Olanzapine reduces urge to drink after drinking cues and a priming dose of alcohol

RATIONALE: Haloperidol, a D2 antagonist, has been shown to moderate the effects of alcohol consumption on craving. OBJECTIVE: The present study was designed to determine whether a single 5-mg dose of olanzapine (a D2/5-HT2 antagonist) would influence responses to alcohol cues or an alcohol challenge. It was hypothesized that olanzapine would attenuate cue-elicited urge to drink, attenuate the effects of alcohol consumption on urge to drink, and reduce the rewarding effects of alcohol. METHODS: To test these hypotheses, 26 heavy social drinkers were randomized to receive either 5 mg olanzapine or placebo approximately 8 h before each of two experimental sessions. Participants consumed a moderate dose of alcohol in one experimental session and a non-alcohol control beverage in another session. RESULTS: Results indicated that mere exposure to alcohol cues and consumption of alcohol increased urge to drink and that olanzapine attenuated these effects. Results also indicated that alcohol increased subjective stimulation and high while olanzapine did not moderate these effects. CONCLUSIONS: These results suggest that olanzapine did not influence the rewarding effects of alcohol but did attenuate the effects of alcohol cues and an alcohol challenge on urge to drink.     

Olanzapine in children and adolescents with chronic anorexia nervosa. A study of five cases

 Psychopathology in severely anorexic patients often seems to be of compulsive and delusional quality rendering therapeutic approaches extremely difficult. With conventional therapeutic regimes failing, administration of the novel antipsychotic olanzapine induced remarkable improvement in five cases reported here. Paranoid ideation concerning body image or weight gain decreased and sedative effects helped to reduce inner tensions and phobia with respect to food intake. Olanzapine, therefore, might represent an important therapeutic tool in anorexic patients who present the following characteristics: long-term history of anorexia nervosa mostly with several hospitalisations, missing perception of their severe state of illness, refusal of therapy, delusional quality of anorexic thinking, risk of discontinuation of therapy with life-threatening consequences. Accepted: 4 December 2000     

Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo: a [123I]epidepride single photon emission tomography (SPET) study

RATIONALE: Previous work suggests clozapine preferentially targets limbic cortical dopamine systems, which could help account for its lack of extrapyramidal side effects (EPS) and superior therapeutic efficacy. OBJECTIVES: To test the hypothesis that olanzapine, a novel atypical antipsychotic drug, occupies temporal cortical D2/D3 receptors to a greater extent than striatal D2/D3 receptors in vivo. METHODS: Nine schizophrenic patients taking either olanzapine [(n=5; mean (SD) age: 32.5 (6.5) years; daily dose: 18.3 (2.6) mg] or sertindole [(n=4; mean (SD) age: 30.3 (7.4) years; daily dose: 16 (5.6) mg] were studied with [123I]epidepride ((S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenz amide) and single photon emission tomography (SPET). An estimate of [123I]epidepride 'specific binding' to D2/D3 receptors was obtained in patients and age-matched healthy volunteers. A summary measure was generated representing striatal and temporal cortical relative %D2/D3 receptor occupancy by antipsychotic drugs. Occupancy data were compared with previously studied groups of patients receiving typical antipsychotic drugs (n=12) and clozapine (n=10). RESULTS: Mean striatal and temporal cortical %D2/D3 receptor occupancy in olanzapine-treated patients was 41.3% (SD 17.9) and 82.8% (SD 4.2), respectively. Unexpectedly low levels of striatal relative %D2/D3 receptor occupancy were seen in two patients with typical antipsychotic-drug-induced movement disorder prior to switching to olanzapine. In the temporal cortex, mean D2/D3 dopamine receptor occupancy levels above 80% were seen for all antipsychotic drugs studied. CONCLUSIONS: The atypical antipsychotic drugs olanzapine and sertindole, in common with clozapine, demonstrate higher occupancy of temporal cortical than striatal D2/D3 dopamine receptors in vivo at clinically useful doses. This could help mediate their atypical clinical profile of therapeutic efficacy with few extrapyramidal side effects. Limbic selective blockade of D2/D3 dopamine receptors could be a common action of atypical antipsychotic drugs.     

Restoration of latent inhibition by olanzapine but not haloperidol in entorhinal cortex-lesioned rats

RATIONALE: Latent inhibition (LI) refers to the decrease in conditioned response induced by the repeated non-reinforced pre-exposure to the conditioned stimulus before its pairing with the unconditioned stimulus during the conditioning stage. LI has been considered as a relevant animal model for the study of the biological bases of schizophrenia. LI has recently been demonstrated to depend on the integrity of the entorhinal cortex, as lesioning of this area disrupted LI. OBJECTIVES: The present study aimed to verify whether the classical neuroleptic haloperidol and/or the atypical antipsychotic olanzapine would prevent the effect of entorhinal cortex lesioning. METHODS: LI was studied in an off-baseline conditioned emotional response (CER) paradigm in which a tone is paired with a footshock. Entorhinal cortex lesions were produced by the electrolytic method. After a recovery period, both lesioned and control rats received either haloperidol (0.3 mg/kg), olanzapine (0.3 mg/kg) or vehicle before both the pre-exposure and conditioning stages of the experiment. RESULTS: In control rats, pre-exposure to the tone induced LI, which was affected by neither haloperidol nor olanzapine. Lesioning of the entorhinal cortex produced a deficit of LI, which was restored by olanzapine but not by haloperidol. CONCLUSIONS: This result suggests a dissociation of the anatomical and pharmacological targets of the two drugs. The possible involvement of dopamine D3 receptors in the effects of olanzapine is discussed.     

奥氮平与奋乃静治疗阳性症状为主的精神分裂症对照研究

目的比较奥氮平与奋乃静治疗阳性症状为主的精神分裂症患者的疗效和副反应。方法60例阳性症状为主精神分裂症患者随机分为奥氮平组与奋乃静组治疗，疗程6周，分别于治疗前、第2、4、6周末采用PANSS量表、TESS量表评分并分析。结果第2、4周末奥氮平组与奋乃静组之间的疗效差异有统计学意义（X^2=18．61，P=0．006）、（X^2=17．34，P=0．031），第6周末两组之间的疗效差异无统计学意义X^2=7．59，P=0．061）；PANSS量表评分均数：奥氮平组在第2、4、6周末均与治疗前比较有统计学意义（P〈0．05），而奋乃静组在第4、6周末与治疗前比较有统计学意义（P〈0．05）；第4、6周末两组之间的TESS量表评分差异有统计学意义（X^2=2．386，P=0．039）、（t=2．295，P=0．016）。结论奥氮平比奋乃静能更快、更有效地控制精神分裂症的阳性症状，且没有明显锥体外系副反应。     

Olanzapine affects locomotor activity and meal size in male rats

Olanzapine is an antipsychotic drug that frequently induces weight gain accompanied by increased fat deposition as a side effect. To investigate how olanzapine affects different aspects of energy balance, we used male rats to determine effects on meal patterns, food preference, locomotor activity and body temperature. In two short-term experiments olanzapine was administered via osmotic minipumps. In the first experiment, we offered rats standard lab chow only. In the second experiment, we offered rats free choice between chow, sucrose and saturated fat. In a third experiment, olanzapine was chronically administered via the drinking water to determine effects on body composition. In each experiment olanzapine decreased locomotor activity and altered meal patterns. Olanzapine caused an increase in average meal size accompanied by reduced meal frequency, without clearly affecting food preference. In the chronic experiment body composition was altered, favoring adipose tissue over lean muscle mass, despite reductions in overall body weight gain. The increase in average meal size implies that the primary effect of olanzapine on feeding is an impairment of the normal satiation process. Furthermore, energy balance is clearly affected by a reduction in locomotor activity. Thus, the effects of olanzapine on adiposity do not depend solely on the presence of hyperphagia.     

国产奥氮平治疗精神分裂症的疗效分析

目的探讨国产奥氮平治疗精神分裂症的临床疗效、不良反应。方法将32例符合CCMD-3诊断标准的精神分裂症病人给予国产奥氮平治疗8周，用阳性与阴性症状量表（PANSS）和副反应量表（TESS）评定其疗效和不良反应。结果完成8周治疗的32例精神分裂症病人，基本痊愈9例（28．1％），显进11例（34．4％），进步7例（21．9％），无效5例（15．6％），总有效率为84．4％，不良反应少。结论国产奥氮平治疗精神分裂症安全有效。     

多受体类非典型抗精神病药物在老年抑郁症治疗中的比较

目的比较抗抑郁药物联合氯氮平、奥氮平、喹硫平治疗老年抑郁症疗效、耐受性与安全性。方法64例抑郁症患者在应用抗抑郁药物的基础上分别联合奥氮平（n=21）、喹硫平（n=23）、氯氮平（n=20），治疗6周，比较HAMD、HAMA、BPRS的变化和不良反应。结果3组患者的HAMD、HAMA、BPRS均有显著性减少，但3组之间无统计学差异（P〉0．05），其中氯氮平组不良反应较明显。结论抗抑郁药物联合多受体类非典型抗精神病药物治疗老年抑郁症的效果较理想，且不良反应少。但是不同药物之间的不良反应存在不同。     

奥氮平与碳酸锂治疗躁狂发作30例对照分析

目的评价奥氮平治疗躁狂症的疗效与耐受性。方法将符合《中国精神障碍分类与诊断标准(第3版)》(CCMD-3)中各型躁狂发作诊断标准的60例住院患者随机分为两组,每组30例,分别用奥氮平和碳酸锂治疗6周。以Bech-Rafaelsen躁狂量表(BRMS)评定疗效,以副反应量表(TESS)及相关辅助检查评价耐受性。结果治疗前后两组BRMS分值均有非常显著性差异,治疗有效率相当;组间比较显示,奥氮平治疗后第1周BRMS评分即显著下降,表明奥氮平较碳酸锂起效迅速。两组的不良反应均少且轻。结论奥氮平可作为心境稳定剂用于躁狂发作的治疗。     

Pretreatment levels of the fatty acid handling proteins H-FABP and CD36 predict response to olanzapine in recent-onset schizophrenia patients

Traditional schizophrenia pharmacotherapy remains a subjective trial and error process involving administration, titration and switching of drugs multiple times until an adequate response is achieved. Despite this time-consuming and costly process, not all patients show an adequate response to treatment. As a consequence, relapse is a common occurrence and early intervention is hampered. Here, we have attempted to identify candidate blood biomarkers associated with drug response in 121 initially antipsychotic-free recent-onset schizophrenia patients treated with widely-used antipsychotics, namely olanzapine (n = 40), quetiapine (n = 23), risperidone (n = 30) and a mixture of these drugs (n = 28). Patients were recruited and investigated as two separate cohorts to allow biomarker validation. Data analysis showed the most significant relationship between pre-treatment levels of heart-type fatty acid binding protein (H-FABP) and response to olanzapine (p = 0.008, F = 8.6, β = 70.4 in the discovery cohort and p = 0.003, F = 15.2, β = 24.4 in the validation cohort, adjusted for relevant confounding variables). In a functional follow-up analysis of this finding, we tested an independent cohort of 10 patients treated with olanzapine and found that baseline levels of plasma H-FABP and expression of the binding partner for H-FABP, fatty acid translocase (CD36), on monocytes predicted the reduction of psychotic symptoms (p = 0.040, F = 6.0, β = 116.3 and p = 0.012, F = 11.9, β = −0.0054, respectively). We also identified a set of serum molecules changed after treatment with antipsychotic medication, in particular olanzapine. These molecules are predominantly involved in cellular development and metabolism. Taken together, our findings suggest an association between biomarkers involved in fatty acid metabolism and response to olanzapine, while other proteins may serve as surrogate markers associated with drug efficacy and side effects.