Respiratory aspiration during treatment with benzodiazepines, antiepileptic and antidepressant drugs in the pharmacovigilance database from VigiBase.

INTRODUCTION: Three psychotropic drug classes, benzodiazepines, antiepileptic drugs (AEDs) and antidepressants (ADs), whether used in treatment or overdose, may be associated with respiratory aspiration. Polypharmacy was defined by counting suspected drugs from these classes or two others, antipsychotics and opioids. The confounding effects of polypharmacy were considered in this study. AREAS COVERED: VigiBase records of respiratory aspiration associated with benzodiazepines, AEDs, and/or ADs from inception until 5 September 2021, were reviewed. VigiBase, the World Health Organization's global pharmacovigilance database, uses a statistical signal for associations called the information component (IC). EXPERT OPINION: The ICs (and IC025) were benzodiazepines 2.8 (and 2.6), AEDs 1.6 (and 1.5), and ADs 1.4 (and 1.3). The cases of respiratory aspiration associated with at least one drug from these 3 classes included: 1) 553 cases absent any known overdose (2.8 ± 1.7 drugs) and 2) 347 overdose cases (2.9 ± 1.8 drugs). Little support for the association of respiratory aspiration and benzodiazepine, AED or AD monotherapy in therapeutic dosages was found. Studies of the association between benzodiazepine monotherapy and respiration aspiration are needed in geriatric patients. ADs added to other medications increased lethality in all cases of respiratory aspiration including those associated with overdose, polypharmacy and/or major medical problems.

Topiramate for the Treatment of Dually Dependent on Opiates and Cocaine: A Single-center Placebo-controlled Trial.

BACKGROUND: Topiramate facilitates gamma aminobutyric acid (GABA) transference and an ideal candidate for reducing cocaine use in methadone patients. The present study evaluated topiramate in Dual dependence on opiate and cocaine. METHODS: This placebo-controlled study (Clinical Trial Registration Code: TCTR20170201001) conducted during the period 2013-2014, Cocaine-dependent individuals maintained on methadone (n=50) were randomized to receive topiramate or identical placebo capsules. Participants' dosage ranged between 25-300 mg/day (12 wk) in escalating doses. Methadone Doses started at 30 mg/day (median 100 mg/day; range 20 -140 mg/day). In addition, all subjects received brief behavioral compliance enhancement treatment (BBCET). The data were analyzed by Chi-square Test, generalized estimating equations (GEE) models, linear mixed effects (LME) model and Analysis of covariance (ANCOVA). Primary outcome measures included twelve weekly urine drug screens (cocaine abstinence, detection of benzoylecgonine) and treatment retention. Secondary outcome measures included correlation between cocaine craving with cocaine urine samples and Side effects of depression. RESULTS: Topiramate was not better than placebo in reducing cocaine use. The secondary outcome showed that Topiramate was better than placebo in reducing cocaine craving. The mean [99% confidence interval (CI)] scores of cocaine craving were 24.31 (18.61-30.01) in experimental group and 21.84 (16.86-26.81) in control group (all P > 0.01). Retention and correlation between cocaine craving and cocaine urine samples were not significantly different between the groups. Topiramate usage was not associated with increase in depression symptoms as a side effect (P>0.05). CONCLUSION: The efficacy of topiramate in cocaine treatment is limited and needs the similar controlled clinical trials and can be used as a complementary intervention.

A cool side effect of valproic acid administration: Single dose-induced hypothermia.

Thermoregulatory derangements secondary to valproic acid (VPA) administration, specifically hypothermia, have been reported throughout the literature, but a handful of times. This case report describes a 28-year-old male presenting status-post multiple tonic-clonic seizures, treated for persistent seizure activity refractory to benzodiazepines with valproic acid (VPA), levetiracetam, and fosphenytoin. After just over an hour, the patient's core temperature fell from 36.8 °C to 34.9 °C. Temperatures were repeated for confirmation, no further doses of VPA were administered, and the patient's temperature returned to normal over the next 7 h with the use of warming blankets. Levetiracetam and fosphenytoin were continued with no further reported development of hypothermia during the patient's admission. After reviewing other potential causes, a thorough drug database review was performed that found VPA to be the only medication administered with published reports of inducing hypothermia. The mechanism of thermoregulatory derangement associated with VPA is not clearly defined and much of the evidence surrounds alterations in gamma-aminobutyric acid (GABA) activity in animal studies. To our knowledge, this case report is the first reported case of VPA-induced hypothermia following a single dose in the emergency department and offers the potential that prompt return to normothermia is likely following discontinuation of the offending agent.

A Novel Therapy for cocaine dependence during abstinence: A randomized clinical trial.

BACKGROUND: Topiramate is an anticonvulsant drug and an ideal candidate for reducing the craving in people relying on cocaine. Contingency management is one of the common therapies in the domain of addiction. OBJECTIVE: The present study aimed to evaluate and compare three medication methods of Topiramate (TPM), Contingency Management (CM) and the combined TPM treatment and cash intervention on craving during abstinence. METHODS: This randomized clinical trial was conducted at Bijan Center for Substance Abuse Treatment in Tehran, Iran, from December 15, 2014 to November 20, 2015. One hundred males (Age range=18-34; SD=4.11) undergoing abstinence were assigned randomly to four groups (n=25) of Topiramate (TPM), Contingency Management (CM) and the Combined Method plus a placebo control group. Treatment was provided for twelve weeks for the experiment groups, and only the control group received the placebo. Participants in the Cash-based and CM Condition had an identical 12-week escalating schedule of reinforcement (cash-based incentives worth $0, $20, $40, and $80). Also, in the Topiramate group, participants' dosage ranged between 25-300 mg/day in escalating doses) 25, 50, 100, 150, 200, 250, 300). In addition, all subjects received brief behavioral compliance enhancement treatment (BBCET). Participants took a urine test twice a week, with a given threshold of > 300 ng/ml, and indicators of cocaine craving (response rate= 91%) was evaluated in two phases of pre-test and post-test. We used Chi square, ANCOVA Univariate Model and Scheffe's post hoc to analyze the primary and secondary outcomes. Also, the qualitative data resulted from demographic evaluations were coded and analyzed by the instrument of analysis of qualitative data i.e. Atlas.ti, Version 5.2. RESULTS: The results showed that all three types of treatment played a significant efficacy in reducing the craving. The mean (95% CI) scores of craving was 12.04 (p=0.05) with TPM, 13.89 (p=0.05) with CM, 10.92 (p=0.01) with Mix and 16.89 (p>0.05) with control. Moreover, the highest variance explaining the changes in craving was assigned to the combined treatment (p<0.01). CONCLUSIONS: The findings of this study, while having applicable aspects in this domain, can be helpful in planning supplementary remedial procedures. TRIAL REGISTRATION: The trial was registered at the Thai Clinical Trial Registration Center with the TCR ID: TCTR20170112001. FUNDING: The authors received no financial support for the research, authorship, and/or publication of this article.

Rechallenge with lamotrigine after a rash: a prospective case series and review of the literature.

OBJECTIVE: To investigate the safety of rechallenge with lamotrigine after an initial rash in patients with refractory bipolar depression. DESIGN: 1) Prospective, open-label case series in a private practice setting. Patients who developed an initial rash on lamotrigine and were refractory to other treatments were offered rechallenge with the drug using very-low-dose titration (5mg every other day or daily for 14 days, then raised every 14 days by daily-dose increments of 5mg; after 25mg/day the titration proceeded according to the manufacturer's guidelines); and 2) A meta-analysis of prior reports of rechallenge with lamotrigine was conducted. MEASURES: A rating scale for rash severity was developed for this study. RESULTS: Of 27 patients rechallenged with lamotrigine, five required discontinuation due to rash or inflammation. Two of these were potentially serious and all resolved with discontinuation of lamotrigine. Review of the literature identified 48 cases of lamotrigine rechallenge with a success rate of 87 percent; in pooled analysis with the current study the success rate was 85 percent. No patients developed Stevens-Johnson syndrome or toxic epidermal necrolysis after rechallenge. The rate of rash was elevated when rechallenge began within four weeks of the initial rash (36% vs. 7%, p=0.002) and reduced when the initial rash had no signs of potential seriousness (0% vs. 23%, p=0.01). CONCLUSIONS: Rechallenge is a viable option after a benign rash on lamotrigine and can be undertaken with more caution after rashes with 1 to 2 signs of potential seriousness. For rashes with three or more signs of seriousness, rechallenge is not well-studied and may carry significant risk. Rechallenge should be avoided within four weeks of the initial rash.

Síndrome DRESS por carbamazepina / DRESS syndrome by carbamazepine

El síndrome DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) es una reacción adversa grave a medicamentos. Consiste en una erupción cutánea, acompañada de fiebre, compromiso multivisceral y eosinofilia. Con una incidencia de 1/10.000 en individuos expuestos a los fármacos implicados y con una mortalidad de un 10%-30% de los casos. Se presenta un caso clínico de una niña de 12 años, epiléptica, que a las 4 semanas de iniciar tratamiento con carbamazepina presenta fiebre y odinofagia, agregando exantema cutáneo con compromiso sistémico. Se realizó diagnóstico de síndrome DRESS, con buena respuesta al tratamiento instaurado. El síndrome DRESS es una reacción adversa grave, potencialmente mortal, cuyo inicio muchas veces se confunde con cuadros virales, por lo que hay que tener presente este síndrome ante un paciente que inicia tratamiento con anticonvulsivantes y desarrolla exantema febril.

DRESS syndrome is a severe adverse reaction to drugs. The presentation consists of a skin rash, fever, eosynophilia and multiorganic failure. The incidence is 1/10000 and the mortality rate is between 10 to 30%.A case of a 12 year old epileptic patient who started with fever, sore throat and a skin rash with sistemic compromise after 4 weeks of starting treatment with carbamazepine is presented. DRESS syndrome was diagnosed having a good evolution with the treatment done.DRESS syndrome is a severe adverse reaction, potencially mortal, which can be confused with other causes of skin rash such as viral diseases.Pediatricians should be alert to the symptoms in a children who started taking antiepileptic drugs.