The natural history of tolerance to the benzodiazepines.

  title={The natural history of tolerance to the benzodiazepines.},
  author={Anna Higgitt and Peter Fonagy and M. H. Lader},
  journal={Psychological medicine. Monograph supplement},
Dependence on benzodiazepines following continued use is by now a well-documented clinical phenomenon. Benzodiazepines differ in their dependence potential. The present studies were aimed at examining the possibility that differential rates of tolerance development might account for differences in dependence risk. Four studies are reported. The first three studies concerned normal subjects. The development of tolerance over a fifteen day period was demonstrated for three different… 

Side effects of treatment with benzodiazepines.

Previous investigations showed that treatment with benzodiazepines may induce anterograde amnesia, and previous studies confirmed occurrence of physical dependence in high percentage of patients in long term treatment with Benzodiazepine at therapeutic dosages.

Lack of effect of a small dose of flumazenil in reversing short-term tolerance to benzodiazepines in normal subjects

The benzodiazepines had the expected effects on the EEG, and event-related potentials (ERP), impaired several psychological tests and induced drowsiness and relaxation and some tolerance was seen with respect to anxiolytic effects, some EEG and ERP variables and some psychological tests, but not those of memory.

Benzodiazepines revisited--will we ever learn?

  • M. Lader
  • Medicine, Psychology
  • 2011
A series of adverse effects that continued to cause concern were noted, such as cognitive and psychomotor impairment, and dependence and abuse remain as serious problems despite warnings and guidelines.

The physicochemical and pharmacokinetic properties of benzodiazepines appearing as new psychoactive substances

The lipophilicity, the pKa and the plasma protein binding were determined for benzodiazepines appearing as new psychoactive substances and these were compared to theoretical values from software packages and none of the software packages were able to predict parameters to a su_cient degree of accuracy and in vitro data is currently preferable.

Characteristics of benzodiazepine long-term users: investigation of benzodiazepine consumers among pharmacy customers

It could be demonstrated by means of multiple stepwise logistic regression analysis that certain characteristic parameters differentiate long-term users and persons with signs of potential abuse and dependence from other bzd users.

The prolonged benzodiazepine withdrawal syndrome: anxiety or hysteria?

It was concluded that PWS is likely to be a genuine iatrogenic condition, a complication of long‐term benzodiazepine treatment.

Effects of alprazolam and lorazepam on catecholaminergic and cardiovascular activity during supine rest, mental load and orthostatic challenge

Alprazolam significantly increased subjective sedation, reduced plasma adrenaline and noradrenaline concentrations and mean blood pressure (MBP) during supine rest, and attenuated plasma adrenaline responses during the CWT and the OCT; these effects appeared to be dose-dependent.



Tolerance to the behavioral actions of benzodiazepines

  • S. File
  • Psychology, Biology
    Neuroscience & Biobehavioral Reviews
  • 1985

Pharmacokinetics of benzodiazepines. Short-acting versus long-acting.

A review is given of the pharmacokinetics of the major benzodiazepines presently available and suggests that compounds with long elimination half-lives of parent drug or active metabolites are of advantage in anticonvulsant and anti-anxiety treatment.

Experimental induction of benzodiazepine tolerance and physical dependence.

  • G. P. RyanN. Boisse
  • Psychology, Medicine
    The Journal of pharmacology and experimental therapeutics
  • 1983
This animal model appears to provide a useful tool for the study of specific mechanisms underlying benzodiazepine tolerance and physical dependence, and the criterion of chronic equivalence was indeed met.

The biological basis of benzodiazepine dependence

It is concluded that the same underlying mechanism mediates the rebound phenomena and tolerance seen after short-term or acute benzodiazepine administration, and also that tolerance is simply another manifestation of this same mechanism.

Dependence liability of the benzodiazepines.

  • D. Ladewig
  • Psychology, Medicine
    Drug and alcohol dependence
  • 1984

Diazepam tapering in detoxification for high‐dose benzodiazepine abuse

Gradual reduction of diazepam dose appears to be an effective and safe approach for detoxifying abusers of high doses of benzodiazepines.

Comparison of the Therapeutic Effect, Tolerance and Safety of Ketazolam and Diazepam Administered for Six Months to Out-Patients with Chronic Anxiety Neurosis

Ketazolam was as efficacious as diazepam in treating anxiety and resulted in fewer side-effects and benzodiazepines were safe and well-tolerated.

The benzodiazepine receptor and receptor tolerance produced by chronic treatment of diazepam.

The results supported the argument that two distinct entities exist for both GABA and benzodiazepine recognition sites which are closely related to each other in their functioning.

Development of tolerance and cross-tolerance to the psychomotor actions of lorazepam and diazepam in man.

The effects of lorazepam were stronger and of longer duration than those of diazepam at the doses used, and tolerance but not cross-tolerance developed on choice reaction errors whereas the opposite was found on flicker fusion.