Actu Psychiatr Scand 1996: 94: 196197 Convriaht

, <, 0 Munksauurd 1996

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An open trial of adjunctive sertraline in the

treatment of chronic schizophrenia
Thakore JH, Berti C, Dinan TG. An open trial of adjunctive sertraline in J. H. Thakore', C. Bert?, T. G. Dinan
the treatment of chronic schizophrenia. 'Department of Psychological Medicine. St
Acta Psychiatr Scand 1996: 94: 194-197. 0 Munksgaard 1996. Bartholomew's Hospital. London and
'Pfizer Ltd. Sandwich. Kent, UK

While the positive symptoms of schizophrenia are amenable to treatment

with standard neuroleptics, negative symptoms are often difficult to treat.
Co-prescribing antidepressants, such as sertraline, for patients on stable
neuroleptic depot preparations is one pharmacological method of
overcoming this problem. A total of 20 patients with chronic schizophrenia
were enrolled in an open trial over a 12-week period during which sertraline
was added to their usual antipsychotic medication. Prior to this, baseline
scores for positive and negative symptoms, and extrapyramidal side-effects, Key words schizophrenia negative symptoms.
were measured. The addition of sertraline resulted in global improvement, sertraline
with a significant reduction in positive and negative symptom scores and no J H Thakore. Department of Psychological Medicine.
increase in undesirable neuroleptic side-effects. Sertraline may act by St Bartholomew's Hospital. London EClA 7BE. UK
indirectly reducing dopaminergic activity. Accepted for publication January 27. 1996

Introduction
The observations that platelet (1) and plasma (2,
3) levels of serotonin (5-HT) are abnormal, while
dynamic endocrine testing of the lactotropic axis
reveals blunted fenfluramine-induced prolactin
responses (4), provide evidence of a dysfunctional
serotonergic system in schizophrenia. Furthermore,
the use of serotonergic agents ameliorates certain
symptom complexes in schizophrenia. For example,
5-hydoxytryptophan, a precursor of serotonin, is
believed to inhibit amphetamine-induced worsen-
ing of psychotic symptoms in schizophrenia (5).
Fenfluramine, a 5-HT releaser, improves negative
symptoms, although this is not a consistent finding
( 6 4 ,while ritanserin and clozapine, which are 5-
HTZaizc receptor antagonists, have been shown to be
effective in ameliorating negative symptoms (9-
11).
Negative symptoms of schizophrenia can prove
to be the most resistant to treatment with tradi-
tional antidopaminergic agents (12, 13). Conse-
quently, various strategies have been employed to
overcome this problem, including the addition
of anti-parkinsonian agents, propranolol, car-
bamazepine, benzodiazepines, lithium and antide-
pressants to conventional neuroleptic therapy (for
review see 14). Even though preliminary studies
used monoamine-oxidase inhibitors and concen-
trated on patients who had concomitant depression
(15, 16), more recent trials have used the more
selective serotonin reuptake inhibitors (SSRIs),
fluvoxamine (17) and fluoxetine (18), in order to
determine the effectiveness of the add-on antide-
pressant paradigm in non-depressed negative-
symptom patients with schizophrenia. Sertraline is
yet another SSRI antidepressant, and it appears to
be one of the most selective and potent serotoner-
gic reuptake inhibitors, with little affinity for other
receptor sites (19). As SSRIs may play a useful role
in the adjunctive treatment of this subtype of
schizophrenia, it was our intention to determine
the safety and efficacy of sertraline in patients with
negative symptoms of schizophrenia.
Material and methods
Twenty patients with a DSM-111-R (20) diagnosis of
chronic schizophrenia took part in the study after
giving their fully informed written consent. The
study was approved by the local ethics committee.
Of the 26 patients who were suitable for inclusion
in the trial, only 20 subjects took part, and the rest
were lost to follow-up after the baseline visit.

194
 Sertraline in chronic schizophrenia

Patients who dropped out did not differ from those Table 1. Clinical data for patients treated witth adjuvant sertraline
who completed the trial with regard to age, neu-
Parameter Mean value Range
roleptic dosage or baseline scores on any of the
scales employed. Patients had been ill for at least Age (years) 36 1 26-51
2 years, had to have a score of at least ‘moderate’ Duration of illness (years) 12 9 2-30
on one of the five global scales of the Schedule for
Daily neuroleptic dosage (mg)
the Assessment for Negative Symptoms (SANS) (chlorpromazine equivalents) 495.0 50-125
(21), and were stabilized on a single depot neu-
Procyclidine dosage (mg) 12 1 0-20
roleptic for at least 1 year prior to entry to the
study. Anticholinergic medication was the only Baseline BPRS scorea 27 8 18-39
other form of medication permitted during the Baseline SANS scorea 69 6 47-96
study period. Exclusion criteria included significant Baseline BAS scorea 04 0-8
concomitant medical illnesses, a DSM-111-R (20)
for major depressive disorder, substance abuse, Baseline EPS score’ 40 0-1 1

personality disorder, and receiving antidepressant
medication within 4 months of commencing the
trial.
Sertraline was administered at a daily dose of 50
mg per day in an open manner during the 12-week
study period. The clinical states of patients were
rated at baseline and at weeks 2, 4, 8 and 12 using
the Brief Psychiatric Rating Scale (BPRS) (22),
SANS (21), Abnormal Involuntary Movement
Scale (AIMS) (23), Barnes Akathesia Scale (BAS)
(24) and Extrapyramidal Side-Effects (EPS) (25).
The mean scores on each of the rating scales at
baseline and at weeks 2,4,8 and 12 were compared
by means of a repeated-measures ANOVA, and
post hoc tests were applied. Student’s t-tests (paired
and two-tailed) were used when appropriate. The
data were analysed using the Statgraphics package
(26), and all results are expressed as mean val-
uesfSEM.
aBPRS, Brief Psychiatric Scale, SANS, Schedule for Assessment of Negative Symp-
toms, BAS, Barnes Akathesia Rating Scale, EPS, Extrapyramidal Side-Effects Scale
occurred at weeks 8 and 12 compared to baseline
(P<0.05) (Fig. 1). Among the negative symptoms,
only affective blunting showed significant improve-
ment (F=2.08, df=4, 95, Pc0.05). Scores on the
AIMS, BAS and EPS did not differ from baseline
values.
Discussion
Patients who were receiving adjunctive treatment
with sertraline displayed a global improvement in
their clinical state as evidenced by a decrease in
their BPRS scores, and they showed a significant
reduction in the magnitude of their negative symp-
toms as indicated by a decrease in their SANS

Results 80 -
The relevant baseline clinical and demographic
data are shown in Table 1. Compared to baseline,
week 12 was associated with significant reductions
in total BPRS scores (36%) (t=4.82, df=9, P<0.001) 60 -
and in total SANS scores (20%) (t=2.70, df=9,
P<O.Ol). A repeated-measures ANOVA revealed
that there was a significant improvement in the
overall clinical state as measured by the BPRS
(F=7.78, df=4, 95, P<0.001), with post hoc tests
’
2 40-

showing that significant reductions occurred at

weeks 4, 8 and 12 compared to baseline (P<0.05)
(Fig. 1). Among the BPRS symptoms, emotional BPRS
20 -
withdrawal (F=4.54, df=4,95, P<0.002), conceptual T
disorganization (F=2.57, df=4, 95, P<0.04), unusual
thought content (F=2.68, df=4, 95, P<0.04) and
affective blunting (F=6.49, df=4, 95, P<0.001) I I

showed significant improvement. 0 2 4 8 12

SANS scores improved significantly over the 12- Weeks
week treatment period, as revealed by a repeated- Fig. 1. Mean valuesfSEM of SANS ( 0 )and BPRS (0)scores
measures ANOVA (F=2.71, df=4,95, P<0.03), with in 20 patients with chronic schizophrenia over a 12-week
post hoc tests showing that significant reductions period.

195
Thakore et al.

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