Psychopharmacology and Psychosomatic Illness J.

ANANTH,

Dorfman (1967) once remarked that pills solved no problems, however, psychotropic medication could often make the patient more accessible to the doctor's attempt to help solve these problems. Wittkower (1960) and Cleghorn (1966) have reiterated that a psycho-analytical view of psychosomatics is restrictive and progress can only be achieved by interdisciplinary integration. Pharmacotherapeutic endeavor in the treatment of psychosomatic disorder is significant. Such an endeavor is consistent with clinical realities as well as with the present state of knowledge. In fact, or in addition, pharmacotherapy can act as a catalyst for the mutual integration of somaticoclinical subjects and psychotherapeutics. PRINCIPLES

Psychiatry and Psychosomatics Since the therapy of psychoses represents the classical domain for the use of psychopharmacology, the relationship between endogenous psychoses and psychosomatics needs elucidation in order to employ psychopharmacological agents in the treatment of psychosomatic disorders. Spiegelberg (1955) reported his experiences of endogenous psychoses delicately dovetailed with psychosomatic syndromes. Scrutiny of many cases of psychosomatic disorders uncovers psychopathological phenomena similar to that of psychoses. It seems probable that the relationship is more intimate with cyclothymic disorders (Lopez-Ibor 1963). Many (Fonesca 1963, and Dorfman 1962) emphasize the role of endogenous depression in psychosomatic disorders including constipation, headache and upper abdominal pressure. Campbell (1950) and Kraines (1958) consider cyclothymia a genuine etiological factor of gastroenteric involvement. Endogenous vital anxiety, free floating or bound to an organic manifestation - represents clearly an indication for pharmacotherapy. The patient who presents only a somatic syndrome free from apparent psychopathological symptoms, poses a difficult clinical situation. In this instance, it is important to note that dramatic improvement has been reported by the use of psychopharmacological agents, imipramine and Assistant Professor, McGill University and Director of Psychiatric Education and Research, St. Mary's Hospital, 3830 Lacombe Ave., Montreal, P.Q. H3T IM5. Presented at The Regional Meeting of The International College of Psychosomatic Medicine at Plattsburgh, N.Y. on October 18·19, 1974. 124

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amitriptyline, in the treatment of bronchial asthma (Spiegelberg 1968). The theoretical justification of a psychopharmacological approach to the treatment of psychosomatic disorders centers around the important question of the occurrence of neurosis by physiogenesis. This does not exclude psychodynamics, the reality of which is not doubted. The most recent studies (Leigh 1966, Rees, 1966, Mirsky 1958) provide ample evidence for the postulation of systemic diseases with underlying psychosomatic conditions. Psychosomatic research in the widest sense is concerned with multiplicity of processes which cannot all be categorized as psychodynamic, biological and cerebral-neurosomatic. In addition, there are the somatopsychic disorders which are very frequent. Every illness entails a causal component of anxiety and every illness breeds anxiety. Fear of anxiety is potentially present in every illness as a cause, effect or complication. separately or in combination. Syndrome shift and pharmacotherapy: In 1957, Groen, Bastiaans and Van der Valk described the sequential alteration of two syndromes or pathological entities and in particular, the replacement of a psychopathological state by a psychosomatic syndrome. The relationship between syndrome shift and psychopharmacotherapy is twofold. On the one hand, after a syndrome shift, we often find ourselves confronted with pharmacotherapeutic decisions. On the other hand, pharmacotherapy represents a frequent cause of syndrome shifts. Syndrome shift is a further manifestation of the ability of the central nervous system to substitute one form of morbid compartment for another. This may occur under the influence of a change in the external life situation, of the central nervous system itself, or of the available output channels. (Groen, Bastiaans and Van der Valk 1964). Aside from the crossover from the psychic to the somatic field as it is involved, for instance, in the alteration of bronchial asthma and depression and the reverse, the alteration of depression and peptic ulcer, a shift from one somatic to another somatic disease (peptic ulcer to ulcerative colitis) can occur. Within the scope of the various syndrome shifts, psychopharmacological treatment is directly linked to the psychopathological entity. When peptic ulcer is embedded with depression, relevant pharmacotherapy is indicated. If involutional melancholia is shifted to bronchial asthma under pharmacotherapy, the treatment modalVolume XVI

PSYCHOPHARMACOLOGY-ANANTH ities include not only the appropriate measures of internal medicine but continued intensified pharmacotherapy. MODELS

Neurophysiological

The central nervous system (CNS) contains integrated mechanisms which on the one hand, regulate activity of various somatic and visceral effectors as well as hormonal secretions, and on the other control the reception and transmission of sensory impulses within the CNS itself. Since one of the resulting functions of the activity of cerebral integrating mechanisms is the control of emotional response, disorders resulting from dysfunction of the regulatory circuits can give rise to various psychophysiological disorders. Experimental evidence suggests that activation of the limbic system constitutes an indispensable initiating factor in the occurrence of psychosomatic diseases. The role of the cortex in psychosomatic illness has been illustrated by the effect of neurosurgical intervention in two psychotic patients who were also suffering from arterial hypertension. A marked reduction of blood pressure was induced in these patients by topectomy of the medial sections of Brodmans' areas 9 and 10. (HernandezPeon et al 1969). Changes in gastrointestinal motility and vesical tone have also been shown to occur in patients after lobotomy. A series of psychophysiological studies in patients suffering from arterial hypertension, gastroduodenal ulcer, ulcerative colitis and others have shown that they all present exaggerated reactions of the corresponding visceral effectors in either spontaneous or experimentally induced conflict situations. In addition, each of the groups affected by similar syndromes presented common personality traits. These patients may be said to respond in an exaggerated way to conditioning symbolic stimuli even when these stimuli are no longer reinforced. One may therefore infer that in these patients a deficiency is present of the central inhibitory mechanisms normally responsible for the extinction of conditioned visceral responses preventing exaggerated responses to intense conditioning stimuli. Psychopharmacological agents act on the neurophysiological substrates, interfere with conditioning and produce improvement in the psychosomatic pathology. Psychopathological

a. If anxiety is the cause of all mental illnesses and the various manifestations depend on the organ vulnerability and defenses, in all psychosomatic disorders the treatment of underlying anxiety may produce amelioration. b. If psychosomatic illnesses are due to repression of dysphoric feelings and drugs like diazepam produce aggressive feelings by disinhibition, this emergence of feelings can be utilized in treatment. The catharsis July / August/September, 1975

or removal of repression and dealing with anxiety by alternate means may produce improvement. THERAPEUTIC APPLICATION

General The choice between drugs with the same psychotropic activity may depend exclusively on their somatic effects. For instance, haloperidol and chlorpromazine are both neuroleptics, but with respect to autonomic side effects, the former induces little, the latter many side effects. In the management of spastic gastrointestinal diseases with a depressive reaction drugs like amitriptyline with high anticholinergic activity are preferable. Specific

a. Asthma Imipramine is reported to be useful in the treatment of asthma by many investigators (Cordova Castro 1962, Fels 1964, Goldfarb and Venutolu 1963, Kaplan, Kravitz and Ross 1961, Mathov 1963, Mathov et al 1962, Sanger 1962, Staehelin et al 1960). This drug has been given to asthmatic patients as adjuvant medication (Kaplan, Kravitz and Ross 1961) or combined with prednisone (Fels 1964). However, Beumer (1966) reported that, in 35 patients subjected to a histamine challenge test, the intramuscular administration of 25 mg. of imipramine afforded partial protection against the effects of histamine. A between patient, double-blind study (Robin and Langley 1964) in which 25 asthmatics received daily doses of 75 mg. imipramine for ten days, failed to reveal any difference in effect between imipramine and placebo. Therefore, imipramine needs further evaluation as an anti-asthmatic agent. Based on Alcock's (1960) results on projective tests that asthmatic children were depressed and the anecdotal evidence by Green (1965) showing the relationship between asthma and depression, eight asthmatics were treated with amitriptyline 50 mg. daily (Meares 1971). All improved. In a further sample of 12 patients, 11 improved. Amitriptyline was reported to be effective in the treatment of asthma in 37 out of 60 patients when the results were judged on clinical evaluation (Sugihara et al 1965). Ananth (1974) and Wilson (1974) reported similar results in individual cases. Double-blind studies to evaluate both the therapeutic and prophylactic potential of this drug may yield valid information. Hydroxyzine was found to be desirable in the treatment of asthma and allergic disorders (Eisenberg 1958; Kessler 1967). Shah, Talwalkar and Karkhanis (1970) treated 84 patients with three capsules of the drug daily for over one month. Analysis of the results showed that the preparation provided complete symptomatic relief in 58, partial relief in 25 and only one patient did not improve. A later study (Hevrich, Souza-Poza and Lyons 1972) 125

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revealed that hydroxyzine increased the airway conductance by 50 percent of the central values in asthmatic patients indicating its potential usefulness in asthma. Some others also have reported successful treatment of asthma with this agent (Britt 1966; Barlow and Barger 1967; Paul 1969). Kann and Jold ( 1968) observed that metaproterenal sulphate combined with oxazepam were superior to metaproterenal alone in treating asthmatics. Spiegelberg (1968) has noted that imipramine or promethazine or a combination of both to be useful in the treatment of asthmatic patients while chlorpromazine may sometimes be life saving in status asthmaticus (Baum et al 1957, Robinson and Zuck 1954). The asthmatic state is in essence an increased sensitivity of the bronchial system which has become excessively reactive both to broncho-constricting and dilating stimuli with edema of the bronchial mucosa and accumulation of mucus as additional factors in obstructing the airway. Therefore, psychopathology and pathophysiology are in fact twin determinants of the pharmacotherapeutic response (Pinkerton 1969). b. Gastrointestinal Disorders There are a number of psychosomatic gastrointestinal disorders, i.e., anorexia, obesity, gastric and duodenal ulcer, ulcerative colitis, diarrhea and constipation. Generally, psychotropic drugs are given for sedative and anxiolytic effects, autonomic stabilizing effect, antidepressant-mood elevating effect, and antidepressallt-psychostimulating effect. Various drugs that have been found to be useful include chlordiazepoxide, diazepam, oxazepam, meprobamate, chlorpromazine, levomepromazine, thioridazine, chlorprothixene, imipramine, amitriptyline and trimipramine. The specific indication for a certain psychotropic drug is thus determined not so much by the localization of the digestive disturbance than by its general character. Hence, it is not usually possible to ascribe a particular drug to a particular gastrointestinal disorder. Anorexia nervosa is a complicated disease manifesting psychopathological, endocrinological and somatic components. As depression is evident in many patients, it is logical to administer antidepressants (Kuhn 1969) . Because of its weight increasing property amitriptyline may be particularly useful (Paykel, Mueller and de la Vergne 1973). Similarly, imipramine has been employed with reported success (Aubert and Feigne 1964 and Chimenes 1964). Crisp (1965) treated anorexia nervosa patients with 400 to 600 mg. of chlorpromazine daily. Frahm (1965) treated 80 patients successfully with a combination of phenothiazines and tube feeding. The mean weight gain in seven weeks was 13.3 Kg (+ 4.4 Kg). Dally and Sargant ( 1960) first reported the use of chlorpromazine in this condition. They used it in conjunction with modified 126

insulin treatment and reported immediate good results in their group of cases in terms of weight gain. In 1962 Crisp and Roberts reported a case of anorexia nervosa treated successfully for the most part with chlorpromazine alone. The nature of the relationship between chlorpromazine and eating behavior is not clear. Over the past ten years, it has become a common observation that patients receiving large doses of chlorpromazine daily tend to put on weight (Winkelman 1964). c. Ulcerative Colitis Imipramine is recommended by some authors as adjuvant treatment for depressive moods in patients suffering from ulcerative colitis (Kirsner 1966). There are a few instances in which ulcerative colitis itself, even when present in an extremely severe form has shown a very good response to imipramine combined with methamphetamine (Spiegelberg 1966). The rationale for the use of imipramine (Spiegelberg 1968) is the fact that many patients with ulcerative colitis manifest endogenous depression. It is significant that lithium, an agent useful in affective disorders is reported to be beneficial in ulcerative colitis (Zibook 1972). Although it is not known how lithium can improve ulcerative colitis, it is important to note that diseases including ulcerative colitis, mucous colitis and irritable colon are reported to be associated with psychiatric illness. Liss et al (1973) reported that 23 of their 25 patients with mucous colitis or irritable colon were having concurrent psychiatric illnesses including an affective disorder. Therefore, it is likely that lithium may improve the primary psychiatric illness with the remission of secondary gastrointestinal symptoms. In addition, transmucosal potential difference across the rectal mucosa was found to be greater in lithium treated patients which may in fact help ulcerative colitis patients. (Rask-Madsen, Baastrup and Schwartz 1972). On the other hand, Varsamis and Wand (1972) reported exacerbation of diarrhea in a patient with regional ileitis and affective disorder while on lithium treatment. Therefore, the usefulness of lithium in ulcerative colitis is at best speculative and needs exploration. d. A llergic Disorders Sanger (1970) treated various allergic disorders with tranquilizers and achieved excellent results. Similarly response to antidepressants was also reported satisfactory. In his series doxepin was superior to placebo. In conclusion psychopharmacological substances have varied use in psychosomatic medicine. The use of psychopharmacological substances may not only alleviate the suffering of the patient, but also bridge the gap between psyche and soma, internist and psychiatrist and between basic scientist and clinician. A careful evaluation of the patient and knowledge of the somatic Volume XVI

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effects of the drugs will assist in the precise application of the proper medication to the patient rather than the disease per se. St. Mary's Hospital, 3830 Lacombe Ave., Montreal, P.Q. H3T IM5, Canada REFERENCES

Alcock, T.: Some personality characteristics of asthmatic children: Brit. Med. J.: 33; 133; 1960. Ananth, J.: Antiasthmatic effect of amitriptyline. Callad. Med. Assoc. J. 110: 1131, 1974. Aubert, P. and Peigne, F.: Deux observations d'anorexie mentale masculine. Rev. Neuropsychiat. Illfant. 12; 515521; 1964. Barlow, P.B. and Barger, J.H.: MEFP and FEV. Marase. Mich. Med. 66: 1259-1262, 1967. Baum, G.L., Schotz, S.A., Gumpel. R.C. and Osgood, C.: The role of chlorimipramine in the treatment of bronchial asthma and chronic pulmonary emphysema. 32; 574-579, 1957. Beumer, H.H.: untersuchurgin uberden Antihistamin-Effekt von imipramin beim. Kenschen-Arzneimittel-Forsch: 10; 1352-1353, 1966. Britt, L.S.: The response of acute asthmatics to a single drug. J. Tell II. Med. Assoc. 59; 459-461, 1966. Campbe 11, J.D.: Mild manic-depressive psychosis, depressive type: Psychiatric and clinical significance. I.N.M.D. 112; 206, 1950. Chimenes, H.: Interet de I'imipramine dans Ie traitement des obesites. Presse MM. 72; 1131-1132, 1964. Cleghorn, R.A.: The place of theory, observation and scientific method in psychosomatic medicine: Paper presented at the Fourth World Congress of Psychiatry, Madrid 1966; Cit. Excerpta. Med. Congress Series: 117; 30, 1966. Cordova Castro, A.: Aspecton psyquiatricos delasma bronquial. Rev. Cuba Med. I; 33-38, 1962. Crisp. A.H.: A treatment regime for anorexia nervosa: Brit. J. Psychiat. 112; 505-512, 1965. Crisp, A.H. and Roberts, F.J.: A case of anorexia nervosa in a male: Post Grad. Med. J.: 38; 350-353, 1962. Dal1y, P. and Sargant, W.: A new treatment for anorexia nervosa. Brit. Med. J. 1; 1770-1773, 1960. Dorfman. W.: Depression and psychosomatic illness: Sth. Western. Med. (Texas) 43, 195, 1962. Dorfman, W.: Closing the gap between medicine and psychiatry in: Psychosomatic Medicine; Eds. E. Dunlop and M.N. Weisman. Excerpta Medica, International Congress Series, No. 134. Dordrecht 1967. First Congress of the Academy of Psychosomatic Medicine. Eisenberg, B.C.: Relief of alIergic symptoms with tranquilizers in combination with other drugs. Clill. Med. 5; 897, 1958. Fels, H.: Theoretische and praktische Gesichts-punkte zu einer kombinierten Behandlung des asthma bronchide 50 Congres. Int. AJergol. Madrid, 1964, p. 155 (Paz. Montalvo 1964 ). Fonseca, A.F. Da: Affective equivalents: Brit. J. Psychiat. 109; 464-469, 1963. Frahm, K.H.: Ergebnisse systematischer intermistischer und endocrinologischer intersuchungen von Kranken mit anorexia nervosa sawie beschreibung einer neuartigen behandlungs methode. Habilarbeit zur erlangung der Venia Legendi an der Universitat Hamburg, 1965. Goldfarb, A.A. and Venutolu, F.: The use of an antidepressant drug in chronically allergic individuals. Ann. Allergy. 21; 667·676, 1963. July / August/September, 1975

Green, R: Asthma and manic depressive psychosis---simultaneously incompatible or coexistent: J. Nerv. Ment. Dis.: 140; 64; 1965. Groen, J.J., Bastiaan, I. and Valk, J.M. Van des: psychosomatic aspects of syndrome shift and syndrome suppression In: Psychosomatics, pp.35-59, Ed. I. Booij (Elsevier Amsterdam 1957). Groen, 1.1., Bastiaan, I. and Valk, J.M. Van der: Syndrome shift. Arch. Intern. Med.: 114: 113-117, 1964. Hernandez-Peon, R, Goldberg, L., Rojas-Ramirez, J.A.: Physiology and psychosomatic medicine: neurophysiological models of emotional behavior and of action of psychotropic drugs. In Psychotropic Drugs in Internal Medicine Eds. A. Pletscher-A. Marino: Excerpta Medica Foundation: International Congress Series No. 180, Amsterdam 1969: p. 16-47. Heurich, A., M. Souza-Poza and Lyons: Bronchodilator effects of Hydroxyzine Hydrochloride. Respiratioll. 29; 135-138, 1972. Kaunn, J. and Jokl, H.: Treatment of asthmatic dyspnea. Med. Klin. 63; 1814-18, 1968. Kaplan. M., Kravetz, R.S. and Ross, W.D.: The effects of imipramine on the depressive components of medical disorders. Proc. 3rd World Congr. Psychiat., Montreal 1961, Vol. 2, pp. 1362-1367 (McGill, Toronto 1961). Kessler, F.: Hydroxyzine HCL in the management of alIergic conditions. Clin. Med. 74; 37-45, 1967. Kraines, S.H.: Seasonal cycles and depressions: Amer. J. Gastroent.: 29; 412·417, 1958. Krisner, I.B.: Drug Therapy in ulcerative colitis. Mod. Med. (Minneap) 34; 115, 1966. Kuhn, R: Psychopathology, pharmacotherapy and psychotherapy of anorexia nervos: In psychotropic drugs in Internal Medicine: Eds. A. Pletscher - A. Marino: Excerpta Medica Foundation: International Congress Series No. 180 Amsterdam 1969: p. 74-80. Leigh, D.: Genetic aspects of asthma and al1ergy: paper presented at the Fourth World Congress of Psychiatry, Madrid 1966: Cit. Excerpta Med. Congress Series, 117; 30; 1966. Liss, I.L., Alpers, D., Woodruff, R.A.: The irritable colon syndrome and psychiatric illness. Dis. Nerl'. Svst. 34; 151157, (April·May) 1973. . Lopez-Ibor, I.J.: Psychosomatische Fo~schung. In: Psychiatrie des Gegenwart, Vol. ~, p. 79 (Springer, Berlin) Guttingin/ Heidelberg, 1963. Malhov, E.: The risks of monoamine oxidase inhibitors in the treatment of bronchial asthma. J. Allergy. 34; 483-488, 1963. Malhov, E., Diaz, A., Greiding, L. and Mazzolli, RE.: Accion de un derivado iminodibencitico en pacientes con asma grave irreductible. Dia. Med. 34; 1766; 1962. Meares, R.A., Mills, J.E., Horvak, T.B., Atkinson, J.M., Dun, L.Q. and Rand, M.J.: Amitriptyline and asthma: The Med. J. Australia.: 2; 25-28, 1971. Mirsky, I.A.: Physiologic, psychologic and social determinants in the etiology of duodenal ulcer. Amer. J. Dcg. Dis: 3; 285, 1958. Paul, K.: Clinicial experiences with a new bronchodilator agent (Marax). Wien. Med. Wschr. 119: 252-253, 1969. Paykel, E.S., Mueller, P.S. and de la Vergne, P.M.: Amitripty· line, weight gain and carbohydrate craving. Brit. J. Psychiat. 123; 501-509. 1973. Pinkerton, P.: Patho-physiology and psychopathology as code· terminants of pharmacotherapeutic response in childhood asthma In psychotropic drugs in Internal Medicine. Ed. 127

PSYCHOSOMATICS A. Pletscher and A. Moreno. Amsterdam 1969. Excerpta Medica Foundation pp. 115-119. Rask-Madsen, I., Baastrup, P.C. and Schwartz, P.: Lithium induced hyperpolarization of the human rectums in vitro. Brit. Med. I. 2: 496-498, 1972. Rees, L.: Trends and issues in psychosomatic medicine: paper presented at the Fourth World Congress of Psychiatry, Madrid 1966; Cit. Excerpta. Med., Congress Series: 117; 30, 1966. Robin, A.A. and Langley, G.E.: A controlled trial of imipramine: Brit. I. Psychiat.: 110; 419-422, 1964. Robinson, K.C. and Zuck, D.: Chlorpromazine in status asthmaticus. Lancet 1; 1349, 1954. Sanger, M.D.: The use of tranquilizers and antidepressants in allergy: Ann. Allergy 20; 705-709, 1962. Sanger, M.D.: Psychosomatic allergy. Psychosomatics, 11; 473476, 1970. Shah, I.R., Talivalkar, C.V. and Karkanis, V.: Observations on the study of an antiasthmatic preparation containing hydroxyzine. Indian I. Chest. Dis. 12; 116-120, 1970. Speigelberg, I.: Uber Beziehungen endoginer psychosen zu ko zperlichen krankheikn. Forbachz. Nellrol.: 23; 221, 1955. Spiegelberg, U.: Kombinierte Behandlung psychosomatischer krankheitszustande. probleme der pharmacopsychiatrichen

kombinations und langzeit behandlung. Rothenburger Gesproch. 1965. pp: 198-207 (Karger Basel 1966). Spiegelberg, U.: Pharmacotherapy and psychosomatics. Int. Pharmacopsychiat. 1: 87-111, 1968. Staehelin, B., Kaege, P., Schuppli, M. and Vogelranger, G.: Behandlung sergebnisse mit dem iminodibenzylderivat Tofranil bei 136. Fiillen von Rhinih's Vasomotoria, Rhinich's pollinosa aud asthma bronchiale. Pyact. Oto-RhinoLaryng. (Basel) 22; 289-307, 1960. Sugihara, H., Ishiara, K. and Noguchi, H.: Clinical experience with amitriptyline (Tryptanol) in the treatment of bronchial asthma: Ann. Allergy: 23; 432, 1965. Varsamis, I. and Wand, R.R.: Severe diarrhea associated with lithium carbonate therapy in regional ileitis. Lancet. 2; 1322, 1972. Wilson, R.C.D.: Antiasthmatic effect of amitriptyline. Canad. Med. Assoc. I. 111; 212, 1974. Winkelman, H.W.: A clinical and socio-cuItural study of 200 psychiatric patients started on chlorpromazine ten and a half years ago: Amer. I. Psychiat. 120; 861-869, 1964. Wittkower, E.D.: Twenty years of North American psychosomatic medicine. Psychosom. Med. 22; 308, 1960. Zibook, S.: Ulcerative colitis: case responding to treatment with lithium carbonate. I.A.M.A. 219; 755, 1972.

Regional Meeting of the Academy A regional meeting of the Academy is scheduled for October 4, 1975 at the University of Arkansas Medical Center in Little Rock, Ark. The theme is "Recent Developments in Psychosomatic Medicine." Speakers will include Dr. Michael I. Daly, Chairman of the Department of Obstetrics and Gynecology, Temple University; Dr. Fred B. Charaton, Chief of Psychiatry, Jewish Institute of Geriatric Care, Long Island, N.Y.; Dr. Fred P. Kolouch, Assistant Professor of Surgery and Psychiatry, University of Utah, Salt Lake City, Utah; and Roger W. Libby, Ph.D., Professor and Acting Research Director, Institute for Family Research and Education, Syracuse, N.Y. For further information contact Fred O. Henker, m, M.D. Department of Psychiatry University of Arkansas Little Rock, Ark.

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Psychopharmacology and psychosomatic illness.

Psychopharmacology and Psychosomatic Illness J. ANANTH, Dorfman (1967) once remarked that pills solved no problems, however, psychotropic medication...
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