Lamotrigine Overdose Research Articles

Is ketamine and lamotrigine interactions responsible for the sub-therapeutic effect of ketamine?

IntroductionThe immediate antidepressant effect of Ketamine has become a breakthrough in the treatment of depression. Cytochrome CYP3A4 and 2B6 primarily metabolize Ketamine.ObjectivesThe present study explores potential pharmacokinetic and pharmacodynamic interactions of Lamotrigine and Ketamine.MethodsA literature search was conducted using (“ketamine” OR “Lamotrigine” AND Interactions in PubMed, Embase, and PsycINFO. Our literature search resulted in 72 hits and result in qualified five studies.ResultsWe found five studies: one RCT study, a RCT, a crossover design, Two case reports, and one murine model study. In the first RCT conducted on 16 healthy normal volunteer subjects. lamotrigine significantly decreased ketamine-induced perceptual abnormalities (P < 0.001), positive (P < 0.001) and negative symptoms (P < 0.05), and learning and memory impairment (P < 0.05) which shows the counter effect of ketamine. Another study revealed Ketamine evoked increases in all the BPRS subscale scores, and all scores were lower after lamotrigine pretreatment. A case report from 2014 reports the failure of ketamine anesthesia in a patient with lamotrigine overdose. Another case report mentions that Lamotrigine reduced the craving in a patient with ketamine use disorder. A murine model study with lamotrigine showed improved PPI (Prepulse inhibition) ketamine-induced disruption. These results suggest that Lamotrigine may exert this effect via a glutamatergic system.ConclusionsThe literature review suggests that Lamotrigine interferes with glutamatergic neurotransmission reducing the effect of Ketamine. It is not clear how this may impact Ketamine’s antidepressant action. Future large scale and well-designed RCTs are required to confirm these findings.Conflict of interestNo significant relationships.

SAT-480 Myxedema Madness: A Rare Case of Severe Hypothyroidism Presenting as Psychosis

IntroductionMyxedema coma is a rare, life-threatening medical emergency resulting from uncontrolled hypothyroidism. Myxedema coma refers to the neurological sequelae of severe hypothyroidism, which classically manifests as depressed mental status. Rarely, myxedema coma can present with a hyperactive mental state and psychosis. We present an unusual case of a drug overdose secondary to myxedema coma-induced psychosis.Clinical CaseA 48 year old woman with a history of seizure disorder and hypothyroidism presented to the hospital after lamotrigine overdose. The patient’s spouse witnessed her ingest forty-five tablets of lamotrigine after an argument. The patient had no previous psychiatric diagnoses or suicide attempts. On examination, the patient was hemodynamically stable but was agitated, disoriented, and uncooperative. She had a normal neurologic exam and no peripheral edema. Her lamotrigine level was 25.4 ug/ml (2.5-15.0 ug/ml). The patient’s mental status did not improve with lamotrigine cessation. Psychiatry determined that the patient’s psychosis was not consistent with lamotrigine overdose. Given these recommendations, alternative causes of psychosis were considered. The patient’s husband stated she had not taken levothyroxine for over one year. Thyroid function tests revealed a thyroid stimulating hormone (TSH) of 299 mcIU/ml (0.35-5.50 mcIU/ml) with a free thyroxine (T4) level of 0.27 ng/dl (0.89-1.76 ng/gl). The patient was started on levothyroxine intravenously. After five doses of intravenous levothyroxine, her mental status improved to baseline and she was transitioned to oral levothyroxine. She denied that the lamotrigine ingestion was a suicide attempt. Based on the patient’s presentation and clinical course, we concluded that her overdose was due to severe hypothyroidism leading to myxedema madness.ConclusionSevere hypothyroidism with myxedema coma often presents with depressed mental status, which can manifest as progressive confusion, lethargy, and eventually coma. However, in the case of our patient, severe hypothyroidism presented as psychosis, a rare manifestation. Remarkably, the patient had no other obvious physical manifestations of severe hypothyroidism. Psychosis, though rare, has been seen in cases typically after thyroidectomy or in patients with previously undiagnosed Hashimoto’s thyroiditis. In this patient’s case, it is likely that her myxedema madness was precipitated by long-term nonadherence with her thyroid replacement therapy, as the patient had no prior psychiatric history. Additionally, her rapid reversal of symptoms after the administration of levothyroxine supports the diagnosis of hypothyroid-induced myxedema madness.

Cerebral edema with Refractory Intracranial Hypertension Secondary to Lamotrigine Overdose (5038)

Cerebral edema with Refractory Intracranial Hypertension Secondary to Lamotrigine Overdose (5038)

Systematic Review of Adult and Pediatric Lamotrigine Overdose

Systematic Review of Adult and Pediatric Lamotrigine Overdose

High dose droperidol and QT prolongation: analysis of continuous 12‐lead recordings

AimsTo investigate the QT interval after high dose droperidol using continuous 12-lead Holter recordings.MethodsThis was a prospective study of patients given droperidol with a continuous Holter recording. Patients were recruited from the DORM II study which included patients with aggression presenting to the emergency department. Patients initially received 10 mg droperidol as part of a standardized sedation protocol. An additional 10 mg dose was given after 15 min if required and further doses at the clinical toxicologist's discretion. Continuous 12-lead Holter recordings were obtained for 2–24 h utilizing high resolution digital recordings with automated QT interval measurement. Electrocardiograms were extracted hourly from Holter recordings. The QT interval was plotted against heart rate (HR) on the QT nomogram to determine if it was abnormal. QTcF (Fridericia's HR correction) was calculated and >500 ms was defined as abnormal.ResultsForty-six patients had Holter recordings after 10–40 mg droperidol and 316 QT–HR pairs were included. There were 32 abnormal QT measurements in four patients, three given 10 mg and one 20 mg. In three of the four patients QTcF >500 ms but only in one taking methadone was the timing of QTcF >500 ms consistent with droperidol dosing. Of the three other patients, one took amphetamines, one still had QT prolongation 24 h after droperidol and one took a lamotrigine overdose. No patient given >30 mg had a prolonged QT. There were no arrhythmias.ConclusionQT prolongation was observed with high dose droperidol. However, there was little evidence supporting droperidol being the cause and QT prolongation was more likely due to pre-existing conditions or other drugs.

Clinical Outcomes in Newer Anticonvulsant Overdose: A Poison Center Observational Study

Clinicians have limited experience with assessment and treatment of overdose from newer anticonvulsant medications. The aim of this investigation was to evaluate clinical effects of newer anticonvulsant overdose, determine if a relationship exists between dose and clinical effect, and if a particular agent appears more toxic in overdose. This was a retrospective study using electronic poison center data, evaluating clinical outcomes from newer anticonvulsant overdose. The Toxicall™ database from January 1, 2002 to December 31, 2011 was queried using key words: "gabapentin," "lamotrigine," "levetiracetam," "tiagabine," "topiramate," "zonisamide," "pregabalin," and "oxcarbazine." Polypharmacy overdose and children less than 15years of age were excluded. Charts were reviewed by two abstractors for pharmaceutical, self-reported dose, clinical effect score, and clinical signs, symptoms, and vital signs recorded in the chart. Ordinal logistic regression was used to evaluate the relationship between drug type, dose, age, and sex to clinical effect score. Out of 501 cases identified, 347 met the final inclusion criteria. There were 116 gabapentin, 67 lamotrigine, 15 levetiracetam, 15 tiagabine, 56 topiramate, 23 pregabalin, and 55 oxcarbazepine cases. Overdose of newer anticonvulsants frequently results in altered mental status. Seizures may be more common with tiagabine, lamotrigine, and oxcarbazepine. There was one death reported from intentional overdose of topiramate. An information index was created to rank drug toxicity based on reported signs and symptoms for each overdose. There was no significant effect of dose on severity of outcome (β = 0.12, p = 0.23). However, the risk of a more severe outcome score was significantly increased with tiagabine relative to other drugs (β = 2.8, p = 0.001). Lamotrigine ranked highest in terms of toxicity (HT = 1.66) and number of interventions performed (HI = 1.17), and levetiracetam the lowest (HT = 0.98; HI = 0.88). We could not identify a dose-effect in these data which likely reflects the limitations of self-reported doses. Despite limitations of these data, the risk of more severe outcome scores appear to be higher with tiagabine overdose while lamotrigine overdose appears to result in more reported signs, symptoms, and interventions.

Failure of ketamine anesthesia in a patient with lamotrigine overdose.

Introduction. It is important to know which clinical situations prevent ketamine from working. Case Report. We present the case of the psychiatric inpatient who was admitted to our emergency department after ingesting a toxic dose of lamotrigine, unknown at that time. On admission, she was clearly in distress, displaying extreme agitation and violent ataxic movements. We opted to achieve sedation using intravenous ketamine boluses. Unexpectedly, after being injected with a total of 250 mg ketamine, our patient displayed no signs of dissociative anaesthesia. Discussion. There was no apparent reason for why ketamine failed, but an interaction between lamotrigine and ketamine was suspected. A literature search was performed. Very few articles describe interactions between lamotrigine and ketamine. Experimental studies, however, demonstrate how lamotrigine attenuates the neuropsychiatric effects of ketamine. Ketamine is classically described as an NMDA antagonist. Ketamine's dissociative effects, however, are thought to be mediated by increased glutamate release via a pathway not dependent on NMDA receptors. Lamotrigine, on the other hand, is known to reduce cortical glutamate release. Conclusion. Lamotrigine reduces the glutamate release needed to mediate ketamine's dissociative anaesthesia. This is important knowledge for anaesthesiologists in the emergency room where ketamine is often administered to unstable patients.

Severe sodium channel blockade and cardiovascular collapse due to a massive Lamotrigine overdose

Background. Cardiac arrest due to lamotrigine (LTG) has been reported after co-ingestion with bupropion, but severe sodium channel blockade in the absence of other toxins has not been described. We report a case of cardiac arrest and status epilepticus following a massive LTG overdose. Case Report. A 48 year-old female was brought to the ED with seizure-like activity subsequent to ingesting 7.5 g of LTG. Vital signs were HR 131, BP 107/68, T 99.4°F, RR 16. She was intubated in the ED for a low GCS. Initial ECG demonstrated a narrow-complex normal sinus rhythm, and her labs were unremarkable. Three hours after intubation she developed status epilepticus, and a pulseless wide-complex tachycardia. She was aggressively resuscitated during which time pulses were periodically reestablished, but lost each time seizures recurred. She was not stabilized until the convulsions were terminated with vecuronium. Her post-resuscitation ECG demonstrated a junctional tachycardia with a 3 mm R-wave in aVR. The LTG level was 74.7 mcg/ml (therapeutic: 3–14 mcg/ml). Comprehensive LC-MS/MS drug screen was negative for all screened compounds. Discussion. This is the first report of cardiovascular collapse due to LTG with the highest drug concentration to date. Conclusion. The degree of neurologic and cardiovascular toxicity seen in this case are novel and illustrate the potential for severe sodium channel blockade after massive LTG poisonings. Drug levels are not clinically relevant in the acute setting due to the time delay in obtaining results, and recurrent seizure activity may be the only clinical finding that precedes severe cardiac toxicity.

Lipid Emulsion as Rescue Therapy in Lamotrigine Overdose

Background Lamotrigine is a sodium channel blocking agent that is widely prescribed for treatment of seizure. Although life-threatening effects are rarely observed in overdose, some previous reports have described the occurrence of cardiac toxicity. The management of sodium channel blocking agent-induced cardiotoxicity conventionally requires sodium bicarbonate administration. Recent case reports describe intravenous lipid administration as a successful treatment for refractory cardiovascular collapse induced by sodium channel blocking medications. Objective The objective of this study is to report the use of intravenous lipid emulsion as adjunctive therapy in a case of lamotrigine overdose in which electrocardiographic changes were unresponsive to bicarbonate therapy. Case Report We report a case of intentional lamotrigine overdose in a 50-year-old woman who lost consciousness and developed electrocardiographic aberrations, including widening of QRS with occurrence of left bundle branch block. The patient was initially treated with sodium bicarbonate without effect. Recovery of cardiac conduction was rapidly achieved after infusion of a 20% lipid emulsion. The exact mechanism of action of lipid emulsion is not fully understood. The lipophilic properties of lamotrigine suggest that it was partially removed by the plasmatic lipid emulsion. Conclusion This case provides additional insight into the potential benefit of using lipid emulsion in refractory sodium channel blocking intoxications.

Complete heart block and death following lamotrigine overdose

Context. Lamotrigine is used for both seizure and psychiatric disorders. Overdoses typically follow a benign course. Case details. A 19-year-old male with bipolar disorder ingested 4 g of lamotrigine. The patient suffered from multiple seizures, charcoal aspiration, respiratory arrest, prolongaton of the QRS interval on electrocardiogram, complete heart block, multiorgan failure and ultimately death. Discussion. We describe the emergency department (ED) and ICU course for this patient and briefly review the toxic effects of lamotrigine and the pharmacokinetics with and without hemodialysis.

Significant lamotrigine overdose associated with acute pancreatitis

In March 2007, a 24-year{old woman was admitted via the Emergency Department after an act of deliberate self{harm. Five hours prior to admission she had taken 4200 mg of lamotrigine. She denied taking any other medication at the time of this overdose. Her relevant medical history included two previous episodes of mixed overdoses (July 2002 and May 2006), depression and a psychotic episode for which she was treated with mirtazepine 30 mg once daily, lamotrigine 100 mg twice daily and risperidone 2 mg twice daily. At the time of admission she reported a regular intake of two 750 mL bottles of wine per evening, but had no previous history of alcohol{related liver or pancreatic problems. She had drunk two bottles of wine with her overdose. On admission, she was tachycardic, lethargic, dehydrated, showed slurred speech, with cerebellar signs of nystagmus and ataxia. She had no evidence of abdominal tenderness. Arterial blood gas measurements revealed a compensated metabolic acidosis. Full blood count, urea, electrolyte and liver function tests were normal. Her blood alcohol level was 100 mg/100 mL. Paracetamol and salicylate were not detected. A lamotrigine level was not taken because it is not routinely available in our institution. An electrocardiogram showed a sinus tachycardia only. Within 24 hours of admission she complained of upper abdominal pain and vomiting. Serum amylase was 1043 U/L (0–110 U/L). Liver transaminase, full blood count, calcium, glucose, urea and electrolyte levels were within reference ranges. The patient was diagnosed with acute pancreatitis, and at 48 hours achieved a Ranson score of 1 on assessment of severity, predicting a good prognosis, with less than 1% mortality. General supportive treatment was started with intravenous fluid resuscitation, analgesia and antiemetics. Abdominal ultrasound two days after onset of symptoms showed a thickened gall bladder wall, with some surrounding fluid and no evidence of gallstones. Her symptoms as well as amylase levels settled within three days and the patient was discharged five days after the initial overdose. An endoscopic ultrasound of the pancreas was performed six weeks after discharge. This showed a normal gallbladder and common bile duct. The pancreas had no features of chronic pancreatitis and had a normal calibre pancreatic duct. In the 12 months following discharge she was seen twice in the Emergency Department with symptoms and signs consistent with significant alcohol abuse, however on both occasions her amylase was normal.

Seizures and Altered Mental Status After Lamotrigine Overdose

Lamotrigine is a commonly prescribed anticonvulsant medication. It is an infrequently reported agent of intentional acute ingestion to poison centers. The spectra of clinical effects of lamotrigine in acute overdose are not well established. We report a case of acute ingestion of lamotrigine and ethanol that resulted in coma requiring ventilatory support, paradoxic seizure activity, and mild rhabdomyolysis.

Acute Lamotrigine Overdose in an Adolescent

From the *Department of Clinical Pharmacology, St. Olavs University Hospital; †Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU); and ‡Department of Pediatrics, St. Olavs University Hospital, Trondheim, Norway. Received for publication November 13, 2006; accepted February 19, 2007. Correspondence: Arne Reimers, MD, Department of Clinical Pharmacology, St. Olavs University Hospital, 7006 Trondheim, Norway (e-mail: [email protected]).

Downbeat, Positional, and Perverted Head-Shaking Nystagmus Associated with Lamotrigine Toxicity

Lamotrigine is an effective antiepileptic drug with few adverse effects. Nystagmus is one of the commonly observable signs of lamotrigine overdose, which may result from central nervous system involvement. However, the physiologic basis of lamotrigine-induced nystagmus is not fully understood. Here we report a patient who presented with lamotrigine-associated nystagmus that was probably related to cerebellar dysfunction.

Evaluation of lamotrigine toxicity reported to poison centers.

Lamotrigine is an antiepileptic drug for the treatment of partial and generalized seizures as well as bipolar disorder. Limited published information exists describing the clinical effects of lamotrigine overdose. To examine the toxicity of exposures to lamotrigine utilizing national poison center data. Data on single-substance exposures to lamotrigine reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System in 2000 and 2001 were retrospectively analyzed. There were 493 cases that met the inclusion criteria. The majority of exposures occurred within the age groups 20-59 years old (n = 198, 40.2%), followed by </=4 years old (n = 173, 35.1%). Overall, the majority of patients (52.1%) exposed to lamotrigine in overdose experienced no toxic clinical effects. The most common clinical effects reported in overdose were drowsiness/lethargy (20.9%), vomiting (11%), nausea (5.1%), ataxia (4.9%), dizziness/vertigo (4.5%), and tachycardia (4.3%). Major clinical effects included coma (n = 6), seizures (n = 8), and respiratory depression (n = 3). Medical outcome was reported as minor in 150 (30.4%), moderate in 73 (14.8%), and major in 13 (2.6%) cases. There were no deaths. These data demonstrate that the majority of patients exposed to lamotrigine in overdose experienced minor or no clinical effects. Although rare, serious effects can also occur.

Lamotrigine childhood overdose

A 2-year-old male developed generalized tonic-clonic seizure activity, tremor of limbs, muscle weakness, ataxia, and hypertonia after he swallowed 16 50-mg tablets of lamotrigine. His vital signs were normal, as were electroencephalography and laboratory investigation tests. The urine toxicologic screen revealed no other drugs. Treatment included midazolam and gastric lavage followed by activated charcoal and fluid loads. Symptoms resolved within 24 hours, and the child was discharged without any further complications. Serial blood samples revealed plasma lamotrigine levels at the high adult therapeutic range (3.8 mg/L) but a slow elimination rate. This is the first report of seizure activity reported in a patient receiving an overdose of lamotrigine. However, no evident concentration-effect–side-effect relationship has been established in children. Interestingly in this child, lamotrigine overdose presented exclusively with treatment-emergent neurologic abnormalities, sparing all other systems.