Trazodone and the Mental Pain Hypothesis of Depression

Abstract

The mental pain hypothesis used to develop trazodone is illustrated, together with its medical and methodological implications. Trazodone possesses a well documented antidepressant activity, which indirectly confirms the above hypothesis. It lacks the aminergic effects of other antidepressants and has a marked adrenolytic activity. Therefore it is potentially indicated in depressive states with adrenergic hyperactivation, such as during alcohol withdrawal. The methodological aspects of the approach taken for trazodone are also discussed, in the context of the strategies of psychopharmacological research.

Degree of Suffering – a Neglected Variable

“…The relationship between the degree of suf fering and the diagnosis, estimated on the basis of clinical observation, has repeatedly been mentioned in the literature. Depression has been claimed to be associated with a state o f 'mental pain' which -similarly as a somatic pain -is produced by a lowered threshold for the perception of suffering [Silvestrini, 1986]. In neurosis, wish fulfillment and suffering are closely tied with each other and the neurotic symptom comes into being due to the suffering, thus freeing the individ ual from guilt feelings [Alexander, 1927], There is more subjective suffering in trau matic neurosis, hypochondria and melan cholia than in hysteria [Freud, 1920], In hys teria, a dissociation of suffering can take place in the form o f'belle indifference' [Blan kenburg, 1981], In schizophrenia, the pri mary disease process manifesting itself in the feeling of 'the end of the world' (Gefühl des Weltuntergangs) can be experienced as inten sive suffering; whereas the productive symp tomatology, presenting an attempt for restitu tion, frequently is not accompanied by a feel ing of suffering [Nunberg, 1971], In addition, there is frequently only minimal primary con dition-related suffering in alcoholism [Feuerlein, 1975] and in sexual deviations [Horn, 1971], Schneider [1940] used the criterion of suffering in defining the group of psycho pathic personalities.…”

Serotonin Reuptake Inhibitors and Their Role in Chronic Pain Management

“…Trazodone (Desyrel™, Oleptro™) is the first non-tricyclic antidepressant approved for the treatment of MDD (1981), and it is also used to treat anxiety, alcohol dependence, insomnia, and chronic pain (off-label). It was developed for the treatment of "mental pain," which was recognized to occur in depression [97]. It acts as a SRI, antagonist of 5-HT A2 receptor, and a partial agonist for 5-HT A1 receptors.…”

Efficacy and tolerability of trazodone retard monotherapy: results of the Serbian non-interventional study

“…Its development was the result of a disease-oriented research approach, first described as the so-called 'mental pain hypothesis of depression' by Silvestrini (1986). Clinical trials in the 1980s made trazodone the most widely prescribed antidepressant in the USA (Burke & Preskorn 1995), which was mainly due to its good tolerability and safety profile over short-and long-term treatment, especially in the elderly (Gershon 1984), along with its hypnotic properties (Mouret et al 1988).…”