Benzodiazepines (commonly referred to as “benzos”) are highly addictive drugs that are among the most commonly abused prescription medications in the United States (second only to opioids). In spite of the significant risk associated with regular benzo use, they are among the most-prescribed drugs as well, with nearly 70 million prescriptions written for the four most-prescribed benzos (Xanax, Klonopin, Valium and Ativan) in 2016. Xanax (generic name alprazolam) was the 19th most prescribed drug in the United States in 2016.
In January 2019, the Journal of the American Medical Association published a report indicating that between 2005 and 2015, benzo prescriptions increased by 50%. This increase in prescribing rates occurred concurrently with an increase in benzo-related deaths.
Medical professionals are voicing concern over the seemingly irresponsible and unnecessary increase in benzodiazepine prescriptions, which are supposed to be prescribed for temporary, intermittent use only but have recently become as ubiquitous as multivitamins among some demographics.
The unfortunate reality is that benzos are powerfully addictive drugs that are very difficult to quit, and many prescribers neglect to take this fact into consideration as they write prescription after prescription to trusting clients. People who consistently receive prescription refills are often unaware of the serious risks associated with regular benzo use, leaving them facing the often overwhelming challenge of overcoming a benzodiazepine use disorder without a medical provider who takes their concerns seriously.
For people who are worried that they are at risk for a benzo use disorder, there are signs and symptoms that can help them understand whether they are in need of an expert opinion. The development of tolerance is a hallmark early sign of developing dependence and addiction.
Benzodiazepine Tolerance Symptoms
Tolerance refers to a state where the brain no longer responds to the prescribed dose in the same way it initially did. As tolerance develops, increasing amounts of the drug are required to achieve the desired effect.
Benzodiazepine tolerance is also often characterized by the development of physical and psychological dependence, which becomes apparent if someone reduces the dose or attempts to stop using the drug.
Benzo Tolerance Withdrawal
Someone who has developed tolerance to and dependence on benzos will exhibit common signs and symptoms of withdrawal if they miss a dose or attempt to reduce or stop taking the drug. Different formulations of benzos have different half-lives and effective time frames, which will alter withdrawal onset and resolution.
Common physical signs of benzo withdrawal include:
- Rapid heart rate
- Muscle cramps
Common psychological signs of benzo withdrawal include:
- Dysphoria (a sense of unease or dissatisfaction)
- Anhedonia (an inability to experience pleasure)
Causes Of Benzodiazepine Tolerance
There are several factors that influence how quickly tolerance is established and the degree to which it takes hold:
- Dosage: Higher doses are associated with more rapid tolerance onset.
- Frequency of use: Increased frequency causes more rapid tolerance development.
- Duration of use: Prolonged benzo use is more strongly linked to tolerance.
- Type of Benzo: Shorter-acting benzos with high potency (notably Xanax, Ativan and Halcion) have substantially higher rates of tolerance development than long-acting, low-potency benzos.
- Interactions with other drugs: Drugs that enhance the effects of benzos (opioids, alcohol and barbiturates, among others) increase the risk of tolerance development. Tolerance is not the only concern: Drug-drug interactions between benzos and alcohol, birth control, antibiotics and over-the-counter drugs like St. John’s wort, can be dangerous.
- Other factors: Age, genetics, metabolism, mental and physical health and even diet can affect benzodiazepine efficacy and tolerance.
Faced with tolerance, many people seek ways to increase the efficacy of their benzo without increasing the dose or frequency of use. Unfortunately, potentiating benzos can have dangerous, even lethal consequences.
Changing how benzos are metabolized can increase the amount of time they are available for use. Common benzo potentiators include:
- Grapefruit juice
- Diphenhydramine (the active ingredient in Benadryl)
- Cimetidine (an active ingredient in heartburn medicines)
- St. John’s wort and valerian root
Potentiating benzodiazepines is never recommended, but there are three drugs that should be absolutely avoided when taking benzodiazepines:
Benzodiazepines are central nervous system (CNS) depressants, as are opioids, barbiturates and alcohol. Combining these drugs has a synergistic effect, meaning that the effect of the combination of drugs is more powerful than what would be expected if the intoxicating effects of the individual drugs were added together. Overdosing on CNS depressants can cause the brain to become so sluggish that unconsciousness, respiratory depression, coma or death may occur.
How To Prevent Benzodiazepine Tolerance
The most effective way to prevent benzo tolerance is to take it infrequently and at the lowest effective dose. Prescribing guidelines for benzodiazepines indicate that they should be prescribed for intermittent, short-term use to avoid concerns associated with tolerance, dependence and addiction.
Benzodiazepine tolerance reversal remains an area of active research. Tolerance development is a complex molecular process, as are potential mechanisms associated with tolerance reversal. Benzos act on receptors in the brain that normally interact with the inhibitory neurotransmitter called GABA. Evidence suggests that specific components of the GABA-A subfamily of GABA receptors can influence tolerance and perhaps reversal.
Intravenous administration of the benzodiazepine antagonist flumazenil may also reverse tolerance. The majority of research done on flumazenil reversal is in the context of people who use benzos to manage epileptic seizures.
It bears repeating that benzo potentiation can be very dangerous. Never attempt to adjust medications without first consulting with a medical professional.
Getting Help With Benzodiazepine Addiction
Despite their popularity and the relative ease with which people can get prescriptions, benzodiazepines are addictive. Among addictive drugs, benzodiazepine detox and withdrawal is notable for being associated with dangerous side effects.
Benzodiazepine addiction treatment often begins with medical detox, which is associated with 24/7 supervision by medical professionals who can intervene in the case of complications. When appropriate, medications can be provided to reduce the severity of withdrawal symptoms. Subsequent participation in residential or outpatient rehab is strongly recommended to reduce the risk of setbacks occurring and inspire long-term recovery.
If you’re ready to address your benzodiazepine addiction, contact The Recovery Village Ridgefield to speak to a representative about how professional treatment can help. You deserve a healthier future, call today.
National Institute on Drug Abuse. “Commonly Abused Prescription Drugs.” October 2011. Accessed September 26, 2019.
ClinCalc. “Benzodiazepine.” July 19, 2018. Accessed October 3, 2019.
Agarwal, Sumit D; Landon, Bruce E. “Patterns in Outpatient Benzodiazepine Prescribing in the United States.” JAMA, January 2019. Accessed September 26, 2019.
Ogbonna, Chinyere I; Lembke, Anna. “Tapering Patients Off of Benzodiazepines.” American Family Physician, November 2017. Accessed September 26, 2019.
National Institute on Drug Abuse. “The Neurobiology of Drug Addiction.” January 2007. Accessed September 26, 2019.
Longo, Lance P; Johnson, Brian. “Benzodiazepines—Side Effects, Abuse Risk and Alternatives.” American Family Physician, April 2000. Accessed September 26, 2019.
Griffin, Charles; et al. “Benzodiazepine pharmacology and central nervous system-mediated effects.” The Ochsner Journal, 2013. Accessed September 26, 2019.
Cheng, Tianze. “Valium without dependence? Individual GABAA receptor subtype contribution toward benzodiazepine addiction, tolerance, and therapeutic effects.” Neuropsychiatric Disease and Treatment, March 2018. Accessed September 26, 2019.
Hood, Sean David; et al. “Benzodiazepine dependence and its treatment with low dose flumazenil.” British Journal of Clinical Pharmacology, January 2014. Accessed September 26, 2019.