Benzodiazepine abuse and dependence

Benzodiazepine abuse and dependence

Most individuals who are not anxious do not find that the effects of benzodiazepines are reinforcing or pleasurable and therefore, benzodiazepines are not usually used for recreational purposes.

Research on benzodiazepine dependence can be differentiated between those that focus on high dose abuse and those that focus on the development of dependence after chronic use at therapeutic doses.


  • 1 Classification dependence on benzodiazepines in previous pathologies
  • 2 Benzodiazepine withdrawal syndromes
  • 3 Risk factors for benzodiazepine dependence
  • 4 Symptoms of benzodiazepine withdrawal
  • 5 Behavioral pharmacology
  • 6 neurochemical effects
  • 7 Detoxification, relapse prevention and abuse prevention
  • 8 Prevention of abuse

Classification dependence on benzodiazepines in previous pathologies

1. Politoxicómanos They also consume benzodiazepines.

2. Alcoholics and patients who abuse the benzodiazepines that have been prescribed for the treatment of chronic anxiety or insomnia.

3. Patients with depression or panic disorders those who have been prescribed high doses of benzodiazepines for prolonged periods of time.

  • Alcoholics and abusive patients receiving chronic anxiety or insomnia treatment, are the most important candidates to develop benzodiazepine dependence. They may receive benzodiazepines for prolonged periods of time and may be biologically predisposed to develop dependence on benzodiazepines, since in these subjects the subjective effects of benzodiazepines may be different.
  • Politoxicómanos can take benzodiazepinas to improve the adverse effects of cocaine, such as self-medication of withdrawal from heroin or alcohol, to increase the effects of methadone, to "place-on" when they do not have other drugs. Rarely benzodiazepines are your favorite drugs. Even though their use of benzodiazepines cannot be described as "abuse" from the point of view of the DSM-V criteria, it is often said that these individuals abuse benzodiazepines since their consumption is carried out outside the context of medical treatment and is part of the pattern of drug consumption. In addition, benzodiazepines are usually obtained in the illegal market.
  • Patients with depression or panic disorders may continue treatment with benzodiazepines at high doses for prolonged periods of time.. Some of these patients will develop dependence on benzodiazepines which, in this context, is not exactly the same as benzodiazepine abuse / dependence disorder.

Benzodiazepine withdrawal syndromes

The first works on Benzodiazepine withdrawal syndromes suggested that these effects occur at high doses, and that these syndromes were very rare in patients receiving therapeutic doses. However, later studies indicated that they could also occur in patients who were receiving therapeutic doses of some benzodiazepines and that their incidence varies between 5% and 35% in patients treated with benzodiazepines for at least one month. Thus, it is currently accepted that chronic consumption of benzodiazepines can cause physical dependence and the appearance of a withdrawal syndrome, both after use at doses higher than therapeutic doses, and after use at therapeutic doses for a long time. 

High dose benzodiazepine withdrawal syndrome.

Human studies established that high doses of chlordiazepoxide and diazepam taken for a month or more produced a withdrawal syndrome clinically similar to the withdrawal syndrome produced by high doses of barbiturates.

Signs and symptoms of benzodiazepine withdrawal include: anxiety, tremor, insomnia, nightmares, anorexia, nausea, vomiting, postural hypotension, seizures, confusional syndrome, hyperpyrexia and death. The picture usually appears 24-48 hours after cessation of a short half-life benzodiazepine or 3-8 days after a long half-life.

Low dose benzodiazepine withdrawal syndrome.

It is also called therapeutic dose withdrawal syndrome, normal dose withdrawal syndrome or benzodiazepine withdrawal syndrome.

Risk factors for benzodiazepine dependence

In therapeutic we have more than 40 different benzodiazepines. Of the 15 most commonly used (alprazolam, bromazepam, chlordiazepoxide, clobazam, clonazepam, diazepam, flunitrazepam, flurazepam, lorazepam, lormetazepam, midazolam, nitrazepam, oxazepam, temazepam, triazolam withdrawal effects have been described in triazolam use, described in triazolam use all of them, except with midazolam, which is usually used only acutely or subacutely. At present it is not clear which are the individual components that are most associated with the withdrawal effects. Probably short-lived benzodiazepines are more associated with these effects due to their pharmacokinetic characteristics: in a daily dose schedule, the levels of these components are more likely to decrease to undetectable concentrations. In contrast, long-lived benzodiazepines such as diazepam and flurazepam are less likely to be associated with withdrawal effects due to their prolonged levels of the primary drug or their active metabolites. Many studies suggest that alprazolam is the benzodiazepine that has more withdrawal syndromes., although pharmacokinetic / pharmacodynamic correlation studies support that such effects are due more to the dose and duration than to specific effects of alprazolam. On the other hand, some researchers have suggested that high potency benzodiazepines are more likely to be associated with withdrawal effects, probably due to a high affinity of the receptor, although neurochemical evidence does not support this hypothesis.


Although it is generally assumed that the probability of occurrence of withdrawal effects increases with dose, the evidence supporting this association is limited. Recent studies of patients receiving chronic treatment with alprazolam indicate that Withdrawal effects increase at high doses and also suggest that there is a threshold from which withdrawal effects are much less likely.


It is generally accepted that the longer duration of benzodiazepine treatment predisposes to the appearance of withdrawal effects.


It is not clear the existence of personality factors predisposing to the appearance of abstinence syndrome of benzodiazepines at low doses.


The withdrawal or withdrawal syndrome after the use of benzodiazepines is variable according to its nature, severity and duration. In general, after benzodiazepine withdrawal, four situations can occur:

  • Absence of effects.
  • Bounce symptoms
  • Withdrawal symptoms
  • Relapse.

Rebound symptoms

Generally characterized by symptoms similar to premorbid but more intense symptoms.

They usually appear 1-2 days after cessation of the administration of a short half-life benzodiazepine or 3-8 days after that of a long half-life. It has a duration of 7-14 days.

Symptoms of withdrawal from benzodiazepines

Generally characterized by symptoms of sympathetic discharge and premorbid symptoms Associated: anxiety, agitation, tachycardia, palpitations, anorexia, blurred vision, muscle cramps, insomnia, nightmares, confusion, muscle spasms, psychosis, hypersensitivity to light and noise and paresthesias.

Signs and symptoms usually appear 1-7 days after the last administration of benzodiazepine or after significant dose reduction.

Behavioral pharmacology

In general, the results of benzodiazepine behavioral pharmacology studies indicate that benzodiazepine withdrawal syndromes are likely to:

1) they relate to the development of tolerance and probably occur only when there is a certain degree of tolerance;

2) depend on the configuration of the benzodiazepine receptor;

3) involve multiple neurotransmission systems beyond the system.

Neurochemical effects

Since the benzodiazepine fixation sites were identified 15 years ago, multiple studies have been conducted on the effect of chronic administration of benzodiazepines on animal experimentation. In general, the data indicate that benzodiazepine tolerance and withdrawal effects correlate with alterations in the function of the benzodiazepine receptor and the corresponding receptor (GABAa), although the molecular basis of these changes is yet to be defined.

Detoxification, relapse prevention and abuse prevention


The clinical situations in which detoxification is indicated can be grouped into three categories:

  • Patients who have maintained maintenance at therapeutic doses for long periods of time.
  • Patients taking very high therapeutic doses.
  • Politoxicomaniac patients who among other drugs also take benzodiazepines.

Usually the dose of the benzodiazepine of abuse is substituted by equivalent doses of a long-lived half-life benzodiazepine (diazepam is the most used) administered in divided doses during the first day. Later on the second day the total dose administered is reduced by 30% and then 5% in the following days. If sweating, tremor or increased vital signs appear during the dose decrease, the decrease should slow down.

Psychological treatments

Several techniques have been described that make it easier for the individual to reduce their anxiety levels using their own resources and that are especially interesting in the case of benzodiazepine dependence. These techniques include the Progressive muscle relaxation, meditation, autogenous training, biofeedback and hypnotic-induced induced relaxation. However, the results obtained so far have been hopeless.

Relapse prevention

It is a difficult problem to assess because there are no reliable data on relapse rates in these patients. In general, the rate of patients who remain abstinent after one year is approximately 50%, while 15% use benzodiazepines at therapeutic doses and only when necessary.

It should be noted that patients who have been dependent on a benzodiazepine are difficult to recover without using other medications. In general it is observed that benzodiazepine is replaced by another medicine with anxiolytic activity many times less effective or with more toxic effects such as chloral hydrate, neuroleptics or antidepressants.

The use of cognitive behavioral techniques or behavioral strategies specially designed to prevent relapse can help the patient avoid restarting benzodiazepine consumption.

Abuse prevention

The prevention of benzodiazepine abuse requires strict control of the prescription of these drugs as well as the design of a therapeutic plan that includes the short-term objectives, and the periodic evaluation of the efficacy and toxicity associated with drug treatment.

There is no evidence that occasional and sporadic use of benzodiazepines leads to abuse and dependence. However, continued use should be the minimum possible and with the lowest possible dose, although always balancing with the expected therapeutic result.

To the extent possible, avoid prescription of benzodiazepines to patients who have histories of abuse or dependence on other medications.