How long does diazepam last
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Duration of Diazepam Effects: A Comprehensive Overview
Introduction to Diazepam Duration
Diazepam, commonly known by its brand name Valium, is a benzodiazepine used primarily for its anti-anxiety, muscle relaxant, and anticonvulsant properties. Understanding the duration of its effects is crucial for both clinical and personal use. This article synthesizes research findings on how long diazepam lasts in the body and its functional impacts over time.
Acute Effects and Initial Duration
Immediate Impact and Short-Term Duration
Upon administration, diazepam exhibits rapid onset of action. Clinically, it is often stated that diazepam acts for approximately 6 to 8 hours1. This duration is supported by studies measuring changes in sensory discrimination thresholds, such as the visual critical flicker fusion threshold (CFFT) and auditory flutter fusion threshold (AFFT), which are sensitive to the effects of centrally acting drugs like diazepam1.
Pharmacokinetics and Half-Life
The pharmacokinetic profile of diazepam reveals that it is rapidly absorbed when taken orally, with blood levels plateauing around Day 7 of continuous administration3. The apparent half-life of diazepam ranges from 21 to 37 hours following intravenous administration, indicating that the drug remains in the system for an extended period3. This prolonged presence is due to the drug's distribution into both shallow and deep peripheral compartments, with the latter being the rate-controlling factor in its elimination3.
Long-Term Administration and Accumulation
Steady-State Concentrations
With prolonged administration, diazepam and its primary metabolite, N-desmethyldiazepam, accumulate in the plasma. Studies have shown that plasma concentrations of diazepam reach a steady state after about 8 days, while N-desmethyldiazepam continues to accumulate, reaching levels two to three times higher than the parent drug2. This accumulation can influence the duration of the drug's effects, extending its functional impact beyond the initial 6 to 8 hours.
Behavioral and Physiological Effects
Chronic administration of diazepam can lead to tolerance, where the initial effects diminish over time despite continued use. For instance, a study comparing diazepam and oxazepam found that while diazepam produced quick effects, tolerance developed, and the effects did not increase with higher dosages4. Additionally, long-term use can result in physiological changes, such as decreased skin conductance and heart rate, which tend to return to baseline levels after discontinuation of the drug7.
Withdrawal and Residual Effects
Withdrawal Symptoms
Upon discontinuation, diazepam and its metabolites decrease slowly, with diazepam having a half-life of 2 to 4 days and N-desmethyldiazepam having a half-life of 4 to 8 days2. Withdrawal symptoms can vary in intensity, with mild to intermediate symptoms observed after 7 days of administration and more severe symptoms, including tremors and convulsions, after 35 days6.
Cognitive and Performance Recovery
Memory and cognitive performance can be impaired by diazepam, particularly in the initial stages of administration. However, tolerance to these impairments can develop with continued use, and no residual memory effects are typically observed following withdrawal10. Performance tends to return to pre-drug levels within two weeks after stopping the medication7.
Conclusion
Diazepam's effects can last for 6 to 8 hours initially, but its pharmacokinetic properties and accumulation in the body extend its functional impact over a longer period. Chronic use leads to tolerance and physiological changes, with withdrawal symptoms varying based on the duration of administration. Understanding these dynamics is essential for optimizing therapeutic use and managing potential side effects.
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Most relevant research papers on this topic
Plasma diazepam concentrations following prolonged administration.
Prolonged administration of diazepam leads to accumulation of its metabolite N-desmethyl, with both diazepam and N-desmethyl concentrations decreasing slowly after discontinuing therapy.
Non-RCTPharmacokinetic profile of diazepam in man following single intravenous and oral and chronic oral administrations.
Diazepam blood levels plateau at approximately Day 7 of treatment, with desmethyldiazepam blood levels remaining within the range of diazepam blood levels for 50 to 99 hr. after the last dose of diazepam on Day 15.
Non-RCT
Highly CitedComparison of two benzodiazepines with differing accumulation: Behavioral changes during and after 3 weeks of dosing
Diazepam has quick effects and recovery, while oxazepam has slower effects and longer duration, both with tolerance developing, and no withdrawal symptoms observed after repeated dosing.
RCTSix-week trial with diazepam: some clinical observations.
Diazepam treatment improves symptoms of anxiety and depression, with sedation being the predominant side effect, and is effective for patients with low education, prior treatment, stress, and low adjustment.
Non-RCTPrecipitated withdrawal by a benzodiazepine receptor antagonist (Ro 15-1788) after 7 days of diazepam.
Ro 15-1788 can precipitate withdrawal symptoms in baboons after 7 days of diazepam treatment, with more intense withdrawal symptoms occurring after 35 days.
Non-RCT
Animal StudyHighly CitedSix Weeks of Diazepam Treatment in Normal Women: Effects on Psychomotor Performance and Psychophysiology
Diazepam's long-term effects can differ from its acute effects, with both acute and long-term effects varying in behavior and physiological processes measured.
RCTDetermination of bioavailability of diazepam in various formulations from steady state plasma concentration data
Diazepam tablets show similar bioavailability to suspensions, with tablets showing higher levels during steady-state absorption compared to suspensions.
Non-RCTHighly CitedMemory and performance effects of single and 3-week administration of diazepam
Diazepam can cause significant memory impairment in immediate and delayed free recall, with some tolerance developing with continued administration, but no residual effects are apparent after withdrawal.
RCT
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