Survival from coma induced by an intentional 36-g overdose of extended-release quetiapine.

Quetiapine is a second-generation antipsychotic drug approved for the treatment of bipolar disorders and schizophrenia. Acute quetiapine overdose is rare, and quetiapine has long been thought to be safer than other antipsychotics. Nevertheless, as reported in the literature, the severity of the effect of quetiapine overdose has not been associated with a high serum concentration of the drug or with the reported ingested dose. In this article, we report a case of survival from coma induced by a massive extended-release (XR) quetiapine ingestion at a dose greater than reported in some previous fatal cases. A 34-year-old woman with chronic schizophrenia ingested 36 g of quetiapine fumarate XR for attempted suicide. She was initially lethargic, but her clinical conditions rapidly deteriorated and she collapsed unconscious. The woman was taken to the nearest hospital, where the medical emergency team found her in deep coma with response only to deep painful stimuli (Glasgow Coma Scale 9). An endotracheal tube was inserted for airway protection, and the patient was transferred to a critical care area for ventilatory support and maintenance of hydration status and electrolytic balance. Spontaneous breathing was restored in approximately 36 hours, and a few days later, she was discharged without reporting clinical complications. This is the first case of coma induced by an intentional 36-g overdose of quetiapine XR. Given the widespread use of quetiapine and the lack of information about its toxicity in overdose, this case report reinforces the importance of closely monitoring patients taking quetiapine and helps to better define the safety of this drug.

Intravenous lipid emulsion as an adjuvant therapy of acute clozapine poisoning.

INTRODUCTION: Clozapine is a frequently prescribed atypical antipsychotic drug. Various case reports documented the successful recovery of acute antipsychotics toxicity in association with the administration of intralipid emulsion (ILE). AIM: This study aimed to assess the adjuvant therapeutic role of SMOF Lipid administration on the outcomes of acute clozapine poisoning. METHODS: Forty patients with acute clozapine poisoning were randomly allocated into two equal groups. The control group received the standard supportive treatment only, whereas the intervention group received the standard supportive treatment plus SMOF Lipid 20% infusion. All patients were subjected to history taking, full clinical examination, and laboratory investigations. The study outcomes were evaluated. RESULTS: The mean Glasgow Coma Scale (GCS) at 6 hours (13.1 ± 2.3 vs 9.2 ± 2, p < 0.001) and 12 hours (14.3 ± 1.5 vs 9.6 ± 2, p < 0.001) after admission was significantly higher in the intervention group compared to the control group. The intervention group showed a significantly lower frequency of prolonged QTc interval 12 hours after admission (p = 0.003), as well as a significantly shorter hospital stay (p < 0.001). CONCLUSIONS: SMOF Lipid infusion seemed to have improved GCS, the prolonged QTc interval, and shortened the length of hospital stay. Furthermore, there were no adverse effects related to its administration.

Sulpiride intoxication: Case report of a rare intoxication.

Intoxications with sulpiride, an antipsychotic, are rare, and only limited literature is available. We describe a successful treatment of a sulpiride intoxication. A 67-year-old female, with a history of intentional suicide attempt, was admitted to the emergency department (ED) because of a suspected out-of-hospital cardiac arrest. At presentation, she was haemodynamically unstable, with a Glasgow Coma Scale of 3 and slight prolongation of QTc time. History taken from her husband raised suspicion of a suicide attempt with medication. Consultation of the on-call pharmacist and performance of a toxicology screening accelerated the diagnosis of a sulpiride intoxication. The patient was intubated because of respiratory insufficiency, admitted to the Intensive Care Unit (ICU) and treated with activated charcoal, laxatives and sodium bicarbonate. The following day, she was extubated with stable haemodynamics and a normalized ECG. Treatment of sulpiride intoxications is mainly symptomatic and consists of supportive care. An important note is the avoidance of antiarrhythmic drugs, except for lidocaine, epinephrine and dopamine, as they might worsen arrhythmia and hypotension.

Vasopressor therapy in atypical antipsychotic overdose.

Hypotension is a common presentation following an overdose of quetiapine. Adrenaline is often used as the vasopressor of choice for hypotension not responding to intravenous fluids. We present a case of quetiapine overdose with hypotension unresponsive to high-dose adrenaline. The patient was commenced on noradrenaline and made a full recovery. We highlight learning points about vasopressor therapy for atypical antipsychotic overdose. Quetiapine-induced hypotension is thought to be mediated by α1-receptor antagonism. Adrenaline is unlikely to improve blood pressure, as it is an agonist at both α- and ß-receptors. Alpha-2- and ß2-agonism can reduce sympathetic outflow and cause vasodilation, respectively, further exacerbating the hypotension. Noradrenaline is the preferred vasopressor of choice for hypotension caused by quetiapine overdose, as it has less affinity for α2- and ß2-receptors, but maintains α1-receptor agonism. Drugs with a similar mechanism of inducing hypotension should also be treated with noradrenaline as the vasopressor of choice.

Patient Survival After Acute Voluntary Poisoning With a Huge Dose of Oxcarbazepine and Olanzapine.

INTRODUCTION: Oxcarbazepine is a carbamazepine pre-drug with less drug interactions. Its adverse effects, including hyponatremia, somnolence and ataxia, are dose dependent. Olanzapine is an atypical antipsychotic drug most commonly used to manage psychoses and symptoms of irritability and aggressive behavior. Main side effects include extrapyramidal and anticholinergic symptoms, weight gain, and hyperglycemia. CASE REPORT: In this manuscript a case of oxcarbazepine and olanzapine intoxication is discussed. A 45-year-old woman, previously diagnosed with bipolar disorder and chronic alcoholism, was presented two hours after ingestion of 30,000mg of oxcarbazepine and 140 mg of olanzapine, combined with alcohol. She was immediately treated with gastric lavage and administration of activated charcoal. During her hospitalization she was hemodynamically and respiratory stable with no neurological signs and symptoms except for somnolence. Another side effect was hyponatremia. She was discharged from our department in stable clinical condition after being evaluated by a psychiatrist. CONCLUSION: Early approach is crucial for the management of drug intoxication. Late symptoms can be avoided through close monitoring of vital signs, mental status and laboratory values. Psychiatric consultation is essential for a better long-term outcome.

Zuclopenthixol-induced neuroleptic malignant syndrome in an adolescent girl.

We present the case of a 14-year-old female who had many characteristics of neuroleptic malignant syndrome (NMS) without pyrexia following a single depot injection of 200 mg of zuclopenthixol. The patient presented with a change in mental status that had progressed over the preceding 48 hours. Subsequently, she became increasingly agitated and confused, and developed diffuse muscular rigidity, mutism, tremor, tachycardia, diaphoresis, sialorrhea, and incontinence. Results of laboratory tests showed elevated CPK levels, leukocytosis, and a low serum iron level. Bromocriptine and diazepam were used as initial treatment of a probable NMS and provided significant improvement. During the next seven days, she clinically improved but continued to exhibit emotional lability, logorrhea, elevated mood, and increased psychomotor activity. Therefore, bromocriptine and diazepam were discontinued and lorazepam and lithium were administered as treatment of a bipolar disorder. Four weeks later, she was discharged in stable condition. The presentation of this case report suggests that the primary psychiatric diagnosis is important in antipsychotic usage in the pediatric population, and that young patients receiving neuroleptic treatment should be monitored for the early signs of NMS. Using the diagnostic criteria of a neuroleptic toxicity spectrum may result in greater clinical awareness and earlier recognition of NMS.

Low-dose intravenous lipid emulsion for the treatment of severe quetiapine and citalopram poisoning.

The treatment of quetiapine and/or citalopram poisoning is mainly supportive and involves gastric lavage, activated charcoal, intubation, and mechanical ventilation. Recently, however, there were reports of successful treatment with intravenous lipid emulsion. Here we report a case of a 19-year-old Caucasian girl who ingested approximately 6000 mg of quetiapine, 400 mg of citalopram, and 45 mg of bromazepam in a suicide attempt. The patient developed ventricular tachycardia and epileptic seizures 12 h after admission to the hospital. As the patient's condition deteriorated, we combined standard therapy (intubation, mechanical ventilation, and vasopressors) with low-dose intravenous lipid emulsion (ILE) (a total of 300 mL of 20 % lipid emulsion) and normalised her heart rhythm and stopped the seizures. She was discharged to the psychiatric ward after 48 h and home after a prolonged (2-month) psychiatric rehabilitation. Intravenous lipid emulsion turned out to be effective even in the lower dose range than previously reported for quetiapine poisoning in patients presenting with seizure and ventricular arrhythmia. To our knowledge, there are no case reports describing the use of ILE in treating citalopram poisoning.

2015 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 33rd Annual Report.

INTRODUCTION: This is the 33rd Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January 2015, 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 9.52 [7.40, 13.6] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system. METHODS: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure. RESULTS: In 2015, 2,792,130 closed encounters were logged by NPDS: 2,168,371 human exposures, 55,516 animal exposures, 560,467 information calls, 7657 human confirmed nonexposures, and 119 animal confirmed nonexposures. US PCs also made 2,695,699 follow-up calls in 2015. Total encounters showed a 3.42% decline from 2014, while health care facility (HCF) human exposure cases increased by 5.09% from 2014. All information calls decreased by 15.5% but HCF information calls increased 2.67%, and while medication identification requests (Drug ID) decreased 31.7%, human exposures reported to US PCs were essentially flat, increasing by 0.149%. Human exposures with less serious outcomes have decreased 2.95% per year since 2008 while those with more serious outcomes (moderate, major or death) have increased by 4.34% per year since 2000. The top 5 substance classes most frequently involved in all human exposures were analgesics (11.1%), household cleaning substances (7.54%), cosmetics/personal care products (7.41%), sedatives/hypnotics/antipsychotics (5.83%), and antidepressants (4.58%). Sedative/Hypnotics/Antipsychotics exposures as a class increased the most rapidly (2597 calls (11.4%)/year) over the last 14 years for cases showing more serious outcomes. The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (13.6%), household cleaning substances (11.2%), analgesics (9.12%), foreign bodies/toys/miscellaneous (6.45%), and topical preparations (5.33%). Drug identification requests comprised 35.0% of all information calls. NPDS documented 1831 human exposures resulting in death with 1371 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). CONCLUSIONS: These data support the continued value of PC expertise and need for specialized medical toxicology information to manage more serious exposures, despite a decrease in calls involving less serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, viral, bacterial, venomous, chemical agent, or commercial product), the identification of events of public health significance, resilience, response and situational awareness tracking. NPDS is a model system for the real-time surveillance of national and global public health.

The safety of olanzapine in young children: a systematic review and meta-analysis.

BACKGROUND: Olanzapine is frequently prescribed in young children for psychiatric conditions. It may be an option for chemotherapy-induced nausea and vomiting (CINV) control in children. The objective of this review was to describe the safety of olanzapine in children less than 13 years of age to determine if safety concerns would be a barrier to its use for CINV prevention. METHODS: Electronic searches were performed in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and Scopus. All studies in English reporting adverse effects associated with olanzapine use in children younger than 13 years or with a mean/median age less than 13 years were included. Adverse outcomes were synthesized for prospective studies. RESULTS: A total of 47 studies (17 prospective) involving 387 children aged 0.6-18 years were included; nine described olanzapine poisonings. Weight gain or sedation were reported in 78 % [95 % confidence interval (CI) 63-95] and 48 % (95 % CI 35-67), respectively. Extrapyramidal symptoms or electrocardiogram abnormalities were reported in 9 % (95 % CI 4-21) and 14 % (95 % CI 7-26), respectively. Elevation in liver function tests or blood glucose abnormalities were reported in 7 % (95 % CI 2-20) and 4 % (95 % CI 1-17), respectively. No deaths were attributed to olanzapine. LIMITATIONS: No studies were identified with a primary focus on evaluating safety, and the adverse effects reported in the included studies were heterogeneous. CONCLUSIONS: Most adverse events associated with olanzapine use in children less than 13 years of age are of minor clinical significance. These findings support the exploration of olanzapine for the prevention of CINV in children in future trials.

Neuroleptic malignant syndrome developing after acute overdose with olanzapine and chlorpromazine.

UNLABELLED: Neuroleptic malignant syndrome (NMS) is a relatively uncommon side effect that may develop after a recent increase in the therapeutic dose of an antipsychotic medication or the addition of a new agent in therapeutic doses. CASE REPORT: We report a case of NMS developing in a 36-year-old female patient 2 days following deliberate self-poisoning with 30 x 10-mg olanzapine tablets, 7 x 100-mg chlorpromazine tablets and an unknown amount of escitalopram. These were the patient's own medications. She had not been taking these for several weeks. The patient initially presented with sedation from her overdose which resolved over the next 24 hours. Following this, over the subsequent 24 hours, she became progressively confused, ataxic, hypertonic, ferbrile and tachycardic, with marked lead pipe rigidity of the limbs. Head CT, lumbar puncture and septic screen were all negative. She was treated with intravenous midazolam infusion, nasogastrically administered bromocriptine, external cooling and was mechanically ventilated. She gradually improved over a period of 10 days, with residual confusion lasting another week, and was discharged well with no deterioration from her premorbid neurologic state. CONCLUSION: To our knowledge, although there are numerous cases reported with therapeutic use, NMS has not been reported to develop following acute olanzapine overdose. Clinicians should be aware that this may be an uncommon side effect of antipsychotic medication.

Clinical toxicology: clinical science to public health.

1. The aims of the present paper are to: (i) review progress in clinical toxicology over the past 40 years and to place it in the context of modern health care by describing its development; and (ii) illustrate the use of clinical toxicology data from Scotland, in particular, as a tool for informing clinical care and public health policy with respect to drugs. 2. A historical literature review was conducted with amalgamation and comparison of a series of published and unpublished clinical toxicology datasets from NPIS Edinburgh and other sources. 3. Clinical databases within poisons treatment centres offer an important method of collecting data on the clinical effects of drugs in overdose. These data can be used to increase knowledge on drug toxicity mechanisms that inform licensing decisions, contribute to evidence-based care and clinical management. Combination of this material with national morbidity datasets provides another valuable approach that can inform public health prevention strategies. 4. In conclusion, clinical toxicology datasets offer clinical pharmacologists a new study area. Clinical toxicology treatment units and poisons information services offer an important health resource.