Benzodiazepines dosages

Several studies have evaluated the usefulness of zolpidem in facilitating withdrawal from long-term benzodiazepine use (e.g., [43, 44]). It appears that most patients on long-term hypnotics can be transferred to zolpidem and that the subsequent withdrawal from zolpidem is much easier. By and large, such strategies should only be resorted to if simple tapering of the benzodiazepine dosage has proven unsuccessful. 

Patients who have been on the medications for some time need to be advised against abrupt discontinuation, which can lead to a severe withdrawal syndrome and possible convulsions. A reduction in dose is likely to lead to a reemergence of the anxiety symptoms for which the person is being treated, such as panic attacks. If this is due only to drug withdrawal, the symptoms usually subside within two weeks. For this reason, as stated above, it is best to taper off benzodiazepine dosage very slowly after prolonged use. 

Benzodiazepine dosage reqnirements vary widely among patients and mnst be individnahzed. Therapy shonld be initiated using low doses (e.g., diazepam 2 mg three times daily, alprazolam 0.25 mg three times a day or eqnivalent doses of other benzodiazepines) and titrated npward to reheve anxiety symptoms and avoid adverse events. After an initial treatment response is achieved, agents with long elimination half-hves can be dosed at bedtime. Dosage adjustments shonld be made weekly. Three to four weeks of a daily dose at the maximum dose constitutes an adeqnate clinical trial. ... 

The interactions of nefazodone with alprazolam, midazolam, triazolam and zopiclone are established and clinically important. The practical consequences are that the effects of alprazolam, midazolam and triazolam are expected to be increased but the extent is uncertain. Be alert for any evidence of any psychomotor impairment, drowsiness etc. and reduce the benzodiazepine dosage if necessary. More study is needed. Lorazepam does not interact with nefazodone. There seems to be no direct information about other benzodiazepines and related drugs. 

Information is limited, but what is eurrentiy known suggests that patients given omeprazole, and possibly esomeprazole, with diazepam may expe-rienee inereased benzodiazepine effeets (sedation, unstable gait ete). If this oeeurs the benzodiazepine dosage should be reduced. Lansoprazole, pantoprazole and rabeprazole do not appear to interaet with diazepam. 

A schizophrenic patient failed to respond to fluphenazine, diazepam, clobazam and lormetazepam having taken the eombination for several weeks. The fluphenazine was stopped and clozapine started at a dose of 25 mg at noon and 100 mg at night. Toxic delirium and severe hypersalivation developed 3 hours later. The patient collapsed (systolic blood pressure 50 mmHg, diastolic blood pressure unrecordable) and stopped breathing. Resuscitation was started, and the patient remained unconscious for 30 minutes. After a few drug-free days clozapine 12.5 mg was successfully re-introduced, and very slowly titrated upwards a low benzodiazepine dosage was also given. ... 

CifiHijClNj. White plates m.p. 125 C. Diazepam is one of several benzodiazepines which are very widely used as minor tranquillizers for allaying anxiety, as hypnotics or, in sufficiently high dosage given intravenously, as pre-anaesthetic sedatives. 

However, lorazepam and oxazepam are relatively safe for older adults when given in normal dosages. Buspirone (BuSpar) also is a safe choice for older adults with anxiety because it does not cause excessive sedation, and the risk of falling is not as great. Before bus-pirone therapy is begun, benzodiazepines and sedatives and hypnotics are gradually withdrawn. Buspirone, unlike most of the benzodiazepines, must be taken regularly and is not effective on an as-needed basis. 

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... 

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. 

Benzodiazepines are excreted more slowly in older adults causing a prolonged drug effect. The drugs may accumulate in the blood, resulting in an increase in adverse reactions or toxicity. For this reason, the initial dose should be small, and the nurse should increase dosages gradually until a therapeutic response is obtained. 

The benzodiazepines currently available for clinical use vary substantially in pharmacokinetics, acute euphoriant effects, and frequency of reported dependence. It is likely, therefore, than not all benzodiazepines have the same potential for abuse. Diazepam, lorazepam, and alprazolam may have greater abuse potential than chlordiazepoxide and clorazepate (Wolf et al. 1990). Similarly, oxazepam has been reported to produce low levels of abuse (Eliding 1978). Jaffe et al. (1983) found that in recently detoxified alcoholic patients, halazepam produces minimal euphoria even at a supratherapeutic dosage. The development of partial agonist and mixed agonist/antagonist compounds at the benzodiazepine receptor complex may offer an advantage over approved benzodiazepines for use in alcoholic patients. 

Clinical situations in which detoxification is indicated can be grouped into three categories 1) for patients who have been taking a maintenance therapeutic dosage for moderate to long periods of time and for whom a trial without medication is warranted, 2) for patients taking supratherapeutic doses (usually in the context of benzodiazepine dependence), and 3) for patients who use benzodiazepines as part of mixed substance dependence. Detoxification should be approached differently in each category. 

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. 

Sporadic use (e.g., for the induction of sleep after a psychostimulant binge) does not require specific detoxification. Sustained use can be treated as described in the previous sections on detoxification from therapeutic or high dosages but with added caution. In mixed opioid and benzodiazepine abuse, the patient should be stabilized with methadone (some clinicians use other oral preparations of opioids) and a benzodiazepine. Buprenorphine should not be administered with benzodiazepines, because a pharmacodynamic interaction is possible (Ibrahim et al. 2000 Kilicarslan and Sellers 2000) and fatalities have been reported with the combination (Reynaud et al. 1998). Sedative-hypnotic withdrawal is the more medically serious procedure, and we usually... 

Wang PS, Bohn RL, Glynn RJ et al. (2001) Hazardous benzodiazepine regimens in the elderly effects of half-life, dosage, and duration on risk of hip fracture. Am J Psychiatry 158(6) 892-898... 

Drugs that increase sedation and give muscle relaxation can have a negative effect on muscle strength and the ability to maintain physical activity, for example, benzodiazepines and other tranquilizers. Corticosteroids have a well known side effect on muscle tissue that leads to muscle atrophy and increases with the dosage. 

Depending on their blood levels, both benzodiazepines and barbiturates produce calming and sedative effects, the former group also being anxiolytic. At higher dosage, both groups promote the onset of sleep or induce it (C). 

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