Benzodiazepines delirium

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. 

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

These differences may become particularly germane if co-prescribing with some antipsychotics is undertaken. For example, in certain individuals, combinations of clozapine with benzodiazepines may lead to unexpected adverse events, including delirium and augmented respiratory depression (Jackson, Markowitz Brewer-ton, 1995 Grohmann et al, 1989). Presumably if there are additive or synergistic effects of ethnicity on clearance of one or both substances, adverse events may be enhanced. Similar interactions are theoretically possible with olanzapine, as adverse interactions have been described between olanzapine and benzodiazepines, at least in the elderly (Kryzhanovskaya etal, 2006). 

Jackson, C.W., Markowitz, J. S. Brewerton, T. D. (1995). Delirium associated with clozapine and benzodiazepine combinations. Ann. Clin. Psychiatry, 7, 139—41. 

Secobarbital exhibits the same pharmacologic properties as other members of the barbiturate class. Most nonmedical use is with short-acting barbiturates, such as secobarbital. Although there may be considerable tolerance to the sedative and intoxicating effects of the drug, the lethal dose is not much greater in addicted than in normal persons. Tolerance does not develop to the respiratory effect. The combination of alcohol and barbiturates may lead to fatalities because of their combined respiratory depressive effects. Similar outcomes may occur with the benzodiazepines. Severe withdrawal symptoms in epileptic patients may include grand mal seizures and delirium. 

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. 

Impairment of memory, delirium and immobility are some of the adverse dmg reactions from benzodiazepines. Elderly patients in nursing homes often receive benzodiazepines inappropriately (Oborne et al. 2003). The frailest elderly, who are most susceptible to ADR from benzodiazepines, use these drugs and often for long term. In a Japanese study it was shown that benzodiazepines were prescribed for longer terms as patient age increased (Nomura et al. 2007). Sometimes elderly patients in nursing homes are treated with benzodiazepines without actually talking to their nurse or physician (Holmquist et al. 2005). This makes it hard evaluate the treatment. 

The use of benzodiazepines should be avoided. There are other safer pharmacological alternatives. Benzodiazepine withdrawal may play a role in the occurrence of delirium in the elderly. Other withdrawal symptoms include tremor, agitation, insomnia and seizures (Turnheim 2003). Thus, when there is long-term use of benzodiazepines abrupt discontinuation might be difficult. Discontinuation should however not be withheld but done slowly and step-wise. If benzodiazepines are used in the elderly, short-acting benzodiazepines such as oxazepam are preferred, because they do not accumulate in the elderly to the same extent (Kompoliti and Goetz 1998). If short-acting benzodiazepines are used they should be prescribed with caution, at low doses, and for short periods. As with all pharmacotherapy the effects should be evaluated. Benzodiazepines are sometimes used as a behavioural control. One should always ask if this use is for the benefit of staff or the benefit of the patient. The presence of staff may be sufficient for behavioural control. 

Medications may be necessary for patients with delirium especially in patients with severe behavioural disturbances and agitation. Any medications used may however be hazardous and actually lengthen the condition. A continuous reassessment of the need for theses kind of drugs should be done. Antipsychotic drugs may be needed especially if vision hallucinations and agitated behaviour are predominant. Short-acting benzodiazepines may be used for a limited time. There is no... 

Korevaar JC, van Munster BC, de Rooij SE (2005) Risk factors for delirium in acutely admitted elderly patients a prospective cohort study. BMC Geriatr 5 6 Kudoh A, Takase H, Takahira Y et al. (2004) Postoperative confusion increases in elderly longterm benzodiazepine users. Anesth Analg 99 (6) 1674-1678 McCusker J, Cole M, Dendukuri N et al. (2001) Delirium in older medical inpatients and subsequent cognitive and functional status a prospective study. Cmaj 165 (5) 575-583 McCusker J, Cole M, Dendukuri N et al. (2003) The course of delirium in older medical inpatients a prospective study. J Gen Intern Med 18 (9) 696-704 McShane R, Areosa Sastre A, Minakaran N (2006) Memantine for dementia. Cochrane Database Syst Rev 19 (2) CD003154... 

Side effects of benzodiazepines include drowsiness and reduced respiratory function. In patients who are severely medically ill, especially those with lung disease, this side effect can be problematic. However, benzodiazepines are much safer in this regard than their predecessors, the barbiturates, and untreated delirium tremens, the most severe form of alcohol withdrawal, can be fatal. 

Although many physicians routinely use benzodiazepines to treat combative, delirious patients, this is not recommended. First, benzodiazepines can cloud consciousness and actually worsen the confusion of delirium. Second, benzodiazepines can worsen the breathing problems of patients with pneumonia or emphysema, two common causes of delirium. The lone exception is a delirium that is caused by alcohol or benzodiazepine withdrawal. A benzodiazepine MUST be used for alcohol... 

Other sleep-inducing benzodiazepines should be avoided. They are more difficult to metabolize and can accumulate in elderly, demented patients. Sedating, low potency antipsychotics should also be avoided. Their strong anticholinergic (acetylcholine-blocking) effects can worsen dementia or cause delirium. 

The withdrawal syndrome from ethanol includes anxiety, insomnia, possibly convulsions and visual hallucinations (delirium tremens - the Dts). It is treated or better still prevented by a calm environment, adequate (but not excessive) hydration, and careful monitoring, with the added use of anticon-vulsive/sedative agents, mainly benzodiazepines to prevent or treat convulsions. The preventive effects of benzodiazepines on withdrawal morbidity has been clearly demonstrated. There do not seem to be major differences between benzodiazepines, such as chlordiazepoxide or diazepam or others. Because of the abuse potential in these highly susceptible patients, these should be rapidly weaned, and proper prevention of relapse instituted. Other drugs such as meprobamate and clomethiazole (Hemineurin) are commonly used in some countries. The effectiveness... 

There is no evidence from randomized trials that general strategies to prevent delirium are successful. Benzodiazepines are significantly better than placebo in preventing delirium and seizures due to alcohol withdrawal, and long-acting benzodiazepines (such as diazepam) are more effective than... 

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. 

Hauser P, Devinsky O, De Beilis M, et al. Benzodiazepine withdrawal delirium with catatonic features. Occurrence in patients with partial seizure disorder. Arch Neuroi 1989 46 696-699. 

Emergence delirium with restlessness, disorientation and unpleasant dreams or hallucinations may occur for up 24 hours following ketamine administration. Their incidence is reduced by psychological preparation of the patient, avoidance of verbal and tactile stimulation during the recovery period, or by concomitant administration of opioids, benzodiazepines, propofol or physostigmine. However, unpleasant dreams may persist. 

The extensive clinical use of triazolam has led to reports of serious central nervous system effects including behavioral disinhibition, delirium, aggression, and violence. While behavioral disinhibition may occur with sedative-hypnotic drugs, it does not appear to be more prevalent with triazolam than with other benzodiazepines. Disinhibitory reactions during benzodiazepine treatment are more clearly associated with the use of very high doses and the pretreatment level of patient hostility. 

Patients with mild symptoms of alcohol withdrawal do not generally require medication therapy. Benzodiazepines, like diazepam or alprazolam, are the treatment of choice for patients with severe alcohol withdrawal syndromes like delirium tremens. Barbiturates can also be used for this disorder, but are often less prescribed because they are not as safe as benzodiazepines. Both barbiturates and benzodiazepines are effective in treating the anxiety, tremor, insomnia, and hand tremors associated with delirium tremens. 

Even though Hoffmann-LaRoche has reformulated Rohypnol tablets to be more easily identified when placed into someone s drink, Rohypnol is still a very potent benzodiazepine and is subject to abuse. Chronic or daily Rohypnol use causes dependence in humans. Once dependence has developed, abstention induces withdrawal symptoms, including headache, muscle pain, extreme anxiety, tension, restlessness, confusion, and irritability. Numbness, tingling of the extremities, loss of identity, hallucinations, delirium, convulsions, shock, and cardiovascular collapse also may occur. Withdrawal seizures can occur in chronic abusers with abrupt cessation of Rohypnol use. 

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