Rapid leptin elevation after initiation of olanzapine?

Weight gain is a common adverse effect associated with olanzapine treatment. Another side effect of olanzapine treatment is a significant increase in circulating leptin levels. This preliminary study monitored the changes in leptin levels for 2 weeks after olanzapine treatment had been initiated. The relationship between the changes in circulating leptin levels and alterations in body weight in 9 patients with schizophrenia who received olanzapine was examined. The results showed that olanzapine may cause a surge in circulating leptin levels before weight gain is manifested. Moreover, higher pretreatment circulating leptin levels predicted lower weight gains after olanzapine treatments (r = -0.93; p < 0.05) after controlling for the effect of sex.     

Olanzapine plasma concentration, average daily dose, and interaction with co-medication in schizophrenic patients

BACKGROUND: Olanzapine, a thienobenzodiazepine, is one of the relatively new atypical antipsychotic drugs. The lowest threshold of effective olanzapine plasma levels in inpatient treatment is assumed to be 9 ng/ml. Very little is known about the plasma concentration in patients at various oral doses of olanzapine or about the clinically relevant interactions with co-medications. METHODS: In 71 schizophrenic patients (age 32.6 +/- 12.1, range 18-63 years; 31 women, 40 men), plasma olanzapine levels were assessed in 377 tests by high-performance liquid chromatography (HPLC) with electrochemical detection. Fifty-six of these plasma levels were assessed while patients were receiving olanzapine as monotherapy; otherwise, the plasma levels were assessed with the patients receiving various co-medications. RESULTS: The mean daily oral dose of olanzapine was 17.5 mg (SD = 7.0, range 5-40 mg), and the mean olanzapine plasma concentration was 54.2 ng/ml (SD 37.8 ng/ml, range 1.2-208 ng/ml). The plasma concentration of olanzapine increased linearly with the daily oral dose (r = 0.64, p < 0.001). A multiple variance analysis considering age and sex as covariables showed a significant difference in the dose-corrected plasma levels of olanzapine among 40 smokers and 31 non-smokers; age and sex did not affect the dose-corrected plasma levels. However, women received a significantly lower daily dose of olanzapine under routine clinical study conditions. No differences could be detected among the dose-corrected plasma concentration of those patients who were taken off olanzapine because they did not respond (n = 14) or because of side effects (n = 5) and those who were discharged while still on olanzapine. Under the co-medication with fluvoxamine, significantly higher dose-corrected olanzapine plasma concentrations were found than with olanzapine monotherapy, whereas significantly lower dose-corrected olanzapine plasma concentrations were detected under lithium and trimipramine co-medication. Under co-medication with amitriptyline, benperidol, carbamazepine, flupentixol, and lorazepam, the dose-corrected olanzapine plasma concentrations were no different than the plasma levels under olanzapine monotherapy. CONCLUSIONS: The relevance of therapeutic drug monitoring is emphasized with respect to the data presented and to the literature. Future studies should examine, in particular, the effects of a wider range of co-medications in a larger patient sample.     

The efficacy of a rapid-acting intramuscular formulation of olanzapine for positive symptoms

Rapid tranquilization of acutely psychotic patients with schizophrenia is usually carried out using typical antipsychotic agents. The objective of such treatment is to control agitation, not to treat psychosis, which usually responds only after a few weeks of treatment. An intramuscular formulation of the atypical antipsychotic olanzapine was developed for treatment of agitation in acutely psychotic patients. Studies conducted to assess control of agitation in schizophrenia also investigated the positive symptom efficacy of olanzapine when used to provide rapid tranquilization. This article summarizes the results of 3 clinical trials with intramuscular olanzapine with regard to positive symptom efficacy as measured by the Brief Psychiatric Rating Scale (BPRS; 0-6 scale) positive subscale. In 2 open-label trials, patients treated with intramuscular olanzapine experienced a mean decrease from baseline in BPRS positive subscale score. In 1 double-blind clinical trial of intramuscular olanzapine versus intramuscular haloperidol and intramuscular placebo, the mean decrease from baseline in BPRS positive subscale score for patients treated with intramuscular olanzapine was statistically significant (p < .05). In all 3 studies, positive symptom improvement continued following transition to oral olanzapine. These results suggest that intramuscular olanzapine has positive symptom efficacy early in the course of treatment and may provide a smooth transition to maintenance therapy with oral olanzapine.     

奥氮平与氯氮平治疗精神分裂症的对照研究

目的 评价奥氮平治疗精神分裂症的疗效和副作用。方法 将39例精神分裂症患者随机分成2组，分别给予奥氮平与氯氮平治疗8周，采用PANSS．CGI评价临床疗效，TESS评价不良反应。结果 奥氮平组与氯氮平组之间疗效无显著性差异，奥氮平组治疗前后PANSS减分率45．7％，有效率78．90％；氯氮平组治疗前后PANSS减分率44．9％，有效率75．0%；氯氮平组副反应明显高于奥氮平组。结论 奥氯平是一种安全有效的新型抗精神病药。     

Muscarinic mechanisms of antipsychotic atypicality

The interactions of the atypical antipsychotic drugs (APD) clozapine, olanzapine, risperidone, quetiapine and ziprasidone with muscarinic receptors were reviewed. Only clozapine and olanzapine have marked affinity for muscarinic receptors in radioligand binding studies; however, the affinity of these compounds is considerably lower than classical muscarinic antagonists. Although functional assays in cell lines transfected with muscarinic receptors suggest that olanzapine and clozapine have weak partial agonist activity at muscarinic receptors, particularly M4 receptors, studies in vitro and in vivo indicate that the compounds function as antagonists. In animal studies and in humans, clozapine has pronounced antimuscarinic effects whereas olanzapine has weak antimuscarinic effects. However, olanzapine significantly occupies central muscarinic receptors in humans. Overall, the role of muscarinic receptors in the antipsychotic effects of clozapine and olanzapine is controversial and complex.     

High-dose olanzapine and prolactin levels

BACKGROUND: This study evaluates whether high-dose olanzapine is associated with elevation of serum prolactin levels. METHOD: Twenty-four patients taking daily doses of olanzapine of 20, 25, 30, and 40 mg for DSM-IV schizophrenia or schizoaffective disorder had serum prolactin levels measured. The patients were all from one author's (J.L.K.'s) clinical practice. The mean duration of olanzapine therapy was 15.3 months at a dose of at least 20 mg/day. Data were gathered in 2000 and 2001. RESULTS: There was no significant correlation between olanzapine dose and prolactin level (Pearson product moment correlation coefficient = 0.09). No significant differences were found between mean prolactin values in each dose group. CONCLUSION: There was no significant elevation of prolactin with higher doses of olanzapine. Thus, preliminary evidence suggests that using higher doses of olanzapine is generally safe with regard to prolactin levels.     

Switch from Olanzapine Long-Acting Injectable to its Oral Equivalent during COVID-19 Pandemic: a Real World Observational Study

Schizophrenia is a psychiatric condition with chronic evolution, one of the most disabling diseases. The main cause for the disease’s progression is considered to be the lack of compliance with the treatment. Long-acting injectable antipsychotics (LAIs) are an important treatment option for patients with schizophrenia. Olanzapine long-acting injection (OLZ-LAI) is a pamoate monohydrate salt of olanzapine that is administered by deep intramuscular gluteal injection. The aim of this paper is to report the effects of a sudden and unplanned switch from olanzapine long-acting injectable to oral olanzapine in remitted patients with schizophrenia due to restrictions caused by the COVID-19 pandemic. An observational study conducted in the Clinical Hospital of Psychiatry and Neurology of Brasov, Romania between April 2020 and March 2021. 27 patients with OLZ-LAI were entered into the study. Of 27 cases, 21 patients preferred to be switched to oral olanzapine (77.77%). Only 6 patients continued with the long-acting formulation. The main reason for the initiation of olanzapine pamoate in all the patients was non-adherence to oral medication (80.95%), and the mean age of starting LAI olanzapine was 36.42 years (SD?±?10.09). Within the following 12 months after switching from olanzapine LAI to OA, 15 patients (71.42%) relapsed, and 12 were admitted to the emergency psychiatric unit. The COVID-19 pandemic has brought multiple disservices to current medical practice. Sudden and unplanned switch from olanzapine long-acting formulation to oral olanzapine was followed by the high rate of relapse in remitted schizophrenia.

     

Obsessive-compulsive symptoms during treatment with olanzapine and risperidone: a prospective study of 113 patients with recent-onset schizophrenia or related disorders

OBJECTIVE: To determine whether severity of obsessive-compulsive symptoms (OCS) differs during treatment with olanzapine or risperidone and to establish whether duration of antipsychotic treatment is related to severity of OCS. METHOD: We conducted a prospective study of consecutively hospitalized young patients (mean age = 22.4 years) with DSM-IV schizophrenia or related disorders (N = 113) who were treated with olanzapine or risperidone. Olanzapine or risperidone was randomly prescribed for patients who were drug-naive or were treated with typical antipsychotics before admission (N = 36). Patients who had started olanzapine (N = 39) or risperidone treatment (N = 23) prior to admission continued with that medication if they showed initial clinical response. Patients who prior to admission started olanzapine (N = 6) or risperidone (N = 9) but showed no response or suffered from adverse effects switched at admission to risperidone or olanzapine, respectively. Medical records, parents, and patients revealed information on duration of treatment and compliance with olanzapine or risperidone prior to admission. The Yale-Brown Obsessive Compulsive Scale (YBOCS) was administered at admission and 6 weeks thereafter. RESULTS: At baseline and 6-week assessments, OCS were found in about 30% of 106 evaluable cases and 15% met DSM-IV criteria for obsessive-compulsive disorder. No differences in OCS were found in the patients randomly assigned to olanzapine or risperidone. The 35 subjects treated with olanzapine at both assessments had significantly (p = .01) more severe OCS at week 6 than the 20 subjects treated with risperidone at both assessments. Duration of treatment with olanzapine was significantly (p < .01) related to severity of OCS. CONCLUSION: There are no differences in the short-term propensity of olanzapine or risperidone to induce or exacerbate OCS. However, severity of OCS was associated with duration of treatment with olanzapine.     

High-dose olanzapine-induced improvement of preexisting type 2 diabetes mellitus in schizophrenic patients

OBJECTIVE: During the last few years there have been numerous publications concerning glucose dysregulation and antipsychotic treatment with new-onset diabetes and exacerbation of existing disease being reported. At the same time three anecdotal reports describing decrease of blood glucose level during clozapine and olanzapine treatment were published. Here we report two cases of clinically significant dose-related reductions in glucose levels in schizophrenic and schizoaffective patients suffering from pre-existing type 2 diabetes during high dose (40 mg/day) olanzapine treatment. To the best of our knowledge, this is a first report of decreasing glucose blood levels in association with olanzapine therapy in pre-existing type 2 diabetes. Antipsychotic treatment with high doses of olanzapine showed that the relationship between olanzapine and glucose regulation is more unambiguous than usually assumed. CONCLUSIONS: There is a need for further studies in order to define the influence of high dose olanzapine for schizophrenic and schizoaffective patients suffering from type 2 diabetes.     

Analyses of treatment-emergent mania with olanzapine/fluoxetine combination in the treatment of bipolar depression

BACKGROUND: Treatment-emergent mania is a potential risk when patients with bipolar disorder are treated with antidepressant agents. These subanalyses compare treatment-emergent mania rates in bipolar I depressed patients treated with olanzapine, placebo, or olanzapine/fluoxetine combination. METHOD: In this 8-week, double-blind investigation, patients with bipolar I depression (DSM-IV criteria) (N = 833, baseline Montgomery-Asberg Depression Rating Scale total score > or = 20) were randomly assigned to olanzapine (5-20 mg/day, N = 370), placebo (N = 377), or olanzapine/fluoxetine combination (6/25, 6/50, or 12/50 mg/day; N = 86). Treatment-emergent mania was evaluated with the Young Mania Rating Scale (YMRS), the Clinical Global Impressions-Bipolar Edition (CGI-BP) Severity of Mania scale, and adverse events records. RESULTS: Overall rates of study discontinuation due to mania were low and not significantly different among the therapy groups (p = .358). Incidence of treatment-emergent mania (defined as a YMRS score < 15 at baseline and > or = 15 at any subsequent visit) did not differ significantly among therapy groups (olanzapine 5.7%, placebo 6.7%, olanzapine/fluoxetine combination 6.4%; p = .861). Subjects receiving olanzapine or olanzapine/fluoxetine combination had greater mean decreases in YMRS scores than those receiving placebo (p < .001 for both). Subjects receiving olanzapine or olanzapine/fluoxetine combination also had greater mean decreases in CGI-BP scores than those receiving placebo (p = .040 and p = .003, respectively). CONCLUSION: These results suggest that olanzapine/fluoxetine combination does not present a greater risk of treatment-emergent mania compared to olanzapine or placebo over 8 weeks of acute treatment for bipolar I depression. Due to the cyclical nature of bipolar disorder, patients taking olanzapine/fluoxetine combination for bipolar depression should still be monitored for signs or symptoms of emerging mania.     

Olanzapine overdose in children and adolescents: two case reports and a review of the literature

Although the atypical antipsychotic olanzapine is increasingly being used in child and adolescent psychiatry, reports of olanzapine overdose in this young population are scarce. We report on two cases of adolescents who attempted suicide with an overdose of olanzapine: (1) A 14-year-old female ingested 275 mg olanzapine, which produced the highest reported nonlethal serum level (1503 ng/mL) and caused somnolence, agitation (acutely), and extrapyramidal symptoms (EPS; after 54 hours) but no major clinical complications. The serum olanzapine level dropped to 129 ng/mL within 48 hours; and (2) a 17-year-old male ingested 400 mg olanzapine, the highest reported nonlethal dose of olanzapine in adolescents, which produced respiratory suppression requiring intubation and mechanical ventilation; he recovered after 3 days. Based on clinical monitoring and postmortem data, the 2 patients survived the ingestion of high doses of olanzapine. We also provide a review of the literature, encompassing all reported cases of olanzapine overdose in children and adolescents and discuss symptoms, diagnosis, and treatment options, based on pharmacokinetic and pharmacodynamic considerations.     

Orally disintegrating olanzapine for the treatment of a manic patient with esophageal stricture plus chronic pharyngitis

An orally disintegrating tablet formulation of olanzapine (ODT olanzapine) is designed to dissolve rapidly upon contact with saliva. We describe a manic patient who has an esophageal stricture and chronic pharyngitis, two conditions that impede the swallowing of medications. She was successfully treated for her mania with this orally disintegrating formulation. This case report shows that ODT olanzapine may be useful in the psychiatric management of manic and other patients for whom olanzapine is appropriate, and who have an underlying medical condition that impedes swallowing oral medications.     

无抽搐电休克合并奥氮平治疗难治性精神分裂症对照研究

目的探讨无抽搐电休克治疗（MECT）合并奥氮平（悉敏）对难治性精神分裂症的疗效及安全性。方法将63例难治性精神分裂症患者随机分为研究组和对照组,分别予以MECT合并奥氮平和单用奥氮平治疗。观察期为12周。分别采用阳性和阴性症状量表（PANSS）、韦氏记忆量表（WMS）及副反应量表（TESS）评定疗效及安全性。结果（1）治疗2周末,MECT合并奥氮平组PANSS量表总分及阳性症状分较前明显下降（P〈0．05）,治疗4周末,奥氮平合并MECT组PANSS量表总分及阳性症状分较单用奥氮平组明显下降（P〈0．01）,治疗12周后,两组PANSS量表总分、阳性症状分、阴性症状分均较治疗前有显著性下降（P〈0．01）;（2）总有效率两组分为67．74％和62．50％,组间比较无差异（P〉0．05）;（3）奥氮平合并MECT组在MECT治疗期间WMS分明显下降（P〈0．01）,但在MECT结束治疗后4～8周恢复,与单用奥氮平组相比无显著性差异（P〉0．05）;（4）两组均未见严重的不良反应。结论MECT合并奥氮平治疗难治性精神分裂症疗效肯定,安全性好,快速控制阳性症状的疗效优于单用奥氯平。     

Olanzapine: preclinical pharmacology and recent findings

Olanzapine possesses a broad pharmacological profile, interacting with a range of different neurotransmitter receptors. Although its affinity for muscarinic receptors is relatively greater than for dopamine receptors, on schedule-controlled behaviour olanzapine displays a profile resembling a dopamine antagonist. Likewise, in a test of cognitive function, olanzapine does not produce anticholinergic-like deficits. In drug discrimination assays, olanzapine substitutes for clozapine in clozapine-trained animals and clozapine generalises to olanzapine in olanzapine-trained animals. Olanzapine also reverses the behavioural deficits produced by inhibiting N-methyl-D-aspartate receptor glutamatergic transmission. This profile suggests that olanzapine will be effective against both positive and negative symptoms of schizophrenia while producing minimal extrapyramidal side-effects.     

Olanzapine plus fluvoxamine and olanzapine alone for the treatment of an acute exacerbation of schizophrenia

The objective of the present study was to compare the efficacy and adverse effects of olanzapine plus fluvoxamine and those of olanzapine alone, in schizophrenic patients with acute exacerbation. A randomized, placebo-controlled, 6-week trial was carried out at a University Hospital in Bangkok, Thailand. The efficacy and adverse effects were assessed biweekly by using the Brief Psychiatric Rating Scale (BPRS) and the Udvalg for Kliniske Undersogelser side-effect scale, respectively. Twenty schizophrenic patients with acute exacerbation were randomly assigned to receive olanzapine plus fluvoxamine or olanzapine alone. The study found that the means of BPRS total and BPRS general psychopathology score changes were significantly larger in olanzapine plus fluvoxamine group (P = 0.037 and P = 0.045, respectively). The incidence of treatment adverse effects is comparable. In conclusion, the study findings suggest that fluvoxamine augmentation to olanzapine is well tolerated and more effective than olanzapine alone for short-term (6-week) treatment of an acute exacerbation of schizophrenia. Due to a number of limitations, further studies are warranted to confirm.     

Olanzapine in Gilles de la Tourette syndrome: beyond tics

Although there only have been a limited number of double-blind, placebo controlled trials, antipsychotics are considered to be effective drugs for the treatment of tics in Gilles de la Tourette syndrome (GTS). Evidence concerning the efficacy of olanzapine and other atypical antipsychotics in the treatment of tics in GTS is growing, but still limited. Little is known about the use of olanzapine in adult GTS patients and about its effect on comorbid behavioural problems. We report on the use of olanzapine in a 25-year old male GTS patient with comorbid obsessive-compulsive behaviours, who was treated with olanzapine. Tic severity was rated using the Yale Global Tic Severity Scale (Y-GTSS). Comorbid obsessive-compulsive symptoms were assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Both scales were performed at admission and after 4 weeks of treatment with olanzapine. Treatment with olanzapine (20 mg) resulted not only in a fast reduction of tic severity and frequency, but also in a reduction of obsessive-compulsive behaviours. CONCLUSIONS: This case report further supports the available literature on the use of olanzapine as a therapeutic strategy for tics in GTS and draws attention to its possible use for comorbid behavioural disorders. Further research of antipsychotics in GTS should include measurements of comorbid behavioural symptom clusters.     

奥氮平与氯氮平治疗躁狂症比较

目的：比较奥氮平与氯氮平治疗躁狂症的疗效与副反应。方法：80例躁狂症随机分成两组，一组服奥氮平，另一组服氯氮平，治疗4周。结果：奥氮平组临床疗效15例治愈，12例进步，7例有效，6例无效；氯氮平组分别为13，13，7和7例。氯氮平组副反应显著多于奥氮平组。结论：奥氮平是一种治疗躁狂症安全有效药物。     

Treatment-resistant schizophrenic patients respond to clozapine after olanzapine non-response.

BACKGROUND: Treatment-resistance in schizophrenia remains a public health problem. Clozapine has been shown to be effective in about one third of this population, but carries with it medical risks and weekly blood draws. As olanzapine is a drug with a very similar biochemical profile to clozapine, it is important to evaluate whether non-response to olanzapine predicts clozapine non-response. METHODS: Forty-four treatment-resistant patients received eight weeks of olanzapine, either in a double-blind trial or subsequent open treatment at a mean daily dose of 25 mg/day. Two of 44 patients (5%) responded to olanzapine treatment. Patients who did not respond could then receive clozapine. Twenty-seven subsequently received an 8-week open trial of clozapine. RESULTS: Patients who did and did not receive clozapine did not differ demographically or in psychopathology. Eleven of 27 (41%) met a priori response criteria during clozapine treatment (mean dose 693 mg/day) after failing to respond to olanzapine. CONCLUSIONS: This study demonstrates that failure to respond to olanzapine treatment does not predict failure to clozapine. Treatment-resistant patients who fail on olanzapine may benefit from a subsequent trial of clozapine.     

Intramuscular olanzapine and intramuscular haloperidol in acute schizophrenia: antipsychotic efficacy and extrapyramidal safety during the first 24 hours of treatment.

OBJECTIVE: To determine the antipsychotic efficacy and extrapyramidal safety of intramuscular (i.m.) olanzapine and i.m. haloperidol during the first 24 hours of treatment of acute schizophrenia. METHOD: Patients (n = 311) with acute schizophrenia were randomly allocated (2:2:1) to receive i.m. olanzapine (10.0 mg, n = 131), i.m. haloperidol (7.5 mg, n = 126), or i.m. placebo (n = 54). RESULTS: After the first injection, i.m. olanzapine was comparable to i.m. haloperidol and superior to i.m. placebo for reducing mean change scores from baseline on the Brief Psychiatric Rating Scale (BRPS) Positive at 2 hours (-2.9 olanzapine, -2.7 haloperidol, and -1.5 placebo) and 24 hours (-2.8 olanzapine, -3.2 haloperidol, and -1.3 placebo); the BPRS Total at 2 hours (-14.2 olanzapine,-13.1 haloperidol, and -7.1 placebo) and 24 hours (-12.8 olanzapine, -12.9 haloperidol, and -6.2 placebo); and the Clinical Global Impressions (CGI) scale at 24 hours (-0.5 olanzapine, -0.5 haloperidol, and -0.1 placebo). Patients treated with i.m. olanzapine had significantly fewer incidences of treatment-emergent parkinsonism (4.3% olanzapine vs 13.3% haloperidol, P = 0.036), but not akathisia (1.1% olanzapine vs 6.5% haloperidol, P = 0.065), than did patients treated with i.m. haloperidol; they also required significantly less anticholinergic treatment (4.6% olanzapine vs 20.6% haloperidol, P < 0.001). Mean extrapyramidal symptoms (EPS) safety scores improved significantly from baseline during i.m. olanzapine treatment, compared with a general worsening during i.m. haloperidol treatment (Simpson-Angus Scale total score mean change: -0.61 olanzapine vs 0.70 haloperidol; P < 0.001; Barnes Akathisia Scale global score mean change: -0.27 olanzapine vs 0.01 haloperidol; P < 0.05). CONCLUSION: I.m. olanzapine was comparable to i.m. haloperidol for reducing the symptoms of acute schizophrenia during the first 24 hours of treatment, the efficacy of both being evident within 2 hours after the first injection. In general, more EPS were observed during treatment with i.m. haloperidol than with i.m. olanzapine.     

Olanzapine increases slow wave sleep and sleep continuity in SSRI-resistant depressed patients

OBJECTIVE: The atypical antipsychotic drug olanzapine has been employed as an augmentation treatment in depressed patients unresponsive to treatment with selective serotonin reuptake inhibitors (SSRIs). In healthy subjects, acute olanzapine administration increases sleep continuity and enhances slow wave sleep (SWS). The aim of the present study was to determine if the addition of olanzapine to SSRI treatment in depressed patients produced similar effects on sleep. METHOD: We measured the effect of open-label olanzapine addition (2.5 mg/day initially) on the polysomnograms of 12 patients referred from primary care sources who met DSM-IV criteria for major depressive disorder and who had had an unsatisfactory response to therapeutic doses of an SSRI. Patients were first enrolled in November 2001; final assessment occurred in November 2003. Sleep polysomnogram recordings were made on 3 occasions: before olanzapine addition, on the first night of olanzapine treatment, and after 3 weeks of olanzapine treatment. RESULTS: After the first night of olanzapine treatment and during the third week, subjects showed improvements in sleep efficiency (p < .001), subjective sleep quality (p < .05), and SWS (p < .01). Scores on the Hamilton Rating Scale for Depression fell significantly (p = .001), with the majority of the decrease being apparent after the first week of treatment. CONCLUSION: Olanzapine improves sleep continuity and increases SWS in patients receiving SSRI treatment. These effects are apparent after the first dose of olanzapine and are maintained for the next 3 weeks. The ability of olanzapine to increase SWS is probably attributable to 5-HT(2A/2C) receptor blockade, which has been identified as a relevant mechanism in the therapeutic effect of olanzapine in SSRI-resistant depressed patients.