A subgroup of patients with drug-resistant epilepsy have seizure clusters, which are a part of the continuum of seizure emergencies that includes prolonged episodes and status epilepticus. When the patient or caregiver can identify the beginning of a cluster, the condition is amenable to certain treatments, an approach known as rescue therapy. Intravenous drug administration offers the fastest onset of action, but this route is usually not an option because most seizure clusters occur outside of a medical facility. Alternate routes of administration have been used or are proposed including rectal, buccal, intrapulmonary, subcutaneous, intramuscular, and intranasal. The objective of this narrative review is to describe the (1) anatomical, physiologic, and drug physicochemical properties that need to be considered when developing therapies for seizure emergencies and (2) products currently in development. New therapies must consider parameters of Fick's law such as absorptive surface area, blood flow, membrane thickness, and lipid solubility, because these factors affect both rate and extend of absorption. For example, the lung has a 50 000-fold greater absorptive surface area than that associated with a subcutaneous injection. Lipid solubility is a physicochemical property that influences the absorption rate of small molecule drugs. Among drugs currently used or under development for rescue therapy, allopregnanolone has the greatest lipid solubility at physiologic pH, followed by propofol, midazolam, diazepam, lorazepam, alprazolam, and brivaracetam. However, greater lipid solubility correlates with lower water solubility, complicating formulation of rescue therapies. One approach to overcoming poor aqueous solubility involves the use of a water-soluble prodrug coadministered with a converting enzyme, which is being explored for the intranasal delivery of diazepam. With advances in seizure prediction technology and the development of drug delivery systems that provide rapid onset of effect, rescue therapies may prevent the occurrence of seizures, thus greatly improving the management of epilepsy.

In several medico-legal cases, bone samples analysis may provide the only source of toxicological information. This case study reports the analysis of a human bone specimen, belonging to a 46-year-old man, found 3 months after his death due to cervical-thoracic injuries in a motorcycle accident. Bone specimen was the only available material for toxicological analysis, among few skull hair and rotten skin. Analysis was performed by a newly developed and validated ultra-high-pressure liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS) method, following simple and efficient sample pretreatment. The results were in accordance with the man's medical record: Alprazolam and zolpidem were found at 2.2 and 5.4 ng/g of bone, respectively. Both these drugs were prescribed to the deceased.

To conduct a proof-of-concept study comparing Lorenz-curve analysis (LCA) with power-law (exponential function) analysis (PLA), by applying segmented regression modeling to 1-year prescription claims data for three medications-alprazolam, opioids, and gabapentin-to predict abuse and/or diversion using power-law zone (PLZ) classification.

Wastewater-based epidemiology (WBE) was applied to estimate the consumption of twelve narcotics within a Southwestern U.S. university campus. Seven consecutive 24-hour composite raw wastewater samples (n = 80) were obtained once per month from sampling locations capturing >95% of campus-generated wastewater. Samples were analyzed for indicators of consumption of morphine, codeine, oxycodone, heroin, fentanyl, methadone, buprenorphine, amphetamine, methylphenidate, alprazolam, cocaine, and MDMA using LC-MS/MS. Eleven indicator compounds (oxycodone, codeine, norcodeine, 6-acetylmorphine, EDDP, amphetamine, alprazolam, alpha-hydroxyalprazolam, cocaine, benzoylecgonine, and MDMA) occurred at 100% detection frequency across the study, followed by morphine-3-glucuronide (98%), noroxycodone (95%), methylphenidate (90%), heroin (7%), norfentanyl (7%), and fentanyl (5%). Estimates of average narcotics consumption ranked as follows in units of mg/day/1000 persons: heroin (474 ± 32), cocaine (551 ± 49), amphetamine (256 ± 12), methylphenidate (236 ± 28), methadone (72 ± 8), oxycodone (80 ± 6), alprazolam (60 ± 2), MDMA (88 ± 35), codeine (50 ± 4), and morphine (18 ± 3). This campus-based WBE study yielded baseline data on 12 narcotics for a U.S. campus and demonstrated for the first time the feasibility of detecting the fentanyl metabolite norfentanyl in this setting.

Recent research emphasizes emotional engagement and between-session extinction, but no longer within-session extinction, as the primary mechanisms underlying exposure therapy for the treatment of PTSD. No previous studies have examined change in subjective units of distress (SUDS) in virtual reality exposure (VRE) for PTSD despite its potential facilitation of engagement (see McLay et al., 2012; Reger & Gahm, 2008). Using in session data from Rothbaum et al. (2014) we examined patterns of within- and between-session SUDS change in veterans receiving VRE for PTSD augmented by d-cycloserine, alprazolam, or placebo. The number of treatment sessions significantly predicted SUDS rating (t = -7.74, p < 0.001). Time in session continued to serve as a significant predictor of SUDS (t = 13.44, p < 0.001). Specifically, engagement increased within session and then reduction (extinction/habituation) was apparent across sessions. Treatment group was a predictor of SUDS rating within treatment sessions (t = 2.26, p < 0.05) but not across sessions, such that participants receiving medication experienced greater increases in SUDS within-session than those receiving placebo. Responder status was a predictor of SUDS reduction across treatment sessions (t = -4.43, p < 0.001) but did not produce an overall or within-session effect on SUDS. Thus, medications impact within-session SUDS changes but do not impact between-session reductions in SUDS- the change most consistently and closely related to magnitude of therapeutic change and responder status.

Because of reports of effects in infants, including sedation, alprazolam is probably not the best benzodiazepine for repeated use during nursing, especially with a neonate or premature infant. A shorter-acting benzodiazepine without active metabolites is preferred. After a single dose of alprazolam, there is usually no need to wait to resume breastfeeding.