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Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
This metabolic vulnerability is probably determined by multiple biological factors, but the nature of these factors is uncertain. Methods: Using an archival follow-forward design, metabolic data were sampled using medical records from 25 randomly selected clozapine treated inpatients. Sampling period included 3-years of first generation antipsychotic (FGA) treatment followed by 3-years of clozapine treatment. Prior to clozapine, subjects were treated only with FGAs. Results: During FGA treatment, 32% of subjects met MS criteria. This increased to 64% with clozapine treatment (p < 0.003), primarily resulting from increases in fasting glucose and triglyceride levels. Mean body mass measures were stable over time. Females starting clozapine treatment after 45 years of age had significantly higher fasting glucose levels than the other groups. Correlations among MS measures were modest at best. Conclusions: Clozapine is associated with increased MS risk – but the underlying causes are uncertain. Prior metabolic history is crucial for interpreting these estimates. Women, and especially those who were older when clozapine was initiated, are at elevated risk. The lack of correlation among the MS measures was surprising, and may suggest some other common pathway may be involved. We have postulated that insulin regulation may be an important variable. A pilot study is underway to explore the influence of insulin. MS measures are being collected, along with C-peptide and HbA1c within the context of the oral glucose tolerance test. These data will be presented as well. References [1] Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry 2007;68:20-27.
542 – A 16 WEEK RANDOMIZED DOUBLE-BLIND, DOUBLEDUMMY TRIAL OF SUBLINGUALLY DISINTEGRATING OLANZAPINE VS. STANDARD OLANZAPINE TABLETS IN PATIENTS WHO GAINED WEIGHT DURING OLANZAPINE James Karagianis 1 , Loren Grossman 1 , Bobbie Lee 1 , Neerav Monga 1 , Leiuwe de Haan 2 , Gerald Maguire 3 , Roumen Milev 4 , Vicki Poole Hoffmann 5 1 Eli Lilly Canada Inc., Toronto, Ontario, Canada; 2 University of Amsterdam, Amsterdam; 3 University of California, Irvine, Irvine, California; 4 Queens University, Kingston, Ontario; 5 Eli Lilly and Company, Indianapolis, Indiana
[email protected] Introduction: Olanzapine is an efficacious second-generation antipsychotic but a commonly observed adverse event is weight gain (1). Olanzapine is available in two oral dosage forms, standard olanzapine tablets (SOT) and orally disintegrating olanzapine (ODO). Preliminary evidence suggests that ODO may be associated with less weight gain than SOT (2). We report the first double-blind comparison of weight gain and metabolic outcomes in patients treated with SOT or ODO. Methods: A total of 149 patients with schizophrenia, bipolar disorder, and related psychotic disorders were randomly assigned to 16 weeks of treatment with either SOT plus orally disintegrating placebo, or ODO plus placebo tablets. For study entry, patients must have either gained 5 kg or had a minimum 1 kg/m2 increase in Body Mass Index (BMI) during olanzapine treatment over 1 to 12 months. Patients taking medications or having medical conditions that might impact weight control were excluded. The primary outcome measure was baseline to endpoint change in BMI; the change was evaluated using a mixed-effects model repeated measures approach. Secondary outcomes included changes in weight, appetite, fasting glucose, fasting lipids, and metabolic syndrome. Results: About three quarters of patients completed the study in Canada, the Netherlands, US and Mexico. Analysis is pending; primary and secondary results will be presented. Conclusions: Further studies are warranted to more fully understand differences in weight distribution profiles and metabolic outcomes in patients treated with ODO and SOT.
Acknowledgements: This presentation represents a collaboration between Eli Lilly Canada and academic authors. References [1] Allison DB et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999;156:1686-96 [2] Karagianis J et al. Orally disintegrating olanzapine and potential differences in treatment-emergent weight gain. Hum Psychopharmacol Clin Exp in press, 2008.
543 – A RANDOMIZED OPEN-LABEL COMPARISON OF THE IMPACT OF ARIPIPRAZOLE VERSUS RISPERIDONE ON SEXUAL FUNCTIONING (RAS STUDY) Henderikus Knegtering 1 , Han Bous 2 , Sjoerd Syteman 2 , Richard Bruggeman 2 , Durk Wiersma 2 1 University Medical Center Groningen, Groningen; 2 University Medical Center Groningen, University of Groningen, The Netherlands
[email protected] Introduction: Postsynaptic antagonistic effects of aripiprazole on the dopamin system may predict inhibiting effects on sexual performance, in constrast, the agonistic effects may predict a decrease of prolactin elevation and improvement of sexual performance. Sexual side effects of antipsychotics are relevant for patients, their quality of life and treatment adherence. Information on the influence of antipsychotics on sexual performance isof theoretical and clinical relevance. Methods: In an open–label trial patients were randomized to either aripiprazole (7.5-30 mg/day) or risperidone (1-6 mg/day) for 6 weeks. After six weeks sexual dysfunction was assessed by the semi structured Antipsychotic and Sexual Functioning Questionnaire (ASFQ) and serum levels of the antipsychotics, metabolites and prolactin were measured. Results: Three patients (25%) on aripiprazole (N=12, mean dose 14.1 mg/day) reported improvement in sexual functioning, one patient (8%) reported sexual dysfunctions. Eight patients (53%) treated with risperidone (N=15, mean dose 3.1 mg/day) reported sexual dysfunctions (Mann-Whitney U 39.00, p=0.005). The mean (SD) prolactin concentration was 191.9 (SD 731.8) mE/L in the aripiprazole group and 1273 (731.8) mE/L in the risperidone group (t-test, p=0.001). Conclusions: In line with earlier studies, patients treated with risperidone reported frequently sexual dysfunctions, serum levels of prolactin were elevated. In contrast, in the aripipiprazole group most patients reported no sexual side effects or an improvement in performance, serum prolactin was slightly decreased. Theoretical implications will be discussed. References [1] Knegtering, H., & Bruggeman, R. (2007). What are the effects of antipsychotics on sexual functioning. Primary Psychiatry febr;14(2):51-56.
544 – INSTRUMENTAL ASSESSMENT OF TONGUE DYSKINESIA Jeroen Koning 1 , P.N. van Harten 1 , R.S. Kahn 2 1 Symfora group, Utrecht; 2 Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, Utrecht, The Netherlands
[email protected] Introduction: Detection and treatment of tardive dyskinesia depends on early and adequate diagnosis. This disabling movement disorder affects 20% of patients with schizophrenia who use antipsychotics and can have a negative effect on the compliance to use medication. Fine lingual movements have been reported to be an early sign of tardive dyskinesia. However, the reliability and sensitivity for the diagnosis is highly dependent upon the experience of the rater and his/her preconceived notion of the subject’s status. Instrumental assessment may overcome these limitations. Our aim is to validate an
Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279 instrumental technique to quantify tongue instability associated with tardive dyskinesia. Methods: Instrumental measurement of tongue instability was carried out 23 psychiatric patients with antipsychotic use (11 with and 12 with out tardive dyskinesia) and 7 normal controls. All subjects were screened for tongue dyskinesia by two experts in movement disorders (using the Abnormal Involuntary Movement Scale; AIMS) (Kappa = 0.73). Instrument test-retest reliability was analysed by Pearson correlation coefficient. Results: Patients with tongue dyskinesia displayed significantly more instrumentally measured tongue instability than patient and controls without tongue dyskinesia. Patients without tongue dyskinesia also displayed significantly more instrumentally measured tongue instability than controls without tongue dyskinesia. Instrument test-retest reliability was very good. Pearson correlation coefficient: 0.89 Conclusions: Instrumental measurement of tongue instability is a reliable and sensitive method for assessing tardive dyskinesia of the tongue and may be used for detecting subclinical tardive dyskinesia in patients using antipsychotics.
545 – ARE SEXUAL SIDE EFFECTS OF PROLACTIN-RAISING ANTIPSYCHOTICSREDUCIBLE TO SERUM PROLACTIN? Henderikus Knegtering 1 , Durk Wiersma 1 , Stynke Castelein 2 , Richard Bruggeman 1 , Jim van Os 3 1 University Medical Center Groningen, Groningen; 2 University Medical Center Groningen, University of Groningen, The Netherlands, Groningen; 3 Dept. of Psychiatry and Neuropsychology, University of Maastricht, The Netherlan, Maastricht
[email protected] Introduction: Many antipsychotics induce sexual dysfunctions. Antipsychotic induced sexual dysfunctions are thought to be related to for instance dopaminergic, noradrenergic or prolactin raising properties. This study aims to assess the degree to which sexual side effects (SSE) are associated with prolactin-raising antipsychotics, and to what degree such SSE are reducible to serum prolactin levels. Methods: In 204 patients treated for six weeks with prolactin-raising and prolactin-sparing antipsychotics was assessed for changes in sexual performance in terms of libido, arousal and orgasm. At six weeks, prolactin levels were assessed and analyzed in relation to sexual performance. Results: Men and women reported SSE (libido and orgasm) with about the same frequency. Prolactin-raising medication induced significantly more SSE than prolactin-sparing medication (adjusted OR=3.4, 95% CI: 1.8-6.5) with 43% of emerging SSE attributable to prolactinraising medication. When adjusted for serum prolactin, the association between prolactin-raising medication and SSE was reduced but remained significant (OR=2.1, 95% CI: 1.0-4.5); 27% of emerging SSE remained attributable to prolactin-raising medication. For erectile and ejaculatory dysfunction in men, the attributable fraction due to prolactin-raising medication was 32% before, and 11% after adjustment for serum prolactin. Conclusions: Around 40% of emerging SSE in schizophrenia are attributable to the prolactin-raising properties of antipsychotic medication. Of this attributable fraction, around one third to two thirds is directly reducible to the effects of serum prolactin. References [1] Knegtering H., Bruggeman R (2007). What are the effects of antipsychotics on sexual functioning? Prim Psychiatry 14(2), 51-56.
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546 – THE EFFECT OF ANTIPSYCHOTICS ON PEPTIDES INVOLVED IN ENERGYBALANCE Rocio Perez Iglesias, Jose L. Vazquez-Barquero, Jose A. Amado, Ana Berja, M. Teresa Garcia-Unzueta, J. Maria Pelayo-Teran, Eugenio Carrasco-Marin, Ignacio Mata, Benedicto Crespo-Facorro Hospital Universitario Marques de Valdecilla, Santander, Spain
[email protected] Introduction: Weight gain has become one of the most common and concerning side effects of antipsychotic treatment. The mechanisms where by antipsychotics induce weight gain are not known. It has been suggested that peptides related with food intake and energy balance could play a role in weight gain secondary to antipsychotic therapy. OBJECTIVE: To better understand the pathophysiology of antipsychotic-induced weight gain we studied the effect of three antipsychotic drugs (haloperidol, olanzapine and risperidone) on peptides involved in energy balance (insulin, ghrelin, leptin, adiponectin, visfatin and resistin) in a population of drug-naïve patients with first episode of psychosis. Results: A significant increase in weight (10.16 kg ±8.30; p
