Benzodiazepine dependence

The disproportionately large occupancy change at low diazepam doses is consistent with the clinical observation of increasing withdrawal severity near zero.

“At low doses, small reductions have disproportionately large effects; for example, 5 to 0 mg changes occupancy by 16.8 p.p., exceeding the change from 100 to 50 mg (13.3 p.p.), consistent with the clinical observation of increasing withdrawal severity near zero (Ashton, 2004).”

A 1 mg reduction is generally tolerable from 20 mg diazepam but not from 5 mg, where smaller decrements are preferred.

“For example, it has been observed that 1 mg reductions are generally tolerable from 20 mg diazepam but not from 5 mg, where smaller decrements are preferred (Ashton, 2004), suggesting a hyperbolic relationship between dose reduction and withdrawal severity.”

Withdrawal symptoms are hyperbolically dose-dependent: larger reductions cause greater severity, particularly at lower doses.

“Withdrawal symptoms also appear to be hyperbolically dose-dependent: larger reductions cause greater severity, particularly at lower doses (Ashton, 2004).”

A 5 to 0 mg diazepam reduction changes GABA-A occupancy by 16.8 percentage points, exceeding the change from 100 to 50 mg (13.3 p.p.).

“At low doses, small reductions have disproportionately large effects; for example, 5 to 0 mg changes occupancy by 16.8 p.p., exceeding the change from 100 to 50 mg (13.3 p.p.), consistent with the clinical observation of increasing withdrawal severity near zero (Ashton, 2004).”