Prq. NeumPsychophannd. &Bid. Psychtat. 1998, Vol. 22, pp. 331-340

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EFFECTS OF PIMOZIDE ON THE PSYCHOPATHOLOGY OF DELUSIONAL DISORDER

HERNAN SILVA4, SONIA JEREZ4, ALEJANDRA RAMIREZ’, PATRICIA RENTERIA”, NELLY ARAVENA,‘, DIEGO SALAZARZand RODRIGO LABARCA’

’ Departamento de Psiquiatrla y Salud Mental, Campus Norte, and ’ Escuela de Salud Publica, Universidad de Chile;3 Centro

Neuropsiquiatrico de Santiago, Chile.

(Final form. November 1997)

Abstract

Silva Hernan, Sonia Jerez, Alejandra Ramirez, Patricia Renteria, Nelly Aravena, Diego Salazar and Rodrigo Labarca: Effects of pimozide on the psychopathology of delusional disorder. Prog. Neuro-Psychopharmacol & Biol Psychiat. 1998, 22. pp. 331-340. o 1998 Elsevier Science Inc.

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The effects of pimozide on the psychopathology of delusional disorder were studied. After six weeks, pimozide (2-l 2 mg/day) administration had no effect on the Brief Psychiatric Rating Scale, or in the psychological, social and occupational functioning, as measured by the Global Assessment of Functioning Scale. When the different dimensions of the delusional experience were looked upon, no modifications were observed in any of them after six weeks of pimozide treatment.

These data failed to support the therapeutic role of pimozide in the treatment of delusional disorder and may suggest, when compared to other disorders with prominent delusions such as schizophrenia, a different neurobiology for the illness.

Kevwords: delusional disorder, delusional experience, dimensions, pimozide.

ws: Brief Psychiatric Rating Scale (BPRS), Global Assessment of Functioning Scale (GAF), high performance liquid chromatography (HPLC), Structured Clinical Interview for DSM-III-R (SCID).

331

332 H. Sflva et cd.

Introduction

The presence of persistent nonbizarre delusions characterize delusional

disorders. Patients with this disorder have delusions as primary

symptoms. In most cases, behavior is not obviously odd or bizarre, and

impairment in daily functioning is rare (American Psychiatric

Association, 1987). Besides delusions, the rest of psychic life remains

normal in most of the patients suffering a delusional disorder, whereas in

other psychotic disorders such as schizophrenia or depressive disorders

this is not the case (Kendler and Tsuang, 1981).

The literature on the pharmacologic treatment of delusional disorders

suggests that these disorders do not respond well to standard neuroleptic

medications. These observations are consistent with the distinctness of

delusional disorders from schizophrenia and affective disorders

(Manschreck, 1995). However, a few open neuroleptic trials suggest that,

at least for a subgroup, patients with delusional disorder do respond to

some extent to neuroleptics (Bilikiewict et al., 1957; Blanc et al.,l970; Ey

and Bohard, 1970; Riding and Munro, 1975; Munro, 1978). The combination

of antidepressants with neuroleptics (Cheng and Fogel, 1963) or lithium

(Forssman and Walinder, 1969; Morrison, 1972) has in anecdotal reports

been claimed to be useful. Moreover, electroconvulsive therapy may not be

a good choice for delusional disorders patients (Huston and Lecher, 1948).

Since none of these are controlled studies, the question still remains as

to whether neuroleptics are effective in the treatment of delusional

disorder (Kendler, 1980).

Pimozide on the psychopathology of delusional disorder 333

Non controlled studies and case reports have suggested that pimotide

may be a good choice in the treatment of some delusional disorders

subtypes such as the somatic (Riding and Munro, 1975; Munro, 1978),

jealous (Pollock, 1982; Byrne and Yatham, 1989) and erotomanic (Munro et

al., 1985) types.

In the present paper the authors report the effects of pimozide on the

psychopathology of patients with delusional disorder.

Methods

Patients

Seven patients (1 male, six female; age range, 29 to 60) (Table 1)

meeting DSM-III-R (American Psychiatric Association, 1987) and ICD-10

(World Health Organization, 1992) criteria for the diagnosis of delusional

disorder and free of physical illness were studied at the day hospital at

Clinica Psiquiatrica Universitaria, Universidad de Chile. Diagnosis was

made by the Structured Clinical Interview for DSM-III-R (SCID) (Spitzer et

al., 1987). The study was approved by the Institutional Review Board.

Drua Administration

After giving informed consent to participate in a double-blind study,

patients were put on placebo for a minimum of two weeks (range:2-4

weeks) after which pimozide was substituted and administered in ranging

doses between 2 and 12 mg/day for six weeks. Patients were started at 2

or 4 mg/day during the first week, and from then on the dose was

increased according to tolerance so by the last of the second week

334 H. Sflva et al

patients received a dose of pimozide of 4.57k1.9 (meanfS.D.). Whenever

necessary, trihexiphenidile was added to avoid extrapiramidal symptoms.

Table 1

Clinical and Demographic Characteristics

----a-_----_-__- -----_-_11 -_-_----- Patients Age Sex Delusional Theme Duration of

(years) (DSM-III-R) Illness (years) ---__-__---_--__l-l_____I____________________

1 60 F Persecutor-y 11 2 35 F Persecutory 11 3 36 F Persecutory 9 4 29 F Persecutory 9 5 32 M Persecutor-y 11 6 48 F Somatic/Persecutory 12 7 56 F Somatic/persecutory 6

Assessment Instruments

Clinical

Behavioral ratings with the Brief Psychiatric Rating Scale

(BPRS)(Overall and Gorman, 1961), the Global Assessment of Functioning

Scale (GAF) (American Psychiatric Association, 1987) and the scale to

measure five dimensions of delusional experience (Kendler et al., 1983)

were obtained weekly by two psychiatrist, none of whom were aware of

the medication status of the patient.

j_aboratory

Plasma pimozide levels were determined once a week by HPLC according

Pimozide on the psychopathology of delusional disorder

to Miyao et al (1983).

335

Data Analvsis

Clinical changes comparing the last week on placebo and the sixth week

on pimozide were analyzed with a paired t test.

Results

In the group of patients, insignificant changes in the behavior were

observed after six weeks of pimozide treatment (Table 2). Thus, BPRS

scores during the last week of placebo were 38.36k6.22 (meanfS.D.) and

34.36*5.86(meanfS.D.) during the sixth week of pimozide; this change did

not reach statistical significance. Moreover, changes in patients

psychological, social and occupational functioning as assessed by the GAF

scale was also marginal (57.36i8.24 (meanfS.D.) during the last week on

placebo vs 60.57k6.72 (meanfS.D.) during the last week of pimozide

treatment). According to the these results, when the effects of pimozide

on the different dimensions of delusional experience were analyzed, no

changes were observed on conviction, extension, bizarreness and

disorganization; a meaningless, non-significant decrease on pressure was

the only change.

The compliance for pimozide was good enough as weekly plasma pimozide

leveis were determined in each patient. In fact, after the second week of

treatment patients received dose of pimozide of 4.57&l .9 (mean+S.D.),

achieving plasma levels of 2.41f0.82 ng/ml (meanfS.D.) and during the

sixth week while patients were receiving a dose of pimozide of 6.57k3.41

336 H. Silva et al.

(meaneS.D.), plasma levels increased to 3.04+0.85 ng/ml (meanfS.D.) thus

supporting that patients were effectivelly receiving the neuroleptic.

Table 2

Effects of Pimozide on Clinical Ratings

_L_-__--_______I_---__l___l_l -_-_-_---

Clinical Rating Last Week Placebo Sixth Week Treatment

BPRS 38.36k6.22 34.36k5.86 GAF 57.3628.24 60.57f6.72 Delusional dimensions: Conviction 4.0 3.93&O. 18 Bizarreness 1 .o 1 .o Extension 1.93kO.80 2.07f0.73 Disorganization 2.14f0.37 2.21 *to.39 Pressure 4.21 zto.95 3.21fl.29

Results are the mean&SD

Discussion

Although the literature on the treatment of delusional disorder with

neuroleptics is very small probably due to the low prevalence of the

disorder and because most of the time patients refuse to get psychotropic

drugs (Manschreck, 1995), so far, the suggestion has been made that

delusional disorders do not respond well to standard neuroleptic

medication (Opler and Klar 1995). There have been a few anecdotal reports

in which delusional disorder patients respond to neuroleptics or other

drugs (Bilikiewicz et al., 1957; Blanc et al.,1 970; Ey and Bohard, 1970),

and particularly, pimozide may be effective when other antipsychotic

Pimozide on the psychopathology of delusional disorder

failed (Riding and Munro, 1975; Munro, 1978; Pollock, 1982; Byrne and

Yathan, 1989; Munro et al., 1985).

337

Clinical Response to Pimozide in Delusional Disorder

The results of the present report failed to support the therapeutic role

of pimozide in the treatment of delusional disorder. In fact, despite the

good patient compliance, no changes were observed in the scores of BPRS,

GAF or the different dimensions of delusional experience after six week

of pimozide treatment. It could be argued that six weeks is not a long

enough period to expect changes. This is not the case with schizophrenia

in which time-dependent changes in psychopathology can be seen after

four weeks of neuroleptic treatment (Pickar et al., 1984), even when low

dosis of standard neuroleptics are used (Labarca et al., 1993).

Dimensions of Delusional Experience and Response to Pimozide

A very important goal of the following protocol was to see whether or

not pimozide would modify the different dimensions of delusional

experience. Clearly the answer was no. The question then become as to

whether delusions reported by delusional patients are neurobiologically

different from the ones reported by schizophrenic patients that do respond

to current neuroleptic treatment (Pickar et al., 1984) and, in this regard,

at least in part, may be dopamine mediated. If newer neuroleptics such as

clozapine, risperidone, olanzapine or others fail to work on delusional

disorders, it would suggest that the neurobiology of delusional disorder

may be different from other psychotic disorders such as schizophrenia.

338 H. Sflva et aL

Conclusions

After six weeks of treatment with pimozide, seven patients with

delusional disorder showed no changes on BPRS, GAF or the different

dimensions of delusional experience. These results suggest that the

neurobiology of delusional disorder may be different from other disorders

such as schizophrenia in which delusion may be also prominent.

Acknowledoements

Supported by a grant from Fondo National de Desarrollo Cientifico y

Tecnologico (FONDECM No 193 1037).

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Inquiries and reprint requests should be addressed to:

Dr. Hernan Silva 1. Clinica Psiquiatrica, Universidad de Chile. Av. La Paz 1003. Santiago de Chile.