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Midazolam is a benzodiazepine drug that is indicated for the treatment of acute seizures, including status epilepticus, and is FDA-approved as a preoperative sedative and anesthetic.

9 Minute Read | Published Oct 04 2023 | Updated Feb 29 2024 Expert Verified
Emma Collins
Written by
Dameisha Gibson
Reviewed by
Emma Collins
Written by
Dameisha Gibson
Reviewed by

Common Brand Names: Versed, Nayzilam, Seizalam

The full spectrum of midazolam’s mechanism of action is still unclear, but clinical studies suggest that midazolam binds to benzodiazepine and gamma-aminobutyric acid (GABA-A) receptors in the central nervous system. Many of the drug’s pharmacological effects are related to its action on GABA-A receptors, including its sedative and anticonvulsant effects, as well as capacity to induce anxiolysis and anterograde amnesia. Midazolam also acts on glycine receptors, which leads to its muscle-relaxing effect.

Midazolam is classified as a Schedule IV drug under the federal drug scheduling system and is considered to have a low abuse potential relative to other scheduled drugs. However, long-term misuse of Midazolam can still lead to dependence and addiction.

What Is Midazolam Used For?

Midazolam is FDA-approved for the following:

  • Preoperative sedation and inducing anxiolysis
  • Inducement of general anesthesia before administration of other anesthetic agents
  • Continuous IV infusion for sedation of intubated and mechanically ventilated patients

Meanwhile, midazolam is contraindicated in patients with documented allergic or hypersensitivity to the drug or any of its components; patients with acute angle-closure glaucoma; and patients experiencing hypotension or shock.

Dose adjustments must also be made for patients with kidney and liver disorders, as well as those with alcohol or substance dependence. For pregnant patients, children, and patients with comorbid psychiatric disorders, caution must be observed when prescribing midazolam. Close supervision of elderly and acutely ill patients taking midazolam is also necessary to prevent midazolam toxicity due to slower drug metabolism.

How Do People Abuse Midazolam?

The World Health Organization’s List of Essential Medicines includes midazolam, which means that it is recommended by the agency as a safe and effective short-term medication. As a Schedule IV drug, it also presents a lower risk for abuse and dependence. However, the potential is still there, and much like other benzodiazepines, midazolam has desirable effects that make it prone to abuse.

Misuse of midazolam usually happens in the following ways:

  • Taking the drug without prescription
  • Prolonged usage
  • Taking larger doses than prescribed
  • Mixing midazolam use with alcohol intake
  • Recreational

Unlike other benzodiazepines, which are often crushed and then snorted, midazolam is usually misused through injection. This is because the drug typically comes in forms that are water soluble. It has also been found that midazolam is often used in tandem with other drugs like heroin and methamphetamine.

Repeated or chronic abuse of midazolam can increase a person’s tolerance to the drug. Over time, it can also lead to dependence and addiction.

Midazolam Drug Interactions

There are various substances that inhibit the metabolism of midazolam, thereby prolonging its effects. These substances include:

  • Protease inhibitors
  • Fluoxetine
  • Erythromycin
  • Clarithromycin
  • Nefazodone
  • Sertraline.

On the other hand, these drugs can enhance the metabolism of midazolam, which results in reduced action:

  • Rifampin
  • Rifabutin
  • Rifapentine
  • Phenytoin
  • John’s wort

There are also substances that enhance the sedative effects of midazolam. These include the following:

  • Sedative antidepressants
  • Phenobarbital
  • Sedative antihistamines
  • Opioids
  • Alcohol

Why Does Midazolam Present a Risk for Addiction?

As a benzodiazepine, midazolam slows down the CNS or central nervous system and produces the following effects:

  • Rest and relaxation. Midazolam can cause sleepiness, which can be helpful for people who are suffering from insomnia and other sleeping disorders.
  • Anxiety relief. Patients suffering from anxiety, panic disorders, and similar conditions may experience less intense symptoms when taking midazolam.
  • Trauma relief. Some people experiencing emotional or mental upheavals may find this effect helpful.

All of the above are common among benzodiazepine drugs that are prone to abuse. What’s more, midazolam  is a ubiquitous anesthesia in operating rooms and also a commonly prescribed benzodiazepine. As such, the drug is rather easy to access.

Midazolam Side Effects

Midazolam is generally a well-tolerated and safe drug. However, just like any other medication, midazolam may cause a variety of side effects. The most common immediate adverse reactions associated with midazolam include:

  • Nausea and vomiting
  • Cough
  • Hiccoughs
  • Pain on injection site
  • Thrombophlebitis

In the elderly, midazolam can also cause:

  • Drowsiness
  • Confusion
  • Anterograde amnesia
  • Body incoordination

Nighttime administration of midazolam can also result in a residual hangover effect that can impair both cognitive and psychomotor function. This may lead to impaired coordination during driving, as well as to slip and fall accidents, particularly among elderly patients.

In patients with a history of alcohol abuse, midazolam use can result in the following paradoxical effects:

  • Uncontrollable crying
  • Aggressive behavior
  • Involuntary movements

Taken concomitantly with other drugs that depress the central nervous system, midazolam can result in severe respiratory depression and even death.

Neonates whose mothers are taking midazolam during their third trimester may suffer from benzodiazepine withdrawal syndrome that can manifest as:

  • Bluish or purple hue to the skin (cyanosis)
  • Interrupted breathing during sleep (apnea)
  • Decreased muscle tone

Some effects of midazolam use can point to a life threatening situation. Contact 911 immediately if you observe the following symptoms in yourself or others:

  • Agitation
  • Restlessness and agitation
  • Aggression
  • Uncontrolled shaking of a body part
  • Jerking or hardening of limbs
  • Uncontrolled rapid eye movements
  • Uncontrollable rapid eye movements
  • Sudden onset of hives or rashes
  • Difficulty breathing or swallowing
  • Seizures

Long-Term Effects of Midazolam

Chronic use of midazolam may also cause the following health effects:

  • Lasting memories deficits (partially reversible after discontinuation of the drug)
  • Tolerance after four weeks of use
  • Withdrawal symptoms following abrupt cessation of midazolam use
  • Benzodiazepine withdrawal symptoms in neonates whose mothers have used midazolam
  • Diarrhea, tremors, and hyperexcitability in neonates whose mothers have used midazolam

Symptoms of Midazolam Overdose

The signs of midazolam overdose are similar to those of other benzodiazepines. In the worst of cases, overdose can lead to death. As such, it’s important to call 911 if you notice any of the symptoms in yourself or in others:

  • Nystagmus or the involuntary rhythmic motion of the eyes
  • Hypotension or having low blood pressure
  • Slurred speech or difficulty in speaking
  • Impaired motor coordination
  • Impaired balance
  • Impaired reflexes
  • Dizziness

Do note that in elderly patients with chronic obstructive pulmonary disorders, rapid intravenous infusion of midazolam can result in an overdose.

Signs of Midazolam Addiction

While midazolam is listed as a Schedule IV medication, chronic misuse of midazolam can still lead to physical dependence and eventually, benzodiazepine addiction.

The Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) lists the following 11 criteria as symptoms for substance use disorders, including addiction that may be caused by midazolam:

  • Taking midazolam in excessive doses or for longer than was prescribed
  • Wanting to stop using midazolam but being unable to
  • Spending a lot of time getting, using, or recovering from use of midazolam
  • Having intense cravings for midazolam
  • Problems handling personal commitments because of midazolam use
  • Continuing to use midazolam even though it causes problems in interpersonal relationships
  • Missing out on important activities because of midazolam use
  • Repeated use of midazolam even if it puts you in danger
  • Continued use of midazolam despite exacerbation of medical problems
  • Developing tolerance or needing higher and higher doses of midazolam to achieve the desired effects
  • Developing withdrawal symptoms after abrupt cessation of midazolam use

Midazolam Withdrawal Symptoms

Some of the most common withdrawal symptoms of benzodiazepines like midazolam include:

  • Irritability
  • Nausea
  • Vomiting
  • Diarrhea
  • Tachycardia
  • Hypertension
  • Clonus or rhythmic muscle contractions
  • Status epilepticus

These symptoms are highly indicative of dependence on the drug. What’s more, it’s entirely possible to be dependent on midazolam even if you haven’t yet developed an addiction to it yet. If you experience any of the above-mentioned withdrawal symptoms, seek medical help immediately so you can undergo detoxification and remove midazolam from your system properly.

Midazolam Detox

In general, the rehabilitation of patients from most substance use disorders begins with detoxification. Detoxification, or simply detox, pertains to the process of eliminating the substance that you’ve developed dependence on—in this case, midazolam—and to prevent acute withdrawal. The goal is to reverse physical dependence and to ultimately remove the drug from your system.

Medical professionals will be on standby throughout the process at your chosen facility to ensure your comfort and safety. Midazolam detox usually involves gradual dose reduction and drug replacement with benzodiazepines with a longer half-life. You may also be given IV fluids, nutritional supplements, and other medications to help ease your withdrawal symptoms.

Rehabilitation and Treatment for Midazolam Addiction

Midazolam is one of the most prescribed benzodiazepines, which means a lot of patients have easy access to the drug. In addition, it also has an elimination half-life of 1.5 to 2.5 hours. Because of this and the drug’s high potency and fast-acting effects, midazolam users may eventually develop tolerance, dependence, and addiction over time.

If you or a loved one is struggling with midazolam use disorder, it’s best to consider professional treatment. Depending on the patient’s condition, the rehabilitation program may either be on an outpatient or inpatient basis.

  • Outpatient midazolam treatment: This type of midazolam rehabilitation is best suited for low-risk patients with a milder addiction and therefore have a higher likelihood of compliance with the prescribed programs. Those who undergo outpatient treatment are usually able to continue with their usual living arrangements and daily routines, such as going to work or school. However they will be required to attend therapy and counseling at the assigned facility.
  • Inpatient midazolam treatment: In contrast to outpatient rehabilitation, inpatient midazolam addiction rehabilitation is the best course for high-risk patients. These are individuals who have developed moderate to severe addiction, which means they may not be able to guarantee treatment compliance. They will be provided with round-the-clock medical supervision, and receive a combination of treatments such as drug education, family therapy, group counseling, and others.

No single treatment is right for everyone. Just like for any other condition, treatment for midazolam addiction must be individualized, holistic, and patient-centered. Therefore, a complete evaluation of the patient is necessary before starting any treatment program.

Get the Help You Need

The road to recovery from midazolam addiction may be difficult. However, the silver lining is that both outpatient and inpatient treatment is covered by most insurance plans. There are also plenty of other options to finance your journey to complete wellness even if you don’t have insurance.

Call Better Addiction Care today at (800) 429-7690 to speak to a recovery support advisor. They will help evaluate your insurance coverage and guide you through the process of finding the best treatment facility for you or your loved one.

A Brief History of Midazolam

Midazolam was first synthesized in 1976 by Armin Walser, Rodney Fryer, and Louis Benjamin, who were then working at the New Jersey office of Hoffman La-Roche (now Roche), a Swiss multinational healthcare company. It received its US FDA approval in 1985.

The intramuscular formulation of midazolam was approved for the treatment of status epilepticus in late 2018, and in May 2019, the nasal formulation was approved for the treatment of stereotypic seizure episodes in patients 12 years and older.

Midazolam is listed in the WHO List of Essential Medicines. As of 2010, it is the most commonly used anesthetic benzodiazepine.


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