By Hector Warnes
Dr. Hassan Azima had a most distinguished career in the field of neuropsychopharmacology in the fifties and early sixties during the golden era at McGill University, when the fields of neurosurgery, neuropsychology, experimental psychology, neurophysiology, neurobiochemistry, transcultural psychiatry and psychoanalysis blossomed.
Azima was born in Iran, in 1922, and died in Montreal at the Royal Victoria Hospital at the age of 39, in 1962. He obtained his BA from the University of California and his M.D. at the University of Kansas, in 1948. After two years’ residency at the University of Paris, working particularly with Jean Delay, he joined the McGill Diploma Course in Psychiatry and completed his studies, in 1955, and his M.Sc. a year later. His wife Dr. Fern J. Cramer Azima was instrumental in several of the research methodologies during his dazzling career. She was an outstanding psychologist who was, as her husband, of international standing. She died in Montreal in 2013. Their many research and clinical contributionswere conducted at the Allan Memorial Institute of Psychiatry, where the Chair of the Department of Psychiatry of McGill University, D. Ewen Cameron, was located.
In my contribution to “Reflections of twentieth century psychopharmacology”, edited by T.A.Ban, D. Healy and E. Shorter, published by Animula Publishing House in Budapest (2004), I wrote on my experience of Hassan Azima’s brillant career with an abrupt and untimely ending at the peak of his creativity.
I shall limit myself to his contributions to the field of neuropsychopharmacology in particular to his clinical research on two paradigmatic drugs: chlorpromazine and imipramine. He introduced psychodynamics in the interpretation of the positive changes brought about by the newer compounds including reserpine. His psychoanalytic bent did not cloud at all his clinical research objectivity. Along with his friend, G. L. Sarwer-Foner, who wrote a memorial on the demise of Azima, published in Recent Adv. Biol Psychiatry (6: 214-216, 1963), he was of the opinión that drugs had a placebo,or symbolic effect based on the doctor-patient relationship, the psychodynamic shifts which Azima described regarding the effects of reserpine and the purely pharmacological effects each interacting with all the others. He goes further to explore this domain in the book edited by G. Sarwer-Foner “Dynamics of Psychiatric Drug Therapy” (Thomas, Springfield, Illinois 1960). Azima attempted to single out the alteration of psychological structure with the administration of drugs, which would allow to influence the psychotherapeutic or psychoanaIytic situation.Though he, himself, used statistical methods, he believed that longitudinal follow-up would shed light on these issues. Freud himself was of the persuation : “…But here we are concerned with therapy in so far as it works by psychological means; and for the time being we have no other. The future may teach us to exercise a direct influence, by means of particular chemical substances on the amount of energy and their distribution in the mental apparatus” (An outline of Psychoanalysis—The Hogarth Press and the Institute of Psychoanalysis- vol. XXIII reprinted 1973, page 182).
In his paper on Anaclitic Therapy, presented at the Third World Congress of Psychiatry (4-10 June, 1961), he took a stand against: “ the use of regressive ECT with or without prolonged sleep is the least satisfactory because of the organic confusion induced, the inaccessibililty of the patient to verbal contact, and the incomprehensibility of the events occcurring owing to the organic vicisitudes” (vol. II, p. 1074).
His pioneer research on the effect of chlorpromazine (Largactil) followed those of Laborit’s observations on ‘Hibernation’, and Jean Delay et al introduction of the drug in the clinical field of mental disorders. H. Azima and W. Ogle (Can. Med. Assoc. J. Aug. 1954 71(2): 116-121) recognized that Lehmann and Hanrahan were the first to use Largactil in NorthAmerica and confirmed the observations of the French authorsregarding its usefulness in psychomotor excitement.
One hundred unselected patients with mental syndromes were treated with an average dose of 400 mg of Largactil daily for an average period of 3 weeks. The sample consisted of44 neurotics, 27 schizophrenics, 25 manic depressives, one paranoid psychosis and 3 with organic brain syndromes. It is of interest that the drug helped moderately the cases of neurotic anxiety but not the obsessional neurosis. Among the schizophrenics there was a reduction of symptoms associated with better socialization. Among the five cases of manic excitement, 3 recovered and 2 were refractory and had to receive ECT. Azima and Ogle noted the sympatholytic and neuroleptic effects along with a tendency to hypometabolism and hypotension in most cases. The side effects reported, including somnolence or apathy, the potentiation of barbiturates, the increase of weight and appetite, maculo-papular rash on the skin plus hepatotoxic potential and Parkinson like symptoms were noted in a few cases.
Azima’s research on imipramine (Tofranil) was published in the Can. Med. Assoc. J. 1959 April 1, 80 (7): 535-540. I shall quote from his introduction “Following R. Kuhn, observations concerning the therapeutic efficacy of an iminodibenzyl compound in a preliminary trial of65 depressed patients and a clinical and psychodynamic study proved this substance to have a potent antidepressant capacity and very little or any effect on other mental syndromes. Concomitantly, Lehmann, Cahn and De Verteuil reached similar conclusions” (p. 535). Approximately half of the 100 depressed patients were neurotic and half were psychotic depressives (agitated, non agitated and involutional)…”Psychotic depression showed twice as greatimprovement as neurotic depression” (p.540). Azima was of the opinion that there was a continium between neurotic and psychotic depression based on the level of regression:
a) the severity of the feeling of depression and guilt;
b) the degree of regression and of ego disorganization;
c) the intensity of self-destructiveness;
d) the intensity of agitation;
e) the involutional age; and
f) the presence or absence of depression or manic attacks in the past or in their relatives.
The dose of Tofranil started with 75 mg up to a maximum of 200 mg daily in a few cases. Generally, there was a lapse of 30 days before the optimal therapeutic response was seen. About 50% of patients responded in 10 days and 70 % in two weeks. He noted that the treatment should continue for at least 3 months and the discontinuation of the drug should be gradual within 10 days…”many patients will require long term maintenance therapy for from 6 to 12 months or more” (p. 537). In 10 patients there was a shift to a manic state and Azima recomended the use of chlorpromazine or promazine to control the symptoms. Regarding the side effects, they were the usual atropinic side effects, including more difficult to control tremors (20%). Lowering the dosewas sufficient to overcome the side-effects. I must cite an amazing observation: “ about 80% of patients requiring ECT may no longer require this treatment” (p.539) and he recommended that the drug could be used in ambulatory care and by general practioners or other specialists not only in the treatment of depressive disorders but in the treatment of premenstrual disorders, skin disorders and addictions.
Azima investigated several compounds, particularly “The effect of thioridazine (Mellaril) on mental syndromes - comparison with chlorpromazine and promazine” H. Azima, H. Durost and Dorothy Arthurs—Can. Med. Asoc. J. Oct. 1 1959, 81 (7): 549-553- The use of Mellaril in the treatment of 75 patients (44 schizophrenics, 6 manic depressive, 2 organic psychotics and 23 neurotics) with an average dose of 400 mg for 3 weeks in acute cases and 3 months in chronic cases, using a single blind method compared longitudinally in 3 groups of 40 patients each with chlorpromazine and promazine. It was found that the response was similar to that of chlorpromazine except for the paucity of side effects of Mellaril particularly the lack of extrapyramidal and liver complications.
It would be beyond the scope of this paper to discuss each of the many studies and publications carried out by H. Azima on consciousness, on homeostasis in schizophrenic patients, anaclitic therapy, perceptual and sensory isolation, on the effects of meprobamate in sustained high dosage, on sleep treatment, on basic science and psychiatry.
September 4, 2014