I have used the works "unidentified complaints" since 1962 for vague physical complaints which can not be accounted for any organic illness. It had been called "bariberoid" or "vegetative syndrome".The complaints, however, are not always associated with autonomic imbalance. This is one of the reasons why I have called them "unidentified clinical syndrome" since 1965.We have classified this syndrome into (1) neurotic, (2) vegetative disorder, (3) psychosomatic types, according to the presence or absence of autonomic imbalance or psychic disturbance.Fundamentally we think it rational to classify the syndrome in these three types, for the purpose of making a clinically effective approach to the patients.Psychosomatic diseases are of wide variety. The vegetative syndrome is not to be considered entirely equal to them. We can say that the view-point of psychosomatic medicine is important for the observation of the syndrome. Psychosomatic type of the unidentified clinical syndrome may be take as one of psychosomatic diseases.

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Prediction of the clinical effects of drugs from pharmacological findings in laboratory animals and normal human beings is a matter of importance, yet this task is especially difficult in the cases of the psychotropic drug. In the present paper, effects of some benzodiazepine derivatives on the averaged photopalpebral reflex (PPR) in man was reported. A 0.5 mg of ID-540,a new benzodiazepine derivative, prolonged latencies of PPR with a statistical significance as compared to the placebo which was administered orally to 6 healthy, male university students under a double-blind, cross-over design. The maximal prolongation of the latencies was obtained 3 hrs. after dosing. The serum concentration of ID-540 reached a peak level 2-3 hrs. after administration, while its principal metabolite, N-desmethyl-ID-540 exhibited a slow, gradual rise in serum. The latencies of PPR were positively correlated to the serum level of ID-540 but not to the N-demethylated metabolite. Two doses of prazepam, 10 mg and 20 mg, diazepam 5 mg and placebo were orally administered to 8 healthy, male university students under a double-blind, cross-over desing. Prazepam prolonged the P_1 latency depending on the doses, though the degree of prolongation of the latency after administration of prazepam 20 mg was less than that after diazepam 5 mg. The two doses of prazepma, dose-dependently, and diazepam 5 mg prolonged the P_2 latency ; however, prolongation of the latency by prazepma 20 mg was more marked than that by diazepam 5 mg. Comparison of these results with the data obtained from animal studies suggested that a myogenic factor might be more involved in P_1 latency and the level of consciousness in P_2 latency as previously described by us. From these results, the PPR test is considered to be a useful method for predicting clinical effects of anxiolytic drugs with several advantages; it may offer a physiological index for the effects of these drugs and it permits quantification of the responses and, accordingly, determination of equipotent doses of different drugs.

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Benzodiazepine derivatives and tricyclic antidepressant drugs are generally used for the treatment of psychosomatic disorders. These psychotropic drugs have several pharmacokinetic characteristics, which are as follows;(1) There is a large interindividual variation in dose/blood level ratios, especially when treatment is short term.(2) Most of them are transformed to active metabolites in the body and some of these metabolites have longer elimination half-lives than their parent componuds.(3) There is a possiblity that one drug may interact pharmacologically and pharmacokinetically with other drugs in the body.(4) Age influences the pharmacokinetics of these drugs. The elimination half-lives are prolonged in the elderly.Therefore, it would be better that dosage of these drugs be individualized according to each patient's pharmacokinetic characteristics, in the future, in order to improve the efficacy and safety of these drugs.

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The clinical evaluation of medical treatments has been done on the basis of clinical trials with experimental designs or exploratory observations gathered. Generally spearking, such clinical evaluations are not so easy because of the complicated situations due to large variety and variation of observations, definition of the population and jointly the ethical point of view.The present paper presents some of the recent works developed by the author and his research colleagues.The first topic is related to the experimental trials, and is to propose a new the extended sequential selection plans based on generalized Play-the-Winner sampling. The plans proposed in a sence of the ethical situation are designed to give minimization of maximum expected loss during and after the medical trials for a finite populatino of patients. The most advantage of the procedure is to be much superior to the ordinal Vector-at-a-Time samling procedure on some major properties of selection plans, namelym, on probablilities of correct selection and wrong selection, expected number of subjects to select one and minimization of maximum expected loss mentioned above.The second is related to a new statistical program package, NISAN system, which is n__-ew i__-nteractive s__-tatistical <an>___-alysis program package constructed by an organization of Japanese statisticians, where author is representative. The package is widely available for both statistical situations, confirmatory analysis and exploratory analysis, and is planned to obtain statistical wisdom and to choose optimal process of statistical analysis for senior statisticians. In view of statistical methodology, the most emphasized functions are as follows; 1) data investigations, 2) graphic representations, 3) generalized methods of optimal scaling, 4) various methods of cluster analysis and multidimensional scaling, and 5) studies on successive processes of statistical inference.

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The author's general discussion was concerned with the drug therapy for psychosomatic disorders, indlucing its meaning, present status and problems involved. He then introduced practical aspects of drug therapy for psychosomatic gastrointestinal disorders which were seen frequently in the practice of internal medicine.It is essential in the treatment of psychosomatic disorders to apply every means in order toe alleviate the patient's pains as quickly as possible. For this purpose, a proper combination of drug therapy with other means of treatment is very important. Each drug must be administered effectively on the basis of accurate evaluation of the patient's conditions. It is the opinion of the author that the use of psychotropic drugs without due consideration should be restrained.

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1) In the treatment of the psychosomatic disorders, proper use of psychotropic drugs is often effective. At the same time, it is essential to make proper combinations of psychotropic drugs with medical treatment and psychotherapy.2) Depressive state which sometimes manifests itself as the complication of psychosomatic disorders and somatic diseases, makes the original diseases intricate and intractable. Antidepressants are effective for these cases and also in controlling intractable pains.3) Anxiolytic drugs of benzodiazepine derivatives bring about marked inprovement in anxiety, tension, irritability, insomania and various vegetative symptoms in the clinical setting. These drugs are useful in the therapy of irritable colon syndrome. Experimentally, diazepam showed an inhibitory effect in volume of gastric secretion and a prophylactic effect of stress ulcer formation in rats.4) Placebo reactors were found in about 30% of the patients with irritable colon syndrome in drug therapy.5) Non-specific factors such as the patient's personality, the doctor's attitude and doctorpatient relationsip, play an important role in drug therapy, together with its specific pharmacological effects.6) In the management of bronchial asthmatic patients with steroid dependence, psychosomatic approaches need to be considered.

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This paper deals with the results of a study undetaken to obtain information on the dropount cases from the clinical double blind comparative methods performed with six kinds of psychotropic drugs in patients with a psychosomatic disease treated in the field of internal medicine.Of 404 patients, 50 or 12.4% were considered dropouts, females accounting for 14.0% and meles for 9.9%.The causes were not clear in more than half of the dropout cases. The causes of dropouts included, side effects of drugs, no change, aggravation or improvement of symptoms, transfer and refusal of taking medicine.According to the degree of illness, the reasons for dropping out were not clear in the majority of severe cases, clear in about a half of the moderate cases, and clear in all the mild cases.With regard to diagnoses, the dropout rate was 17.5% for neurosis, 11.3% for depression, and 10.0% for psychosomatic disease.According to the results of psychological tests, the dropunt rate was relatively high in the Type IV cases of CMI evaluated by the Abe method, in the cases of MAS showing a high score but lacking in reliability or reasonableness, and in the YG personality test showing B or E types.On the other hand, an investigation was carried out to determine the effect of a beta-blocker, other than the psychotropic agents, on psychosomatic diseases such as cardiac neurosis, various types of tremor, and labile hypertension from the standpoint of anxiety and tension. Judging from the favorable responses which a beta-blocker elicited in such psychosomatic diseases, it seems that this drug finds its increasing usefulness in clinical application.

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Various hormonal drugs, autonomic regulators and anxiolytic drugs were administered to 939 patients with climacteric disturbances, vegetative neurosis and menstrual difficulty all having unidentified complaints, and the efficacy of these drugs were compared between those having psychological factors and those having no psychological factors. As the result, they were found less effective in those patients having psychological factors which were related to the onset of illness.The patients with the same diagnosis were classified according to the theory of Alvan R. Feinstein who was introduced by T.Doi to Japan. That is, our 255 female patients with unidentified complaints were grouped into the following four clinical stages : 1) those having only psychological symptoms, 2) those having only physical symptoms, 3) those having both psychological and physical symptoms and 4) those having no symptoms despite suspected illness.Furthermore, these patients were classfied according to their motivatino for treatment into the following four types : 1) those wishing to knwo of their illness, 2) those having fear of discovering their illness, 3) those rejecting to know of their illness and 4) those who did not fall into the above three categories.Combinatinos of these 2 classifications resulted in 15 detailed clinical stages, and each patient was located on the most suitable spot on the spectrum. It was found that the efficacy of hormonal drugs, anxiolytic drugs and anti-depressants administered was different on different stages. It was also confirmed that on which stages the patients with vegetative neurosis, psychosomatic disorders and depression were tended to be located. It is our opinion that this approach is very practical in the drug therapy for psychosomatic disorders as it provides us with the standard of selection for most suitable drugs.

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Allmost all patients with chronic pains except for those repeating the relapse of pain are psychosomatic. As the psychosomatic treatment is not widely practiced, these patients often become trouble-makers in the clinical setting. At first, the kind of chronic pains has to be classified by using medicine which is suitable for relieving the pain. For example carbamazepine can be used in case of trigeminal neuralgia. A nerve block is often applied to it as well as medicine. An anodyne should not be used for more than three weeks because no effect is expected any longer.The placebo has to be applied with skillful methods for a psychosomatic pain and any side effect should be avoided. Continuous medication will result in a damage of stomach, liver or kidney and giving up of the therapy for psychosomatic pain, although, today, careless medication is being practiced on the long term basis.Of course, the treatment by minor-tranquilizers has to be attended and it is better for the psysician to get consultation with a specialist in psychosomatic medicine.

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1. The wide uses of tricyclic antidepressants in patients with anxiety and depression in the field of psychiatry were discussed.2. The degrees of correlation were studied between the blood levels of amitriptyline and antidepressive effects, and between the blood levels and incidences of side effects.i) The effective group (excellent and good) had an amitriptyline blood level of 19.4±4.0 ng/ml, and the ineffective group (fair and unchanged) 47.0±6.3 ng/ml. And there was statistically significant difference between the two groups.ii) The correlations between the blood levels of amitriptyline and the efficacy, namely, the percentage changes in Hamilton's scores showed the lower bood levels in the patients with higher effectiveness (P<0.05).iii) These was no statistically significant difference in the incidence of side effects between the low level group and the high level group of amitriptyline blood concentration.

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