The timing, specificity and clinical prediction of tricyclic drug effects in depression

Abstract

SynopsisThis research was aimed at studying the rate of action of tricyclic drugs in depressive disorders, specifying the behavioural effects associated with recovery, and predicting clinical response. The research design involved comparison of a recovered group with a group treated for the equivalent four weeks, who showed minimal to no response. The findings indicated significant differences in baseline characteristics between responders and non-responders. Further, the drugs were found to act early in the responders, within the first week of treatment. Specific changes at one week which distinguished responder and non-responder groups occurred in the disturbed affects, and in cognitive functioning. Improvements also occurred in somatic symptoms, but these latter changes were general and not associated with later recovery. At 2½ weeks, all facets of the depressed condition showed positive change in the responders. Implications of the results for assessing rate of tricyclic drug actions, their effects on the interaction of affect and neurochemistry, and the practical application of the results for the clinical situation, are discussed.

Enhancing the Technology of Clinical Trials and the Trials Model to Evaluate Newly Developed, Targeted Antidepressants

“…They have also been shown to be effective for generalized anxiety disorder (even early on, imipramine was demonstrated to be more effective than the then leading "anti-anxiety" drug (Kahn et al 1979)), selected phobias, and obsessive-compulsive disorders (Insel 1991). It appears that reductions in anxiety and hostility are the initial signs of response in depressed patients to the tricyclic drugs, preceding the reduction of depressed mood (Haskell et al 1975;Katz et al 1987Katz et al , 1991. Such evidence supports the results of earlier research by Kielholz and Poldinger (1968) and Carlsson et al (1969), indicating that the tricycle drugs have multiple actions, i.e.…”

“…The hostility variable, viewed as a core element in several theories of the genesis and nature of the depressive disorders (Freud 1959;Abraham 1949), is not even included as a symptom in the HDRS and in the MADRS. This is so despite the evidence that hostility has been shown to be a very sensitive index of tricyclic drug action in treatmentresponsive patients (Fava et al 1986;Katz et al 1987). 3.…”

“…When the symptoms are mild, however, their comparative severities are more difficult for the rater to estimate from the brief interview period of observation. Some affective states, such as hostility, are more likely to be reported and more sensitively recognized by the patient than by trained raters (Weissman et al 1971;Katz et al 1987 Raskin et al 1967), and the Inventory of Depressive Symptomatology-SelfReport (IDS-SR) (Rush et al 1986(Rush et al , 1996. 2.…”

Psychopharmacology and the Etiology of Psychopathologic States: Are We Looking in the Right Way?

“…To exemplify how the componential approach was used to study the basis of drug action, the process of be havioral change in those patients who responded to the tricyclic drugs will be briefly described (Katz et al 1987. To identify treatment responders stringent out come criteria (not simply "marked" improvement) were tt � \1'" P <0·05 P < 0·02 P < 0·0\ P < O·OOI.…”

“…Although they have demonstrated antidepressant pro perties, it may be that the well-known pharmacologic action of the drugs on brain amine systems is more related to their anxiolytic properties than to their effects on the disorder itself (Katz et al 1987); that is, the an tidepressant action of the drugs is due to some presently unknown biologiC effect. If this very likely scenario is correct, then efforts to relate brain nor adrenergic mech anisms in depression, per se, have a "built in" failure element.…”