The development of the treatment of chronic pain by psychotropic drugs

Arthur TAUB

Yale University School of Medicine, 46-48 Prince Street, New Haven, CT 06519, USA
Tel. 203-7892151, Fax. 203-7891810


Tricyclic ìantidepressantî agents (imipramine, amitriptyline) were first observed to exert an ìanalgesic-sedativeî effect in a variety of chronic, painful, clinical situations. This was initially thought necessarily to depend upon the association of depression with pain and specifically upon relief of depression. It only gradually became clear, however, that the relief of chronic pain obtained with the use of tricyclic agents was independent of the presence of depression.

An ìantipsychoticî butyrophenone (benperidol), acting alone, was demonstrated in an open study to exert an analgesic effect dependent upon the mechanism of the painful disorder, and not upon personality factors. Benperidol was not widely used for this purpose, perhaps largely due to butyrophenone extrapyramidal side effects.

The combination of amitriptyline and the ìantipsychoticî substituted ìalertingî phenothiazine, fluphenazine, in low dose, was demonstrated in open studies by the author to be effective alone in the control of spontaneous pain and evoked dysesthesia first in post herpetic neuralgia, and then in diabetic and other forms of peripheral neuropathy, and in central dysesthesia, all previously resistant to treatment. It was later shown to be effective adjunctively with opioids in disseminated visceral neoplasm. The combination came into wide use, and was the subject of a number of successful confirmatory open aund double blind trials.

A contemporaneous open study by others using amitriptyline as the tricyclic, pericyazine as the substituted phenothiazine, and the antihistaminic phenothiazine promethazine adjunctively, demonstrated its effectiveness in a variety of conditions, including postherpetic neuralgia. The combination of amitriptyline pericyazine and/or promethazine was not widely used, however, perhaps largely due to the combined sedating effects of the agents.


Plenary 5   (Samuel Tissot Lecture)
Friday, 17 September 1999

The Neurosciences and Psychiatry: Crossing the Boundaries

Joint Congress of the European Association for the History of Psychiatry (EAHP), the European Club for the History of Neurology (ECHN), and the International Society for the History of the Neurosciences (ISHN)

Zurich and Lausanne, Switzerland, 13-18 September 1999