Status epilepticus after massive carbamazepine overdose

We report two patients who experienced status epilepticus after carbamazepine overdose. The first patient was an 18-year-old female with a history of epilepsy. She experienced 4 hour of persistent and prolonged seizures resistant to sodium amytal therapy. The status epilepticus ended with her death. The second patient was an 18-year-old male with a history of bipolar disorder. He experienced 5 hour of persistent and prolonged seizures that appeared to be resistant to diazepam, phenytoin, and phenobarbital. The seizures abated with the infusion of midazolam. This is a report of status epilepticus associated with wide complex tachycardia after carbamazepine overdose, which may be resistant to conventional therapy.     

Prospective comparative assessment of buprenorphine overdose with heroin and methadone: Clinical characteristics and response to antidotal treatment

Buprenorphine is a partial opioid agonist with a “ceiling effect” for respiratory depression. Despite this, it has been associated with severe overdoses. Conflicting data exist regarding its response in overdose to naloxone. We compared clinical overdose characteristics of buprenorphine with heroin and methadone and assessed responses to naloxone and flumazenil. Patients admitted to two intensive care units with severe opioid overdoses were enrolled into this 4-year prospective study. Urine and blood toxicological screening were performed to identify overdoses involving predominantly buprenorphine, heroin, or methadone. Eighty-four patients with heroin (n = 26), buprenorphine (n = 39), or methadone (n = 19) overdoses were analyzed. In the buprenorphine group, sedative drug coingestions were frequent (95%), whereas in the methadone group, suicide attempts were significantly more often reported (p = .0007). Buprenorphine overdose induced an opioid syndrome not differing significantly from heroin and methadone in mental status (as measured by Glasgow Coma Score) or arterial blood gases. Mental status depression was not reversed in buprenorphine overdoses with naloxone (0.4–0.8 mg) but did improve with flumazenil (0.2–1 mg) if benzodiazepines were coingested. In conclusion, buprenorphine overdose causes an opioid syndrome clinically indistinguishable from heroin and methadone. Although mental status and respiratory depression are often unresponsive to low-dose naloxone, flumazenil may be effective in buprenorphine overdoses involving benzodiazepines.     

Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup

Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty-three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n = 38). The workgroup assessed isoniazid as “Moderately Dialyzable” by hemodialysis for patients with normal kidney function (quality of evidence = C) and “Dialyzable” by hemodialysis for patients with impaired kidney function (quality of evidence = A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABA_A receptor agonists (weak recommendation, very low quality of evidence).     

Cardiotoxic Overdose Treated with Intravenous Fat Emulsion and High-Dose Insulin in the Setting of Hypertrophic Cardiomyopathy

High-dose insulin (HDI) and intravenous fat emulsion (IFE) are used in overdoses, although rarely combined. To our knowledge, IFE therapy has not been reported in overdoses of diltiazem, metoprolol and amiodarone. We report a severe overdose of these drugs treated with HDI and IFE in a patient with hypertrophic cardiomyopathy (HCM). We also discuss the potential clinical implications of the inotropic effects of HDI in the setting of HCM and the use and efficacy of IFE in this overdose.     

A case of sustained massive gabapentin overdose without serious side effects

Gabapentin is an antiepileptic agent that is indicated for use as adjunctive therapy for partial seizures. It has a relatively benign side effect profile, but little data exists on massive overdoses with this agent. The authors present a case of a patient who received a massive overdose of this agent but suffered no clinically significant toxicity.     

What heroin users tell us about overdose

This study describes overdose experiences of heroin users, both the overdoses they themselves experienced, as well as those that they witnessed. A structured interview was performed with 101 current heroin users in Albuquerque, New Mexico from January 7, 2002 to February 26, 2002. Heroin-related overdoses were found to be common in this sample of heroin users. Three or more persons were reported to be present during 80 of the 95 most recently witnessed overdoses. An ambulance was called in only 42 of the 95 witnessed overdoses. Seventy-five percent of the respondents who witnessed an overdose stated concern over police involvement was an important reason for delay or absence of a 911 call for help. One hundred of the 101 respondents reported willingness, if trained, to use rescue breathing and to inject naloxone to aid an overdose victim. New methods need to be found to reduce heroin overdose death. Scientific studies are needed on the efficacy of take-home naloxone.     

Isoniazid overdose : a case series, literature review and survey of antidote availability

Tuberculosis has re-emerged as a significant public health threat over the last decade both globally and within Australia. This is thought to be largely due to the HIV epidemic, a growing itinerant population, and immigration. The antibiotic isoniazid remains an integral part of drug therapy. With the numbers of patients receiving isoniazid remaining high, the number of cases of acute poisoning is expected to be significant. This paper presents a series of two cases of isoniazid poisoning presenting to a tertiary referral centre in North Queensland. Isoniazid toxicity produces a triad of coma, metabolic acidosis and seizures. The seizures are often refractory to traditional antiepileptics. A specific antidote is available (pyridoxine [vitamin B6]) and both patients were administered this as part of their treatment. We also surveyed all hospitals in Australia with an accredited adult Emergency Department to assess the availability of pyridoxine.     

Potentiation of pyridoxine by depressants and anticonvulsants in the treatment of acute isoniazid intoxication in dogs

Treatments for acute isoniazid (INH) intoxication have included, singly and in various combinations, a great variety of drugs. As a consequence it is difficult to evaluate the efficacy of these antidotes, except for pyridoxine, the most commonly recommended one. In some cases of INH poisoning evaluation is further complicated because of concurrent alcohol ingestion. The objectives of this investigation were to determine whether ethanol enhances the toxic effects of acute INH overdose, as suggested by some clinical reports, and to evaluate the antidotal efficacy of phenobarbital, pentobarbital, phenytoin, ethanol, or diazepam when each is administered in combination with pyridoxine. Male dogs were either pretreated with iv ethanol and challenged 1 hr later with po INH, 50 or 75 mg/kg, or they were given INH, 75 mg/kg, and injected iv 30 min later with the test drugs, alone or in combination with pyridoxine. Ethanol pretreatment not only did not enhance the toxicity of INH but, in fact, it reduced the severity of convulsions, although it did not change the mortality rate. In the antidotal study, none of the five CNS depressants or anticonvulsants protected against clonic-tonic seizures or death. Pyridoxine, however, reduced the severity of the seizures and prevented death, although it did not completely block convulsions. The combination antidotal treatments (pyridoxine plus each of the CNS drugs) were the most effective; they prevented both convulsions and lethality. It is suggested that pyridoxine is the basic antidote for treatment of acute INH poisoning, and that the addition of an anticonvulsant or a CNS depressant to the therapy enhances effectiveness.     

丙戊酸钠静脉注射治疗癫痫持续状态

目的 :探讨丙戊酸钠注射液治疗癫痫持续状态的疗效和安全性。方法 :丙戊酸钠组 (n =19)和地西泮组 (n =2 2 ) ,均在负荷量丙戊酸钠 10～ 15mg·kg- 1或地西泮 10～ 2 0mg推注后 ,继续 2 4h维持治疗 (分别为 1mg·kg- 1·h- 1和 0 .1～ 0 .2mg·kg- 1·h- 1) ,观察其抗癫痫状态的疗效和不良反应。结果 :丙戊酸钠组和地西泮组起效时间为 (2 3±s18)min和 (7± 5 )min(P <0 .0 1) ,有效率分别为4 7%和 73% (P >0 .0 5 )。丙戊酸钠对不同的癫痫状态类型的疗效无显著差异 (P >0 .0 5 )。丙戊酸钠组治疗前后的生命体征无明显变化 ,血、尿常规 ,肝、肾功能及心电图也无明显改变 ,癫痫状态控制后 ,意识恢复较地西泮组快。结论 :丙戊酸钠注射液治疗癫痫状态有效 ,尤其适用于危重病伴发癫痫持续状态者     

Which drugs cause overdose among opiate misusers? Study of personal and witnessed overdoses

Concern has been expressed at the widespread prescribing of methadone in view of its inherent toxicity. Commentators have opined that methadone is more toxic than heroin and causes more overdose deaths. However, data deficiencies and flawed analyses leave continuing uncertainty about this crucial policy issue. The relative contributions of heroin, other opiates (e.g. methadone) and non-opiate drugs to overdose and overdose deaths among drug misusers were examined in a community-recruited sample of 312 injecting drug misusers in London. Data were collected on last personal overdose (n=117), last witnessed overdose (n=167) and last witnessed fatal overdose (n=55), and on the different drugs that had been involved with these overdoses. Heroin was involved in 83% of last personal overdoses, 90% of last witnessed overdoses and 80% of last witnessed fatal overdoses, while other opiates were involved in only 18%, 8% and 26%, respectively. Methadone accounted for about half of these "other opiate" overdoses. Overdoses involving a combination of heroin and a non-opiate were common - 29%, 21% and 39%, respectively. Heroin was the drug most frequently involved in overdose across all three areas of study. However, combinations of heroin and a non-opiate were surprisingly frequent, especially in witnessed fatal overdoses (as reported recently by other investigators using different methodologies). Considering the wide extent of methadone prescribing to this group, methadone was remarkably infrequently reported as responsible (solely or in combination) for either personal overdoses, witnessed overdoses or witnessed fatal overdoses.     

A Physiologically Based Pharmacokinetic (PBPK) Model for Predicting the Efficacy of Drug Overdose Treatment With Liposomes in Man

Physiologically based pharmacokinetic (PBPK) models were developed for design and optimization of liposome therapy for treatment of overdoses of tricyclic antidepressants and local anesthetics. In vitro drug-binding data for pegylated, anionic liposomes and published mechanistic equations for partition coefficients were used to develop the models. The models were proven reliable through comparisons to intravenous data. The liposomes were predicted to be highly effective at treating amitriptyline overdoses, with reductions in the area under the concentration versus time curves (AUC) of 64% for the heart and brain. Peak heart and brain drug concentrations were predicted to drop by 20%. Bupivacaine AUC and peak concentration reductions were lower at 15.4% and 17.3%, respectively, for the heart and brain. The predicted pharmacokinetic profiles following liposome administration agreed well with data from clinical studies where protein fragments were administered to patients for overdose treatment. Published data on local cardiac function were used to relate the predicted concentrations in the body to local pharmacodynamic effects in the heart. While the results offer encouragement for future liposome therapies geared toward overdose, it is imperative to point out that animal experiments and phase I clinical trials are the next steps to ensuring the efficacy of the treatment.     

Using a group approach to preventing heroin overdose in North London

Aims: This study used group psycho-education methods to assist injecting heroin users in preventing, and responding to overdose. Methods: An ‘OD Prevention’ group was advertised in a London prescribing service and associated primary care unit. The intervention took place in a small group over one afternoon (3.5 hours), and trained participants in recognizing, and responding to heroin overdoses (defining overdose, discussing known risk factors and on-site instruction in cardio-pulmonary resuscitation (CPR). Participants were all injecting heroin users in service contact with the primary care unit, drug dependence unit, or hostels for the homeless in central London. Participants self-referred, or were referred by key workers. Participants completed pre- and post-group questionnaires concerning their personal experience of overdose, the witnessing of others’ overdoses and fatalities, their current response in overdose situations, and their overall confidence in helping others who have overdosed. Findings: In total 107 people attended the group. Of these, 42% had witnessed others’ overdose, and 29% had witnessed one or more deaths as a result of overdose. Following the group intervention more participants reported feeling ‘quite or very confident’ in managing an OD situation, confident in undertaking CPR with someone who had overdosed, and were less likely to pursue ‘folklore’ remedies to overdose. Conclusions: Using psycho-educational group approaches can be an effective tool in attempts to prevent and respond to heroin overdoses, and is seen as useful by users.     

Social network correlates of self-reported non-fatal overdose

The leading cause of death among heroin users is drug overdose. The present study examined the relationship between history of self-reported drug overdoses and social network characteristics among cocaine and opiate users. Data were from cross-sectional surveys administered from March 2001 through February 2003 as part of follow-up of an experimental network oriented HIV prevention intervention. A total of 838 participants with histories of cocaine and opiate use completed the survey. Several social network variables were found to be significantly associated with drug overdose in the prior 2 years, including larger number of network members who were injection drug users and a larger number of conflictual ties among the network members. Even after controlling for age, gender, frequency of injection drug and alcohol use, and health status, network variables continued to have a strong association with history of recent overdose. These data suggest that large drug networks should be targeted for drug overdose prevention interventions.     

Assessment of age-related isoniazid hepatotoxicity during treatment of latent tuberculosis infection

BACKGROUND: Since the introduction of new recommendations for the treatment of latent tuberculosis infection (LTB1) disregarding age as a limitation, increasing numbers of older individuals are expected to undergo treatment with isoniazid for the prevention of tuberculosis, raising the potential for an increase in isoniazid hepatotoxicity. OBJECTIVE: To compare the frequency of hepatotoxicity requiring withdrawal of isoniazid therapy for LTB1 in patients under and over 35 years of age, managed according to current practice guidelines. DESIGN: A retrospective analysis of 300 patients who underwent isoniazid therapy for LTB1 according to a protocol based on the current practice guidelines. SETTING: Public health clinic of Passaic County, NJMain outcome measures: The frequency of symptomatic isoniazid hepatitis in various age groups. RESULTS: Of 165 patients < 35 years of age, 3(2%) patients developed hepatitis (AST > 3 times the upper limit of normal). Of 135 patients > or = 35 years of age, 4(3%) patients developed hepatitis. Statistical comparison between the two groups failed to show a significant difference (p = 0.705). CONCLUSIONS: No difference was detected in the frequency of isoniazid hepatotoxicity between patients < 35 and > or = 35 years of age. Clinically monitored isoniazid therapy of LTB1 patients > or = 35 years of age may not predispose subjects to an increased risk of hepatotoxicity. Limitations of this work include the small sample size and the retrospective nature of the study.     

Opioid overdose in the age of fentanyl: Risk factor differences among subpopulations of overdose survivors

BackgroundAlthough fentanyl is the drug most frequently implicated in overdose deaths, the association between overdose risk and attitudes and behaviors surrounding fentanyl in opioid-using communities has remained understudied. Possible subpopulation differences in fentanyl-related overdose risk remain equally unexamined. This paper addresses these gaps by exploring the association between overdose and fentanyl-related attitudes/behaviors in three subpopulations of overdose survivors.MethodsIn this cross-sectional study, we sampled 432 individuals who currently or recently used opioids from New Jersey methadone and acute residential detoxification programs. Using multinomial regression analysis, we compared overdose risk factors, including fentanyl-related attitudes/behaviors, of those who never overdosed with three subgroups of overdose survivors who experienced: 1. recent overdoses occurring after, but not before, fentanyl expansion; 2. past overdoses occurring before, but not after, fentanyl expansion; 3. persistent overdoses occurring before and after fentanyl expansion.ResultsForty percent of respondents had knowingly used fentanyl and 38% deliberately sought overdose-implicated drugs. Respondents with persistent overdoses represented under 10% of the sample but accounted for 44% of all lifetime overdoses (x̅ =8.03 vs. 1.71 for the full sample). This was also the only subgroup for whom PTSD (AOR=3.84; 95%CI=1.45–10.16; p=.01) and fentanyl-seeking (AOR=1.50; 95% CI=1.16–1.94; p=.01) were significant overdose risk factors. Those with recent overdoses engaged in frequent drug combining (AOR=2.28; 95% CI=1.19–6.98; p=.05), which could have led to inadvertent fentanyl use. Those with past overdoses were not at overdose risk from fentanyl-seeking or drug combining and had rates of methadone treatment comparable to rates of those with no overdoses.ConclusionHarm reduction strategies will need to address consumers’ evolving drug preferences as fentanyl continues to saturate local drug markets. Targeting comprehensive interventions, including mental health treatment, to the small group of opioid users with longstanding overdose histories may reduce the burden of overdose in opioid-using communities.     

Refractory generalised convulsive status epilepticus : a guide to treatment

The patient with status epilepticus has continuous or rapidly repeating seizures. Generalised convulsive status epilepticus (GCSE) is the most common form of the disorder and is a life-threatening condition that requires prompt medical management. Status epilepticus that does not respond to first-line benzodiazepines (lorazepam or diazepam) or to second-line antiepileptic drugs (phenytoin/fosphenytoin, phenobarbital or valproate) is usually considered refractory and requires more aggressive treatment.The optimal treatment of refractory GCSE has not been defined, but patients should be treated in an intensive care unit, as artificial ventilation and haemodynamic support are required. Invasive haemodynamic monitoring is often necessary and EEG monitoring is essential.The drug treatment of refractory GCSE involves general anaesthesia with continuous intravenous anaesthetics given in doses that abolish all clinical and electrographic epileptic activity, often requiring sedation to the point of burst suppression on the EEG. Barbiturate anaesthetics, pentobarbital in the US and thiopental sodium in Europe and Australia, are the most frequently used agents and are highly effective for refractory GCSE both in children and adults. Indeed, they remain the only way to stop seizure activity with certainty in severely refractory cases. Other options are midazolam for adults and children and propofol for adults only.Regardless of the drug selected, intravenous fluids and vasopressors are usually required to treat hypotension. Once seizures have been controlled for 12-24 hours, continuous intravenous therapy should be gradually tapered off if the drug being administered is midazolam or propofol. Gradual tapering is probably not necessary with pentobarbital or thiopental sodium. Continuous EEG monitoring is required during high-dose treatment and while therapy is gradually withdrawn. During withdrawal of anaesthetic therapy, intravenous phenytoin/fosphenytoin or valproate should be continued (these agents having been administered during earlier phases of GCSE) to ensure an adequate baseline of antiepileptic medication so as to prevent the recurrence of status epilepticus. If additional medication is needed, the most appropriate antiepileptic drugs are gabapentin for focal seizures and levetiracetam and topiramate for all seizure types, as these drugs can be started at high doses with a low risk of idiosyncratic reactions.Even with current best practice, mortality in patients who experience refractory GCSE is about 50% and only the minority return to their premorbid functional baseline. Therefore, new treatment options are urgently needed. The ideal new drug for refractory GCSE would be one that has the ability to stop seizures more effectively and safely than current drugs, and that has neuroprotective properties to prevent the brain damage and neurological morbidity caused by GCSE.     

Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity

AIMS

Paracetamol (acetaminophen) poisoning remains the major cause of severe acute hepatotoxicity in the UK. In this large single centre cohort study we examined the clinical impact of staggered overdoses and delayed presentation following paracetamol overdose.

RESULTS

Between 1992 and 2008, 663 patients were admitted with paracetamol-induced severe liver injury, of whom 161 (24.3%) had taken a staggered overdose. Staggered overdose patients were significantly older and more likely to abuse alcohol than single time point overdose patients. Relief of pain (58.2%) was the commonest rationale for repeated supratherapeutic ingestion. Despite lower total ingested paracetamol doses and lower admission serum alanine aminotransferase concentrations, staggered overdose patients were more likely to be encephalopathic on admission, require renal replacement therapy or mechanical ventilation and had higher mortality rates compared with single time point overdoses (37.3% vs. 27.8%, P = 0.025), although this overdose pattern did not independently predict death. The King''s College poor prognostic criteria had reduced sensitivity (77.6, 95% CI 70.8, 81.5) for this pattern of overdose. Of the 396/450 (88.0%) single time point overdoses in whom accurate timings could be obtained, 178 (44.9%) presented to medical services >24 h following overdose. Delayed presentation beyond 24 h post overdose was independently associated with death/liver transplantation (OR 2.25, 95% CI 1.23, 4.12, P = 0.009).

CONCLUSIONS

Both delayed presentation and staggered overdose pattern are associated with adverse outcomes following paracetamol overdose. These patients are at increased risk of developing multi-organ failure and should be considered for early transfer to specialist liver centres.     

A descriptive study of racial and ethnic differences of drug overdoses and naloxone administration in Pennsylvania

IntroductionDrug overdose is a significant public health problem, yet little is known about racial/ethnic differences in drug overdose rates and/or in responses to a drug overdose following naloxone administration. This paper examines differences in rates of survivorship, response, revival and administration of naloxone by race and ethnicity among those who experienced a drug overdose in Pennsylvania between January 1, 2018 and December 31, 2019. Spatio-temporal variations in drug overdose locations were examined to facilitate understanding of service development, planning, and delivery of effective treatment need.MethodsTen thousand two hundred and ninety drug overdose incidents were analyzed from the Pennsylvania Overdose Information Network (ODIN). The ODIN is a centralized repository that contains information on drug overdoses victims including age, gender and race/ethnicity, naloxone administrations and survivorship, drug(s) suspected of causing the overdose, victim outcomes (e.g. hospitalizations and arrests) and average naloxone dosage per victim. Between group differences were tested using χ2 -tests of independence. Multivariate logistic regression was used to estimate the predicted probability of survivorship according to victim characteristics. All statistical analyses and mapping were performed using the R statistical programming environment.ResultsAbout eighty-seven percent of drug overdose response victims were white, and seventy-one percent were between the ages of 20–39. White females were more likely to receive an overdose response compared to black or Hispanic females. A non-opioid was indicated more frequently in overdoses involving black victims compared to either whites or Latinos. Latinos and blacks were more likely to survive a drug overdose. However, following naloxone administration, no racial or ethnic differences in survivorship were noted. Differences in responsiveness to naloxone and transitions to care following the drug overdose event were also found. Finally, overdoses among Blacks and Latinos demonstrated a stronger spatial patterning across counties compared to whites.ConclusionsThis study found a significant, disparate impact of race/ethnicity on fatal drug overdoses when naloxone is not administered. Further, individuals who were administered naloxone and subsequently received medical care in a hospital experienced lower drug-related mortality, suggesting that first responders are critical intervention points for individuals in need of medical treatment following a drug overdose. However, while naloxone administration is a necessary first step in the recovery process, longitudinal pathways towards treatment are critical to stem the drug overdose crisis.     

Seizures induced by theophylline and isoniazid in mice.

Isoniazid-induced seizures respond poorly to anticonvulsants but well to pyridoxine (Vitamin B6); theophylline produces difficult-to-treat seizures with substantial morbidity and mortality. Theophylline therapy depresses plasma pyridoxal-5'-phosphate (PLP), the active metabolite of pyridoxine, suggesting that theophylline-induced seizures might be amenable to treatment with pyridoxine. Our study established the dose-response relationship for convulsions due to isoniazid and theophylline in mice and determined if pyridoxine antagonized such seizures. Female CD-1 outbred mice weighing 25 to 30 g were used. Clonic seizures had clonic activity lasting 5 sec; tonic seizures had loss of the righting reflex with tonic hindlimb extension. Groups of 10 mice received single doses of 50, 100, 150, 200, 250 or 300 mg aminophylline/kg i.p. or 100, 150, 200, 250, 300 or 350 mg isoniazid/kg i.p. and were observed for seizures or death. Pyridoxine or saline with aminophylline or isoniazid were administered simultaneously. The LD50 for aminophylline was 266 mg/kg; for isoniazid it was 160 mg/kg. Doses of 150 mg aminophylline/kg or 100 mg isoniazid/kg did not induce seizures. Pyridoxine with aminophylline or isoniazid did not alter the frequency or time of onset of seizures or death. This was unexpected because pyridoxine antagonizes theophylline-induced seizures in mice and reverses isoniazid-induced seizures in humans. We found no evidence that PLP depletion in mice is a mechanism for seizures induced by isoniazid or aminophylline in a fashion similar to isoniazid in humans.