Mg Of Olanzapine Research Articles

Differences in Prolactin Elevation and Related Symptoms of Atypical Antipsychotics in Schizophrenic Patients

The aim of this cross-sectional study was to investigate the degree and frequency of prolactin (PRL) elevation and related symptoms in patients treated with 3 different atypical antipsychotics: clozapine, olanzapine, and risperidone. Twenty-eight patients receiving clozapine, 29 patients receiving olanzapine, and 18 patients receiving risperidone (all meeting DSM-IV criteria for schizophrenia, schizophreni-form disorder, or schizoaffective disorder) were studied. The median daily dose was 400 mg of clozapine, 10 mg of olanzapine, and 3 mg of risperidone. Fasting morning blood samples were analyzed for PRL, and the occurrence of hyper-prolactinemic symptoms in the patients was evaluated. Elevated PRL levels were found in 16 (89%) of the patients receiving risperidone and in 7 (24%) of the patients receiving olanzapine, but in none of the patients receiving clozapine. In addition, there was a significant difference in median PRL level among the treatment groups (p < .0001), in that the PRL level was higher both in the patients treated with risperidone and in the patients treated with olanzapine, compared to those treated with clozapine. Moreover, hyperpro-lactinemic symptoms-menstrual disturbances, galactorrhea, impotence, oligospermia, and decreased libido-were reported in 8 (44%) of the risperidone-treated patients and in 1 (3%) of the olanzapine-treated patients, but in none of the clozapine-treated patients. Treatment with risperidone was frequently associated with hyperprolactinemia and related symptoms, whereas the occurrence of PRL elevation and related symptoms was modest in patients receiving olanzapine and nonexistent in those receiving clozapine. Thus, atypical anti-psychotics in therapeutic doses differ with regard to effect on PRL secretion.

A phase II trial of olanzapine for the prevention of chemotherapy induced nausea and vomiting (CINV)

8046 Background: In a previous Phase I study, olanzapine (Zyprexa) was demonstrated to be a safe and effective agent for the prevention of delayed emesis in chemotherapy naïve cancer patients receiving cyclophosphamide, doxorubicin, and/or cisplatin. Methods: Using the maximum tolerated dose of olanzapine in the Phase I trial, a Phase II trial was performed for the prevention of CINV in chemotherapy naive patients. The regimen was 5mg/day of oral olanzapine on the two days prior to chemotherapy, 10mg of olanzapine on the day of chemotherapy, day 1, (added to intravenous granisetron, 10 mcg/kg, and dexamethasone 20 mg) and 10 mg/day on days 2–4 after chemotherapy (added to dexamethasone, 8 mg p.o. BID, days 2,3, and 4 mg p.o. BID, day 4). Thirty patients (median age 58.5 yrs, range 25–84; 23 females; ECOG PS 0,1) consented to the protocol and all were evaluable. Results: Complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 hours post chemotherapy) and 80% for the delayed period (days 2–5 post chemotherapy) in 10 patients receiving highly emetogenic chemotherapy (HEC) (cisplatin, ≥ 70 mg/m2). CR was also 100% for the acute period and 85% for the delayed period in 20 patients receiving moderately emetogenic chemotherapy (MEC) (doxorubicin, ≥ 50 mg/m2). Nausea was well controlled in the patients receiving HEC with no patient having more than minimal nausea (≤2 on scale of 0–10, M.D. Anderson Symptom Inventory, MDASI) in the acute or delayed periods. Nausea was also well controlled in patients receiving MEC with minimal or no nausea in 85% of patients in the acute period and 70% in the delayed period. There were no Grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes or restlessness experienced by the patients. CR and control of nausea in subsequent cycles of chemotherapy (25 patients, cycle 2; 25 patients, cycle 3; 21 patients, cycle 4) were equal to or greater than cycle 1. Conclusions: Olanzapine is safe and highly effective in controlling acute and delayed CINV in patients receiving HEC and MEC. No significant financial relationships to disclose.

A phase II trial of olanzapine for the prevention of chemotherapy induced nausea and vomiting (CINV)

8046 Background: In a previous Phase I study, olanzapine (Zyprexa) was demonstrated to be a safe and effective agent for the prevention of delayed emesis in chemotherapy naïve cancer patients receiving cyclophosphamide, doxorubicin, and/or cisplatin. Methods: Using the maximum tolerated dose of olanzapine in the Phase I trial, a Phase II trial was performed for the prevention of CINV in chemotherapy naive patients. The regimen was 5mg/day of oral olanzapine on the two days prior to chemotherapy, 10mg of olanzapine on the day of chemotherapy, day 1, (added to intravenous granisetron, 10 mcg/kg, and dexamethasone 20 mg) and 10 mg/day on days 2–4 after chemotherapy (added to dexamethasone, 8 mg p.o. BID, days 2,3, and 4 mg p.o. BID, day 4). Thirty patients (median age 58.5 yrs, range 25–84; 23 females; ECOG PS 0,1) consented to the protocol and all were evaluable. Results: Complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 hours post chemotherapy) and 80% for the delayed period (days 2–5 post chemotherapy) in 10 patients receiving highly emetogenic chemotherapy (HEC) (cisplatin, ≥ 70 mg/m2). CR was also 100% for the acute period and 85% for the delayed period in 20 patients receiving moderately emetogenic chemotherapy (MEC) (doxorubicin, ≥ 50 mg/m2). Nausea was well controlled in the patients receiving HEC with no patient having more than minimal nausea (≤2 on scale of 0–10, M.D. Anderson Symptom Inventory, MDASI) in the acute or delayed periods. Nausea was also well controlled in patients receiving MEC with minimal or no nausea in 85% of patients in the acute period and 70% in the delayed period. There were no Grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes or restlessness experienced by the patients. CR and control of nausea in subsequent cycles of chemotherapy (25 patients, cycle 2; 25 patients, cycle 3; 21 patients, cycle 4) were equal to or greater than cycle 1. Conclusions: Olanzapine is safe and highly effective in controlling acute and delayed CINV in patients receiving HEC and MEC. No significant financial relationships to disclose.

The use of antiparkinsonian agents in the management of drug-induced extrapyramidal symptoms.

Antipsychotic drugs induce extrapyramidal symptoms such as dystonia, akathisia and parkinsonian symptoms early in treatment, and tardive dyskinesia later in treatment. With the advent of atypical antipsychotic drugs, the incidence of extrapyramidal symptoms has decreased, but the danger still exists. There are many reasons that extrapyramidal symptoms are still a problem. Most often, psychiatrists use doses higher than the recommended dose of atypical antipsychotic agents. For example, the use of 8 to 10 mg of risperidone, 30 to 40 mg of olanzapine, or 1200 to 1500 mg of quetiapine daily is not uncommon. In addition, combinations of both conventional and atypical antipsychotic drugs are used together in many instances. Extrapyramidal symptoms produce unnecessary suffering and add to the health burden; therefore, prompt recognition of these symptoms is necessary. If EPS occur, it is of paramount importance to start an antiparkinsonian agent immediately to provide relief to the patient. In high-risk patients, prophylactic antiparkinsonian therapy is indicated but routine prophylaxis with antiparkinsonian agents is harmful. As only a segment of patients may develop EPS, many patients receive prophylactic medication unnecessarily, and the side effects of antiparkinsonian drugs prescribed without clinical indication may add to the health burden of the patient. If prophylactic antiparkinsonian treatment is initiated, it should be discontinued at least two weeks after its initiation. The long term use of antiparkinsonian treatment is not therapeutically beneficial to the patient, and studies indicate that the gradual withdrawal of antiparkinsonian medication will not produce recurrence of EPS.

New Drug Combination

Back to table of contents Previous article Next article Letter to the EditorFull AccessNew Drug CombinationRichard Winslow, M.D.Richard WinslowSearch for more papers by this author, M.D.Published Online:19 Mar 2004https://doi.org/10.1176/pn.39.6.0075aI believe that Psychiatric News crossed the line in the December 19, 2003, issue from news to advertising in its enthusiastic article about OFC, the Eli Lilly product that the FDA is expected to approve soon.There is no doubt that an olanzapine-fluoxetine combination therapy is useful for many patients. However, combining the two medications in one pill appears to be a marketing technique, not an advance in patient care. Currently, we practicing psychiatrists can choose from a variety of olanzapine and fluoxetine dosage strengths and adjust each separately as needed for patient benefit. With the advent of generic fluoxetine this past year, self-pay patients and third-party payers alike have saved large amounts of money on patients who take this medication. And with more competition in the antipsychotic arena, even the cost of olanzapine has, thank goodness, decreased somewhat.OFC does not appear to come in a great variety of dosage combinations (just three were mentioned in one of the Web abstracts). Additionally, neither the article nor the abstracts made any mention of cost. Thus, unless each combination is less expensive than two separate prescriptions for brand-name Zyprexa and generic fluoxetine, OFC will just be one more expensive, unnecessary drug in the marketplace.Editor’s note: In view of the issues that Dr. Winslow raised, we contacted Eli Lilly and were given the following information: Symbyax is available in four strengths (mg olanzapine/mg fluoxetine): 6/25, 6/50, 12/25, and 12/50. The pricing of Symbyax is comparable, based on dosing, to Zyprexa alone. There is no additional cost for the fluoxetine component. Thus, the dosages with 6 mg of olanzapine will be priced similarly to 5 mg of Zyprexa, and 12 mg of olanzapine will be priced between 10 mg and 15 mg of Zyprexa.Mercer Island, Wash. ISSUES NewArchived

Managed care: improving psychiatric drug benefit management: I. Lessons from Massachusetts.

Managed care: improving psychiatric drug benefit management: I. Lessons from Massachusetts.

Olanzapine in the Management of Cancer Pain

In cancer patients, cognitive impairment, psychological distress, and anxiety may accompany and aggravate pain. Neuroleptics are frequently used to control these symptoms and may be used to treat pain that has been unresponsive to more conventional approaches. Because of prominent side effects of traditional neuroleptics and conflicting data regarding their analgesic efficacy, their use in the treatment of pain remains controversial. Olanzapine, an atypical neuroleptic, might offer advantages because of its safer side effect profile. It has also been shown to have an independent antinociceptive activity in animals. The use of olanzapine in the management of cancer pain has not been previously described. We prospectively collected the data on 8 cancer patients with severe pain, uncontrolled in spite of aggressive opioid titration, who received olanzapine to treat severe anxiety and mild cognitive impairment. Patients did not meet criteria for delirium and their cognitive impairment was defined as cognitive disorder not otherwise specified (NOS) according to DSM-IV. Patients received 2.5 to 7.5 mg of olanzapine daily. In all patients, opioid requirements had escalated rapidly prior to starting olanzapine. Levels of pain, sedation, and opioid use were measured 2 days before and 2 days after olanzapine was started. Cognitive state was assessed daily. All 8 patients had marked reduction of the daily pain scores. The average daily opioid use decreased significantly in all patients. Cognitive impairment and anxiety resolved within 24 hours of initiating olanzapine. In these 8 patients, decreased pain scores and opioid requirements may have resulted from improvement in cognitive function and the known anxiolytic effect of olanzapine. Other mechanisms may include independent or adjuvant analgesic effects of olanzapine. We conclude that olanzapine may be useful in the treatment of patients with uncontrolled cancer pain associated with cognitive impairment or anxiety. Further studies to evaluate possible analgesic effect of olanzapine are needed.

Efficacy of Olanzapine in the Treatment of Psychosis in Dementia with Lewy Bodies

Objective: This study sought to determine whether patients with dementia with Lewy bodies (DLB) and psychosis responded to treatment with olanzapine. Methods: This was a post hoc analysis of a subgroup of patients with DLB included in a larger double-blind, placebo-controlled, randomized parallel group trial of olanzapine for the treatment of psychosis in patients with Alzheimer’s disease. Patients meeting the consensus criteria for DLB and exhibiting parkinsonism and visual hallucinations were selected from the initial study. Psychosis was assessed with the Neuropsychiatric Inventory/Nursing Home (NPI-NH) version and the Brief Psychiatric Rating Scale (BPRS). Extrapyramidal symptoms were evaluated with the Simpson-Angus scale. Results: Twenty-nine patients met the criteria for DLB; 10 were randomized to placebo, 5 received 5 mg of olanzapine, 7 received 10 mg of olanzapine and 7 received 15 mg of olanzapine. Patients with DLB treated with 5 mg of olanzapine showed significant reductions in delusions and hallucinations. Patients treated with 10 mg showed a significant reduction in the NPI-NH delusion subscale score. No significant differences were found between the 15-mg group and the placebo group. Confirmatory findings emerged from an analysis of the BPRS. Caregivers reported decreased disruptions in their occupational routines for the group receiving 5 or 10 mg of olanzapine. There was no significant exacerbation of parkinsonian symptoms in any study group, no decrement in Mini-Mental State Examination scores in any of the treatment groups, and symptoms suggestive of anticholinergic toxicity did not differ among treatment groups. Conclusions: This preliminary analysis suggests that olanzapine (5 or 10 mg) reduces psychosis in patients with DLB without worsening parkinsonism.

PMH9: HEALTH CARE UTILIZATION AND COSTS IN SCHIZOPHRENIC PATIENTS TAKING RISPERIDONE VERSUS OLANZAPINE IN A VETERANS ADMINISTRATION POPULATION

OBJECTIVES: To compare the change in health care utilization and costs from one year before (preperiod) and one year after (postperiod) starting treatment with risperidone or olanzapine in schizophrenia patients in a Veterans Administration population. METHODS: Patients with a diagnosis of schizophrenia (ICD-9 CM code 295) in the preperiod, who had an initial prescription for risperidone or olanzapine dispensed between 3/97 and 3/99, were included. Patients who received any atypical antipsychotic in the preperiod were excluded. Comparisons of average change in utilization and cost from the preperiod to the postperiod were made between the groups for: inpatient hospitalizations, outpatient clinic visits, medications, and total health care cost. Analysis of covariance was used to analyze the data using age, gender, and race as covariates. RESULTS: 304 patients in the olanzapine group and 344 in the risperidone group were included. The olanzapine group had significantly more inpatient admissions per patient (0.09 vs. −0.24, p = 0.026), longer inpatient lengths of stay (4.3 days vs. −4.2 days, p = 0.004), and higher cost of inpatient admissions ($2735 vs. −$3226, p = 0.003) than the risperidone group. There was a significantly lower cost of antipsychotic for the risperidone group than for the olanzapine group ($650 vs. $1660, p < 0.001). The mean daily doses were 3.4 mg of risperidone and 12.0 mg of olanzapine. The olanzapine group also had a significantly higher change in cost for all drugs ($1492 vs. $683, p < 0.001) and all health care costs ($5,665 vs. −$1,167, p < 0.001) than the risperidone group. CONCLUSIONS: The changes in total health care costs, number, length of stay, and cost of inpatient admissions, and medication costs for risperidone-treated patients were significantly lower compared with olanzapine-treated patients.

Psychopharmacology: rational and irrational polypharmacy.

Psychopharmacology: rational and irrational polypharmacy.

Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT 2C receptors in vivo

Background: The study aimed to determine the effects of the atypical antipsychotic agent, olanzapine, on the polysomnogram in healthy subjects. We predicted that olanzapine, via serotonin 2C (5-HT 2C) receptor blockade, would increase slow-wave sleep (SWS). Methods: We studied the effects of single evening doses of olanzapine (5 mg and 10 mg orally) on the polysomnogram of 9 healthy male volunteers, using a placebo-controlled, double-blind, cross-over design. Results: Compared to placebo, the 5-mg and 10-mg doses of olanzapine significantly increased SWS, sleep continuity measures, and subjective sleep quality. In addition, 10 mg of olanzapine suppressed rapid eye movement (REM) sleep and increased REM sleep latency. Conclusions: Olanzapine (5 mg and 10 mg) produced substantial (59.1% and 83.3%) and highly significant dose-related increases in SWS in humans probably via blockade of brain 5-HT 2C receptors. 5-HT 2C receptor antagonism may account for some of the therapeutic and adverse effects of olanzapine therapy.

Olanzapine-Related Fatality

A 43-year-old male psychiatric outpatient died within hours of ingesting as much as 600 mg of olanzapine, a newer antipsychotic agent related to clozapine. Analysis of postmortem blood and urine by gas chromatography with nitrogen-selective detection yielded olanzapine concentrations of 1238 and 6987 micrograms/L, respectively, greatly in excess of levels expected following therapeutic administration of the drug. Based on the toxicology findings, the decedent's known history of suicide attempts, and the circumstances surrounding the death, this case was ruled a suicide by olanzapine overdosage.

Plasma level monitoring of olanzapine in patients with schizophrenia: determination by high-performance liquid chromatography with electrochemical detection.

A sensitive high-performance liquid chromatography method with electrochemical detection for the determination of olanzapine in human plasma is described. Olanzapine from plasma samples was isolated by a simple one-step liquid--liquid extraction with 15% methylene chloride in pentane with an extraction recovery of approximately 94% of the total olanzapine in plasma. The compound was separated on a cyano column. Under the conditions described, commonly coadministered drugs and other common antipsychotic drugs did not interfere with the analysis of olanzapine. The lower limit of determination of the assay was 0.25 ng of olanzapine per ml when 1 ml of plasma was used for the analysis. The interaassay and intraassay variance was (CV%) less than 10%. The standard curve was linear within the range of 0.25 to 50 ng/ml of olanzapine. This method has been used for the determination of plasma levels of olanzapine in patients with schizophrenia who were treated with daily oral doses of 10, 15, and 20 mg of olanzapine. The results indicate that the plasma level of olanzapine increases linearly with the administered daily oral dose (r = 0.6889, p = 0.01).