department of Psychiatry, University Hospitals of Lausanne
Introduction


Quetiapine was found to be efficacious in the treatment of acute mania, as
monotherapy1-3 or in combination with other mood stabilisers4,5 at doses up
to 800 mg/day, and at doses of up to 600 mg/day as monotherapy for the
treatment of bipolar depression6.
The aim of this retrospective study was to investigate the efficacy, tolerability
and clinical reasons for the use of high doses (>800 mg/day) of quetiapine, in
routine clinical practice, in a sample of inpatients with bipolar disorder (BPD)
and schizoaffective disorder (SA).

Similarly, a statistically significant MADRS reduction over time was
found (F=156.2, p<0.0005). Depressive patients improved more than
patients presenting with mixed episodes (p=0.01). For MADRS
scores reduction, no difference between high (>800 mg/day) and low
(<800 mg/day) quetiapine groups could be seen (p=0.7).

At discharge, 77.8% of patients with mixed states, and 85.7% of
patients with depressive state were considered responders with
regard to the MADRS scores (reduction of MADRS scores of at least
50%).

With regard to tolerance, a “yes or no binary variable” (defined as
chart notification of side effect), no differences in reported side effects
between the low (<800 mg/day) and the high (<800 mg/day)
quetiapine dose group were found (p=0.8).

A logistic regression was performed to attempt to classify quetiapine
doses (high vs. low) with the following candidate predictors: episode
type, sex, MAS scores at entry. An overall percentage of 74% of the
cases were correctly classified. The R2 Nagelkerke statistic showed
that 49% of the variation in the outcome variable was explained by
the model.

Only episode type (p=0.02) was a significant predictor of quetiapine
group whereas sex and MAS scores at admission were not.
Compared to those with mixed episodes, patients with manic
symptoms were less likely to be in the high dose category (O.R=0.19
and IC [0.04; 0.80]).
Methods


Data are based on a systematic chart review of all adult inpatients with BPD
or SA, who received quetiapine treatment for a major mood episode between
December 1999 and February 2005 in the mood and anxiety disorder
treatment unit of the University Psychiatric Department of Lausanne.
These charts also included the assessment of manic and depressive
symptoms on admission and at discharge using the Bech-Rafaelsen Mania
Scale (MAS)7, and the Montgomery-Asberg Depression Rating Scale
(MADRS)8, respectively.
Results

Ninety four charts were analysed
Limitations


Open-label, retrospective design.
Observation period was limited to the hospitalization period.
Conclusions



The present study confirms quetiapine efficiency and tolerability in the
treatment of bipolar episodes, even at doses >800 mg, and found a
link between mixed episodes and quetiapine doses.
Particularly, mixed episodes seem to respond well to quetiapine, but
mostly at higher dosages than for pure manic episodes.
Quetiapine dosage >800 mg/day is predicted by mixed episodes.
References


ANOVA for repeated measures, to test the evolution of MAS and MADRS,
revealed a statistically significant MAS scores reduction between admission
and discharge (F=171.4, p<0.0005); with greater reductions seen in MAS
scores for manic episodes than mixed episodes (p=0.03). For MAS score
reductions, no difference between high (>800 mg/day) and low (<800 mg/day)
quetiapine groups was found (p=0.9).
At discharge, 81.8% of patients with mixed states, and 70.7% of patients with
mania were considered responders with regard to the MAS (reduction of MAS
scores of at least 50%).
1.
Vieta E et al. Quetiapine monotherapy for mania associated with bipolar disorder: combined analysis
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2.
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Aknoledgement
Study supported by AstraZeneca Pharmaceuticals
Service d’abus de substances
Département de Psychiatrie