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Safety, efficacy and quality of life of olanzapine in first-episode schizophrenia — Results of the EFESO study
P.2. Psychotic disorders and antipsychotics
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menstrual irregularities of 30.3 (SD 23.9) months, and a mean BMI of 29.7 (SD 8.71). The BMD was significantly reduced in trabecular bone of the forearm (mean T-score: -0.80, CI: -1.19;-0.40, p<0.002)/mean Z-score: -0.73, CI:-1.14;-0.32, p<0.003) but not at other sites. Trabecular forearm values did not correlate with cortical forearm or values from other skeletal sites who all correlated significantly with each other. Ovarian hormone, LH and FSH levels were consistent with prolactin-induced anovulation in all cases. Mean prolactin levels were 1252 (SD 795.5) mU/L and significantly negatively correlated with BMD in all selected skeletal sites except for the forearm trabecular bone which only showed a tendency towards correlation. There was no significant relationship of any bone measurements with age, BMI, exercise levels, alcohol and nicotine intake, duration of menstrual irregularity, or measures of bone metabolism. Conclusion: The data indicate that women with antipsychoticinduced hyperprolactinaemia and amenorrhoea or oligomenorrhoea of 12 or more months duration have significantly decreased BMD in the trabecular bone of the forearm. The absence of effects on other bone sites may be explained by the relatively short duration of ovarian dysfunction, the greater sensitivity of trabecular as compared to cortical bone to oestrogen deficiency and the superiority of CT measurements.
Olanzapine-treated patients also showed significantly improved AWAD scores. Conclusions: In first-episode schizophrenics, olanzapine was efficient, had a low incidence of extrapyramidal symptoms, and improved quality of life and subjective acceptance of medication factors that are associated to better treatment-adherence 2-3.
References [1] G6mezJC, SacristanJA, Hern~indezJ, Breier A, Ruiz Carrasco P, Anton Saiz C, FontovaCarbonell E: The safety of olanzapine compared with other antipsychoticdrugs: results of an observationalprospective study in patients with schizophrenia(EFESO study). J Clin Psychiatry 2000; 61:335-343. [2] Kampman O, Lehtinen K: Compliance in psychoses. Acta Psychiatr Scand 1999; 100:167-175. [3] Hogan TP, Awad AG, Eastwood R: A self-report scale predictive of drug compliancein schizophrenics:reliability and discriminantvalidity. Psychol Med 1983; 13:177-183.
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Reboxetine but not fluoxetine attenuates olanzapine-induced weight gain in first-episode schizophrenia patients
M. Poyurovsky 1, I. Isaaks 2, A. Pashnian2, C. Fuchs 3, M. Schneidman1, S. Faragian 1, R. Weizman4, A. Weizman5.
1Tirat Carmel Mental Health Center, Tirat Carmel, Israel; 2~rat Carmel Mental Health Center, Department of First References Admission, Tirat Carmel, Israel, 3Tel Aviv University, Department [1] Wieck A & Haddad P (2002) Hyperprolactinaemiacaused by matipsy- of Statistics and Operations Research, Tel-Avio, Israel," 4Ramat Chen Psychiatric Clinic, Tel-Aviv, Israel," 5Geha Psychiatric chotic drugs. BMJ, 324: 250-252. [2] Schlechte J (1995) Clinical impact of hyperprolactinaemia. Bailleres Hospital, Research Unit, Petah Tiqva, Israel Clin Endocrin Metab, 9 (2): 35~366.
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Safety, efficacy and quality of life of olanzapine in first-episode schizophrenia - Results of the EFESO study
A. Ciudad 1, J.M. Montes2, J. Gasc6n3, J.-C. G6mez 1. EFESO
Study Group. 1Lilly Research Laboratories, Madrid, Spain," eUniversidad de Almeria, Almeria, Spain," 3Hospital Mutua de Tarrasa, Tarrasa, Spain Objective: Treatment of first-episode schizophrenia requires an antipsychotic that offers efficacy and good tolerance in order to improve quality of life and prevent relapses due to noncompliance. This study evaluates the efficacy, safety, and quality of life offered by olanzapine in first-episode schizophrenia. Method: One hundred eighty-two first-episode schizophrenics (ICD-10) drawn from a larger naturalistic, open-label, nonrandomized, comparative study (EFESO 1) were evaluated after six months of treatment with olanzapine, risperidone, or conventional antipsychotics (CA). Clinical status was assessed using the Clinical Global Impression-Severity (CGI-S) and Global Assessment of Function (GAF) scales. The AWAD and EuroQol scales assessed patients' attitude towards medication and quality of life, respectively. Results: Olanzapine, risperidone, and CA similarly reduced CGI-S scores, whereas olanzapine and risperidone showed significantly greater increases in the GAF scores. Treatment-emergent, extrapyramidal symptoms were significantly lower in olanzapinetreated patients (17.8 %) than in the risperidone (46.4 %) and CA (62.2 %) groups. Compared to CA, olanzapine and risperidone showed significantly higher increases in EuroQol scores.
Objective: Though the pathophysiological mechanisms that underlie antipsychotic drug induced weight gain are yet to be determined, serotonergic and noradrinergic systems appear to be involved. Olanzapine and clozapine have the greatest potential of all atypical antipsychotics to induce weight gain. Previously untreated first episode schizophrenia patients seem to be particularly vulnerable to olanzapine-induced weight gain. In a series of randomized controlled trials we aimed to determine the putative weight attenuating affect of the selective norepinephrine reuptake inhibitor (NRI) reboxetine and the selective serotonin reuptake inhibitor (SSRI) fluoxetine in first episode schizophrenia patients treated with olanzapine. Method: Subjects for both studies were enrolled from the same facility (Tirat Carmel MHC) and included a consecutive sample of first-episode DSM-IV hospitalized schizophrenia patients. Study 1:30 first-episode hospitalized schizophrenia patients were randomly assigned in an eight weeks double-blind design, olanzapine (10 mg/day) coadministered with either fluoxetine (20 mg/day; n=15) or placebo (n=15) (Poyurovsky et al, 2002A). Study 2: 26 patients hospitalized for first-episode DSM-IV schizophrenic disorder were enrolled and randomly allocated in a double-blind design to receive olanzapine (10 rag/day) coadministered with either reboxetine (2 mg/day b.i.d, n=13) or placebo (b.i.d., n=13) for six weeks (Poyurovsky et al, 2002B). Results: Study 1: The olanzapine/fluoxetine group showed significantly less improvement on positive and disorganized dimensions than the olanzapine/placebo group. Both groups demonstrated similar substantial gradual weight gain (7.94-4.6 kg in the olanzapine + fluoxetine group and 6.0+4.2 kg in the olanzapine + placebo group (t=0.78; dr=22; p=0.44, NS). Study 2: Olanzapine/reboxetine completers (n=10) demonstrated significantly lower increase in body weight over the 6-week
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menstrual irregularities of 30.3 (SD 23.9) months, and a mean BMI of 29.7 (SD 8.71). The BMD was significantly reduced in trabecular bone of the forearm (mean T-score: -0.80, CI: -1.19;-0.40, p<0.002)/mean Z-score: -0.73, CI:-1.14;-0.32, p<0.003) but not at other sites. Trabecular forearm values did not correlate with cortical forearm or values from other skeletal sites who all correlated significantly with each other. Ovarian hormone, LH and FSH levels were consistent with prolactin-induced anovulation in all cases. Mean prolactin levels were 1252 (SD 795.5) mU/L and significantly negatively correlated with BMD in all selected skeletal sites except for the forearm trabecular bone which only showed a tendency towards correlation. There was no significant relationship of any bone measurements with age, BMI, exercise levels, alcohol and nicotine intake, duration of menstrual irregularity, or measures of bone metabolism. Conclusion: The data indicate that women with antipsychoticinduced hyperprolactinaemia and amenorrhoea or oligomenorrhoea of 12 or more months duration have significantly decreased BMD in the trabecular bone of the forearm. The absence of effects on other bone sites may be explained by the relatively short duration of ovarian dysfunction, the greater sensitivity of trabecular as compared to cortical bone to oestrogen deficiency and the superiority of CT measurements.
Olanzapine-treated patients also showed significantly improved AWAD scores. Conclusions: In first-episode schizophrenics, olanzapine was efficient, had a low incidence of extrapyramidal symptoms, and improved quality of life and subjective acceptance of medication factors that are associated to better treatment-adherence 2-3.
References [1] G6mezJC, SacristanJA, Hern~indezJ, Breier A, Ruiz Carrasco P, Anton Saiz C, FontovaCarbonell E: The safety of olanzapine compared with other antipsychoticdrugs: results of an observationalprospective study in patients with schizophrenia(EFESO study). J Clin Psychiatry 2000; 61:335-343. [2] Kampman O, Lehtinen K: Compliance in psychoses. Acta Psychiatr Scand 1999; 100:167-175. [3] Hogan TP, Awad AG, Eastwood R: A self-report scale predictive of drug compliancein schizophrenics:reliability and discriminantvalidity. Psychol Med 1983; 13:177-183.
•
Reboxetine but not fluoxetine attenuates olanzapine-induced weight gain in first-episode schizophrenia patients
M. Poyurovsky 1, I. Isaaks 2, A. Pashnian2, C. Fuchs 3, M. Schneidman1, S. Faragian 1, R. Weizman4, A. Weizman5.
1Tirat Carmel Mental Health Center, Tirat Carmel, Israel; 2~rat Carmel Mental Health Center, Department of First References Admission, Tirat Carmel, Israel, 3Tel Aviv University, Department [1] Wieck A & Haddad P (2002) Hyperprolactinaemiacaused by matipsy- of Statistics and Operations Research, Tel-Avio, Israel," 4Ramat Chen Psychiatric Clinic, Tel-Aviv, Israel," 5Geha Psychiatric chotic drugs. BMJ, 324: 250-252. [2] Schlechte J (1995) Clinical impact of hyperprolactinaemia. Bailleres Hospital, Research Unit, Petah Tiqva, Israel Clin Endocrin Metab, 9 (2): 35~366.
•
Safety, efficacy and quality of life of olanzapine in first-episode schizophrenia - Results of the EFESO study
A. Ciudad 1, J.M. Montes2, J. Gasc6n3, J.-C. G6mez 1. EFESO
Study Group. 1Lilly Research Laboratories, Madrid, Spain," eUniversidad de Almeria, Almeria, Spain," 3Hospital Mutua de Tarrasa, Tarrasa, Spain Objective: Treatment of first-episode schizophrenia requires an antipsychotic that offers efficacy and good tolerance in order to improve quality of life and prevent relapses due to noncompliance. This study evaluates the efficacy, safety, and quality of life offered by olanzapine in first-episode schizophrenia. Method: One hundred eighty-two first-episode schizophrenics (ICD-10) drawn from a larger naturalistic, open-label, nonrandomized, comparative study (EFESO 1) were evaluated after six months of treatment with olanzapine, risperidone, or conventional antipsychotics (CA). Clinical status was assessed using the Clinical Global Impression-Severity (CGI-S) and Global Assessment of Function (GAF) scales. The AWAD and EuroQol scales assessed patients' attitude towards medication and quality of life, respectively. Results: Olanzapine, risperidone, and CA similarly reduced CGI-S scores, whereas olanzapine and risperidone showed significantly greater increases in the GAF scores. Treatment-emergent, extrapyramidal symptoms were significantly lower in olanzapinetreated patients (17.8 %) than in the risperidone (46.4 %) and CA (62.2 %) groups. Compared to CA, olanzapine and risperidone showed significantly higher increases in EuroQol scores.
Objective: Though the pathophysiological mechanisms that underlie antipsychotic drug induced weight gain are yet to be determined, serotonergic and noradrinergic systems appear to be involved. Olanzapine and clozapine have the greatest potential of all atypical antipsychotics to induce weight gain. Previously untreated first episode schizophrenia patients seem to be particularly vulnerable to olanzapine-induced weight gain. In a series of randomized controlled trials we aimed to determine the putative weight attenuating affect of the selective norepinephrine reuptake inhibitor (NRI) reboxetine and the selective serotonin reuptake inhibitor (SSRI) fluoxetine in first episode schizophrenia patients treated with olanzapine. Method: Subjects for both studies were enrolled from the same facility (Tirat Carmel MHC) and included a consecutive sample of first-episode DSM-IV hospitalized schizophrenia patients. Study 1:30 first-episode hospitalized schizophrenia patients were randomly assigned in an eight weeks double-blind design, olanzapine (10 mg/day) coadministered with either fluoxetine (20 mg/day; n=15) or placebo (n=15) (Poyurovsky et al, 2002A). Study 2: 26 patients hospitalized for first-episode DSM-IV schizophrenic disorder were enrolled and randomly allocated in a double-blind design to receive olanzapine (10 rag/day) coadministered with either reboxetine (2 mg/day b.i.d, n=13) or placebo (b.i.d., n=13) for six weeks (Poyurovsky et al, 2002B). Results: Study 1: The olanzapine/fluoxetine group showed significantly less improvement on positive and disorganized dimensions than the olanzapine/placebo group. Both groups demonstrated similar substantial gradual weight gain (7.94-4.6 kg in the olanzapine + fluoxetine group and 6.0+4.2 kg in the olanzapine + placebo group (t=0.78; dr=22; p=0.44, NS). Study 2: Olanzapine/reboxetine completers (n=10) demonstrated significantly lower increase in body weight over the 6-week