Benzodiazepines: A versatile clinical tool

Acute agitation. Agitated patients often have acute psychosis and/or mania or dyscontrol secondary to axis II disorders.²⁴ Patients may be paranoid, hostile, disruptive, and combative. Rapidly initiating medication can prevent the need for more restrictive measures, such as seclusion or restraint. Antipsychotics—especially high-potency agents such as haloperidol—and benzodiazepines, as monotherapy or in combination, are a mainstay treatment. Although treatment protocols favor atypical antipsychotics over typical antipsychotics, benzodiazepines are a viable option because of their anxiolytic and sedative effects. Advantages of benzodiazepine monotherapy include decreased extrapyramidal symptoms, greater patient acceptance/preference, and increased sedation compared with antipsychotics. Lorazepam, 1 to 2 mg intramuscularly (IM) or orally, is well tolerated because of its favorable drug-drug interaction profile and lack of significant cardiac side effects. Benzodiazepines can cause respiratory depression in patients with chronic lung disease and additive sedation secondary to opiates, other sedatives/hypnotics, or alcohol. Behavioral disinhibition is rare and is associated with preexisting CNS pathology or mental retardation.²⁵ The IM olanzapine package insert warns against coadministering IM lorazepam because of additive cardiorespiratory depressive effects and excessive somnolence.²⁶

Catatonia. The characteristic symptoms of catatonia are immobility, negativism, muteness, and failure to eat or drink. Benzodiazepines improve these symptoms in approximately 70% to 80% of catatonic patients with affective disorders. Response rates are lower in catatonia in patients with schizophrenia.²⁷ If catatonia in a patient with psychosis is missed, giving antipsychotics before benzodiazepines may worsen catatonic symptoms or precipitate neuroleptic malignant syndrome in some cases. When you suspect a patient has catatonia, start with lorazepam, 1 to 2 mg IV or IM, and examine the patient for diminishing catatonic signs within 1 to 2 hours. If catatonia signs lessen, begin regularly scheduled lorazepam, with dosing varying by age—be more cautious in geriatric patients—and symptom severity. Titrate benzodiazepines for stuporous patients more slowly (eg, 1 mg 3 times a day as a starting dose) than for excited catatonic patients. Lorazepam can be increased gradually as tolerated; it is not unusual for patients to require up to 8 to 12 mg/d. Electroconvulsive therapy (ECT) is the treatment of choice when catatonic patients respond poorly or partially to high-dose benzodiazepines.^28,29

Benzodiazepine reversal for ECT

Benzodiazepines have anticonvulsant properties that may interfere with the therapeutic efficacy of ECT.³⁰ A multi-center study demonstrated that lorazepam (up to 4 mg/d as needed) in the 48 hours before the first ECT session was not associated with effects on seizure threshold or duration; however, larger lorazepam dosages were associated with briefer EEG seizure duration.³¹ Some patients may not tolerate withholding or tapering benzodiazepines in preparation for ECT. Studies investigating flumazenil for pre-ECT benzodiazepine reversal are lacking. One retrospective analysis showed that flumazenil administration immediately before and after ECT resulted in adequate seizures with no difference in clinical outcome compared with patients who were not receiving benzodiazepines or flumazenil.³²

Tapering benzodiazepines

Slow discontinuation of benzodiazepines is recommended to avoid withdrawal symptoms, such as rebound anxiety, agitation, insomnia, or seizures, particularly when use exceeds 8 weeks. The onset of withdrawal symptoms varies, depending on the medication used. Withdrawal symptoms may appear in 1 to 2 days for agents with shorter half-lives, but may not appear until 3 to 7 days for agents with longer half-lives.³³Table 2 lists recommended durations for tapering benzodiazepines.^33,34 In general, decrease the total daily dose by 25% the first week, another 25% the second week, then 10% a week until discontinuation. When benzodiazepine use exceeds 1 year, a slower taper is recommended; for example, decrease 10% every 1 to 2 weeks. When 20% of the dosage remains, begin a 5% dose reduction every 2 to 4 weeks. Monitor patients for withdrawal symptoms or symptom exacerbation. If either occur, consider maintaining the current benzodiazepine dose or increasing the dose for 1 to 2 weeks or longer, if necessary, then continue to taper at a slower rate.³⁴

Table 2

Recommendations for tapering benzodiazepines