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Monday, 24.02.2020

Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Education in the Field in the Post-Neuropsychopharmacology Era

Background to An Oral History of the First Fifty Years
Psychopharmacology (Volume Four): 2b. Contributions of Interviewees
Bulletin 46


            Psychotropic drug development has been the driving force in psychopharmacological research; four of the interviewees, Ban, Gallant, Goldstein and Simpson, were involved, as Early Clinical Drug Evaluation Unit (ECDEU) investigators, in clinical studies that led to the registration of several of the first-generation psychotropic drugs.Thomas A. Ban contributed to the clinical characterization of several phenothiazines, butyrophenones, thioxanthenes, diphenyl-putylpepridines, tricyclic and other antidepressants (Ban 1964, 1965, 1974, 1977, 1978, 1981; Ban, Ferguson and Lehmann 1963; Ban and Lehmann 1962; Ban, Papathomopoulos and Schwarz 1962; Ban and Schwarz 1963; Chouinard, Lehmann and Ban 1970; Chouinard, Lehmann, Ban and Ananth 1970; Lehmann and Ban 1969; St.Laurent, Cahn and Ban 1962). He was first to detect the antidepressant effect of trazodone in the 1970s and to demonstrate the antidepressant effect of reboxetine in the 1990s (Ban, Amin, Nair and Engelsman 1974; Ban, Gaszner, Aguglia et al. 1998). He was also first in 1964 to report dose-dependent cardiac conduction changes with thioridazine (Ban and St. Jean 1964) To translate pharmacological findings into clinical effects, Ban developed in the 1960s a conditioning test procedure (Ban, Lehmann and Saxena 1970). He also developed two instruments, Diagnostic Criteria for Research (DCR) Budapest-Nashville (in collaboration with Bertalan Petho), and Composite Diagnostic Evaluation for Depressive Disorders (CODE-DD), for the identification of pharmacologically more homogeneous diagnostic populations than in consensus-based classifications (Ban 1969; Petho, Ban et al. 1988). Ban’s findings indicate an inverse relationship between the therapeutic and adverse effects of psychotropic drugs, e.g., tardive dyskinesia with neuroleptics, toxic psychosis with lithium (Ban 1990).

            Donald M. Gallant contributed to the clinical characterization of several psychotropic drugs, including triperidol, thiothixene, cinanserin and penfluridol (Gallant and Bishop 1968, 1969; Gallant, Bishop and Shelton 1966; Gallant, Bishop, Timmons and Steele 1963). He also extended clinical investigations with some of the new drugs, e.g., doxepin for the treatment of chronic alcoholism (Gallant, Bishop, Guerrero-Figureoa et al. 1969; Gallant, Mielke, Spirtes et al. 1974). Gallant and his team provided further substantiation of cardiac conduction changes with thioridazine and were first to report on similar changes with mesoridazine (Dillenkopfer, George, Bishop and Gallant 1974). As early as the 1970s Gallant addressed ethical issues related to psychopharmacology research (Gallant and Force 1978).

            Burton J. Goldstein contributed to the clinical characterization of several psychotropic (Goldstein 1966, 1973; Goldstein, Brauzer, Clyde and Caldwell 1969; Goldstein, Brauzer, Steinbook   and Jacobson 1973; Goldstein and Clyde 1966; Goldstein, Dominguez and Weiss 1985; Goldstein and Pinosky 1969; Goldstein and Weiner 1970; Goldstein, Weiner and Banas 1969).   Goldstein, with his collaborator Benjamin Brauzer, was first to use “symptomatic volunteers” in clinical investigations with psychotropic drugs (Goldstein and Brauzer 1971).

            George M. Simpson contributed to the clinical characterization of several antipsychotic and antidepressant drugs (Kline, Simpson and Brodie 1962; Simpson, Amin, Angus et al. 1972).  The wide range of neuroleptics he studied included fluphenazine, haloperidol, thiothixene, oxypendyl, prothipendyl, molindone, clozapine and risperidone (Simpson, Amin, Kunz and McCafferty 1965; Simpson and Angus 1967a,b; Simpson, Angus and Edwards 1967; Simpson and Iqbal 1965; Simpson and Krakow 1968; Simpson and Lindermayer 1997; Simpson and Varga 1974). In collaboration with Thomas Cooper he explored the relationship between plasma levels and clinical response; and with Angus he developed an extrapyramidal symptom rating scale (ESRS) that was to become one of the standard instruments in the evaluation of antipsychotic drugs (Simpson and Angus 1970). He also developed, in collaboration with Lee, Zuobolc and Gardos, a severity scale for tardive dyskinesia (Simpson, Lee, Zuobolc and Gardos 1978). Simpson was among the first to report on withdrawal effects after discontinuation of treatment with phenothiazines in schizophrenia (Simpson, Amin and Kunz 1965).

            George Gardos collaborated with Simpson on the development of the severity scale for tardive dyskinesia (TD). Focusing on late neurological side effects of neuroleptics, he found an interaction between drug and disease related factors in the pathogenesis of TD (Gardos, Casey Perenyi et al. 1994; Gardos and Cole 1984; Gardos, Cole and LaBrie 1977). In his early research Gardos found that not all benzodiazepines increased hostility and that the therapeutic profile of thiothixene was different in low than in high doses (Gardos and Cole 1973; Gardos, DiMascio, Salzman and Shader 1968).





Ban TA. The butyrophenones in psychiatry. In Lehmann HE, Ban TA, editors. The Butyrophenones in Psychiatry. Montreal: Quebec Psychopharmacological Research Association: 1964. p. 120-34.

Ban TA. Trimipramine in psychiatry. In: Lehmann HE, Berthiaume M, Ban TA, eds. Trimipramine A New Anti-Depressant. Montreal; Quebec Psychopharmacological Research Association; 1964, p. 95-6.

Thomas A. Ban: Depression and the Tricyclic Antidepressants. Ronalds Federated Graphics Limited. Montreal, 1974. (74 pages).

Ban TA. Introduction to the Psychopharmacology of Doxepin. Pfizer; Montreal, 1977.

Ban TA. Psychopharmacology of Thiothixene. Raven Press,New York, 1978.

Ban TA. Psychopharmacology of Depression. Karger, New York, 1981.

Ban TA. CODE DD Composite Diagnostic Evaluation of Depressive Disorders. Brentwood: JM Productions; 1989.

Ban TA. Clinical pharmacology and Leonhard’s classification of endogenous psychoses. Psychopathology1990; 23: 331-8.

Ban TA, Amin M, Nair NPV, Engelsman F. Comprehensive clinical studies with trazodone in Canada. In: Ban TA, Silvestrini B, eds. Trazodone. Modern Problems in Pharmacopsychiatry Vol 9. Basel: Karger; 1974, p. 110-26.

Ban TA, Ferguson K, Lehmann HE. The effect of clopenthixol on chronic psychiatric patients.  Am J Psychiatry 1963; 119: 984 - 5.

Ban TA, Gaszner P, Aguglia E, Batista R, Castillo A, Lipcsey A, Macher J-P, Torres-Ruiz A, Vergara L. Clinical efficacy of reboxetine: a comparative study with desipramine, with methodological considerations. Human Psychopharmacology 1998; 13 (Supplement): S29-S39.

Ban TA, Lehmann HE. Clinical trial with desmethylimipramine, a new antidepressant.  Canadian Psychiatric Association Journal 1962; 86: 1020-1.

Ban TA, Lehmann HE, Saxena BM. A conditioning test battery for the study of psychopathological mechanisms and psychopharmacological effects. Canadian Psychiatric Association Journal 1970; 15: 301-8. 

Ban TA, Papathomopoulos E, Schwarz L. Clinical studies with thioproperazine (Majeptil) Comprehensive Psychiatry 1962; 3: 284-91.

Ban TA, Schwarz L. Systematic studies with levomepromazine. Journal of Neuropsychiatry 1963; 5: 112-7.

Ban TA, St. Jean A. The effect of phenothiazines on the electrocardiogram. CMAJ 1964; 91: 537-40.

Chouinard G, Lehmann HE, Ban TA. Pimozide in the treatment of chronic schizophrenic patients. Current Therapeutic Research 1970; 12: 598-603.

Chouinard G, Lehmann HE, Ban TA, Ananth JV. Fluspiriline in the treatment of chronic schizophrenic patients. Current Therapeutic Research 1970; 12: 604-8.

Dillenkoffer RL, George RB, Bishop MP, Gallant DM. Electrocardiographic evaluation of thiothixene: a double-blind comparison with thioridazine. Adv Biochem. Psychopharmacol. 1974; 9: 487-95.

Gallant DM, Bishop MP. Cinanserin (SQ 10,643): a preliminary evaluation in chronic schizophrenic patients.  Curr Ther Res 1968; 10:461-3.

Gallant DM, Bishop MP. IM thiothixene and trifluoperazine. Psychopharmacol Bull 1969; 5:46-8.

Gallant DM, Bishop MP, Guerrero-Figureoa R, Selby M, Phillips R. Doxepin vs diazepam a controlled evaluation in chronic alcoholic patients. J Clin Pharmacol J New Drugs 1969; 9: 57-65

Gallant DM, Bishop MP, Shelton W. A preliminary evaluation of P-4657B: a thioxanthene derivative. Am J Psychiatry 1966; 123: 345-6.

Gallant D, Bishop M, TimmonsE, Steele CA. A comparative evaluation of triperidol (R2498): a new potent psychopharmacologic agent.  Curr. Ther Res 1963; 5: 463-6.

Gallant DM, Force R, editors. Legal and Ethical Issues in Human Research and Treatment: Psychopharmacology Considerations. New York: Spectrum Publishing; 1978.   

Gallant DM, Mielke DH, Spirtes MA, Swandon WC, Bost R. An efficacious long-acting oral antipsychotic compound. Am J Psychiatry 1974; 133: 609 – 702.

Gardos G, Casey DE,  Perenyi  A, Cole JO,  Kocsis E,  Arato M,  Conley C,  Samson J. Ten year follow-up study of tardive dyskinesia and drug-induced Parkinsonism. Psychiatria Hungaric 1994; 9: 137-45. 

Gardos G, Cole JO. The dual action of thiothixene. Arch Gen Psychiatry 1973; 29: 222-5. 

Gardos G, Cole JO. Tardive dyskinesia and affective disorder. In:  Gardos G, Casey DE, editors. Tardive Dyskinesia and Affective Disorders. Washington: American Psychiatric Press; 1984. p. 69-80.

Gardos G, Cole JO, La Brie RA. Drug variables in the etiology of tardive dyskinesia. Progress in Neuro-Psychopharmacology & Biological Psychiatry 1977; 1: 147-54.

Gardos G, DiMascio A, Salzman C, Shader RI.  Differential action of chlordiazepoxide and oxazepam on hostility. Arch Gen Psychiatry 1968; 18; 757-60.

Goldstein BJ.  Haloperidol in controlling the symptoms of acute psychosis:  Part I. A preliminary investigation. Current Therapeutic Research. 1966; 8: 231-4.

Goldstein BJ, Brauzer B. Symptomatic volunteers – A new patients’ treatment model.  In: Vinar O, Votava Z, Bradley PB, editors. Advances in Neuropsychopharmacology Amsterdam/Prague: North Holland Publishing Company/Avicenna Czechoslovak Medical Press; 1971. p. 375-88.

Goldstein BJ, Brauzer B. Thiothixene in the treatment of mixed anxiety and depression. J Clin Pharmacol 1973; 13: 167-73.

Goldstein BJ, Brauzer B, Clyde DJ, Caldwell JM.  The differential prediction of response to haloperidol and perphenazine.  Psychosomatics.  1969;10: 193-7.

Goldstein BJ, Brauzer B, Steinbook RM, Jacobson AF. Psychotropic drug treatment of mixed anxiety and depression in non-psychiatric office patients: expected and unexpected findings – comparing doxepin, chlordiazepoxide and placebo. South Med J 1973; 66: 892-7.

Goldstein BJ, Clyde DJ. Haloperidol in controlling the symptoms of acute psychosis.  Part II. A double-blind evaluation of haloperidol and trifluoperazine.  Current Therapeutic Research 1966; 8:235-9.

Goldstein BJ, Dominguez RA, Weiss BL.  Amoxapine in psychotic depression.  Journal of Clinical Psychiatry 1985; 3: 14-6.

Goldstein BJ, Pinosky DG. Clinical evaluation of doxepin in anxious depressed outpatients. Psychosomatics 1969; 10:37-8.

Goldstein BJ, Weiner DM.  Comparative evaluation of benzoctamine and diazepam in treatment of anxiety.  Journal of Clinical Pharmacology 1970; 10:194-8.

Goldstein BJ, Weiner D, Banas F.  Clinical evaluation of thiothixene in chronic ambulatory. In Lehmann HE, Ban TA, editors The Thioxanthenes. Basel: Karger; 1969, pp.45 – 52.

Kline NS, Simpson G, Brodie BB. The clinical application of desmethylimipramine: A new type of antidepressant drug. International Journal of Neuropharmacology 1962; 1: 55-60

Lehmann HE, Ban TA. Studies with thioxanthenes. In: Ban TA, Lehmann HE, editors. The Thioxanthenes. Basel: Karger: 1969. p. 85-9.

Petho B, Ban TA. DCR Budapest-Nashville in the Diagnosis and Classification of Functional Psychoses. Psychopathology 1988; 21: 153-240.

Simpson GM, Amin M, Angus JWS, Edwards JG, Go SH, Lee JH. Role of antidepressants and neuroleptics in the treatment of depression. Arch Gen Psychiatry27: 337-45.

Simpson GM, Amin M, Kunz E, McCafferty FV. Studies on a second long-acting fluphenazine. Am J Psychiatry 1965; 121: 784 - 7.

Simpson GM, Angus JWS, Edwards  JG.  A controlled study of haloperidol in chronic schizophrenia. Current Therapeutic Research 1967; 407: 407-12. Simpson , GM, Iqbal  J. A preliminary study of thiothixene in chronic schizophrenics.   Current Therapeutic Research  1965; 7:  697-700. Simpson GM, Angus JWS. A preliminary study of oxypendyl in chronic schizophrenia. Curr Ther Res 1967a; 9: 225 - 8.

Simpson GM, Angus JWS. A preliminary study of prothipendyl in chronic schizophrenia. Curr Ther Res 1967b; 9: 265-8.

Simpson GM, Angus IWS. A rating scale for extrapyramidal side effects. Acta Psychiatrica Scandinavica 1970; 212 (Supplement): 11 -9.

Simpson GM, Angus IWS, Edwards JG. A controlled study of haloperidol in chronic schizophrenia. Current Therapeutic Research 197; 407: 407-12.

Simpson GM, Iqbal J.A preliminary study of thiothixene in chronic schizophrenics. Current Therapeutic Research 1965; 7: 697-700.

Simpson GM, Krakow L. A preliminary study of molindone (IN 1733A) in chronic schizophrenia. Curr Ther Res 1968; 19: 41-6. 

Simpson GM, Lee LH, Zuobock B, Gardos G. A rating scale for tardive dyskinesia. Psychoharamacologia 1978; 64: 171-9.

Simpson GM, Lindmayer JP. Extrapyramidal symptoms in patients treated with risperidone. J Clin Psychopharmacol 1997; 17: 194 – 201.

Simpson GM, Varga E. Clozapine – a new antipsychotic agent. Current Therapeutic Research 1974; 18: 679-81.

St. Laurent, Cahn C, Ban TA. Treatment of psychiatric patients with a phenothiazine derivative (prochlorperazine) with special reference to after care. Am J Psychiatry 1962; 118: 938 – 40.


November 29, 2018