SUBSTANCE USE DISORDER
Bupropion-naltrexone therapy shows promise
At present, no drugs are FDA-approved to treat methamphetamine use disorder, but in clinical trials, bupropion and naltrexone used individually have shown some efficacy. Bupropion is an antidepressant of the aminoketone class and naltrexone is an opioid antagonist.
To investigate whether using these two drugs together is a safe and effective therapy, researchers conducted a multisite, double-blind, two-stage, placebo-controlled trial in adults with moderate or severe methamphetamine use disorder. Participants were randomly assigned to receive either extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day), or a matching injectable and oral placebo treatment for 6 weeks (stage 1). Those in the placebo group with no response in stage 1 were randomly reassigned to receive naltrexone-bupropion or placebo for an additional 6 weeks (stage 2). A total of 403 participants were enrolled in stage 1, and 225 in stage 2. The primary outcome was a response defined as at least three methamphetamine-negative urine samples out of four samples. The study was conducted over a 12-week period.
In stage 1, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In stage 2, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. Most adverse reactions in the naltrexone-bupropion group were mild to moderate, including gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Eight of 223 participants who received naltrexone-bupropion experienced a serious adverse reaction such as seizure or hypertensive crisis.
The study authors noted that most participants in the trial were severely affected by methamphetamine use disorder, using the drug almost daily. "The percentage of participants who had a response in each stage of the trial was low; however, there was a significant difference in the weighted response (11.1 percentage points) between the naltrexone-bupropion group and the placebo group." They recommend more research with a more naturalistic effectiveness design to replicate their results.
Several authors disclosed financial ties to the pharmaceutical industry.
Source: Trivedi MH, Walker R, Ling W, et al. Bupropion and naltrexone in methamphetamine use disorder. N Engl J Med. 2021;384:140-153.
COVID-19 DRUG THERAPIES
Virtual drug screening identifies candidates
New research suggests that pralatrexate, a chemotherapy medication developed to treat lymphoma, could be repurposed to treat COVID-19. Using a novel virtual screening process, scientists simulated drug-virus interactions to evaluate 1,906 existing drugs for their potential to inhibit replication of SARS-CoV-2, the virus that causes COVID-19. They identified four promising drugs and tested them against SARS-CoV-2 in lab experiments. Two of these drugs, pralatrexate (a dihydrofolate reductase inhibitor) and the macrolide antibacterial drug azithromycin, successfully inhibited viral replication. Further experimentation showed that pralatrexate more strongly inhibited viral replication than did remdesivir, an antiviral drug currently used to treat some patients with COVID-19.
Pralatrexate is approved for use in patients with relapsed or refractory peripheral T-cell lymphoma and can cause significant adverse reactions such as hepatic toxicity, so whether it will be used to treat patients with COVID-19 patients is uncertain. However, the scientists say their study "demonstrates the feasibility of fast and accurate anti-viral drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19."
Sources: Zhang H, Yang Y, Li J, et al. A novel virtual screening procedure identifies pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro. PLoS Comput Biol. [e-pub December 31, 2020] Lab Manager. Existing drug that inhibits COVID-19 virus identified. News release. January 4, 2021.
HIV INFECTION
Monthly injectable formulation approved
The FDA has approved cabotegravir and rilpivirine, injectable formulation (Cabenuva) as a complete regimen for the treatment of HIV type 1 (HIV-1) infection in adults. The new drug is indicated to replace a current antiretroviral regimen in patients who are virologically suppressed on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. This is the first FDA-approved injectable, complete regimen for HIV-infected adults that is administered once a month. The new approval gives some patients the option of receiving treatment with a single monthly injection instead of daily oral medications.
The safety and efficacy of the new drug were established in two randomized, open-label, controlled clinical trials involving 1,182 patients. At the conclusion of each study, patients continued to show virologic suppression, and no clinically relevant change from baseline in CD4+ cell counts was observed.
The most common adverse reactions were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. The new drug is contraindicated in patients who have had a previous hypersensitivity reaction to cabotegravir or rilpivirine, and in patients who are not virally suppressed.
Source: US Food and Drug Administration. FDA approves first extended-release, injectable drug regimen for adults living with HIV. News release. January 21, 2021.
ANESTHESIA
Accidental awareness high in obstetric patients
From May 2017 to August 2018, 3,115 consenting patients receiving general anesthesia for obstetric surgery were recruited to a study designed to examine the incidence, experience, and psychological implications of accidental conscious awareness during general anesthesia. Patients received three repetitions of standardized questioning over 30 days to determine awareness experiences. Twelve patients were found to have certain/probable or possible accidental awareness, an incidence of 1 in 256 for all obstetric surgeries and 1 in 212 for cesarean section surgery. Distressing experiences were reported by seven of these patients, paralysis by five patients, and paralysis with pain by two. Nine patients experienced accidental awareness during induction and emergence. Factors associated with accidental awareness were high body mass index (BMI), low BMI, out-of-hours surgery, and use of ketamine or thiopental for induction. In addition, standardized psychological impact scores at 30 days were significantly higher in awareness patients than in patients without awareness, and four patients had a provisional diagnosis of posttraumatic stress disorder.
The authors concluded that "direct postoperative questioning reveals high rates of accidental awareness during general anesthesia for obstetric surgery, which has implications for anesthetic practice, consent, and follow-up."
Source: Odor PM, Bampoe S, Lucas DN, et al., for the DREAMY Investigators Group. Incidence of accidental awareness during general anaesthesia in obstetrics: a multicentre, prospective cohort study. Anaesthesia. [e-pub January 12, 2021]