Midazolam (Versed®) Side Effects

How does midazolam work?

Understanding how Versed® affects the brain helps explain its benefits and risks. Midazolam is a benzodiazepine that binds to gamma-aminobutyric acid (GABA) receptors, the primary inhibitory neurotransmitter in the brain. ^[1] GABA naturally slows nerve impulses; by binding to GABA-A receptors, midazolam amplifies this effect, producing sedation, lowering anxiety, and causing short-term memory loss. ^[1]

Unlike longer-acting benzodiazepines, midazolam has a short half-life, which often allows patients to recover more quickly from procedural sedation. ^[2] Still, how a person metabolizes midazolam depends on organ functions (liver and kidneys), age, other medical conditions, and concurrent medications. When midazolam is combined with opioids, alcohol, or other central nervous system depressants, risky sedation can occur. ^[1][2]

When administering midazolam, healthcare providers typically monitor respiration (breathing), oxygen saturation (the percentage of oxygen carrying capacity of the blood), blood pressure, and heart rate for the onset of midazolam side effects. ^[3]

Common midazolam side effects

Mild-to-moderate side effects occur for a significant portion of people receiving midazolam. They typically resolve once the medication wears off. ^[4]

• Drowsiness and fatigue: Because Versed® suppresses CNS activity, sedation may linger for a few hours, making it unsafe to drive or operate machinery soon afterward.
• Dizziness and lightheadedness: Changing positions quickly (e.g., standing up) can spur feelings of imbalance or lightheadedness, especially in older adults.
• Short-term memory gaps: Patients sometimes cannot recall events that occur while under the influence of midazolam.
• Headaches: Mild headaches occasionally arise once sedation wears off.
• Nausea: Some people notice gastrointestinal problems, particularly when midazolam is used with opioid pain relievers or taken on an empty stomach.
• Blurred vision: Transient vision changes may occur, but they usually resolve as the drug’s half-life elapses.

The following additional side effects are reported after IV administration: ^[4]

• Pain during injection and at the injection site
• Induration at the injection site
• Hiccups
• Vomiting
• Coughing
• Diplopia

These common side effects usually do not call for medical intervention. Rest, gradual return to activities, and adequate hydration help address temporary discomfort. However, if symptoms intensify or last longer than expected, seeking medical guidance is prudent.

Severe side effects

Although midazolam (Versed®) is recognized as safe under professional supervision, specific serious side effects remain inevitable:

• Respiratory depression: Breathing can slow, causing dangerously low oxygen intake. ^[5]
• Paradoxical reactions: Rather than sedation, a small percentage of people given Versed® experience agitation, restlessness, or even aggression. ^[6]
• Significant drops in blood pressure: People given midazolam may experience hypotension, causing sudden dizziness or fainting. ^[6][7]
• Arrhythmias: Although uncommon, abnormal heart rhythms may emerge in susceptible patients taking/given Versed®, particularly those with existing heart problems. ^[8]
• Psychiatric side effects: People who are given midazolam may experience euphoria, emergence delirium, paresthesia, confusion, disorientation, emotional and mood disturbances, hallucinations, and dysphoria. ^[6]
• Allergic reactions: Signs (like swelling of the throat or lips, hives, or labored breathing) may signal an acute allergy following Versed® administration and require urgent medical care. ^[6]

Risks and complications

Various factors can intensify midazolam side effects and lead to worse or altered outcomes.

Midazolam abuse and dependence

Midazolam’s appeal lies in its speed of onset—it offers a rapid, calming rush followed by a quick offset. ^[1] That same pharmacokinetic profile invites redosing and tolerance within days, particularly when the drug is taken outside short-procedure settings. ^[11] 

Some people chase the brief amnesic “black-out” effect as a form of escapism, or they may inject oral/IV formulations for a faster high. ^[12][13] As tolerance rises, physical dependence often develops, and the withdrawal cluster (rebound anxiety, tremor, perceptual distortion, and potentially seizures) can appear within hours of a missed dose. ^[14]

There are some indicators of midazolam misuse: ^{[11][12][13][14][15]}

• Escalating the dose or taking extra add-on doses sooner than prescribed.
• Mixing midazolam with alcohol, opioids, or other gabaminergic sedatives to deepen the dissociative effect.
• Acute distress or agitation when a dose is delayed.
• “Doctor shopping” or sourcing veterinary or illicit midazolam to bridge gaps in supply.
• Injecting midazolam without medical supervision.

Midazolam withdrawal and tapering

Abruptly stopping midazolam, especially after prolonged use, IV use, or use of high doses, can cause withdrawal symptoms, including increased anxiety, tremors, insomnia, and (in severe cases) seizures. ^[4]

A structured tapering protocol, where the midazolam dose is incrementally lowered over a set period, reduces midazolam withdrawal symptoms. One tapering schedule is the cut and hold method, in which the dosage of midazolam is reduced by 5–10% every 2–4 weeks, and each dose is maintained until symptoms are stable. Tapering midazolam may take up to a few months for some patients. ^[16] 

Sometimes doctors switch to a long-acting benzodiazepine (like diazepam) before tapering down further, ensuring more stable blood levels throughout the process. ^[16] 

Supportive measures, such as counseling or cognitive-behavioral therapy (CBT), while tapering help address the psychological aspects of withdrawal and help patients build healthier strategies to manage anxiety or insomnia without relying on benzodiazepines.