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Disinhibitory Effect of Benzodiazepines

When benzodiazepines are prescribed for anxiety and the behavioral disorders of dementia, there is a well-documented risk of dizziness, sedation, falls, fractures subsequent to falls, and cognitive impairment associated with these agents in the elderly. In addition, the concept of disinhibition should be considered as a possible complication of therapy in this population. The release of previously suppressed behavior has been called the disinhibitory effect.

“Benzodiazepines dilute the controlling capacity of the ego, allowing one to lose the intensity of normal control mechanisms,” says Lucy Rea Sarkis, M.D., Executive Director, South Beach Psychiatric Center, Staten Island, NY. “The premorbid personality determines how disinhibition is expressed clinically.” Dr. Sarkis elaborates, “It depends on the normal tendencies of the individual.” For instance, in an elderly individual with a premorbid personality possessing sexual preoccupation, a benzodiazepine may precipitate sexually inappropriate behavior. If an aging adult had a premorbid personality possessing obsessive-compulsive features, an increase in anxiety and ritualistic behavior may follow the introduction of a benzodiazepine. If paranoid thinking and/or tendencies existed premorbidly, a benzodiazepine may induce an increase in verbally abusive behavior and an increase in paranoid thinking and behavior.

Furthermore, “in dementia, the area of compromise is very often the determinant of benzodiazepine response variability,” explains Dr. Sarkis. For instance, she adds, if the cerebellum is compromised, a benzodiazepine may increase the risk of falling; with a compromised hippocampus, the center of emotional response, a benzodiazepine may elicit emotional lability; alternatively, a benzodiazepine used with a compromised frontal lobe may produce significant cognitive impairment.

For treating uncomplicated, generalized anxiety in the elderly, shorter-acting benzodiazepines are recommended with scheduled dosing at lower doses than those for younger patients (Table 3). They are relatively rapid in action and effective in reducing feelings of panic, fear, and tension. They should not, however, be prescribed casually for simple situations resulting in tension and anxiety, or for those who suffer from chronic anxiety. The course of therapy is often short (e.g., up to 4 to 6 weeks) since most bouts of anxiety are short-lived, although recurrent in nature. Discontinuation after extended use is difficult due to psychologic and physical dependence; gradual tapering every few days over 3 to 4 weeks is recommended, as withdrawal may lead to rebound anxiety. In a dying patient who appears uncomfortably anxious, an assessment for treatable causes (e.g., hypoxemia, pain, fear) should be undertaken, and if necessary, a short-acting benzodiazepine is recommended.

An alternative to the benzodiazepines is buspirone, initially dosed at 5 mg BID and usually up to 10 mg BID or TID. Using the slow titration guideline of increasing by 5 mg/day every 2 to 3 days as needed up to 20 to 30 mg/day (maximum daily dose of 60 mg/day) helps to avoid or minimize side effects (e.g., dizziness, drowsiness) while providing adequate dosing for effectiveness. Response to treatment is generally seen within 1 to 2 weeks of continuous therapy, with a maximum effect after 3 to 4 weeks. Although this delay in onset of action may be perceived as a disadvantage to buspirone therapy, it should be noted that there is little potential for abuse with this agent.

Hydroxyzine — due to its potent anticholinergic properties — and meprobamate — due to its highly addictive and sedating properties — are not recommended for use in the elderly. Due to adverse effects associated with the antipsychotic drugs (noted above), they should not be used for anxiety disorders unless frank psychotic symptoms (e.g., paranoia, delusions, hallucinations) are present.

In the elderly with anxiety disorders, for whom the tricyclic antidepressants (TCAs) are indicated, imipramine and nortriptyline are well tolerated (75 mg at bedtime; range 50-150 mg/day). Due to strong anticholinergic and sedating properties, amitriptyline is rarely the TCA of choice in the elderly. The TCAs are contraindicated in patients with narrow-angle glaucoma, a frequent comorbidity in older adults. The selective serotonin reuptake inhibitors (SSRIs), also indicated in anxiety disorders, may be useful in patients at risk for sedation, hypotension, and anticholinergic effects of TCAs.The benzodiazepines are often used adjunctively for anxiety disorders, on an intermittent basis, with the TCAs or SSRIs.

Conclusion

Benzodiazepines have demonstrated their utility in relieving anxiety, including the anxiety that accompanies dementia. However, along with other documented potential adverse effects in this patient population, disinhibition may occur. In disinhibition, inappropriate social behavior such as sexual advances or verbal abuse/pananoid behavior may manifest as a side effect. The best outcome from benzodiazepine use in the elderly is obtained from short-term use (4 to 6 weeks) of smaller doses of shorter-acting benzodiazepines.