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P.3.d.028 Effectiveness and tolerability of nalmefene in alcohol use dependence comorbid with schizophrenia
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P.3.d. Psychotic disorders and treatment − Treatment (clinical)
References [1] Takekita Y., Kato M., Wakeno M., Sakai S., Suwa A., Nishida K., Okugawa G., Kinoshita T., 2013 A 12-week randomized, open-label study of perospirone versus aripiprazole in the treatment of Japanese schizophrenia patients. Prog Neuropsychopharmacol Biol Psychiatry. Jan 10; 40: 110−4. Disclosure statement: This work was supported by a grant from the Promotion and Mutual Aid Corporation for Private Schools of Japan and Grant-in-Aid for Scientific Research (no. 23791357).
P.3.d.028 Effectiveness and tolerability of nalmefene in alcohol use dependence comorbid with schizophrenia D. Vasile1 ° , O. Vasiliu1 , G.A. Sopterean1 , R.E. Bratu1 , F. Androne1 , F. Vasile1 1 Emergency University Military Hospital, Psychiatry Clinic, Bucharest, Romania Background: Patients with schizophrenia have a lifetime prevalence of comorbid use disorder of 50% with alcohol having a negative effect on brain structure and function evident in this dual diagnosed population [1]. An administered as-needed drug could be provocative in a sensitive population in terms of insight like that of schizophrenia diagnosed patients. Nalmefene is associated with favorable response in alcohol use disorders and decrease the substance consumption [2] and the same drug was used as augmentation treatment in antipsychotic-stabilized schizophrenic patients with some positive results [3]. Objective: To assess the efficacy of pharmacological management with nalmefene in alcohol dependence and chronic schizophrenia dual diagnosed patients. Methods: A group of 22 patients, 12 female and 10 male, mean age 44.2, diagnosed with schizophrenia and alcohol dependence, according DSM IV TR criteria, were admitted to our department for an exacerbation of schizophrenia. After a mean duration of 2.7 weeks of psychotic symptoms stabilization under treatment with an atypical antipsychotic (olanzapine n = 13, risperidone n = 6, amisulpride n = 3), they received also treatment with nalmefene orally 18 mg taken as needed. Patients’ alcohol consumption was evaluated at baseline and every 4 weeks for 6 months using Inventory of Drug Taking Situations − alcohol focused version (IDTS) and gamma-glutamyl transpeptidase level (GGT). With the same frequency we applied Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and Clinical Global Impressions − Severity/Improvement (CGI-S/I). Inclusion criteria: high drinking risk level (alcohol >60 g/day for men and >40 g/day for women), IDTS score over 100, age between 18 and 65. Exclusion criteria: previous treatment with nalmefene, positive pregnancy test, alcohol withdrawal symptoms, other comorbid axis I disorder (including other drug related/induced disorders) or axis III chronic pathology. Intent-to-treat-analysis and last-observationcarried-forward were used in the statistical processing of data. Results: At week 24, patients had an overall improved PANSS score of 15.4% reported to baseline, with an IDTS score amelioration of 25.4 points at endpoint (p < 0.05) and a greater improvement was observed in the area of ‘physical discomfort’ (p = 0.032). The GGT level decrease with 70% at week 8, had a fluctuant evolution after that, but at week 24 the value was significantly lower compared to baseline (p = 0.002). CGI-S decreased from a mean value of 4.2 to 1.8 at week 24 and the GAF scores increased with 11.5% at endpoint. A number of 4 patients discontinued treatment due to either adverse events (vomiting,
nausea, abdominal pains, n = 3) or non-adherence (n = 1). Mild and moderate adverse events were reported in 12 patients, especially gastro-intestinal discomfort and sedation. Conclusions: Nalmefene could be used in schizophrenia diagnosed patients with alcohol dependence, due to its efficacy and relatively low rate of adverse events. Nalmefene decreased significantly alcohol consumption in situations of ‘physical discomfort’. The psychotic symptoms features had an overall good evolution during the combined antipsychotic and nalmefene treatment. References [1] Thoma P, Daum I. Comorbid use disorder in schizophrenia: a selective overview of neurobiological and cognitive underpinnings. Psychiatry Clin Neurosci 2013; 67(6): 367−83. [2] Sinclair J, Chick J, Soerensen P et al. Can alcohol dependent patients adhere to an ‘as-needed’ medication regimen? Eur Addict Res 2014; 20(5):209–217. [3] Rapaport HM, Wolkowitz O, Kelsoe JR et al. Beneficial effects of nalmefene augmentation in neuroleptic-stabilized schizophrenic patients. Neuropsychopharmacology 1993; 9(2): 111−5. Disclosure statement: The presenting author was speaker for Astra Zeneca, Bristol Myers Squibb, CSC Pharmaceuticals, Eli Lilly, Janssen Cilag, Lundbeck, Organon, Pfizer, Servier, Sanofi Aventis and participated in clinical research funded by Janssen Cilag, Astra Zeneca, Eli Lilly, Sanofi Aventis, Schering Plough, Organon, Bioline Rx, Forenap, Wyeth, Otsuka Pharmaceuticals, Dainippon Sumitomo, Servier.
P.3.d.029 Analyzing the efficacy of second-generation antipsychotic drugs in treatment-resistant schizophrenia: a meta-analysis M. Dold1 ° , S. Leucht1 1 Technical University Munich, Psychiatry and Psychotherapy, Munich, Germany Background: As treatment resistance to antipsychotic drugs is very common in schizophrenia, the investigation of pharmacological options in this condition is clinically highly meaningful. Ambiguity exists in this context especially regarding the role of the second-generation antipsychotics (SGAs). Therefore, we conducted a meta-analysis to determine their efficacy, acceptability and tolerability in therapy-refractory schizophrenia. Methods: We included all published and unpublished blinded randomized controlled trials (RCTs) that compared SGAs with first-generation antipsychotics (FGAs) and SGA head-to-head in treatment-resistant schizophrenia. The literature search was mainly based on the Cochrane Schizophrenia Group trial register and followed the methodological standard of the Cochrane Collaboration. Primary outcome was overall antipsychotic efficacy measured by mean changes in the Positive and Negative Syndrome Scale [PANSS] total score or Brief Psychiatric Rating Scale [BPRS] total score. Secondary endpoints were positive and negative schizophrenic symptoms as well as all-cause discontinuation. Standardized mean differences Hedges’s g were calculated for continuous outcomes and risk ratios for dichotomous outcomes. We used the random-effects model of Der-Simonian and Laired to pool the individual RVTs. Heterogeneity was explored statistically with I2 statistic and chi2 test of homogeneity. Publication bias was examined by funnel-plot visualization and Egger‘s regression intercept test. The effect of the clozapine dose on the primary outcome was evaluated by maximum-likelihood meta-regressions. Results: All in all, we included 35 RCTs with 42 direct drug comparisons and 4997 participants. Clozapine was the most frequently investigated drug (N = 19, n = 1121) followed by olanzapine (N = 14, n = 792), risperidone (N = 12, n = 485) and haloperidol (N = 11, n = 755). In terms of overall antipsychotic efficacy,
P.3.d. Psychotic disorders and treatment − Treatment (clinical)
References [1] Takekita Y., Kato M., Wakeno M., Sakai S., Suwa A., Nishida K., Okugawa G., Kinoshita T., 2013 A 12-week randomized, open-label study of perospirone versus aripiprazole in the treatment of Japanese schizophrenia patients. Prog Neuropsychopharmacol Biol Psychiatry. Jan 10; 40: 110−4. Disclosure statement: This work was supported by a grant from the Promotion and Mutual Aid Corporation for Private Schools of Japan and Grant-in-Aid for Scientific Research (no. 23791357).
P.3.d.028 Effectiveness and tolerability of nalmefene in alcohol use dependence comorbid with schizophrenia D. Vasile1 ° , O. Vasiliu1 , G.A. Sopterean1 , R.E. Bratu1 , F. Androne1 , F. Vasile1 1 Emergency University Military Hospital, Psychiatry Clinic, Bucharest, Romania Background: Patients with schizophrenia have a lifetime prevalence of comorbid use disorder of 50% with alcohol having a negative effect on brain structure and function evident in this dual diagnosed population [1]. An administered as-needed drug could be provocative in a sensitive population in terms of insight like that of schizophrenia diagnosed patients. Nalmefene is associated with favorable response in alcohol use disorders and decrease the substance consumption [2] and the same drug was used as augmentation treatment in antipsychotic-stabilized schizophrenic patients with some positive results [3]. Objective: To assess the efficacy of pharmacological management with nalmefene in alcohol dependence and chronic schizophrenia dual diagnosed patients. Methods: A group of 22 patients, 12 female and 10 male, mean age 44.2, diagnosed with schizophrenia and alcohol dependence, according DSM IV TR criteria, were admitted to our department for an exacerbation of schizophrenia. After a mean duration of 2.7 weeks of psychotic symptoms stabilization under treatment with an atypical antipsychotic (olanzapine n = 13, risperidone n = 6, amisulpride n = 3), they received also treatment with nalmefene orally 18 mg taken as needed. Patients’ alcohol consumption was evaluated at baseline and every 4 weeks for 6 months using Inventory of Drug Taking Situations − alcohol focused version (IDTS) and gamma-glutamyl transpeptidase level (GGT). With the same frequency we applied Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and Clinical Global Impressions − Severity/Improvement (CGI-S/I). Inclusion criteria: high drinking risk level (alcohol >60 g/day for men and >40 g/day for women), IDTS score over 100, age between 18 and 65. Exclusion criteria: previous treatment with nalmefene, positive pregnancy test, alcohol withdrawal symptoms, other comorbid axis I disorder (including other drug related/induced disorders) or axis III chronic pathology. Intent-to-treat-analysis and last-observationcarried-forward were used in the statistical processing of data. Results: At week 24, patients had an overall improved PANSS score of 15.4% reported to baseline, with an IDTS score amelioration of 25.4 points at endpoint (p < 0.05) and a greater improvement was observed in the area of ‘physical discomfort’ (p = 0.032). The GGT level decrease with 70% at week 8, had a fluctuant evolution after that, but at week 24 the value was significantly lower compared to baseline (p = 0.002). CGI-S decreased from a mean value of 4.2 to 1.8 at week 24 and the GAF scores increased with 11.5% at endpoint. A number of 4 patients discontinued treatment due to either adverse events (vomiting,
nausea, abdominal pains, n = 3) or non-adherence (n = 1). Mild and moderate adverse events were reported in 12 patients, especially gastro-intestinal discomfort and sedation. Conclusions: Nalmefene could be used in schizophrenia diagnosed patients with alcohol dependence, due to its efficacy and relatively low rate of adverse events. Nalmefene decreased significantly alcohol consumption in situations of ‘physical discomfort’. The psychotic symptoms features had an overall good evolution during the combined antipsychotic and nalmefene treatment. References [1] Thoma P, Daum I. Comorbid use disorder in schizophrenia: a selective overview of neurobiological and cognitive underpinnings. Psychiatry Clin Neurosci 2013; 67(6): 367−83. [2] Sinclair J, Chick J, Soerensen P et al. Can alcohol dependent patients adhere to an ‘as-needed’ medication regimen? Eur Addict Res 2014; 20(5):209–217. [3] Rapaport HM, Wolkowitz O, Kelsoe JR et al. Beneficial effects of nalmefene augmentation in neuroleptic-stabilized schizophrenic patients. Neuropsychopharmacology 1993; 9(2): 111−5. Disclosure statement: The presenting author was speaker for Astra Zeneca, Bristol Myers Squibb, CSC Pharmaceuticals, Eli Lilly, Janssen Cilag, Lundbeck, Organon, Pfizer, Servier, Sanofi Aventis and participated in clinical research funded by Janssen Cilag, Astra Zeneca, Eli Lilly, Sanofi Aventis, Schering Plough, Organon, Bioline Rx, Forenap, Wyeth, Otsuka Pharmaceuticals, Dainippon Sumitomo, Servier.
P.3.d.029 Analyzing the efficacy of second-generation antipsychotic drugs in treatment-resistant schizophrenia: a meta-analysis M. Dold1 ° , S. Leucht1 1 Technical University Munich, Psychiatry and Psychotherapy, Munich, Germany Background: As treatment resistance to antipsychotic drugs is very common in schizophrenia, the investigation of pharmacological options in this condition is clinically highly meaningful. Ambiguity exists in this context especially regarding the role of the second-generation antipsychotics (SGAs). Therefore, we conducted a meta-analysis to determine their efficacy, acceptability and tolerability in therapy-refractory schizophrenia. Methods: We included all published and unpublished blinded randomized controlled trials (RCTs) that compared SGAs with first-generation antipsychotics (FGAs) and SGA head-to-head in treatment-resistant schizophrenia. The literature search was mainly based on the Cochrane Schizophrenia Group trial register and followed the methodological standard of the Cochrane Collaboration. Primary outcome was overall antipsychotic efficacy measured by mean changes in the Positive and Negative Syndrome Scale [PANSS] total score or Brief Psychiatric Rating Scale [BPRS] total score. Secondary endpoints were positive and negative schizophrenic symptoms as well as all-cause discontinuation. Standardized mean differences Hedges’s g were calculated for continuous outcomes and risk ratios for dichotomous outcomes. We used the random-effects model of Der-Simonian and Laired to pool the individual RVTs. Heterogeneity was explored statistically with I2 statistic and chi2 test of homogeneity. Publication bias was examined by funnel-plot visualization and Egger‘s regression intercept test. The effect of the clozapine dose on the primary outcome was evaluated by maximum-likelihood meta-regressions. Results: All in all, we included 35 RCTs with 42 direct drug comparisons and 4997 participants. Clozapine was the most frequently investigated drug (N = 19, n = 1121) followed by olanzapine (N = 14, n = 792), risperidone (N = 12, n = 485) and haloperidol (N = 11, n = 755). In terms of overall antipsychotic efficacy,