olanzapine and Fever

Neuroleptic malignant syndrome (NMS) is the most dangerous life-threatening complication of antipsychotic medication. It's development is connected with the blockade of dopaminergic transmission (D2 receptors) in the nigrostriatal system of the brain. Fever is one of the main symptoms of this syndrome and it's elevation is due to the activation of the immune system. Numerous studies report that treatment with clozapine (doses 37.5-600 mg) or olanzapine (doses 10-25 mg) or the use of these drugs in polytherapy cause pyrexia between 37.8-40.6 °C. Additionally, levels of proinflammatory interleukins such as IL-6, IL-1,TNF-α were increased. The aim of this article is to describe how olanzapine and clozapine influence fever development in NMS, in relation to the dose of the drug taken by schizophrenic patients including changes in immunological system.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Fever; Humans; Inflammation Mediators; Interleukins; Neuroleptic Malignant Syndrome; Olanzapine; Schizophrenia

The second generation antipsychotics clozapine and olanzapine are known to cause weight gain. However, only clozapine is associated with drug-induced fever. Cytokines have been linked to the induction of both weight gain and drug-induced fever. We investigated these potential side effects of clozapine and olanzapine and studied their differential effects on cytokine secretion. Thirty patients suffering from schizophrenia, schizophreniform disorder or schizoaffective disorder were treated with either clozapine (mean modal dose: 266.7+/-77.9mg) or olanzapine (21.2+/-2.5mg) in a randomized, double-blind, 6-week study. Body mass index (BMI), tympanic temperature, and plasma levels of leptin and cytokines (tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 and 2 (sTNFR-1/2), soluble interleukin-2 receptors (sIL-2R), interleukin-6) were determined weekly. BMI, leptin and cytokines significantly increased over time, except interleukin-6 and sTNFR-1 in the olanzapine group. All cytokines numerically increased compared to baseline already during the first week of treatment in both groups. Leptin, TNF-alpha, sTNFR-1, sTNFR-2 and sIL-2R levels correlated with the BMI. Five patients who received clozapine (33%) developed drug-induced fever (>/=38 degrees C). In these, interleukin-6 peak levels were significantly (p<0.01) higher than in those patients treated with clozapine who did not develop fever. In conclusion, increase of BMI appears to be related to clozapine's and olanzapine's similar effects on cytokine systems, whilst drug-induced fever appears to be related to clozapine's differential effects on interleukin-6.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Cytokines; Double-Blind Method; Female; Fever; Humans; Leptin; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Weight Gain

In December 2019, the novel coronavirus (SARS-CoV-2) infection was first reported in Wuhan city, central China, which has spread rapidly. The common clinical features of patients with SARS-CoV-2 infection included fever, fatigue, and damage to the respiratory or digestive system. However, it is still unclear whether SARS-CoV-2 infection could cause damage to the central nervous system (CNS) inducing psychiatric symptoms.. Herein, we present the first case of SARS-CoV-2 infection with manic-like symptoms and describe the diagnosis, clinical course, and treatment of the case, focusing on the identifications of SARS-CoV-2 in the specimen of cerebrospinal fluid (CSF). The patient developed manic-like symptoms when his vital signs recovered on illness day 17. After manic-like attack, the detection of SARS-CoV-2 specific IgG antibody in CSF was positive, while the reverse transcriptase-polymerase chain reaction (RT-PCR) on CSF for the SARS-CoV-2 was negative. The patient received Olanzapine for treatment and his mood problems concurrently improved as indicated by scores of Young Manic Rating Scale (YMRS).. This is a single case report only, and the RT-PCR test for SARS-CoV-2 in CSF was not performed simultaneously when SARS-CoV-2 was positive in samples of sputum and stool.. This first case of COVID-19 patient with manic-like symptoms highlights the importance of evaluation of mental health status and may contribute to our understanding of potential risk of CNS impairments by SARS-CoV-2 infection.

Topics: Antibodies, Viral; Antipsychotic Agents; Antiviral Agents; Betacoronavirus; Bipolar Disorder; Brain; Chest Pain; China; Clinical Laboratory Techniques; Cobicistat; Coronavirus Infections; COVID-19; COVID-19 Testing; Darunavir; Dyspnea; Fever; Glucocorticoids; Humans; Indoles; Magnetic Resonance Imaging; Male; Methylprednisolone; Middle Aged; Moxifloxacin; Olanzapine; Pandemics; Pharyngitis; Pneumonia, Viral; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2

Topics: Adult; Antipsychotic Agents; Fever; Humans; Male; Olanzapine; Schizophrenia, Paranoid

Olanzapine, a frequently used second-generation antipsychotic, has rarely been implicated as a cause of drug-induced fever in the absence of neuroleptic malignant syndrome. We describe a patient who developed isolated fever following olanzapine monotherapy, which subsided after discontinuation of olanzapine. Blockade of dopaminergic receptors and elevated cytokines concentration are possible mechanisms of fever development during treatment with olanzapine. This case calls for attention to olanzapine-induced fever in clinical practice.

Topics: Adult; Antipsychotic Agents; Female; Fever; Humans; Olanzapine; Schizophrenia

Topics: Acute Kidney Injury; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Fever; Humans; Hydrotherapy; Male; Neuroleptic Malignant Syndrome; Olanzapine; Ramipril

Topics: Adolescent; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Fever; Fructose; Humans; Olanzapine; Rhabdomyolysis; Topiramate

In female rats olanzapine (4 mg/kg b.i.d., i.p.) induced acute hypothermia, followed by very rapid full tolerance. With more prolonged treatment (over > 10 days) the hypothermic effect of olanzapine was reinstated. Subsequent withdrawal after 18 days of treatment induced very rapid onset (within 1 day) hyperthermia, which was time limited, dissipating completely over 3-4 days. These findings are similar to previous findings with clozapine [Goudie A Smith J Robertson A Cavanagh C (1999). Clozapine as a drug of dependence. Psychopharmacology; 142: 369-374.]. Although the mechanism(s) involved in the secondary hypothermic effect of olanzapine are, at present, unclear; the withdrawal hyperthermia observed represents the first report of a clear discontinuation effect of olanzapine. Such discontinuation effects are probably observed with many antipsychotic drugs. Since they have been suggested to facilitate relapse to psychosis and to interfere with subsequent clinical responses to antipsychotics, they merit further detailed analysis in both clinical and preclinical studies.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Body Temperature; Drug Tolerance; Female; Fever; Olanzapine; Rats; Rats, Wistar; Substance Withdrawal Syndrome

It is hypothesized that atypical antipsychotic drugs have neuroprotective effects which may be one of the mechanisms in treatment of schizophrenia. We investigated the neuroprotective effects of olanzapine (OLA), an atypical antipsychotic drug, on methamphetamine (METH)-induced neurotoxicity in rats. After pretreatment with OLA (2 mg/kg/day) by intraperitoneal injection for 2 weeks, rats were administered METH (7.5 mg/kg, four times at 2-h intervals) by subcutaneous injection while their body temperature was monitored. The rats were sacrificed 24 h after the last injection of METH for immunohistochemistry. METH-induced 24 h mortality was effectively reduced and METH-induced decrease of tyrosine hydroxylase immunoreactivity in caudate putamen (CPu) was significantly attenuated by OLA chronic pretreatment. Furthermore, we showed that the above neuroprotective potential of OLA might be associated with its attenuating effects on METH-induced hyperthermia and with its preventative actions on METH-induced decrease of Bcl-2, an anti-apoptotic gene product, in the CPu. Our results suggest that OLA may be a neuroprotective agent and that its neuroprotective potential may contribute to its therapeutic effects in treatment of schizophrenia.

Topics: Analysis of Variance; Animals; Apoptosis; Benzodiazepines; Brain Diseases; Dopamine; Fever; Immunohistochemistry; Male; Methamphetamine; Neostriatum; Neuroprotective Agents; Neurotoxins; Olanzapine; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Survival Rate; Tyrosine 3-Monooxygenase

Life-threatening hyperthermia occurs in some individuals taking 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). In rabbits, sympathetically mediated vasoconstriction in heat-exchanging cutaneous beds (ear pinnae) contributes to MDMA-elicited hyperthermia. We investigated whether MDMA-elicited cutaneous vasoconstriction and hyperthermia are reversed by clozapine and olanzapine, atypical antipsychotic agents. Ear pinna blood flow and body temperature were measured in conscious rabbits; MDMA (6 mg/kg, i.v.) was administered; and clozapine (0.1-5 mg/kg, i.v.) or olanzapine (0.5 mg/kg, i.v.) was administered 15 min later. One hour after MDMA, temperature was 38.7 +/- 0.5 degrees C in 5 mg/kg clozapine-treated rabbits and 39.0 +/- 0.2 degrees C in olanzapine-treated rabbits, less than untreated animals (41.5 +/- 0.3 degrees C) and unchanged from pre-MDMA values. Ear pinna blood flow increased from the MDMA-induced near zero level within 5 min of clozapine or olanzapine administration. Clozapine-induced temperature and flow responses were dose-dependent. In urethane-anesthetized rabbits, MDMA (6 mg/kg, i.v.) increased ear pinna postganglionic sympathetic nerve discharge to 217 +/- 33% of the pre-MDMA baseline. Five minutes after clozapine (1 mg/kg, i.v.) discharge was reduced to 10 +/- 4% of the MDMA-elicited level. In conscious rats made hyperthermic by MDMA (10 mg/kg, s.c.), body temperature 1 hr after clozapine (3 mg/kg, s.c.) was 36.9 +/- 0.5 degrees C, <38.6 +/- 0.3 degrees C (Ringer's solution-treated) and not different from the pre-MDMA level. One hour after clozapine, rat tail blood flow was 24 +/- 3 cm/sec, greater than both flow in Ringer's solution-treated rats (8 +/- 1 cm/sec) and the pre-MDMA level (17 +/- 1 cm/sec). Clozapine and olanzapine, by interactions with 5-HT receptors or by other mechanisms, could reverse potentially fatal hyperthermia and cutaneous vasoconstriction occurring in some humans after ingestion of MDMA.

Topics: Anesthesia; Animals; Antipsychotic Agents; Benzodiazepines; Body Temperature; Clozapine; Disease Models, Animal; Dose-Response Relationship, Drug; Ear; Fever; N-Methyl-3,4-methylenedioxyamphetamine; Olanzapine; Pirenzepine; Rabbits; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Skin; Sympathetic Nervous System; Tail; Treatment Outcome; Vasoconstriction; Wakefulness

Rhabdomyolysis is a disorder characterized by skeletal muscle injury and fatal complications at times. The causes of rhabdomyolysis are usually traumatic and non-traumatic, such as neuroleptic malignant syndrome and rhabdomyolysis associated to septicemia. The cases of 2 schizophrenic patients with rhabdomyolisis during pneumonia infection and neuroleptic therapy are reported. At admission, both patients had important respiratory distress and hyperthermia; the clinical conditions required endotracheal intubation. Blood and urine cultures were always negative, while the bronchial sputum culture was positive. The diagnosis of rhabdomyolysis was confirmed by myoglobinemia dosage and ortholuidine test. Pneumonia infection was treated with antibiotic specific therapy whereas renal failure was treated with adequate hydratation and strained diuresis. The absence of muscle rigidity, the improvement of X-r images and the reduction of corporeal temperature, during antibiotic treatment, excluded neuroleptic malignant syndrome. The impro-vement allowed extubation and discharge of the patients from intensive care unit. In both cases neuroleptic malignant syndrome was excluded, therefore rhabdomyolysis was the consequence of pneumonia infection or of a combination of factors capable to cause an important damage of skeletal muscles.

Topics: Acute Kidney Injury; Adult; Antipsychotic Agents; Benzodiazepines; Diagnosis, Differential; Fever; Humans; Male; Middle Aged; Muscle Rigidity; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Pneumonia, Bacterial; Rhabdomyolysis; Risperidone; Schizophrenia

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Disease Models, Animal; Fever; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Olanzapine; Serotonin Antagonists

Hypersensitivity syndrome is defined as a drug-induced complex of symptoms consisting of fever, rash, and internal organ involvement. The hypersensitivity syndrome is well recognized as being caused by anticonvulsants. Olanzapine is an atypical antipsychotic agent whose side effects include sedation, weight gain, and increased creatinine kinase and transaminase levels. To date, there have been no reports of hypersensitivity syndrome related to this drug. A 34-year-old man developed a severe generalized pruritic skin eruption, fever, eosinophilia, and toxic hepatitis 60 days after ingestion of olanzapine. After termination of olanzapine treatment, the fever resolved, the skin rash was reduced, eosinophil count was reduced to normal, and the transaminase levels were markedly reduced. Clinical features and the results of skin and liver biopsies indicated that the patient developed hypersensitivity syndrome caused by olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chemical and Drug Induced Liver Injury; Diagnostic Errors; Drug Eruptions; Drug Hypersensitivity; Dyspnea; Eosinophilia; Fever; Humans; Male; Olanzapine; Pirenzepine; Pruritus; Respiratory Hypersensitivity; Respiratory Insufficiency; Schizophrenia, Paranoid; Syndrome

The study objectives were to examine the effects of the atypical antipsychotic drugs olanzapine, risperidone, and quetiapine on core temperature in the rat in relation to such effects produced by clozapine and to compare possible in vivo intrinsic efficacy of olanzapine, risperidone, and quetiapine at dopamine (DA) D(1) receptors with such effects previously shown for clozapine. Core temperature measurements were made in adult male Wistar rats maintained under standard laboratory conditions using a reversed 12-h daylight cycle. Clozapine (0-32 micromol/kg s.c.), olanzapine (0-32 micromol/kg s.c.), and risperidone (0-4 micromol/kg s.c.) all produced a dose-dependent hypothermia. Except for slight nondose-dependent hyperthermia, there were no effects of quetiapine (0-16 micromol/kg s.c. or i.p.) on the core temperature. The hypothermia produced by clozapine, but not that produced by equipotent doses of olanzapine or risperidone, was fully antagonized by pretreatment with the DA D(1) receptor antagonist SCH-23,390 (0.1 micromol/kg s.c.). On the other hand, quinpirole-induced hypothermia (4 micromol/kg s.c.) was partially antagonized by olanzapine (2 micromol/kg s.c.), risperidone (4 micromol/kg s.c.), and quetiapine (16 micromol/kg s.c.) but not by clozapine (1 micromol/kg s.c.). Clozapine preferentially stimulates DA D(1) receptors in comparison with olanzapine and risperidone, whereas olanzapine, risperidone, and quetiapine preferentially block DA D(2) receptors compared with clozapine. It is suggested that stimulation of DA D(1) receptors, presumably in the prefrontal cortex, is a distinguishing feature of clozapine responsible for its favorable profile on cognitive functioning in schizophrenia.

Topics: Animals; Antipsychotic Agents; Benzazepines; Benzodiazepines; Clozapine; Dibenzothiazepines; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Interactions; Fever; Hypothermia; Male; Olanzapine; Pirenzepine; Quetiapine Fumarate; Quinpirole; Rats; Rats, Wistar; Receptors, Dopamine; Risperidone; Time Factors

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Fever; Humans; Male; Mental Disorders; Muscle Rigidity; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine