quetiapine-fumarate and Respiratory-Insufficiency

Opioid poisoning is a frequent cause of death in drug addicts and occurs with opioid treatment. Quetiapine is often found in forensic autopsies and may increase the risk of fatal opioid poisoning by enhancing sedation, respiratory depression, hypotension and QT prolongation. We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone. Case reports describing toxicity of quetiapine combined with morphine or methadone were also included. We retrieved one human study that observed pharmacokinetic interaction between quetiapine and methadone, and 16 other human studies. Fourteen investigated the combination of droperidol and morphine in treatment doses, and some indicated an additive sedative effect. Five animal studies with acepromazine in combination with morphine or methadone were located and indicated an additive effect on sedation and hypotension. Six forensic case reports in which death could have been caused solely by quetiapine, the opioid, or other drugs were found. Thus, acute toxicity of quetiapine combined with morphine or methadone has not been studied. Because of quetiapine's effects on alpha-adrenoceptors, muscarinic and histamine receptors, human ether-a-go-go-channels and methadone kinetics, we suggest further research to clarify if the indicated additive effects of opioids and droperidol or acepromazine are also true for quetiapine.

Topics: Adolescent; Adult; Analgesics, Opioid; Animals; Antipsychotic Agents; Arrhythmias, Cardiac; Autopsy; Cause of Death; Consciousness; Drug Interactions; Drug Overdose; Female; Forensic Toxicology; Humans; Hypotension; Male; Methadone; Middle Aged; Morphine; Opioid-Related Disorders; Quetiapine Fumarate; Respiratory Insufficiency; Risk Assessment; Risk Factors

Opioids can cause severe respiratory depression by suppressing feedback mechanisms that increase ventilation in response to hypercapnia. Following the addition of boxed warnings to benzodiazepine and opioid products about increased respiratory depression risk with simultaneous use, the US Food and Drug Administration evaluated whether other drugs that might be used in place of benzodiazepines may cause similar effects.. To study whether combining paroxetine or quetiapine with oxycodone, compared with oxycodone alone, decreases the ventilatory response to hypercapnia.. Randomized, double-blind, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) with 25 healthy participants from January 2021 through May 25, 2021.. Oxycodone 10 mg on days 1 and 5 and the following in a randomized order for 5 days: paroxetine 40 mg daily, quetiapine twice daily (increasing daily doses from 100 mg to 400 mg), or placebo.. Ventilation at end-tidal carbon dioxide of 55 mm Hg (hypercapnic ventilation) using rebreathing methodology assessed for paroxetine or quetiapine with oxycodone, compared with placebo and oxycodone, on days 1 and 5 (primary) and for paroxetine or quetiapine alone compared with placebo on day 4 (secondary).. Among 25 participants (median age, 35 years [IQR, 30-40 years]; 11 female [44%]), 19 (76%) completed the trial. The mean hypercapnic ventilation was significantly decreased with paroxetine plus oxycodone vs placebo plus oxycodone on day 1 (29.2 vs 34.1 L/min; mean difference [MD], -4.9 L/min [1-sided 97.5% CI, -∞ to -0.6]; P = .01) and day 5 (25.1 vs 35.3 L/min; MD, -10.2 L/min [1-sided 97.5% CI, -∞ to -6.3]; P < .001) but was not significantly decreased with quetiapine plus oxycodone vs placebo plus oxycodone on day 1 (33.0 vs 34.1 L/min; MD, -1.2 L/min [1-sided 97.5% CI, -∞ to 2.8]; P = .28) or on day 5 (34.7 vs 35.3 L/min; MD, -0.6 L/min [1-sided 97.5% CI, -∞ to 3.2]; P = .37). As a secondary outcome, mean hypercapnic ventilation was significantly decreased on day 4 with paroxetine alone vs placebo (32.4 vs 41.7 L/min; MD, -9.3 L/min [1-sided 97.5% CI, -∞ to -3.9]; P < .001), but not with quetiapine alone vs placebo (42.8 vs 41.7 L/min; MD, 1.1 L/min [1-sided 97.5% CI, -∞ to 6.4]; P = .67). No drug-related serious adverse events were reported.. In this preliminary study involving healthy participants, paroxetine combined with oxycodone, compared with oxycodone alone, significantly decreased the ventilatory response to hypercapnia on days 1 and 5, whereas quetiapine combined with oxycodone did not cause such an effect. Additional investigation is needed to characterize the effects after longer-term treatment and to determine the clinical relevance of these findings.. ClinicalTrials.gov Identifier: NCT04310579.

Topics: Adult; Analgesics, Opioid; Antidepressive Agents; Benzodiazepines; Carbon Dioxide; Double-Blind Method; Female; Humans; Hypercapnia; Oxycodone; Paroxetine; Quetiapine Fumarate; Respiration; Respiratory Insufficiency

Atypical antipsychotics are used in cardiac intensive care units (CICU) to treat delirium despite limited data on safety in patients with acute cardiovascular conditions. Patients treated with these agents may be at higher risk for adverse events such as QTc prolongation and arrhythmias. We performed a retrospective cohort study of 144 adult patients who were not receiving antipsychotics before admission and received olanzapine (n = 50) or quetiapine (n = 94) in the Michigan Medicine CICU. Data on baseline characteristics, antipsychotic dose and duration, length of stay, and adverse events were collected. Adverse events included ventricular tachycardia (sustained ventricular tachycardia attributed to the medication), hypotension (systolic blood pressure <90 mm Hg attributed to the medication), and QTc prolongation (QTc increase by ≥60 ms or to an interval ≥500 ms). Twenty-six patients (18%) experienced an adverse event. Of those adverse events, 20 patients (14%) experienced QTc prolongation, 3 patients (2%) had ventricular tachycardia, and 3 patients (2%) had hypotension. Patients who received quetiapine had a higher rate of adverse events (25% vs 6%, p = 0.01) including QTc prolongation (18% vs 6%, p = 0.046). Intensive care unit length of stay was shorter in patients who received olanzapine (6.5 vs 9.5 days, p = 0.047). Eighteen patients (13%) had their antipsychotic continued at discharge from the hospital. In conclusion, QTc prolongation was more common in patients treated with quetiapine versus olanzapine although the number of events was relatively low with both agents in a CICU cohort.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Arrhythmias, Cardiac; Coronary Care Units; Delirium; Endocarditis; Female; Heart Arrest; Heart Failure; Humans; Hypotension; Length of Stay; Long QT Syndrome; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; Shock, Cardiogenic; ST Elevation Myocardial Infarction; Tachycardia, Ventricular

Second-generation antipsychotics (SGAs) are far more commonly used in the United States compared to first-generation antipsychotics (FGAs), but the relative safety of SGAs compared to FGAs following acute toxic ingestions has not been studied.. A retrospective cohort study was performed by chart review of the California Poison Control System electronic database of 1975 cases from the 10-year period 1997 to 2006 involving patients aged 18 to 65 years who ingested a single SGA or FGA. Cases were coded for overall severity of adverse outcome as defined by the American Association of Poison Control Centers criteria and for presence of specific symptoms and treatments. Odds ratios were calculated between SGAs and FGAs for various symptoms, treatments, and outcome severity.. Odds of a major adverse outcome or death were significantly higher for SGAs than FGAs (OR = 1.71, 95% CI = 1.09 to 2.71). Patients taking SGAs had higher odds of respiratory depression (OR = 2.39, 95% CI = 1.09 to 5.26), coma (OR = 2.18, 95% CI = 1.30 to 3.65), and hypotension (OR = 1.80, 95% CI = 1.23 to 2.63) compared to those taking FGAs but lower odds of dystonia (OR = 0.12, 95% CI = 0.08 to 0.19) or rigidity (OR = 0.30, 95% CI = 0.10 to 0.90).. SGAs appear no safer than FGAs in acute overdose. While neuromuscular symptoms appear less frequently with SGAs compared to FGAs, the relatively greater rates of central nervous system depression associated with SGA overdose may be more dangerous.

Topics: Antipsychotic Agents; Cause of Death; Cohort Studies; Coma; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Dyskinesia, Drug-Induced; Follow-Up Studies; Humans; Hypotension; Long QT Syndrome; Neuroleptic Malignant Syndrome; Odds Ratio; Poison Control Centers; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; Risk Factors; Schizophrenia; Survival Analysis

To report a case of acute respiratory failure after a single dose of quetiapine fumarate in an elderly patient with a history of chronic obstructive pulmonary disease (COPD).. A 92-year-old woman with a history of COPD was admitted to the hospital with pneumonia. Her symptoms improved with antibiotics. Because of acute agitation and delirium, quetiapine 50 mg twice daily was started. After receiving the first dose, the woman developed acute respiratory failure and severe central nervous system depression. She required mechanical ventilation and supportive care in the intensive care unit (ICU). She had a full recovery within 24 hours.. Quetiapine is an atypical antipsychotic that has been used successfully for the treatment of schizophrenia and bipolar disorder for many years. Recently, it has also been used to treat delirium and agitation. It has proven to be very safe, even in the elderly. In previously reported cases, serious adverse effects were seen in patients who ingested very high doses of quetiapine. Those patients required intubation and supportive care in the ICU. To our knowledge, as of January 19, 2006, this is the first case report of acute respiratory failure of such severity with one dose of quetiapine. Using the Naranjo probability scale, we conclude that the acute respiratory failure observed in this patient was probably related to quetiapine.. This case suggests that quetiapine can have significant adverse effects even with a single 50 mg dose. Elderly patients, especially those with significant underlying pulmonary pathology, should be monitored closely when started on this medication.

Topics: Aged, 80 and over; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Psychomotor Agitation; Pulmonary Disease, Chronic Obstructive; Quetiapine Fumarate; Respiration, Artificial; Respiratory Insufficiency

To report a case of quetiapine/venlafaxine intoxication associated with multiple complications and to review their possible relationship with these 2 drugs.. A 53-year-old white man was admitted to the hospital for loss of consciousness secondary to voluntary intoxication with venlafaxine and quetiapine. Several complications were attributable to this intoxication including seizures, prolonged coma, respiratory depression, neuroleptic malignant syndrome, prolonged QRS and QTc intervals, and a possible venlafaxine withdrawal syndrome.. Quetiapine could be responsible for the neuroleptic malignant syndrome presented in this case. Moreover, venlafaxine intoxication, fever, autonomic instability, and myoclonus presented serotonin syndrome as a differential diagnosis. Potential causes of seizures and prolongation of the QRS and QTc intervals are reviewed. Finally, prolonged coma and late venlafaxine withdrawal are discussed with regard to the pharmacodynamics and pharmacokinetics of drug elimination in the context of intoxication.. Clinicians should be aware of possible complications following intoxication with atypical antipsychotics and anti-depressants, including protracted altered mental status.

Topics: Coma; Cyclohexanols; Diagnosis, Differential; Dibenzothiazepines; Drug Overdose; Electrocardiography; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Quetiapine Fumarate; Respiratory Insufficiency; Seizures; Serotonin Agents; Serotonin Syndrome; Substance Withdrawal Syndrome; Venlafaxine Hydrochloride

We describe the effects of quetiapine in overdose.. Quetiapine poisonings were identified from a prospective database of poisoning admissions to a regional toxicology service. Data extracted included details of ingestion, clinical features, investigations (including ECG), and other outcomes (length of stay and ICU admission rate).. There were 45 cases of quetiapine overdose, of which 18 patients with quetiapine assay results were included. Median length of stay was 35 hours (interquartile range [IQR] 14 to 42 hours) for the 18 patients, and 9 were admitted to the ICU. The median ingested dose was 3.5 g (IQR 1.7 to 6.2 g), and reported ingested dose was highly correlated with estimated peak drug concentration (r(2)=0.84; P<.0001), confirming patient-provided history of ingestion. Seizures occurred in 2 patients, delirium occurred in 3 patients, and mechanical ventilation was required in 4 patients. No arrhythmias or deaths occurred. Six of the 18 patients ingested quetiapine alone, with a median length of stay of 35 hours, and 3 were admitted to the ICU. In 1 patient who ingested 24 g, hypotension and seizures occurred. For 10 patients for whom ECGs were available and who had ingested no cardiotoxic drugs, tachycardia occurred in 8 patients. For these 10 patients, the mean corrected QT (QTc) interval was increased at 487 ms, but the mean uncorrected QT interval was 349 ms. Reported dose and peak quetiapine concentrations were significantly associated with ICU admission and length of stay more than 24 hours. A reported dose less than 3 g and a Glasgow Coma Scale score not less than 15 predicted patients not requiring ICU admission or length of stay more than 24 hours.. Quetiapine overdose causes central nervous system depression and sinus tachycardia. In large overdoses, patients may require intubation and ventilation for associated respiratory depression. Although a prolonged QTc occurs, its clinical significance is unclear because it is most likely caused by an overcorrection caused by the tachycardia. In our experience, a reported dose of less than 3 g for patients who are not drowsy (with a Glasgow Coma Scale score of 15) at least 4 hours after ingestion and who did not coingest another toxic agent defined a group not requiring ICU admission or inpatient admission greater than 24 hours.

Topics: Adult; Antipsychotic Agents; Central Nervous System Diseases; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Drug Therapy, Combination; Female; Glasgow Coma Scale; Humans; Intensive Care Units; Length of Stay; Male; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; Seizures

Previous reports of gabapentin overdose have described mild symptoms of somnolence, ataxia and slurred speech. Quetiapine has produced a false positive for cyclic antidepressants on immunoassay drugscreens. Quetiapine overdose is associated with coma, QTc prolongation and hypotension. We report a case of massive gabapentin and presumptive quetiapine overdose with the highest recorded serum gabapentin concentration (104.5 u/ml) associated with coma, respiratory depression requiring mechanical ventilation, and hypotension.

Topics: Acetates; Amines; Anti-Anxiety Agents; Antipsychotic Agents; Coma; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Drug Overdose; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Hypotension; Middle Aged; Quetiapine Fumarate; Respiration, Artificial; Respiratory Insufficiency; Suicide, Attempted