Benzodiazepines withdrawal reactions

Withdrawal reactions are more problematical. Hypnotics, by and large, are benzodiazepine like in their pharmacology, receptor binding, etc. The main differences relate to duration of action and to putative selectivity of binding. The benzodiazepine withdrawal reaction has been described many times, and rating scales have been developed to measure the symptoms. Withdrawal reactions from hypnotics would be expected to display similar symptomatic patterns and to follow time-courses dictated by the pharmacokinetic properties of the drug. 

The problems in using flumazenil are those of dose adjustment, the risks of panic anxiety, seizures, or other signs of excessively rapid benzodiazepine withdrawal. Its use is also commonly associated with vomiting and headache, and rarely with psychosis or sudden cardiac death f7T ], especially in mixed overdoses. It can occasionally cause a benzodiazepine withdrawal reaction [72 ]. 

Although rare, benzodiazepine toxicity may occur from an overdose of the drug. Benzodiazepine toxicity causes sedation, respiratory depression, and coma. Flumazenil (Romazicon) is an antidote (antagonist) for benzodiazepine toxicity and acts to reverse die sedation, respiratory depression, and coma within 6 to 10 minutes after intravenous administration. The dosage is individualized based on the patient s response, widi most patients responding to doses of 0.6 to 1 mg. However, die drug s action is short, and additional doses may be needed. Adverse reactions of flumazenil include agitation, confusion, seizures, and in some cases, symptoms of benzodiazepine withdrawal. Adverse reactions of flumazenil related to the symptoms of benzodiazepine withdrawal are relieved by die administration of die benzodiazepine. 

Busto U, Sellers EM, Naranjo CA, et al Withdrawal reaction after long-term therapeutic use of benzodiazepines. N Engl] Med 315 854-859, 1986a... 

It is important to be aware of possible adverse drug withdrawal events (ADWE). These events may be caused by physiological withdrawal reaction, but it is also possible that the underlying disease is worsened. An example of ADWE is delirium or seizures that may occur after abrupt discontinuing of benzodiazepines or alcohol. 

Drug withdrawal reactions - tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, barbiturates, alcohol, opioids. 

Drowsiness, disinhibi-tion, agitation, confusion depression Withdrawal reactions Potential risk for abuse and dependence Less risk for rebound and withdrawal reactions Same as other benzodiazepines Higher risk for rebound and withdrawal reactions... 

Benzodiazepines have a low abuse potential when they are properly prescribed and their use is supervised (American Psychiatric Association 1990). However, physical dependence often occurs when benzodiazepines are taken at higher-than-usual doses or for prolonged periods. If benzodiazepines are discontinued precipitously, withdrawal effects (including hyperpyrexia, seizures, psychosis, and even death) may occur. Signs and symptoms of withdrawal may include tachycardia, increased blood pressure, muscle cramps, anxiety, insomnia, panic attacks, impairment of memory and concentration, perceptual disturbances, and delirium. In addition, withdrawal-related derealization, hallucinations, and other psychotic symptoms have been reported. These withdrawal symptoms may begin as early as the day after discontinuation of the benzodiazepine, and they may continue for weeks to months. Evidence indicates that withdrawal reactions associated with shorter-half-life benzodiazepines peak more rapidly and more intensely. 

As well as unwanted effects related to direct drug effects, hypnotics, like many other medications, are associated with offset effects, namely withdrawal reactions after discontinuation, abrupt or gradual [4], Numerous terms are used in this context, and include those relating to non-medical use, i.e., abuse and addiction. The purpose of this chapter is to review briefly the clinical problems that can be encountered when discontinuing hypnotic dmgs within the normal therapeutic context. For a review on the abuse and dependence potential of the non-benzodiazepine hypnotics, zolpidem and zopiclone, reference should be made to the paper by Hajak et al. [5],... 

Rebound may be contrasted with a withdrawal reaction in which stopping the hypnotic is followed by the emergence of new symptoms, not previously experienced by the patient. Muscle tension and pain, loss of appetite and weight, and perceptual changes such as hyperacusis are cardinal features of withdrawal reactions from benzodiazepine-type depressants. 

To make it absolutely clear, to this day I never start my patients on psychiatric drugs. I only prescribe drugs to patients who have come to me already taking medication, and then almost always for the purpose of eventually withdrawing them. In a few cases, when withdrawal reactions have proven unendurably painful, I have continued patients on low doses of antidepressants or benzodiazepines because there has been no satisfactory alternative. 

Flumazenil can provoke acute withdrawal reactions and extreme anxiety (16). Its duration of action (less than 1 hour) is generally shorter than that of the original benzodiazepine, whose effects can therefore return while the patient is unobserved. 

Treatment. Historically benzodiazepines have been seen as the most effective treatment for GAD for they rapidly reduce anxiety and improve sleep and somatic symptoms. Consequently patients like taking them but the chronic nature of GAD raises issues of duration of treatment, tolerance, dependence and withdrawal reactions. 

Buspirone is generally less effective and slower in action than benzodiazepines emd does not improve sleep it does not benefit benzodiazepine withdrawal symptoms. The advantages are that it does not seem to cause dependence or withdrawal reactions and does not interact with alcohol. It appears to be less effective in patients who have previously received benzodiazepines and is therefore probably best used in benzodiazepine naive patients. A disadvantage is that useful anxiolytic effect is delayed for 2 or more weeks. 

B Triazolam. Triazolam has short onset of action and short duration of action. These properties increase the risk for withdrawal reactions. The other benzodiazepines have longer durations of action that decrease the potential for withdrawal reactions. 

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