- Email: [email protected]
Clozapine — A survey of protocols and prescribing
176S
Poster session m
BIOL. PSYCHIATRY 1991;42:IS--mS
(Petit et ai, 1996, Psychopharmacol BuU, 32, 61), is particularly effective In treating anxiety/depression in schlzophrenlc patients (ibid; Fleischhacker et ai, 1969, Psychopharmacol Bull, 25. 97). Here, we examine zotepine in models predictive of antidepressant activity. Methods: Male, CD rats (-200 g) or CD1 mice (-25 g) were used in all tests. For behaviour. zotepine was administered po, 1 h before test evaluation. Reserpine hypothermia (RH), Porsolt swim test (PS) and reserpine ptosis (RP) were determined as previously (Luscombe et ai, 1993 Neuropharmacology, 26, 129). Noradrenaline (NA) uptake In rat cortical synaptosomes in vitro was adapted (ibId). Catalepsy was measured as descnbed (Needham et ai, 1996, pSychopharmacol Bull. 32, 126). Results: Zotepine inhibited NA uptake (Ki '" 21 nM), reversed RH (EDso 26 mglkg) and increased PS motility (100 mglkg). RP was unaffected by 30 mglkg, (am~riptyline RP EDso • 48 mglkg); at higher doses, zotepine alone caused ptosis. Catalepsy EDso values for zotepine, in rat and mouse, were 31 and 26 mglkg, po. respectively. Discussion: RH data are consistent with zotepine's potent inhibition of NA uptake, but Increases in motility were surprising in view of the catalepsy EDso, and are in marked contrast to the neuroleptic chlorpromazine, which also Inhibits NA uptake, but decreases motility in the Porsolt test at eqUiv• alent doses. These findings demonstrate an antidepressant mechanism for zotepine which may contribute to its beneficial clinical profile.
165-69 1 Antipsychotics haloperidol and rlsperldone and psychotomimetic amphetamine affect neuropeptldes and monoamlnes Susanne H.M. Gruber, A.A. Mathe. Karollnska InstItute, Inst Clin Neuroscience, St G6ran's HospItal, Stockholm. Sweden Background and RaUonale: Neuropeptides are stored and co-released with classical neurotransmitters In CNS. CBlwonln gene-related peptide, neuropeptlde Y and neurotensin are of particular interest In the study of psychotic disorders as they interact with dopamine (DA) and noradrenaline (NA) in selected brain regions. Previously we found that psychotomimetics, such as amphetamine as well as MK-801 and phencyclidine affect both tissue and microdialysate peptide concentrations. Consequently we decided to explore whether antipsychotic drugs also have an effect on peptldes and if those actions are of pathophYSiologic and/or therapeutic relevance. experimental Design: Rats were fed chow supplemented with haloperi• dol (1.15 or 2.3 mgl100 glood), risperidone (1.15 mg/100 g food), or vehicle. After 30 days the rats were assigned to one of the two subgroups: (1) animals were sacrificed, the brains dissected into hypothalamus, frontal cortex, stria• tum. occipital cortex and hippocampus and the peptides and monoamines extracted from the same samples. CGRP, NPY and NT were measured with AlA and CA, COPAC, HVA, serotonin, 5-HIAA, NA and MHPG measured with rp-HPLC, (2) ventral segmental area was microdialysed and the samples col· lected before and after injection of amphetamine (1.5 mglkg) or saline. Results: Complicated pattem of neuropeptide and monoamine changes, both in tissues and dialysates emerged and will be presented. Conclusion: We have shown that both antipsychotics and psychotomimet• ics affect neuropeptide tissue concentrations in and release from brain regions. The findings indicate a novel property of these compounds. Supported by the Swedish Medical Aesearch Council, 1110414, Karolin• lka Institute and the Swedish Medical AssociationlSc5derstrOm·KOnigska Foundation.
165-70 I Distribution of fos expression Induced by
long-acting haloperidol decanoate treatment In rat brain
chronic haloperidol-treated rats also Induced comparable increases in Fos ImmunoreaClJvlty In most of these areas. The rats treated with acute vehicle after chronic haloperidol showed persistent Fos increases in the confined brain regions including the amygdala, lateral septum, and entorhinal cortex. The persisting effects of haloperidol in the amygdala. lateral septum and entorhlnaJ area may be of significance to the efficacy of long-term hal~ treatment
165-71
I Clozaplne - A survey of protocols and prescribing
A. Thampi, S.J. Cooper. Department of Mental Health, Queen's University of Belfast, N Ireland The Aim of this survey was to assess adherence to locally agreed prescribing
protocols and identify problems encountered. Methods: note review and patient Interviews were used to COllect data on all patients commenced on clozapine since 1990 in a Belfast psychiatric unit. Results: A total of 23 patients were identified. The mean duration of illness prior to clozapine treatment was eight years with an average eight previous admissions. All patients had received trials of two neuroleptics prior to treatment and 65% had received doses greater than 1000 chlorpromazine eqUivalents. The mean duration 01 treatment with clozapine was 19 months with 57% receiving doses greater than 300 mg and a mean dose of 364 mg. In this group, 53% showed good response and 30% partial response to treatment Eighty-seven percent had documented side effects, most commonly Sedation (48%) and sialorrhoea (26%). Seven patients were w~hdrawn from c10zapine treatment. Patients reported high levels of satisfaction with treatment in terms of reduced symptoms. While some knowledge of side effects was knowledge of relative risks were inaccurate. Conclusions: this survey confirmed adherence to prescribing ProtOCOls and identified high levels of patient satisfaction with c10zapine treatment
case
common.
165-721
Continual antipsychotic therapy 8S a condition for the maintenance of remission In schizophrenic patients
Lj. TrajanovlC, O. tiki~. O. Skaki~. ClInic for Mental Health, Clinical Center Ni6. N/~, Yugoslavia
The most frequent question, that schizophrenic patients asked for, is why they have to take drugs after the acute episode of disease is improved. The aim of this research is to show that the continuity of antipsychotic drugs treatment significantly Impacts the maintenance of remission period of schizophrenia, and so gives the answer to the question mentioned above. Method: The 60 SCH patients were followed one year after the improve• ment of the last acute episode of disease. With all 60 subjects maintenance antipsychotic drug therapy was recommended. Resulta: After one year period, 30 subjects had the remission that lasted 12 months, other 30 had the relapse of the disease. In the first group 24 patients were taking their medication continuously. In the Second group ~Iy 10 patients were taking antipsychotic drugs, while 20 of them spontan~ and self-Initiatively stopped taking their drugs. Statistical data processing shows that continuity and regularity in maintenance antipsychotic medication: one year after the last episode of SCH disease, is statistically very significant (p < 0.001) factor for the maintenance of remission In a chronic SCH patients. This research also gives the evidence about the justification of the antipsychotic long-term treatment of SCH.
Y.oJ. Sun, M. SUZUki, M. Murata, M. Kurachi. Department of NeuropsychIatry. Toyama Medical and Pharmaceutical UniversIty, Toyama, Japan
165-731
To identify sites of antipsychotic drug action, effects of haloperidol decanoate on Fos protein expression in rat brain regions were examined immunohis• tochemically. Male Wlstar rats were injected with haloperidol decanoate (40 mglkg, I.m.) or vehicle. Fourteen days after the injection, each rat received acute administration with either haloperidol (0.25 mglkg) or vehicle Intramus• cularly, and was perfused 2 hours after the last injection. A single dose of haloperidol to the chronic vehicle-treated rats produced significant increases in Fos positive neurons in the several cortical areas, caudate-putamen, nucleus accumbens, lateral septum, hippocampal areas, amygdala, and mecencephalic dopaminergic nuclei. Additional haloperidol injection to the
L Femil.ndez-Novoa, L. Corzo, X.A. Alvarez, R. Cacabelos. EuroEspes BiomedIcal Research Center. La Coruna, Spain
Whole blood and serum histamine In healthy subjects and In schizophrenic patients: Correlation analysis with transcranlal Doppler Ultrasonography
Schizophrenia Is a psychiatric disorder thet affects 1% of the POPUlation. In this study, we evaluated the correlations between whole blood (BHA) and serum histamine (SHA), and transcranial Doppler Ultrasonography (TCO parameters in healthy subjects (C) and In schizophrenic patients (SCHj) In previous studies, we observed that SChizophrenic patients shoWed ~ decrease In resistance (RI) and pulsatility (PI) Indices and an Increase • the effective pulsatility range (EPA) in both middle cerebral arteries (MeAi.
Poster session m
BIOL. PSYCHIATRY 1991;42:IS--mS
(Petit et ai, 1996, Psychopharmacol BuU, 32, 61), is particularly effective In treating anxiety/depression in schlzophrenlc patients (ibid; Fleischhacker et ai, 1969, Psychopharmacol Bull, 25. 97). Here, we examine zotepine in models predictive of antidepressant activity. Methods: Male, CD rats (-200 g) or CD1 mice (-25 g) were used in all tests. For behaviour. zotepine was administered po, 1 h before test evaluation. Reserpine hypothermia (RH), Porsolt swim test (PS) and reserpine ptosis (RP) were determined as previously (Luscombe et ai, 1993 Neuropharmacology, 26, 129). Noradrenaline (NA) uptake In rat cortical synaptosomes in vitro was adapted (ibId). Catalepsy was measured as descnbed (Needham et ai, 1996, pSychopharmacol Bull. 32, 126). Results: Zotepine inhibited NA uptake (Ki '" 21 nM), reversed RH (EDso 26 mglkg) and increased PS motility (100 mglkg). RP was unaffected by 30 mglkg, (am~riptyline RP EDso • 48 mglkg); at higher doses, zotepine alone caused ptosis. Catalepsy EDso values for zotepine, in rat and mouse, were 31 and 26 mglkg, po. respectively. Discussion: RH data are consistent with zotepine's potent inhibition of NA uptake, but Increases in motility were surprising in view of the catalepsy EDso, and are in marked contrast to the neuroleptic chlorpromazine, which also Inhibits NA uptake, but decreases motility in the Porsolt test at eqUiv• alent doses. These findings demonstrate an antidepressant mechanism for zotepine which may contribute to its beneficial clinical profile.
165-69 1 Antipsychotics haloperidol and rlsperldone and psychotomimetic amphetamine affect neuropeptldes and monoamlnes Susanne H.M. Gruber, A.A. Mathe. Karollnska InstItute, Inst Clin Neuroscience, St G6ran's HospItal, Stockholm. Sweden Background and RaUonale: Neuropeptides are stored and co-released with classical neurotransmitters In CNS. CBlwonln gene-related peptide, neuropeptlde Y and neurotensin are of particular interest In the study of psychotic disorders as they interact with dopamine (DA) and noradrenaline (NA) in selected brain regions. Previously we found that psychotomimetics, such as amphetamine as well as MK-801 and phencyclidine affect both tissue and microdialysate peptide concentrations. Consequently we decided to explore whether antipsychotic drugs also have an effect on peptldes and if those actions are of pathophYSiologic and/or therapeutic relevance. experimental Design: Rats were fed chow supplemented with haloperi• dol (1.15 or 2.3 mgl100 glood), risperidone (1.15 mg/100 g food), or vehicle. After 30 days the rats were assigned to one of the two subgroups: (1) animals were sacrificed, the brains dissected into hypothalamus, frontal cortex, stria• tum. occipital cortex and hippocampus and the peptides and monoamines extracted from the same samples. CGRP, NPY and NT were measured with AlA and CA, COPAC, HVA, serotonin, 5-HIAA, NA and MHPG measured with rp-HPLC, (2) ventral segmental area was microdialysed and the samples col· lected before and after injection of amphetamine (1.5 mglkg) or saline. Results: Complicated pattem of neuropeptide and monoamine changes, both in tissues and dialysates emerged and will be presented. Conclusion: We have shown that both antipsychotics and psychotomimet• ics affect neuropeptide tissue concentrations in and release from brain regions. The findings indicate a novel property of these compounds. Supported by the Swedish Medical Aesearch Council, 1110414, Karolin• lka Institute and the Swedish Medical AssociationlSc5derstrOm·KOnigska Foundation.
165-70 I Distribution of fos expression Induced by
long-acting haloperidol decanoate treatment In rat brain
chronic haloperidol-treated rats also Induced comparable increases in Fos ImmunoreaClJvlty In most of these areas. The rats treated with acute vehicle after chronic haloperidol showed persistent Fos increases in the confined brain regions including the amygdala, lateral septum, and entorhinal cortex. The persisting effects of haloperidol in the amygdala. lateral septum and entorhlnaJ area may be of significance to the efficacy of long-term hal~ treatment
165-71
I Clozaplne - A survey of protocols and prescribing
A. Thampi, S.J. Cooper. Department of Mental Health, Queen's University of Belfast, N Ireland The Aim of this survey was to assess adherence to locally agreed prescribing
protocols and identify problems encountered. Methods: note review and patient Interviews were used to COllect data on all patients commenced on clozapine since 1990 in a Belfast psychiatric unit. Results: A total of 23 patients were identified. The mean duration of illness prior to clozapine treatment was eight years with an average eight previous admissions. All patients had received trials of two neuroleptics prior to treatment and 65% had received doses greater than 1000 chlorpromazine eqUivalents. The mean duration 01 treatment with clozapine was 19 months with 57% receiving doses greater than 300 mg and a mean dose of 364 mg. In this group, 53% showed good response and 30% partial response to treatment Eighty-seven percent had documented side effects, most commonly Sedation (48%) and sialorrhoea (26%). Seven patients were w~hdrawn from c10zapine treatment. Patients reported high levels of satisfaction with treatment in terms of reduced symptoms. While some knowledge of side effects was knowledge of relative risks were inaccurate. Conclusions: this survey confirmed adherence to prescribing ProtOCOls and identified high levels of patient satisfaction with c10zapine treatment
case
common.
165-721
Continual antipsychotic therapy 8S a condition for the maintenance of remission In schizophrenic patients
Lj. TrajanovlC, O. tiki~. O. Skaki~. ClInic for Mental Health, Clinical Center Ni6. N/~, Yugoslavia
The most frequent question, that schizophrenic patients asked for, is why they have to take drugs after the acute episode of disease is improved. The aim of this research is to show that the continuity of antipsychotic drugs treatment significantly Impacts the maintenance of remission period of schizophrenia, and so gives the answer to the question mentioned above. Method: The 60 SCH patients were followed one year after the improve• ment of the last acute episode of disease. With all 60 subjects maintenance antipsychotic drug therapy was recommended. Resulta: After one year period, 30 subjects had the remission that lasted 12 months, other 30 had the relapse of the disease. In the first group 24 patients were taking their medication continuously. In the Second group ~Iy 10 patients were taking antipsychotic drugs, while 20 of them spontan~ and self-Initiatively stopped taking their drugs. Statistical data processing shows that continuity and regularity in maintenance antipsychotic medication: one year after the last episode of SCH disease, is statistically very significant (p < 0.001) factor for the maintenance of remission In a chronic SCH patients. This research also gives the evidence about the justification of the antipsychotic long-term treatment of SCH.
Y.oJ. Sun, M. SUZUki, M. Murata, M. Kurachi. Department of NeuropsychIatry. Toyama Medical and Pharmaceutical UniversIty, Toyama, Japan
165-731
To identify sites of antipsychotic drug action, effects of haloperidol decanoate on Fos protein expression in rat brain regions were examined immunohis• tochemically. Male Wlstar rats were injected with haloperidol decanoate (40 mglkg, I.m.) or vehicle. Fourteen days after the injection, each rat received acute administration with either haloperidol (0.25 mglkg) or vehicle Intramus• cularly, and was perfused 2 hours after the last injection. A single dose of haloperidol to the chronic vehicle-treated rats produced significant increases in Fos positive neurons in the several cortical areas, caudate-putamen, nucleus accumbens, lateral septum, hippocampal areas, amygdala, and mecencephalic dopaminergic nuclei. Additional haloperidol injection to the
L Femil.ndez-Novoa, L. Corzo, X.A. Alvarez, R. Cacabelos. EuroEspes BiomedIcal Research Center. La Coruna, Spain
Whole blood and serum histamine In healthy subjects and In schizophrenic patients: Correlation analysis with transcranlal Doppler Ultrasonography
Schizophrenia Is a psychiatric disorder thet affects 1% of the POPUlation. In this study, we evaluated the correlations between whole blood (BHA) and serum histamine (SHA), and transcranial Doppler Ultrasonography (TCO parameters in healthy subjects (C) and In schizophrenic patients (SCHj) In previous studies, we observed that SChizophrenic patients shoWed ~ decrease In resistance (RI) and pulsatility (PI) Indices and an Increase • the effective pulsatility range (EPA) in both middle cerebral arteries (MeAi.