ANXIOLYTIC DRUGS

V. John Massari, Ph.D.(c)

I. Anxiety is a universal human emotion, closely related to appropriate fear, and often serving psychobiologically adaptive purposes. It is also an inevitable component of many medical and surgical condigitons. Furthermore it is a cardinal symptom of many psychiatric disorders, including depression, phobias, obsessive compulsive disorder, eating disorders, and many personality disorders. When anxiety is a result of identified psychiatric disorders (ie depression) appropriate drug therapy should be directed to the underlying disorder rather than the symptom (anxiety); ie treatment with antidepressants. When no treatable primary illness is found, it is common and appropriate to use anxiolytic drugs. Anxiolytics are sometimes also used in the short term management of psychotic patients with severe anxiety.

II. Benzodiazepines

A. They are the most commonly employed anxiolytic agents for generalized anxiety. For generalized anxiety, the specific benzodiazepine selected seems to make relatively little difference. Nine benzodiazepines are recommended for treatment of anxiety. They are chlordiazepoxide, diazepam, oxazepam, clorazepate, lorazepam, prazepam, alprazolam, halazepam and clonazepam. Although these drugs are commonly advertised for their anxiolytic properties, you should remember that they are also effective sedative-hypnotic drugs too. In fact, the other benzodiazepines which are used for sedation and hypnosis more often, may have almost equally effective anxiolytic effects as these recommended nine drugs. Virtually all benzodiazepines are also have anticonvulsant effects, however, clonazepam, diazepam, and clorazepate are most commonly used clinically for their anticonvulsant effects.

1. In the elderly or in patients with impaired hepatic function oxazepam is currently favored due to its brief action and rapid elimination by the kidneys. Lorazepam is another choice for the same reasons.

B. In severe anxiety attacks accompanied with strong autonomic overactivity symptoms such as "panic disorder" alprazolam, clonazepam, and lorazepam are effective.

C. The most favorable responses to the benzodiazepines are obtained in situations that involve relatively acute anxiety reactions in patients who have primary anxiety disorders.

D. Although there is appropriate concern about the potential for the develpment of tolerance and physical dependence, studies suggest that physicians tend to be conservative in their prescriptions and often undertreat patients with anxiety. Because of the long half lives of these drugs and/or their metabolites, withdrawal symptoms may not appear for a week after discontinuation of chronic medication. In most cases gradual withdrawal from long acting benzodiazepines does not lead to a withdrawal syndrome.

E. In a previous lecture we have discussed the metabolism of the benzodiazepines and noted how their metabolites may be potent drugs which have much longer half lives than the parent drug. The elimination half life can be misleading however because lipophilic benzodiazepines exert their effects in the CNS rapidly (generous blood flow to the brain, and are rapidly taken up by the lipophilic brain). The rate of redistribution from the brain to the periphery then determines the duration of clinical effectiveness. Thus diazepam has a rapid onset and short duration of action even though the elimination half life is long.

III. Otherdrugs used for anxiety

A. Obsolete drugs, including barbiturates and meprobamate

B. Propranolol, atenolol, or clonidine reduce autonomic symptoms, but probably are not very useful for generalized anxiety or panic attacks.

C. Some antihistamines have sedative hypnotic anxiolytic properties (hydroxyzine)

D. Azapirones (buspirone, (ipsapirone, tiaspirone, gepirone)

1. Buspirone

a. They are Serotonin 1A receptor agonists. They do not interact with Serotonin 2 or GABA receptors!

b. Not anticonvulsants either

c. Repeated use does not appear to be associated with the development of tolerance or physical dependence.

d. Effective in generalized anxiety of limited severity. Not useful in severe anxiety associated with panic attacks.