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

Update (Volume Nine): 3b. Interviewee’s Contributions

(Bulletin 72)


          Of the remaining nine interviewees of Volume 9 (Update) Thomas A. Ban was among the first, in 1961, to report on the psychomimetic properties of phencyclidine. He also noted that dose and pre-existing psychopathology determined the response to the substance (Ban 1965; Ban, Lohrenz and Lehmann 1961). Ban contributed to the clinical characterization of several phenothiazine, butyrophenone, thioxanthene, diphenylbutylpiperidine antipsychotics and several tricyclic and other antidepressant drugs (Ban 1964, 1965b, 1974, 1977, 1978, 1981; Ban, Ferguson and Lehmann 1963; Ban and Lehmann 1962; Ban and Schwarz 1963; Ban, Papathomopoulos and Schwarz 1962;  Chouinard, Lehmann and Ban 1970a,b;  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). In his studies with psychotherapeutic dugs in the 1960s, Ban found no difference in therapeutic efficacy between  pharmacologically different tricyclic antidepressants (e.g., desipramine and trimipramine) in depression and between “incisive” and “sedative” neuroleptics (e.g., thioproperazine and levomepromazine) in schizophrenia (Ban 1965; Ban and Lehmann 1962; Ban, Papathomopoulos and Schwarz  1962; Ban and Schwarz 1963). Ban’s findings also indicated an inverse relationship between the therapeutic and adverse effects of psychotropic drugs, e.g., tardive dyskinesia with neuroleptics, toxic psychosis with lithium (Ban 1990). Reviewing all available psychotropic drugs from structure-activity relationships to clinical effects in his Psychopharmacology, in 1969 Ban concluded that the pharmacological heterogeneity within psychiatric diagnoses was an impediment for progress in neuropsychopharmacology research and pharmacotherapy of mental illness  (Ban 1969).  To translate pharmacological findings into clinical effects, in the 1960s Ban developed a conditioning test procedure (Ban, Lehmann and Saxena 1970; Ban and Levy 1961). He also developed, in the 1980s and 1990s, instruments for the identification of pharmacologically more homogenous diagnostic populations than provided by consensus-based classifications. Included among these instruments are the Diagnostic Criteria for Research Budapest-Nashville (DCR Budapest-Nashville) he developed in collaboration with Bertalan Petho; the Composite Diagnostic Evaluation of Depressive Disorders (CODE-DD); and the Composite Diagnostic Evaluation of Hyperthymic Disorders (CODE-HD),  developed in collaboration with Peter Gaszner (Ban 1989; Gaszner and Ban 1998; Petho and Ban 1988). In 2005 Ban embarked on the development of a methodology he referred to as “nosologic homotyping”  that can provide arguably the most homogeneous psychiatric populations that psychopathology and psychiatric nosology can offer for neuropsychopharmacology research (Ban 2007).  

          In 1962, Donald F. Klein discovered that imipramine reduced the frequency of panic attacks (Klein and Fink 1962). He followed up this lead and in 1964 delineated two distinct drug-responsive anxiety syndromes (Klein 1964). Klein was among the first, in the 1960s, to recognize the importance of psychiatric diagnosis in predicting drug effects (Klein 1967). In 1969 he published his text Diagnosis and Treatment of Psychiatric Disorders, co-authored with John Davis (Klein and Davis 1969). In the 1970s, with the employment of “pharmacological dissection,” Klein identified “endogenomorphic depression” (Klein 1974). By that time he had extended his research to children and introduced imipramine in the treatment of “separation anxiety” (Klein and Gittelman-Klein 1978; Klein, Gittelman-Klein, Quitkin and Rifkin 1980). In the 1980s Klein re-conceptualized anxiety and in the 1990s he formulated his hypothesis that “spontaneous panics” are “false suffocation alarms” (Klein1981, 1993). In 2010 Klein, with his research team, reported findings which were suggestive of the involvement of the endogenous opioid system in panic (Preter, Lee, Petkova et al. 2010).

          In 1962 George M. Simpson was among the first to report on the antidepressant effect of desipramine (Kline, Simpson and Brodie 1962). He was also among the first, in 1965, to report on withdrawal effects with phenothiazines (Simpson, Amin and Kunz 1965). During the 1960s Simpson was involved in clinical investigations with neuroleptics, including haloperidol, molindone and thiothixene  (Simpson 1970; Simpson, Angus and Edward 1967; Simpson and Iqbal 1965; Simpson and Krakow 1968). In 1970 Simpson  introduced, with Scott Angus, a rating scale for measuring the severity of extrapyramidal symptoms; developed a rating scale for measuring the severity of tardive dyskinesia; reported on differences in efficacy  between 150 mg and 300 mg  of imipramine in the treatment of hospitalized depressed patients; demonstrated the antipsychotic effect of clozapine; and became involved with Thomas Cooper in pharmacokinetic studies with psychotropic drugs (Simpson and Angus  1970; Simpson, Cooper, Bark et al.  1980;  Simpson, Lee, Cuculik and Kellner  1976; Simpson, Lee, Zoubok and  Gardos  1978;  Simpson and Varga 1974). Simpson has continued with his research: in the mid-1980s he published on the heterogeneity of the neuroleptic malignant syndrome and in the late -1990s on dose-response relationships with clozapine (Carroll, Miller, Ross and Simpson 1980; Jaffe and Simpson 1999; Levinson and Simpson 1986; Simpson, Josiassen, Stanilla et al. 1999).  Simpson led the team that reported in 2006 on the efficacy and tolerability of ziprasidone and olanzapine in acutely ill patients with schizophrenia and schizoaffective disorder (Simpson, Loebel, Warrington and Yang 2006).

          In 1963 Herman van Praag published findings supportive of a relationship between monoamine oxidase inhibition and antidepressant effects and in 1965 proposed a structured interview for diagnosing the “vital depressive syndrome” (Van Praag and Leijnse 1963a,b; Van Praag, Uleman and Spitz  1965). In 1970 Van Praag was among the first to report changes in in the concentration of 5-hydroxyindoleacetic acid levels in the cerebrospinal fluid in depressed patients with the employment of probenecid (Van Praag, Korf and Puite 1970). By the mid-1980s Van Praag became a proponent of “denosologization” of psychiatry (Van Praag 1997; Van Praag Kahn, Asnis  et al. 1987). Yet, he continued his research and in 2002 published findings, Stress, the Brain and Depression, a monograph co-authored with de Kloet and van Os (Van Praag, de Kloet and van Os 2002). 

          In 1965 Martin M. Katz was among the first in the United States to address the methodology of classifying psychiatric diseases (Katz, Cole and Barton 1965).   In 1969 he published findings on the influence of symptom perception, past experience and ethnic background on diagnostic decisions (Katz, Cole and Lowery 1969). By the end of the 1970s the focus of Katz’s research shifted to the psychobiology of depression (Katz, Secunda, Hirschfeld and Koslow 1979). In 1987 Katz’s team was first to challenge pharmacological findings that indicate a two- to three-week time-lag between initiation of treatment and antidepressant effects (Katz, Koslow, Maas et al. 1987). Subsequently, in 1994, they published findings on the relationship between drug-induced actions on neurotransmitter systems and changes in the behavior and emotions of depressed patients; in 2004 on the onset and early behavioral effects of pharmacologically different antidepressants; and in 2010 on “links” between neural and behavioral changes in the course of treatment of depression with antidepressants (Katz, Bowden and Frazer 2010; Katz, Maas, Frazer et al. 1994; Katz, Tekell, Bowden  et al. 2004).

          In 1969 Jerome Levine co-authored a paper with Arnold Ludwig, Louis Stark and Robert Lazar on negative findings with LSD-25 in the treatment of alcoholism; in 1971 he co-edited a book with Burtrum Schiele and Lorraine Bouthilet, Principles and Problems in Establishing the Efficacy of Psychotropic Drugs (Levine, Schiele and Bouthilet 1971; Ludwig, Levine and Stark 1970; Ludwig, Levine, Stark and Lazar 1969). In the mid-1980s Levine developed SAFETEE, in collaboration with Nina Schooler, for the systematic assessment of side effects in clinical trials with psychotropic drugs; in the 1990s he became involved in the utilization of neuroleptics; and in 2002 co-authored paper with A. Jaffe on an analysis of neuroleptic use from 1994 to 2000 in a state hospital system (Levine and Jaffe 2003; Levine and Schooler 1986).

          In 1969 Herbert Y. Meltzer reported on the state-dependent elevation of serum creatine phosphokinase and aldolase activity in acute psychoses and newly admitted schizophrenic patients (Bengzon, Hippius and Kanig 1966; Meltzer 1969; Meltzer, Elkim and Moline 1969; Schiavone and Kaldor 1966). In the 1980s Meltzer was member of the team that demonstrated the effectiveness of clozapine in some treatment-resistant patients with schizophrenia; in the 1990s a member of the team that showed improvement in cognitive functions with the substance in some similar patients (Hager, Buckley, Kenny et al. 1993; Kane, Honigfeld, Singer and  Meltzer 1985). In 1989 Meltzer was first to classify, in collaboration with Matsubara and Lee, typical and atypical neuroleptics on the basis of dopamine-D1, D2 and serotonin pk1 values (Meltzer, Matsubara and Lee 1988). Subsequently, he led the team of the “international suicide prevention trial” that reported reduced suicidality in clozapine-treated schizophrenic patients (Meltzer, Alps, Green et al. 2002). 

          In 1971 David S. Janowsky reported on monoamines and ovarian-hormone-linked sexual and emotional changes (Janowsky, Fann and Davis 1971). One year later, based on findings with physostigmine, he formulated a cholinergic-adrenergic hypothesis of mania and depression (Janowsky, El-Yousef, Davis and Sekerke 1972). In 1973 Janowsky demonstrated that methylphenidate provoked exacerbation of symptoms in some schizophrenic patients (Janowsky, El-Yousef, Davis and Sekerke 1973). Continuing with his research, in 2003 Janowsky published findings on the effects of antidepressants, methylphenidate and amphetamine on depression and dysphoria-induced changes on the interpersonal perception of moods and caring relationship; in 2007 he discussed the possible use of scopolamine as an antidepressant; and in 2008 reported that relapse after antipsychotic withdrawal predicts future relapses in institutionalized adults with severe intellectual disability (Janowsky  2003, 2007; Janowsky, Barnhill, Khalid and Davis  2008).

          In 1973 Rachel Gittelman-Klein discussed the diagnosis of “school phobia” in light of its responsiveness to imipramine (Gittelman-Klein and Klein 1973). In 1976 she led the team that reported on comparative effects of methylphenidate and thioridazine in hyperkinetic children (Gittelman-Klein, Klein, Katz et al. 1978). In 2008 Gittelman-Klein co-authored paper with Monnuzza and Moulton that reported on lifetime criminality among boys with attention deficit hyperactivity disorder (ADHD) (Monnuzza, Gittelman-Klein and Moulton 2008).  In 2010 she was a member of the team that reported carbon dioxide hypersensitivity in separation anxiety offspring of parents with panic disorder (Robertson-Nay, Klein, Gittelman-Klein et al.  2010).




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Ban TA. Psychopharmacology of Thiothixene. New York: Raven Press; 1978.

Ban TA. Psychopharmacology of Depression. Basel: Karger; 1981. 

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

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Gittelman-Klein R, Klein DF, Katz S, Saraf K, Pollack E. Comparative effects of methylphenidate and thioridazine in hyperkinetic children. Archives of General Psychiatry 1976; 33: 1217-31.

Hagger C, Buckley P, Kenny JT, Friedman L, Ubogy D, Meltzer HY. Improvement in cognitive functions and psychiatric symptoms in treatment refractory  schizophrenic patients  receiving clozapine. Biol Psychiatry 1993; 34: 702-12.

Jaffe ME, Simpson GM. Reduction of tardive dystonia with olanzapine. Am J Psychiatry 1999; 156: 2016-7.

Janowsky DS. Depression and dysphoria effects on the interpersonal perception of negative and positive moods and caring relationships: effects of antidepressants, amphetamine and methylphenidate. Curr Psychatr Rep 2003; 5: 451-9.

Janowsky DS. Scopolamine as an antidepressant agent: theoretical and treatment considerations. Curr Pschiat Rep 2007; 9: 47-8.

Janowsky DS, Barnhill LJ, Khalid AS, Davis JM. Antipsychotic withdrawal-induced psychosis predicts future relapses in institutionalized adults with severe intellectual disability. Journal of Intellectual Disability Research 2008; 28: 401-5.

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Kane J, Honigfeld G, Singer J, Meltzer HY. Clozapine Collaborative Study Group. Clozapine for the treatment resistant schizophrenia. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988; 45: 789-98.

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Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D1, D2 and serotonin pk 1 values. J Ep Ther 1988; 251: 238-48.

Monnuzza S, Gittelman-Klein R, Moulton JL. Lifetime criminality among boys with ADHD: A prospective follow-up study into adulthood using official arrest records. Psychiatry Research 2008; 160: 237-46.

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Preter M, Lee SH, Petkova E, Vannucci M, Kim S, Klein DF. Controlled cross-over study in normal subjects of naloxone preceding lactate infusions: respiratory and subjective responses; relationship to endogenous opioid system, suffocation false alarm theory and childhood parental loss. Psychol Med 2010; 6: 1-9.

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June 13, 2019