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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.

Behavioral disturbances in the elderly are probably the most important facet of dementia prompting institutionalization. The referral for pharmacologic intervention is often the result of the need for management of mood and behavior. Symptoms tend to be superficially described as “agitated,” “combative,” “depressed,” “acting out,” “inappropriately accusing,” etc., by spouses, family members, and caregivers.

Dementia may be the most common cause of anxiety in the elderly, with an increased risk of anxiety seen in patients initially transferred to a long-term care facility from the hospital or from home. Trauma or a stressful event may induce an acute, short-lived, situational anxiety. Anxiety disorders (also known as anxiety and phobic neuroses) are classified as phobic disorders, posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), and panic disorder (Table 1).

Attempts at alleviating anxiety in the elderly, and especially in those with dementia, should be attempted through nonpharmacologic intervention whenever possible. This may include providing a more structured environment with consistent routines, simplifying everyday tasks, avoiding over- or understimulation in the environment, providing soothing background music, and providing support to caregivers. Testing for adequate hearing and vision is also essential. Supportive psychotherapy, behavioral therapy, biofeedback, relaxation therapy, and paced exercise therapy may be used as nonpharmacologic and adjunctive therapy where appropriate.

Reversible etiologies of anxiety related to adverse drug effects and concomitant medical disorders should not be overlooked. When possible, eliminating medications known to contribute to or induce anxiety and treating medical conditions that may cause anxiety or similar symptoms (Table 2) may help avoid unnecessary intervention with an anxiolytic. For example, eliminating anxiety and agitation secondary to depression with the use of an antidepressant may be sufficient.

Benzodiazepines are often prescribed for elderly dementia patients with behavioral disorders because of a prescriber preference over the antipsychotics that carry a liability of extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). Extrapyramidal reactions are more common in the elderly, with up to 50% of patients developing these reactions after age 60; incidence may be more common in dementia patients. The prevalence rate of tardive dyskinesia in the elderly may be as high as 40%; elderly women are especially at risk. Up to 20% of older adults take benzodiazepines, and their use is more common among women than men. Benzodiazepines are useful in treating general anxiety disorders, panic disorders, and depression, as an adjunct to antidepressants. They are also indicated in insomnia, on a short-term basis. In addition, they are useful for preprocedure/preoperative sedation (e.g., dental procedures, MRI screenings) and in cases of status epilepticus.

Generalized anxiety disorder is one of the most misunderstood mental illnesses, yet experts estimate that it affects five to ten percent of the world population. This week at the annual meeting of the American Psychiatric Association in Chicago, the International Consensus Group on Depression and Anxiety announced the results of their recent meeting on this condition, also referred to as generalized anxiety gisorder.

The consensus meeting on generalized anxiety gisorder, attended by an international group of psychiatric experts, took place in March of this year. Their principal findings, presented in Chicago, summarize the available data on this condition.

“The medical community has learned much about this devastating anxiety disorder in recent years,” stated Dr. James Ballenger of the Medical University of South Caroline, who chaired the consensus group. “It’s a complex condition, most often accompanied by depression and/or another anxiety disorder.”

Ballenger and his colleagues “hope that our new report will highlight the problem of significant under-diagnosis and undertreatment of generalized anxiety gisorder.”

The medical community has debated whether generalized anxiety gisorder is a distinct medical condition or part of other anxiety disorders. The consensus group concluded that existing data clearly support the diagnosis of generalized anxiety gisorder as a distinct illness, although patients with the condition frequently also suffer from depression and from other anxiety disorders.

The group also reported that generalized anxiety gisorder is more common than was previously thought — it’s actually as common as other conditions such as panic disorder. Fewer than 20% of those who suffer from generalized anxiety gisorder ever totally eliminate their symptoms. Usually, individuals with the condition have had symptoms for five to ten years before their illness is diagnosed and treated.

People with generalized anxiety gisorder often go to general practitioners with physical symptoms such as muscle tension, irritability, fatigue, and insomnia. The consensus group recommends that when physicians have patients who come in with unexplained physical symptoms on two or more occasions, they should consider the possibility of generalized anxiety gisorder.

The group’s report will be published later this year in the Journal of Clinical Psychiatry, said Ballenger.

Editorial Commentary: Generalized Anxiety Disorder has remained at the periphery of psychiatric diagnosis in part because it has very general criteria that many feel don’t capture a single illness, but a segment of humanity at one end of the anxiety spectrum. Still, treatment can be somewhat helpful, both relaxation therapies and medication.