Richard J. Kahn

Tricyclic antidepressants and peripheral anticholinergic activity

Peripheral anticholinergic activity of single acute doses of three tricyclic antidepressants (amitriptyline 50 mg, desipramine 50 mg, doxepin 100 mg) and placebo was assessed by several physiologic measures in normal male volunteers. Amitriptyline and doxepin produced similar significant depressions in salivary flow and finger sweating compared to placebo, while desipramine produced no change. Supine and standing blood pressures and standing pulse yielded significant differences among the drugs. Measures in at least three areas (salivation, perspiration, and pulse-blood pressure) offer a simple and reliable battery of tests for the peripheral autonomic effects of tricyclic antidepressants.

Tricyclic treatment of generalized anxiety disorder

While tricyclic antidepressants (TCAs) have now long been used in treatment for depressive and panic-phobic disorders, we reviewed and reported on their efficacy in generalized anxiety states. These ill-defined states usually have admixtures of anxiety and depression. While there is no neat diagnostic categorization to fit this wasteland of yet-to-be-defined disorders, they show surprising responsiveness to imipramine. The onset of efficacy appears to begin at about 2 weeks or later and is probably superior to at least one well-known benzodiazepine, chlordiazepoxide, well beyond that time. It is not possible to dismiss these observed antianxiety effects as secondary to antidepressant effects or as attributable to the unintended inclusion of a peculiarly sensitive subset of individuals such as panic-phobic patients. These findings indicate that affect regulation by TCAs applies to so-called generalized anxiety as well as to depression and panic-phobic disorder. Brief reminders and guidelines are outlined for the possible clinical use of TCAs in anxiety disorders, but there remain more questions than answers. Several replication studies concerning the results reviewed here are now under way.

Persistence of a drug-personality interaction in psychiatric outpatients

CLINICAL drug trials with psychiatric outpatients usually span brief time periods. Investigators rarely follow up such trials. Apparently only one previous study reported an objective and comprehensive follow-up of a clinical trial of mild tranquilizers.1 Unfortunately it used different measures during the clinical trial and at follow-up, and psychiatric status for the two periods could not be compared. This paper reports a follow-up four months after the end of a double-blind trial of diazepam (Valium).a-4-t The 2-week trial indicated that a personality characteristic (Acquiescence) and medication had significant joint, or interactive, effects upon outcome. Patients had been classified as High or Low Acquiescers by their frequency of agreement with 35 glib generalizations from the Bass Social Acquiescence Scale.5

Amoxapine and amitriptyline

After twa weeks of treatment Low Acquiescers had improved more on drug than on placebo, while High Acquiescers had improved more on placebo than on drug. Figure 1 depicts the interaction pattern on a typical criterion. The research questions in the follow-up phase concerned: (1) the persistence of the medication-personality interaction; (2) the effects of the clinical trial upon subsequent treatment and clinical progress.

A Controlled Outpatient Trial of Perphenazine—Amitriptyline and Chlorpromazine

Speed of onset of antidepressant effect was studied in 20 depressed outpatients assigned double-blind to equipotent doses of amoxapine or amitriptyline. In counterbalanced order, each patient had 2 periods of 3 weeks on active agent interspersed with 2 similar periods of placebo control. On daily and weekly self-ratings, amoxapine was found to reduce symptoms significantly more rapidly than amitriptyline. Psychiatrist-ratings were consonant with selfreports.

Imipramine and Chlordiazepoxide in Depressive and Anxiety Disorders: II. Efficacy in Anxious Outpatients

NXIETY states have generally been treated pharmacologically by antianxiety or tranquilizing medication. However, it is well recognized that many people who seek treatment for anxiety have either overt depressive symptoms or an underlying depression which is obscured by their anxious symptomatology. For such patients, it was proposed that treatment of both symptoms, anxiety and depression, would be more beneficial than treatment only of the anxiety. To test such a proposition, this study compared the effects of a tranquilizer-antidepressant combination, perphenazine-amitriptyline, and ehiorpromazine (a phenothiazine, as is perphenazine, generally used in psychoses, but often prescribed in low doses for neurotic anxiety) in a sample of anxious, nonpsychotic outpatients. Several studies’3 have reported the efficacy of this combination, but be-