Treatment of alcoholism with the antidepressant mianserin

s21

Poster B. Psychopharmaca

effects such as lower affinity for D, receptors and higher affinity for the D,, D, and D, than the classical antipsychotic drugs. It also has antagonistic effects at al-adrenerglc, a2adrenergic, SHT,-serotonergic, H,-histamimc and p-mouscarinic receptors. Which of these or which combination of these may be the mediators of clozapine’s special clinical efficacy is yet unknown. Purpose: The study aimed to investigate the therapeutic effect of clozapine on schizophrenic patients resistant to conventional antipsychotic drugs. Subjects and Method: Patients were included in the study after the agreement of two independent psychiatrists on the diagnosis made using standard clinical interviews and patients records. Forty-five male patients (mean age-+SD: 31.128.4, range 18-50) suffering from DSM-IIIR schizophrenia switched to clozapine from neuroleptics and completed the study. Another three patients discontinued treatment due to side effects. One of the above manifested agranulocytosis. The 45 patients had responded unsatisfactorily to two conventional antipsychotic drugs from different chemical classes. Twenty-six were with undifferentiated, sixteen with paranoid and 3 with disorganized subtype of schizophrenia. Their duration of illness was 10.724.9 years. They all gave written informed consent for participating in the study. Interrater reliability for the BPRS was 0.89. Results: After 6 weeks treatment with clozapine (mean+SD: 300.52 109.2, range 150-500) total BPRS score decreased significantly. Positive, negative and general psychopathology symptom scores from BPRS also decreased significantly (Table). More frequent adverse effects were those of sedation, salivation, hypotension and fatigue. Table Baseline

After

Wreduction F

P

32.0 34.5 21.5 39.5

O.CHXl o.coO 0.002 o.ooo

Table Baseline

After risperdone

84.4217.5 54.3211.2 PANSStotal score PANSSpositivesymptomscore 19.525.5 12.323.4 24.8t6.3 16.8?5.1 PANSSnegativesymptemscore PANSSgeneralpsychopathologyscan 40.628.9 25326.3 mean?SD

F % RedUCtiOtl 37.5 37.0 32.2 37.7

P

41.9 0.8 19.8 39.2

o.ooo O.OC02 O.wO7 0.000

ANOVA

Also, risperidone treatment reduced significantly the total item-score of each one of five factors disclosed after principal component analysis of the PANSS symptoms (256 patients, included risperidone-treated): Negative (Fl): p=O.OOOl, Excited (F2): p=O.OOO, Depressive (F3). Positive (F4): p=O.OOOl and Disorganized (cognitive disturbance, F5): ~~0.01 1. As the patients were exposed to high dose of risperidone, extrapyramidal symptoms were reported. Administration of antiparkinsonian drugs was necessary resulting in reduction of these side effects. Nausia, fat&ability anxiety were also reported. Conclusions: The preliminary results of our ongoing study indicate that risperidone improves both positive and negative symptoms of schizophrenic patients.

References Marder, S.R. (1994) Risperidone in the treatment of schizophrenia. Am. J. Psychiatry 151, 825-835. Ubricht, D. and Kane J. (1995) Risperidone. Schiz. Bull. 21, 593-606.

clozapine Total BPRS score PositiveBPRS score NegativeBPRS score GeneralPsychopathology BPRS score

46.1k9.9 20.626.2 13.5-t4.5 11.9t4.8

31.4~6.7 13.6~3.9 10.6t4.4 7.2+2.6

67.7 41.9 10.8 14.9

mean I SD, ANOVA. Conclusions: These data suggest that clozapine is effective for treatment of patients with schizophrenia who are not responsive to typical antipsychotics.

References Coward, D.M. (1992) General pharmacology of clozapine. Br. J. Psychiatry. 160 (suppl. 17) S5-Sll. Umbrlcht, D.S.G., Lieberman, J.A. and Kane J.M. (1995) The clinical efficacy of clozapine in the treatment of schizophrenia. Rev. Contemp. Pharmacoth. 6, 165-186.

IB-65

Risperidone in negative symptoms of schizophrenia. Preliminary findings

L. Lykouras, J. Hatzimanolii, I? Oulis, G.N. Christodoulou. Department of Psychiatry, Athens University, Eginition Hospital, Athens 115 28, Greece Purpose: The aim of the study was to assess therapeutic and side effects of risperidone on schizophrenic patients with preponderant negative symptoms. Subjects and Method: The study completed 20 male DSM-IIIR schizophrenic patients (mean age: 32.7 years, SD: 7.8). Another four patients prematurely discontinued treatment with risperidone because of refusal. Assessments were performed at baseline and at the end of a six weeks treatment period with risperidone by means of the Positive and Negative Syndrome Scale for Schizophrenia (PANNS). Extrapyramidal symptoms were assessed by means of Saint Hans Scale. Risperidone was gradually increased according to the patients condition, up to a daily dose of 16 mg in patients. Eight patients received a maximal daily dose of 10 mg and two were treated in a dose of maximally 8 mg daily. Results: After six weeks treatment with risperidone, the 20 patients showed a statistically significant decrease in the total score of the PANSS as well as in the positive, negative and general psychopathology subscales (Table).

I

B-66

Prozac versus anafranil in the therapy of social phobia and agoraphobia

Diana Ilies-Alexandru, Carmen Zaharia, Ana-Maria Grigorescu. ty Hospital of Psychiatry “Socola” Zasi, Romania

Universi-

Social Phobia and Agoraphobia as entities of Anxiety Disorders is to be found in l-2% out of general population with a significant invalidating potential. Various antidepressant drugs have been used in acute and maintenance therapy of these disorders besides cognitive and exposure psychotherapy. Our investigation focuses on a comparative estimation of the efficiency of Prozac (fluxetine) and Anafranil (clomipramine) in two homogeneous groups comprising each 36 patients, average age 33.5 and 32.7 respectively, followed for 1 year. The measurement of the efficiency included CGI and Hamilton Rating Scale for Anxiety. The therapy comprised doses of 20-40 mgslday, single intake of Prozac and 50-100 mgs/day, in two doses of Anafranil respectively. The assessment was performed after CGI and Hamilton Rating Scale for Anxiety after 8 and 10 weeks of therapy with Anafranil and 6 and 8 weeks with Prozac respectively. The rate of negative results (the therapy inefficiency or recurrences) was 25-30% in patients treated with Anafranil and 15-20% in patients with Prozac. Concluding the estimation of the efficiency of both drugs for the treatment of these disorders, we remarked a better improvement of the symptoms’with Prozac and with a satisfactory tolerance in the long term therapy.

1

B-67

Treatment of alcoholism mianserln

with the antidepressant

N.N. Ivanets. Research Institute on Addictions, Ministry of Health of Russian Federation, Moscow Z2192/, Russia Antidepressants, as anticraving drugs, become now a common item of the programs for treatment of alcohol dependence. It was the purpose of this work to study the anticraving efficacy of mianserin. in comparison with that of amitriptyline and relanium, in the treatment of alcohol withdrawal and postwithdrawal syndromes. Besides, the influence of mianserin on metabolism of biogenic amine neurotransmitters was studied and clinicobiological correlations were obtained. 60 patients with alcohol dependence syndrome (DSM-IV) were included in the study. 30 patients were given mianserin (60 mg, during 30 days), 15-amitriptyline (50 mg, during 30 days), and 15-relanium (10 mg, during 7 days). Psychotherapy also was included in the therapeutic

S28

Poster B. Psychopharmaca

program. The catamnestic examination of all patients was made in 3 months. The results obtained permit us to conclude that mianserin has a pronounced anticraving, anxiolytic, antidepressive, hypnotic, sedative, and vegeto-corrective action. Positive clinico-biochemical correlations were found. All said above permit us to recommend mianserin as an anticraving drug that may be. given to alcoholic patients to achieve stable remission and to prevent relapses of the disease.

I-B 68

Citeloprem versus venilafexine in the treatment of mafor depresslon

admission, were: 17, 44, 18, 18, 55 and 17 respectively. Mr K.G., was treated successf&ly with a combination of paroxetine (40 mglday) &p&done (3 mglday), &anepam (2Q. f id levomaPmm&ne (50 m&day). Upon discharge (2.5 months later) the patient’s scores dropped to 1, 89, 2, 2, 23 and 6 respctively. The concomitant administration of a serotonin receptor antagonist, like tisperidone, and an SRI, like paroxetine, seems to be antagonistic. However, contrary to that, there are several explanations for this w-thempeutie intervention, such as, the hypothesis of the down-regulation of many serotonin receptor subtypes or the possible biphasic action of risperkkme on obseseionscompulsions, enhancing them in high doses and reducing them in lower ones.

N. Kaya, H. Herken, R. R&in, M. Telcioght, A.S. Cilli. Medical Faculty of Se&k

University, Department

of Psychiatry,

42080, Konya, Turkey

To compare the efficacy, safety and tolerability of citalopram (20 mgla day) versus venlafaxine (150 mglday) in the treatment of Major Depressive Disorder (MDD). Method: Outpatients and hospitalized patients with DSM-IV detined MDD and score of >on the 18 Hamilton Depression Scale (HAMD-S) and >30 on the Montgomery-A&erg Depression Rating Scale (MADRS) were randomized to Citalopram (n=Zl) or Venlafaxine (n=24). Clinical evaluations were conducted before and after washout period, after fifteen days, after one month throughout the 2-month trial using the HAMD-S, MADR-S. Results: 44 patients completed the trial. Improvement in MDD symptoms from baseline to end week 8 of the trial was found in both venlafaxine and citalopram- treated groups. The most adverse events with citalopram were nausea, sedation, irritability. Whilst venlafaxine was tremor, sedation, nausea, constipation, hypertension. Differences of side-effects were statistically not significant. However, one of venlafaxine-treated patients dropped out because of severe side-effects. Conclusion: At fixed doses, both citalopram and venlafaxiue have shown a similar therapeutic efficacy in the treatment of MDD. Venlafaxine produces more side-effects than citalopram. The results indicate. that effectiveness of citalopram and venlafaxine are found to be the same in the treatment of MDD but citalopram is better tolerated. Objective:

References Cunningham, L.A., Depression in the medically ill: Choosing an antidepressant. J Clin Psychiatry 1994; 55: 90-97. Montgomery, S.A., Rasmussen, J.G.C., Tanghoj, P., A 24-week study of 20 mg citalopmm, 40 mg citalopram of major depression. International Clinical Psychopharmacology, 1993; 8: 181-183.

IB-69

L compuieive dlsorSucceesful tn#rtmcHlt oi obses&e der with concurrent schhntypsl perecnMty disorder

V. Kontaxakis, D. Dikeos, E. Eschenbecher, G.N. Christodoulou. Depurtment of Psychiatry, University of Athens, Sophias avenue, 115 28 Athens, Greece

Eginition Hospital

74 Vas.

The Serotonin Reuptake Inhibitors (SRI) are the drugs of choice for the drug-treatment of Obsessive-Compulsive Disorder (GCD). However, 50% of patients do not have an adequate response to this medication. We present the case of a patient with OCD and a concurrent diagnosis of Schizotypal Personality Disorder (SPD), refractory to many therapeutic interventions, who was treated successfully with a combination of paroxetine and risperidone. Mr K.G., a 18 year-old single male, was admitted to the Psychiatric Department, Athens University, Eginition Hospital, suffering from treatment resistant OCD with concurrent SPD (DSM-IV criteria). At the time of his admission, Mr. K.G., had experienced, overvalued obsessive ideas, obsessive thoughts, compulsive checking, ordering and washing, ideas of association, suspiciousness, high levels of anxiety and aggressive behaviour against his parents. Upon admission the psychopathological condition of the patient was evaluated using the Yale-Brown Obsession and Compulsion Scale (Y-BGCS), the Global Assessment Scale (GAS), the Hamilton’s Scale for Depression (HAM-D) and for Anxiety (HAM-A), the Brief Psychiatric Rating Scale (BPRS) and a consmtc&l scale based on the DSM-IV criteria for SPD. The patient’s score in the SPD-Scale, ranged from O-27 (range O-3 for each of the 9 items). The patient’s scores on the above scales, upon

Remington, G., Adams, M., Risperidone and obsessive-compulsive symptoms. J. Clin. Psychophatmacology. 1994, 14: 358-359.

IB-70

Drug tmafmeMofdepmWvediewderLnpetients -1IIwd

D. Kostitsh, M. Simeonovitsh, M. Takaeh-Kostitsh. Medic42 Clinical Center “‘Dr Drug&a Misovitsh”, Clinic of Psych&try, Department of Psychosomatic and ConsultationlLiuison Psychiatry, N.H. Milana Tepitshe 1, Belgrade, llW, Yugoslavia Depression occurring in medical illness is still considered as seriously under-diagnosed, under-treated and under-researched (l), despite its high prevalence (2). Due to consultation-liaison activities at internal ward of general hospital we conducted a follow-up study on presence and management of depressive disorder among medically ill patients. Objective: (1) to estimate the frequency and the type of depressive disorder occurring in non-psychiatric medical patients; (2) to estimate the frequency and the type of depressive disorder depending on sort of medical illness; (3) to establish the most available scheme for psychiatric therapeutically procedure. Methods: The sample was chosen by applying semistandardized interview and Zung Self-Rating Depression Scale (score 233%) among the patients with physical disorder admitted in Clinic of internaldisease Medical Clinical Center “Dr Dragisha Misovitsh” in Belgrade in the last trimester in 1997. The type of depressive disorder was determined by Structured Interview for DSM IV (SCID) and ICD-IO Symptom Checklist for Mental Disorders-SCMD ICD-10 (Affective disorders F32-F39). Once a week the psychiatrist estimated the course of depressive disorder by Hamilton Depression Rating Scale (HAMD). HAMD and Clinical Global Impression Scale (CGI) were used for improvement evaluation. It was done within and at the end of the period of physical examination and medication conveyed by internists. The psycbiabic tmatment was ruled according to type of depression and also regarding the results of laboratory and physical investigation, as well as the nature of medical illness and medical agents administered. Results: Depressive disorder is more frequent in persons 250 years of age, particularly in female; The significantc&relation between severity of medical illness and depressive disorder appeamd; The newer atttidepmssants (SSRls and Trazodon) alone or combined with psychotherapy were found as advantageous to therapist choice. Conclusion: Depressive disorder is the most common psychiatric disorder among the patients suffering from organic clinical disease and its non-recognition by non-psychiatrist is obvious. The occurrence of depressive disorder may precede the physical disorder for a few months, may appear as with its acute onset as well as in any of its phase, and also co-morbidity is not rare. The management of depressive disorder is rather limited: -well known side-effects and contraindications of antldepmssants makes them unconcordant with the state and medication of physical disorder; -appropriate psychotherapy is strongly disturbed by time-shortage and environmental conditions, especially in intensive cam units.

Clark, D.M., McKenzie, D.P., Smith, G.C., The recognition of depression in patients referred to a consultation-liaison service. J Psychosom Res, 1995; 39: 327-334. Fava, G.A., Sonino, N., Depression associated with medical illness: treatment considerations. CNS Drugs, 1996; 5: 175-189.