How long do diazepam last
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Duration of Diazepam Effects: Pharmacokinetics and Behavioral Impact
Pharmacokinetics of Diazepam: Absorption and Elimination
Diazepam, a widely used benzodiazepine, exhibits a complex pharmacokinetic profile. When administered intravenously, diazepam follows a three-compartment model, with an elimination half-life ranging from 21 to 37 hours3. Orally administered diazepam is rapidly and completely absorbed, reaching steady-state blood levels by approximately Day 7 of treatment3. The primary metabolite, N-desmethyldiazepam, has a longer half-life, ranging from 50 to 99 hours, indicating prolonged presence in the system even after cessation of the drug3.
Behavioral Effects and Duration
Clinically, diazepam is typically said to act for 6 to 8 hours4. However, its effects can vary based on dosage and duration of administration. For instance, a study involving healthy subjects showed that diazepam produced quick effects followed by relatively rapid recovery, with no significant withdrawal symptoms observed after discontinuation1. Another study noted that the acute effects of a 5 mg dose of diazepam on psychomotor performance were not significant, but long-term administration over six weeks led to physiological changes such as decreased skin conductance and heart rate, which returned to baseline levels two weeks after discontinuation6.
Accumulation and Withdrawal
Prolonged administration of diazepam leads to accumulation in the plasma, with concentrations plateauing after about 8 days2. Upon discontinuation, both diazepam and its metabolite decrease slowly, with diazepam having a half-life of 2-4 days and N-desmethyldiazepam having a half-life of 4-8 days2. Withdrawal symptoms can occur, particularly after extended use. For example, baboons given diazepam for 45 days exhibited mild to intermediate withdrawal symptoms, which intensified with longer administration periods5. In humans, a six-week course of diazepam for generalized anxiety resulted in rebound anxiety and withdrawal symptoms, suggesting that even moderate doses can lead to dependence8.
Cognitive and Performance Effects
Diazepam's impact on cognitive functions has been well-documented. A single administration can significantly impair memory, particularly in tasks requiring immediate and delayed recall10. Chronic administration over 21 days showed some development of tolerance to these memory impairments, with no residual effects observed after withdrawal10. This indicates that while diazepam can affect cognitive performance, the body may adapt over time, and normal function can resume after the drug is discontinued.
Conclusion
Diazepam's effects can last from several hours to several days, depending on the dosage and duration of use. Its pharmacokinetic properties, including rapid absorption and prolonged elimination of its metabolites, contribute to its lasting presence in the body. Behavioral and cognitive effects can vary, with potential for tolerance development and withdrawal symptoms after prolonged use. Understanding these dynamics is crucial for optimizing therapeutic use and managing potential dependence.
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Comparison 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.
RCTPlasma 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 CitedPrecipitated 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.
RCTControlled study of withdrawal symptoms and rebound anxiety after six week course of diazepam for generalised anxiety.
Diazepam, even in moderate doses and for a safe length of time, can produce rebound anxiety and withdrawal symptoms.
RCTHighly CitedDetermination 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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