Benzodiazepines discontinuation

Garfinkel D, Zisapel N, Wainstein J, et al. Facilitation of benzodiazepine discontinuation by melatonin a new clinical approach. Arch Intern Med 1999 159 2456-2460. 

Romach MK, Kaplan HL, Busto EU, et al. A controlled trial of ondansetron, a 5-HT 3 antagonist, in benzodiazepine discontinuation. J Clin Psychopharmacol 1998 18 121-131. 

Gatzonis SD, Angelopoulos EK, Daskalopoulou EG, et al. Convulsive status epilepticus following abrupt high-dose benzodiazepine discontinuation. Drug Alcohol Depenc 2000 59 95-97. 

Burrows GD, Norman TR, Judd FK, et al. Short-acting versus long-acting benzodiazepines discontinuation effects in panic disorders. J Psychiatr Res 1990 24[Suppl 2] 65-72. 

When benzodiazepines are used or abused chronically, they may cause adaptive changes in benzodiazepine receptors such that their power to modulate GABA-A receptors in response to a benzodiazepine decreases with time (Fig. 13—32). These patients may become irritable or anxious or even experience panic attacks if they suddenly stop taking the drugs (Fig. 13—33). This shift in benzodiazepine abusers to a desensitized receptor (Fig. 13—32) may manifest itself as the need to take higher doses of benzodiazepines to get high. This receptor desensitization is most likely to be uncovered once chronic abusive benzodiazepine administration is discontinued, particularly if discontinuation is sudden (Fig. 13-33). This desensitized receptor worsens the impact of benzodiazepine discontinuation because the brain, which is... 

FIGURE 13-33. Acute withdrawal of benzodiazepines in a benzodiazepine-dependent individual. If benzodiazepines are suddenly stopped in a patient who is tolerant to them and dependent on them, benzodiazepine receptors will experience this as an acute deficiency at their binding sites. Thus, the presence of desensitized benzodiazepine receptors actually worsens the impact of benzodiazepine discontinuation. The brain, which is used to too much benzodiazepine at its receptors, is suddenly starved for benzodiazepine. Therefore, the brain experiences the reverse of benzodiazepine intoxication, namely, dysphoria and depression instead of euphoria anxiety and agitation instead of tranquility and lack of anxiety insomnia instead of sedation and sleep muscle tension instead of muscle relaxation and at worst, seizures instead of anticonvulsant effects. These actions continue either until benzodiazepine is replaced or until the receptors readapt to the sensitivity they had prior to excessive benzodiazepine use. Alternatively, one can reinstitute benzodiazepines but taper them slowly, so that the receptors have time to readapt during dosage reduction, and withdrawal symptoms are prevented. 

Garfinkel D., N. Zisapel, J. Wainstein, et al. Facilitation of Benzodiazepine Discontinuation by Melatonin. A New Clinical Approach. Archives of Internal Medicine 159, no. 20 (November 1999) 2456-60. 

Rickels, K., Lucki, I., Schweizer, E., Garcia-Espana, F., Case, W. (1999). Psychomotor performance of long-term benzodiazepine users before, during, and after benzodiazepine discontinuation. Journal of Clinical Psychopharmacology, 19, 107-113. 

Withdrawal symptoms are the emergence of new symptoms and a worsening of pre-existing symptoms after benzodiazepine discontinuation. Symptoms may persist for days to weeks and resolve gradually over months. 

Benzodiazepine withdrawal may occur when use of the antianxiety drugs is abruptly discontinued after 3 to 4 months of therapy. Occasionally, withdrawal symptoms may occur after as little as 4 to 6 weeks of therapy. Symptoms of benzodiazepine withdrawal include increased anxiety, concentration difficultiesi, tremor, and sensory disturbances, such as paresthesias photophobia, hypersomnia, and metallic taste. To help prevent withdrawal symptoms, the nurse must make sure the dosage of the benzodiazepine is gradually decreased over a period of time, usually 4 to 6 weeks... 

Patients requiring detoxification from high or supratherapeutic dosages of benzodiazepines constitute a smaller number of patients, but they are at greater risk for life-threatening discontinuation symptoms, such as seizures, delirium, and psychoses. There has been more experience with inpatient detoxification in this group, but outpatient detoxification is possible if conducted slowly (5% reduction in dose per week), with frequent contact, and in the context of a therapeutic alliance with the patient. Often, such an alliance proves unworkable because the patient s impoverished control results in supplementation from outside sources or early exhaustion of prescribed supplies meant to be tapered. In these cases, as in the cases of patients with a history of seizures, delirium, or psychoses during previous detoxification attempts, inpatient detoxification is indicated. 

Not cross-tolerant to benzodiazepines and should not be used for acute withdrawal high doses may be used to treat anxiety disorders to help maintain long-term discontinuation after abstinence has been achieved. 

In two studies in which benzodia2epines were gradually tapered, concurrent cognitive-behavioral therapy (CBT) did not increase the proportion of patients who were able to successfully discontinue their use of these agents (Oude Voshaar et al. 2003 Vorma et al. 2003). On the other hand, other studies of patients with panic disorder found that CBT facilitated the discontinuation of benzodiazepine use (Otto et al. 1993). Similarly, CBT may be superior to supportive medical management in preventing the reoccurrence of panic attacks in panic disorder patients in whom alprazolam has been tapered (Bruce etal. 1999). 

Fyer AJ, Liebowitz MR, Gorman JM, et al Effects of clonidine on alprazolam discontinuation in panic patients a pilot study. J Clin Psychopharmacol 8 270—274,1988 Garvey MJ, Tollefson GD Prevalence of misuse of prescribed benzodiazepines in patients with primary anxiety disorder or major depression. Am J Psychiatry 143 1601-1603, 1986... 

Miller LG, Greenblatt DJ, Roy RB, et al Chronic benzodiazepine administration, II discontinuation syndrome is associated with upregulation of gamma-aminobutyric acid receptor complex binding and function. J Pharmacol Exp Ther 246 177-182, 1988b... 

Otto MW, Pollack MH, Sachs GS, et al Discontinuation of benzodiazepine treatment efficacy of cognitive-behavioral therapy for patients with panic disorder. Am J... 

If possible, discontinue any benzodiazepines, as they may cause paradoxical agitation and delirium. Evaluate for reversible etiologies... 

Benzodiazepines are used commonly in SAD however, there are limited data supporting their use. Clonazepam has been effective for social anxiety, fear, and phobic avoidance, and it reduced social and work disability during acute treatment.58 Long-term treatment is not desirable for many SAD patients owing to the risk of withdrawal and difficulty with discontinuation, cognitive side effects, and lack of effect on depressive symptoms. Benzodiazepines may be useful for acute relief of physiologic symptoms of anxiety when used concomitantly with antidepressants or psychotherapy. Benzodiazepines are contraindicated in SAD patients with alcohol or substance abuse or history of such. 

Zolpidem, chemically unrelated to benzodiazepines or barbiturates, acts selectively at the y-aminobutyric acidA (GABAA)-receptor and has minimal anxiolytic and no muscle relaxant or anticonvulsant effects. It is comparable in effectiveness to benzodiazepine hypnotics, and it has little effect on sleep stages. Its duration is approximately 6 to 8 hours, and it is metabolized to inactive metabolites. Common side effects are drowsiness, amnesia, dizziness, headache, and GI complaints. Rebound effects when discontinued and tolerance with prolonged use are minimal, but theoretical concerns about abuse exist. It appears to have minimal effects on next-day psychomotor performance. The usual dose is 10 mg (5 mg in the elderly or those with liver impairment), which can be increased up to 20 mg nightly. Cases of psychotic reactions and sleep-eating have been reported. 

The underlying cause of acute acidosis should be treated aggressively (e.g., administration of bronchodilators for bronchospasm or discontinuation of respiratory depressants such as narcotics and benzodiazepines). Bicarbonate administration is rarely necessary and is potentially harmful. 

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. 

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