olanzapine and Anorexia

Anorexia occurs in 30%-80% of patients with advanced malignancies, which may be worsened with chemotherapy. This trial assessed the efficacy of olanzapine in stimulating appetite and improving weight gain in patients receiving chemotherapy.. Adults (≥18 years) with untreated, locally advanced, or metastatic gastric, hepatopancreaticobiliary (HPB), and lung cancers were randomly assigned (double-blind) to receive olanzapine (2.5 mg once a day for 12 weeks) or placebo along with chemotherapy. Both groups received standard nutritional assessment and dietary advice. The primary outcomes were the proportion of patients with weight gain > 5% and the improvement in appetite (assessed by the visual analog scale [VAS] and the Functional Assessment of Chronic Illness Therapy system of Quality-of-Life questionnaires Anorexia Cachexia subscale [FAACT ACS]). Secondary end points were change in nutritional status, quality of life (QOL), and chemotherapy toxicity.. We enrolled 124 patients (olanzapine, 63 and placebo, 61) with a median age of 55 years (18-78 years), of whom 112 (olanzapine, 58 and placebo, 54) were analyzable. The majority (n = 99, 80%) had metastatic cancer (gastric [n = 68, 55%] > lung [n = 43, 35%] > HPB [n = 13, 10%]). The olanzapine arm had a greater proportion of patients with a weight gain of > 5% (35 of 58 [60%]. Low-dose, daily olanzapine is a simple, inexpensive, well-tolerated intervention that significantly improves appetite and weight gain in newly diagnosed patients on chemotherapy.

Topics: Adult; Anorexia; Double-Blind Method; Humans; Lung Neoplasms; Middle Aged; Olanzapine; Quality of Life; Weight Gain

Clinical observations of cancer patients treated with selinexor have reported high incidence of nausea and anorexia. The study objective was to investigate the adoption of prophylactic olanzapine for the prevention of nausea, vomiting and anorexia in cancer patients receiving selinexor and standard chemotherapy.. We retrospectively reviewed supportive care interventions in patients receiving selinexor and recorded frequency of adverse events (NCI-CTAE). Association between categorical variables were analyzed using Fisher's exact tests; repeated measures analysis was performed to assess weight changes over time.. Of 124 evaluable patients, 83 (66.9%) were female, 93 were white (75.0%), and the most common cancer was ovarian (N = 30, 24.2%). One hundred and four patients (83.9%) received olanzapine, of which 93 (89.4%) were prophylactically treated, the majority (86.5%) receiving low 2.5 mg daily dose. Other anti-emetics included ondansetron in 90 patients (72.6%), dexamethasone prescribed in 50 patients (40.3%) and metoclopramide in 49 patients (39.5%), while aprepitant/fosaprepitant (N = 2, 1.6%) were prescribed infrequently. Cancer patients receiving prophylactic olanzapine (N = 93) compared to patients who never received olanzapine (N = 20) had more Grade 1 + anorexia (31.2% vs 20.0%), less nausea (53.8% vs 70.0%), less vomiting (33.3% vs 40.0%), and increased hyperglycemia (29.0% vs 10.0%), but differences were non-statistically significant. In addition, there was minimal weight loss over time in both groups and no statistically significant differences in weight loss between groups.. Prophylactic olanzapine decreased nausea, vomiting and maintained weight over 3 months but did not prevent anorexia in patients receiving selinexor and chemotherapy. Low dose olanzapine was well tolerated but associated with hyperglycemia.

Topics: Adult; Aged; Anorexia; Antiemetics; Female; Humans; Hydrazines; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Triazoles; Vomiting; Young Adult

The purpose of the study was to determine the effectiveness of megestrol acetate (MA) and olanzapine (OLN) for the treatment of cancer-related anorexia (CRA).. Eighty adult patients with advanced gastrointestinal cancer or lung cancer (stages III and IV) with CRA (loss of appetite and greater than or equal to 5% loss of preillness stable weight) were randomized to receive daily MA or MA plus OLN for a period of 8 weeks. Patients were assessed weekly using the M.D. Anderson Symptom Inventory with specific measurement of weight, appetite, nausea, and quality of life (QOL) measures.. For the 37 patients receiving MA, 15 patients had a greater than or equal to 5% weight gain, 2 patients had an appetite improvement, 3 patients had an improvement in nausea, and 5 patients had an improvement in QOL at both 4 and 8 weeks. For the 39 patients receiving MA plus OLN, 33 patients had a greater than or equal to 5% weight gain, 25 patients had an appetite improvement, 21 patients had an improvement in nausea, and 23 patients had an improvement in QOL at both 4 and 8 weeks, and there was an improvement in general activity, mood, work, walking, and enjoyment at 8 weeks. There were no grade III or IV treatment-related toxicities in patients receiving MA or the combination of MA plus OLN.. The combination of MA and OLN appears to be an effective intervention for patients with CRA.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Appetite; Appetite Stimulants; Benzodiazepines; Body Weight; Drug Therapy, Combination; Female; Gastrointestinal Neoplasms; Humans; Lung Neoplasms; Male; Megestrol Acetate; Middle Aged; Nausea; Neoplasm Staging; Olanzapine; Quality of Life; Selective Serotonin Reuptake Inhibitors

Anorexia nervosa (AN) patients often show extreme hypophagia and excessive physical activity. Activity-based anorexia (ABA) is considered an animal model of AN and mimics food restriction and hyperactivity in rats. This study investigated whether treatment with olanzapine (Zyprexa) reduces the development of ABA in rats. The effect of olanzapine treatment in AN patients was also evaluated in a small open-label study.. Rats were chronically (1 week) infused with olanzapine (7.5 mg/kg) and exposed to the ABA model or ad libitum feeding. Hyperactive AN patients were followed for up to 3 months of olanzapine treatment (5 mg/kg).. Olanzapine treatment reduced development of ABA in rats by reducing running wheel activity, starvation-induced hypothermia and activation of the hypothalamus-pituitary-adrenal axis. Olanzapine treatment reduced activity levels of AN patients compared with untreated AN patients, without affecting body weight and plasma leptin levels.. Olanzapine treatment reduced wheel running and thereby diminished development of ABA in rats. Olanzapine treatment also reduced physical activity in hyperactive AN patients in a small open-label study. These data support the need for controlled studies investigating the putative beneficial effects of olanzapine treatment in AN patients.

Topics: Adipose Tissue; Adolescent; Adrenocorticotropic Hormone; Animals; Anorexia; Antipsychotic Agents; Behavior, Animal; Benzodiazepines; Body Temperature; Body Weight; Corticosterone; Disease Models, Animal; Drug Administration Schedule; Eating; Female; Humans; Male; Motor Activity; Olanzapine; Radioimmunoassay; Rats; Rats, Wistar; Running; Time Factors

Chemotherapy-induced delayed emesis (DE) can affect up to 50% to 70% of patients receiving moderately and highly emetogenic chemotherapy, although rates are improving. DE most commonly occurs within the first 24 to 48 hours of chemotherapy administration and can persist for 2 to 5 days. Olanzapine, due to its activity at multiple dopaminergic, serotonergic, muscarinic, and histaminic receptor sites, has potential as antiemetic therapy. A phase I study was designed with olanzapine, using a four-cohort dose escalation of 3 to 6 patients per cohort, for the prevention of DE in cancer patients receiving their first cycle of chemotherapy consisting of cyclophosphamide, doxorubicin, platinum, and/or irinotecan. All patients received standard premedication. Olanzapine was administered on days -2 and -1 prior to chemotherapy and continued for 8 days (days 0-7). Episodes of vomiting as well as daily measurements of nausea, sedation, and toxicity were monitored at each dose level. Fifteen patients completed the protocol. No grade 4 toxicities were seen, and three patients experienced a dose-limiting toxicity (grade 3) of a depressed level of consciousness during the study. The maximum tolerated dose appeared to be 5 mg (for days -2 and -1) and 10 mg (for days 0-7). Four of six patients receiving highly emetogenic chemotherapy (cisplatin, > or = 70 mg/m2) and nine of nine patients receiving moderately emetogenic chemotherapy (doxorubicin, > or = 50 mg/m2) had complete control (no vomiting episodes) of DE. Therefore, olanzapine may be an effective agent for the prevention of chemotherapy-induced DE. A phase II trial is underway.

Topics: Adult; Aged; Anorexia; Antiemetics; Antineoplastic Agents; Benzodiazepines; Camptothecin; Cohort Studies; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Female; Humans; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Mood Disorders; Nausea; Neoplasms; Olanzapine; Organoplatinum Compounds; Time Factors; Treatment Outcome; Vomiting

The atypical antipsychotic drug olanzapine is prescribed despite clinical studies on olanzapine treatment showing mixed results on treatment efficacy in anorexia nervosa. We investigated the effect of systemic and intranasal administration of olanzapine in the activity-based anorexia (ABA) model. Rats were habituated to a running wheel and exposed to the ABA model while treated with olanzapine. During ABA rats had 1.5 h of daily access to food and ad libitum access to a running wheel for seven consecutive days. Olanzapine was administered via an osmotic minipump (1, 2.75, and 7.5 mg/kg) or intranasally 2 h before dark onset (1 and 2.75 mg/kg). We monitored body weight, food intake, wheel revolutions, body temperature, and adipose tissue. We found 2.75 and 7.5 mg/kg systemic olanzapine decreased wheel revolutions during ABA. Relative adipose tissue mass was increased in the 7.5 mg/kg olanzapine-treated group while body weight, food intake, and body temperature were unaltered by the systemic olanzapine. 1 and 2.75 mg/kg intranasal olanzapine diminished wheel revolutions and body temperature during the first 2 h after administration. The intranasal olanzapine-treated rats had a higher body weight at the end of ABA. We find that olanzapine has beneficial outcomes in the ABA via two administration routes by acting mainly on running wheel activity. Intranasal olanzapine showed a rapid effect in the first hours after administration in reducing locomotor activity. We recommend further exploring intranasal administration of olanzapine in anorectic patients to assist them in coping with restlessness.

Topics: Administration, Intranasal; Animals; Anorexia; Anorexia Nervosa; Body Weight; Disease Models, Animal; Eating; Olanzapine; Rats

Cancer patients often experience symptoms such as anorexia, anxiety and insomnia, which can impact their quality of life. Randomized placebo-controlled trials support prophylactic use of olanzapine for the prevention of nausea and vomiting due to moderate and high-emetic risk chemotherapy. In the setting of palliative care, olanzapine is increasingly utilized as an off-label treatment of symptoms including anorexia-cachexia, anxiety, and insomnia. The following case reports will highlight the potential benefits and risks of off-label olanzapine use for symptom management in cancer patients.. Patient 1 is a female in her 70s with stage IV infiltrating ductal carcinoma of the right breast was having trouble tolerating treatment with letrozole, palbociclib, and denosumab due to uncontrolled nausea resulting in weight loss. Her nausea was refractory to multiple anti-emetics. Low dose olanzapine (2.5 mg) prevented nausea and allowed her to tolerate treatment. Patient 2 is a male in his 50s with renal cell carcinoma, who was receiving treatment with cabozantinib, presented with uncontrolled pain improved with opioid rotation from oxycodone to morphine. He was also experiencing uncontrolled anxiety despite treatment with alprazolam. Alprazolam was weaned and replaced with olanzapine resulting in improvement of his symptoms. Patient 3 is a male in his 60s with pancreatic adenocarcinoma who presented with muscle weakness and fatigue resulting in discontinuation of gemcitabine plus cisplatin. He also had symptoms of depression, poor appetite, and sleep problems. He was prescribed short course of dexamethasone 4 mg by mouth twice daily and olanzapine 5 mg by mouth nightly to improve symptoms. One week after, he presented with confusion and workup revealed hyperammonia which was treated with lactulose, which led to the return of baseline mentation.. Olanzapine antagonizes multiple receptors and has potential to treat a host of symptoms including nausea, anorexia, anxiety, and insomnia, but healthcare providers should be mindful of potential risks and unclear benefits for off-label indications. More research and funding are needed evaluating off-label use of olanzapine for palliation of symptoms in cancer patients who are often frail and susceptible to adverse events.

Topics: Adenocarcinoma; Aged; Alprazolam; Anorexia; Antiemetics; Cisplatin; Female; Humans; Male; Middle Aged; Nausea; Off-Label Use; Olanzapine; Palliative Care; Pancreatic Neoplasms; Quality of Life; Risk Assessment; Sleep Initiation and Maintenance Disorders; Vomiting

Anorexia nervosa (AN) is an eating disorder characterized by extreme hypophagia, hyperactivity, and fear of weight gain. No approved pharmacological treatments exist for AN despite high mortality rates. The activity-based anorexia (ABA) phenomenon models aspects of AN in rodents, including progressive weight loss, reduced food intake, and hyperactivity. First, we optimized the ABA paradigm for mice. We compared mouse strains (Balb/cJ, A/J) for susceptibility with ABA, and evaluated the effects of different food access durations (2, 4, 6, 8, and 10 h) on ABA parameters. Balb/cJ mice exhibited significantly shorter survival time (days until 25% bodyweight loss) in the ABA paradigm compared with A/J mice. Furthermore, 6 h of food access reduced survival in mice housed with wheels without reducing survival in mice housed without wheels. We then evaluated the effects of chronic treatment with fluoxetine (4 weeks) or subchronic treatment with olanzapine (OLZ) (1 week) on ABA in BALB/cJ mice. OLZ (12 mg/kg/day) significantly increased survival and reduced food anticipatory activity (FAA). However, OLZ did not alter food intake or running wheel activity during ad-lib feeding (baseline) or restriction conditions, or in mice housed without wheels. Fluoxetine (18 mg/kg/day) increased food intake and reduced FAA, but did not alter survival. Here, we report for the first time that OLZ, but not fluoxetine, reduces ABA in mice. Our findings indicate further need for clinical investigations into the effects of OLZ, but not selective serotonin reuptake inhibitors, on core features of AN.

Topics: Animals; Anorexia; Benzodiazepines; Body Weight; Disease Models, Animal; Dose-Response Relationship, Drug; Eating; Female; Fluoxetine; Mice; Motor Activity; Olanzapine; Running; Selective Serotonin Reuptake Inhibitors; Survival Rate

Recent investigations suggest the efficacy of olanzapine in cancer patients with intractable vomiting or chemotherapy-induced nausea. Olanzapine,indicated for schizophrenia in Japan, has an affinity for multiple neurotransmitter receptors including dopaminergic, serotonergic, histaminergic, adrenergic and muscarinic receptors. This pharmacological activity thus has a potential role in the treatment of nausea and vomiting. In the present study, olanzapine was given to five cancer patients with refractory vomiting to standard medications. In 3 cases, olanzapine resolved vomiting completely and also improved anorexia, In 2 cases, vomiting was controlled for a limited period. No adverse effect was observed. These results suggest olanzapine is a useful agent for the management of both vomiting and anorexia.

Topics: Aged; Anorexia; Antiemetics; Benzodiazepines; Female; Humans; Male; Middle Aged; Neoplasms; Olanzapine; Vomiting, Anticipatory

Topics: Adult; Anorexia; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Fluoxetine; Humans; Mianserin; Mirtazapine; Olanzapine; Selective Serotonin Reuptake Inhibitors