Benzodiazepine Toxicity Treatment & Management: Approach Considerations, Prehospital Care, Flumazenil

Despite the lack of evidence regarding the long-term effectiveness of benzodiazepines and their potential harmful effects, prescriptions for the drug have significantly increased in the US over the past decade. This article reviews best practices for prescribing benzodiazepines in primary care and explains how providers can best prevent and treat benzodiazepine use disorder and other harmful effects. Another study that tested a different standardized education protocol showed more promising results [73]. The experimental group in this study was counseled on the first visit for 15–20 min on the effects, dangers, and alternatives to chronic BZD use and dependence [73]. The subjects were interviewed with surgery-based consultations for approximately 10 min [12].

Which benzodiazepines are available outside the U.S.?

Potent benzodiazepines with shorter elimination half-lives (triazolam, alprazolam, lorazepam) may be the most prone to causing problems with tolerance and dependence. Nayzilam (midazolam) and Valtoco (diazepam) are nasal sprays now approved for the treatment of seizure clusters (also known as acute repetitive seizures). Nayzilam is approved by the FDA to be used in patients 12 years of age and older, and Valtoco in used in those 6 years and older. Clonazepam is the benzodiazepine most frequently used for long-term control and prevention of chronic seizure disorders; however, in general benzodiazepines are not usually the first choice for seizure prevention. There is normally no need to aid breathing in conscious sedation; however, a deeper level of sedation may rarely occur, therefore respiratory and resuscitative equipment should always be available to healthcare providers. Benzodiazepines open GABA-activated chloride channels and allow chloride ions to enter the neuron.

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As discussed, the development of tolerance to benzodiazepines is a medical condition, known as physical dependence. Tolerance is the process by which the brain becomes increasingly accustomed to the drug and, for this reason, requires more of it in order for the person to get the familiar high. When the brain does not get its familiar dose, because the person is abstaining or reducing the familiar amount, withdrawal is triggered. Withdrawal from benzodiazepines is considered to be particularly dangerous, and in some instances, it can be fatal. A unique toxidrome related to parenteral formulations of diazepam and lorazepam is propylene glycol poisoning. Current treatment for withdrawal is through tapering with clonazepam, and overdose should be treated with flumazenil [67].

• More studies will need to be carried out on the non-pharmacologic treatment of BZD withdrawal, as it is showing some promise for the successful discontinuation of the drugs.
• Some people, such as those with a history of complicated withdrawal, seizures, or severe mental illness, may be better suited for an inpatient setting.
• This drug is best known as Rohypnol (or by the slang term “roofies”), and it’s infamous for its use as a “date rape” drug.
• The treatment of seizures, which typically involves benzodiazepines, would be rendered useless, as the flumazenil has blocked the benzodiazepine receptors.

2. Pharmacologic Management of Withdrawal Symptoms

The evaluation consists of 11 yes or no questions that are intended to be used as an informational tool to assess the severity and probability of a substance use disorder. The test is free, confidential, and no personal information is needed to receive the result. If your reasons for quitting benzodiazepines are that benzodiazepine withdrawal you were abusing them or unable to control your use, then you may require further substance use treatment. This is particularly true if you are also giving up other substances, like alcohol or opioids. If you are pregnant or are thinking about becoming pregnant, talk to your OBGYN or psychiatrist about your plans.

Many traditional benzodiazepines are broken down in the liver and when combined with drugs that block this action, blood levels can rise, leading to side effects. Lorazepam, oxazepam and temazepam are less likely to have this risk due to fewer liver enzyme interactions. All of the nonbenzodiazepine agents are approved only for the treatment of insomnia.

However, no set schedule for a taper has been validated in the current literature. Pregnant women and fetuses are at increased risk for adverse effects of withdrawal; they both metabolize BZD slowly, and the drug can cross the placenta to cause concentrations to build up to significant levels in the neonate https://ecosoberhouse.com/ [18]. While a therapeutic dose has not been proven teratogenic, use during pregnancy has been linked to low birth weight, preterm labor, and intrauterine growth restriction. The unborn fetus is at high risk for “floppy infant syndrome,” characterized by muscle laxity, failure to suckle, and oversedation.

Can Anxiety Relief Come at the Cost of Cognitive Health?

In a 12-month period spanning 2014 and 2015, experts estimate that at least 30.5 million people in the U.S. took benzodiazepines prescribed by a healthcare provider. The researchers used a unique lab model called “Guwiyang Wurra-TSPO knockout,” a healthy mouse lacking a protein present in the mitochondrion, the cell’s energy-providing organelle (5). Anti-anxiety drugs like diazepam bind to TSPO on the surface of microglial cell organelles. Microglial cells are the brain’s first immune responders and are implicated in dementia, long COVID, chronic fatigue and other cognitive impairments. Some people, such as those with a history of complicated withdrawal, seizures, or severe mental illness, may be better suited for an inpatient setting. This can involve living at a detox facility or hospital for several weeks, where you can receive constant medical monitoring and psychological support.

Can you prevent withdrawal?

Mirtazapine (Remeron) and buspirone are also effective in GAD for patients who do not respond to at least two trials of SSRIs or SNRIs. Long-term use of benzodiazepines for GAD should be avoided, when possible, due to addictive risk. Drug treatment will depend upon the level of anxiety, patient characteristics such as age and organ function, and patient preference. For patients who do not want to use medications, cognitive behavioral therapy and relaxation therapy have been shown to be effective; however the combination may work best. GAD is the most frequent anxiety disorder, affecting 6.8 million adults or about 3% of the U.S. population, but more than half remain untreated. If you’ve taken benzodiazepines at high doses for an extended period, you may experience long-term withdrawal symptoms, also called post-acute withdrawal syndrome (PAWS) or protracted withdrawal.