Psychopharmacology and psychiatry

Abstract

Psychopharmacology is an interdisciplinary science in which many techniques and branches of knowledge are brought together. In seeking to modify human behaviour by the use of chemical substances, it lies at the crossroads of the biological sciences and the humanities, because every psychopharmacological problem concerns the relationship between the body and the mind. Psychiatry should try to find a co-relation by experimental methods between the physiological and the mental phenomena which are involved, in order that practical applications of this relationship might be made. Mental pathology is one of the fields of application, and the author in his capacity as a clinical worker offers some ideas on the psychopharmacological perspectives in psychiatry.

Details

Author: Jean DELAY
Pages: 1 to 6
Creation Date: 1967/01/01

Psychopharmacology and psychiatry *

Towards a classification of psychotropic drugs

Professor Jean DELAY Membre de l'Académie française

Psychopharmacology is an interdisciplinary science in which many techniques and branches of knowledge are brought together. In seeking to modify human behaviour by the use of chemical substances, it lies at the crossroads of the biological sciences and the humanities, because every psychopharmacological problem concerns the relationship between the body and the mind. Psychiatry should try to find a co-relation by experimental methods between the physiological and the mental phenomena which are involved, in order that practical applications of this relationship might be made. Mental pathology is one of the fields of application, and the author in his capacity as a clinical worker offers some ideas on the psychopharmacological perspectives in psychiatry.

In its early state psychopharmacology was based on purely empirical knowledge but it is now becoming a scientific discipline which uses experimental methods. Though it is young as a science, psychopharmacology is also an ancient art. It has been one of the oldest preoccupations of mankind to heal the troubles of the spirit by herbs and philtres, and the history of medicinal plants tells us that psychopharmacology was known and practised in ancient times. It is fascinating to sift legend from reality in the psychological powers attributed to plants like mandragora, cannabis, passion flower, bella donna, rauwolfia serpentina and the coca bush. Magic and chemistry both played a part in the powers attributed to these plants, and, in certain cases where they might have been confused, it would be necessary to distinguish a simple placebo effect from the truly pharmacodynamic action.

Homer speaks in the Odyssey of "pharmakon" which he also calls "nepenthes". The latter word means "absence of sorrow ", and nepenthes had the marvellous power of quieting grief and turning it into a kind of emotional neutrality. In the fourth book of the Odyssey, Telemachus recites the story of the siege of Troy to other Greeks seated sround him and all of them are greatly moved in hearing him evoke the misfortunes of Hellas. At this point, Helen, daughter of Zeus, drops a balm called nepenthes into their wine cups, and this gives them forgetfulness from sorrow. "He who had drunk of this potion would not shed tears for a whole day even if his mother and his father were to die, and even if his most beloved son were slaughtered before his eyes. And the daughter of Zeus possessed this excellent liquor which had been given to her by Polydamna, a woman of Thebes born in Egypt, that fertile land which produces many balms, some full of goodness, others deadly. The doctors of Egypt are indeed skilful."

Excerpts from Professor Delay's presidential address to the International Congress or Neuro-psychopharmacology, Washington, 1966, which was published in full in La Presse médicale, 74 (22):1151-1156:

What was "nepenthes"? In all probability it was opium, the ancestor of all our tranquillizers of today. The ataraxic effects of the opiates are of course very different from those produced by the neuroleptic substances, the latter especially being more easily adaptable to therapeutic use. In so far as the ataraxic effect is concerned, both groups of substances raise the same psychopharmacological problem which is the possibility of reducing emotion by means of medicaments.

Another example of this, and one which is no less instructive, is that of the medicinal plants with psychotropic qualities used in ancient Mexico. Among the Aztecs, as in most archaic civilisations, the priest would preside over religious rites but he was at the same time the healer and medicine-man. In the ancient ceremonies he partook of certain plants which were considered magical and which put him in communication with the gods and their supernatural world. For a long time the states of trance and the miraculous cures obtained from collective ecstasies such as those of the Aztecs were considered by psychiatrists as arising out of a state of hysteria. Today we have to concede at least part of the credit for these results to psychopharmacology. Among the plants used in these ceremonies were peyotl, teonanacatl and ololiuqui. The first-named of these contains mescaline, teonanacatlhas psilocybin and psilocin, while ololiuqui contains derivatives of lysergic acid diethylamide LSD: in other words, all contain hallucinogenic drugs. The worship of the mushroom Psilocybe mexicana in Mexico for one thousand years, of which stone statues reproducing its phallic shape still stand testimony, can now be explained as recognition of the psychotropic principle that this mushroom contained. The conditions that are now studied under the name of artificial psychoses were therefore known to our ancestors of long ago. The ceremonies with which they accompanied the collective absorption of hallucinogenic substances proved that after their fashion they had understood the part that environment and milieu play in the reactions brought about by psychotropic substances.

Since several years and particularly since 1952 when a phenothiazine, specifically chlorpromazine, was applied in psychiatry, there has been a great increase both in number and in diversity of the psychotropic drugs that can be used in therapy. Indeed, the practitioner finds himself a bit confused before this plethora of agents, and he would like to have a readily applicable key to the identity and properties of these drugs which would help him in his practice. The following paragraphs make an elementary and purely clinical systematization of these psychotropic drugs in order to meet this need.

The general term psychotropic is used for a whole group of chemical substances - whether natural or artificial - which bring about psychological changes, or which modify mental activity, whatever be the nature of the changes or modifications. Psychiatrists now dispose of a great variety of such drugs with which they can deliberately modify behaviour in one sense or another, e.g. towards relaxation, towards stimulation, towards a state of dreaming or of delirium. Depending on whether it gives rise to depression or stimulation, or to a state which is deviate from either of these, a drug might be placed in one of three groups. In each group an identification can usefully be made of the principal action that a drug is likely to have on mood, on alertness, on the emotional or the intellectual state, or the visceral condition as opposed to the mental.

In the psycholeptic group of drugs fall all those substances which depress mental activity, whether this fall in the psychological note is due to reduced alertness, reduced intellectual energy or to a sedation of emotional tension. This vast group of drugs then subdivides itself into sub-groups of which the two main are those which depress alertness (called the nooleptic) and those which depress mood ( thymoleptic). The alertness depressers, that is to say those which reduce the function of vigilance, which controls the oscillations between waking and sleeping, are comprised of all the hypnotics, barbiturates or not barbiturates. The drugs which depress mood, in other words the thymic action which controls the play of the emotions between the poles of sympathy and reactivity to the world on one hand, and indifference and apathy on the other, are comprised of the tranquillizers which substitute a state of reactivity by a state of indifference. The tranquillizers are sometimes called ataraxic because ataraxy is by definition the absence of emotional trouble, the state of being imperturbable, but it appears exaggerated to speak of a true ataraxy in connexion with most tranquillizers. It should also be noted that the contradistinction between hypnotics and tranquillizers is altogether relative because in small doses the barbiturates are tranquillizers and in large doses the tranquillizers induce sleep.

A classification of psychotropic drugs

 
1) hypnotics (or nooleptics)
Exampleschloral hydrate barbiturates
A. Psycholeptics (or psychic sedatives)
2) neuroleptics (or thymoleptics)
Pheno-thiazines-reserpine-butyro-phenones
 
3) tranquillizers
Meprobamate azacyclonol
 
1) stimulants of vigilance (or nooanaleptics)
psychotonic amines
B. Psychoanaleptics (or psychic stimulants)
2) stimulants of mood (or thymoanaleptics)
isoniazid iproniazid imipramine
 
3) other stimulants
vitamin C, etc.
C. Psychodysleptics (or psychic deviators)
Hallucinogens - drugs producing the effect of depersonalization
Mescalinelysergamidepsilocybin

There is a major group of tranquillizers which deserve to be identified, and which have a particular interest because of their remarkable effect in the chemotherapeutic treatment of the psychoses : this group is that of the neuroleptics which comprises in particular the phenothiazines, reserpine and the butyrophenones. The neuroleptics are so named because of the psychological or rather psycholeptic effects to which they give rise, this being accompanied by a neurological syndrome of motor and psycho-motor type.

In the psycho-analeptic group enter all those substances which stimulate mental activity, without considering for the moment whether this rise in psychological key is due to an increase of alertness which might go as far as insomnia, or an increase of intellectual energy or a raising of the emotional tone which in their turn might go as far as euphoria or even anxiety. This large group is also sub-divided into two main subgroups, viz. the stimulants of alertness ( noo-analeptic) and the stimulants of mood ( thymo-analeptic). The stimulants of alertness are comprised of all the psychotonic amines which simultaneously facilitate intellectual effort and makes it difficult to sleep. The action of these phenamines, the drugs of waking, is opposite to that of the barbiturates, drugs of sleep. The stimulators of mood comprise all those substances which can raise the emotional tone. Some of them have an anti-depressive action which makes them ideal chemico-therapeutic agents for states of depression in which their effects may go as far as to produce a complete inversion of mood such as euphoria and expansiveness. This is for example the case of the hydrazines and imipramine, which offer such a strong anti-depressive chemiotherapy that because of their use it has been possible to reduce electro-shock treatment. It must be admitted that this distinction between the stimulants of alertness and the stimulants of mood is a purely schematic one. Thus the psychotonic effects of the amphetamines are accompanied by a certain euphoria, and the anti-depressive effect of iproniazide or of imipramine can go along with a degree of insomnia.

Among anti-depressive drugs, it would be clinically useful to put in a special column those drugs which inhibit the action of monoamine-oxydase, not because a correlation has been found between the inhibition of monoamine-oxydase and the antidepressive action, but because, from the practical point of view, the clinical worker should be able to distinguish between these drugs and the other anti-depressives with which they may be dissimilar in some ways.

In the psycho-dysleptic group fall all those substances which disturb the activity of the mind, and cause delirium so that the judgment of reality becomes distorted. These drugs create illusions and hallucinations, they confuse and de-personalise, and the subject is put into a state of dreaming or he perceives all phenomena as if they were a dream. Mescaline (the alkaloid of peyotl), lysergic acid or LSD 25, psilocybin, ditran (ethotrimeprazine) are such psycho-dysleptic substances. From the pharmacological point of view it is possible to distinguish among hallucinogens those which are indolic like LSD or psilocybin, and those which are anticholinergic like ditran. Nevertheless it must not be thought that the indolic core or the anticholinergic action explain the hallucinogenic property because that at present is no more than a hypothesis.

All psycho-dysleptic drugs can create artificial psychoses during the period of their action, and for this reason they are also called psycho-mimetic or psychoso-mimetic. In this respect, they are the opposite of the psycholeptics which reduce or prevent artificial psychoses - the hallucinogenic effect of mescaline is reduced by the hallucinolytic effect of chlorpromazine, and the prior administration of neuroleptics inhibits the appearance of experimental hallucinations. On the other hand, the distinction between the hallucinogens and the psycho-analeptics is more open to criticism: cocaine which is a stimulating and euphoric agent when taken in small doses, becomes an agent of hallucination and delirium when taken in strong doses. Psycho-dysleptic drugs certainly stimulate intellectual activity but the positive phenomena, to which they give rise, and which appear to be new, are in fact no more than the result of negative phenomena which can only be understood in the Jacksonian terms of the "escape of control" or the dissolution and liberation of the functions of the mind.

This clinical grouping of the psychotropic drugs into three groups has been made on the criterion of the predominant action of each of them; it is bound to be modified as more comes to be known about the correlation between the different pharmacological structures and psychological reactions, in other words the response that a part of the brain gives to a certain psychotropic agent and the relationship this response has to the neurophysiological and biochemical mechanism of the agent in question. Whatever the usefulness of present research into this field it is still premature to claim a satisfactory classification of psychotropic drugs before the science of psychopharmacology becomes better established.

Clinical psychopharmacology forces the psychiatrist to think in physiological terms and it thus brings his science closer to neurology than it had been before. For a long time psychiatry remained behind and outside of the great biological current which was renovating the medical sciences but it has moved rapidly, and psychopharmacology has assisted in this evolution. The psychopharmacological approach has channelled research towards the biological foundations of mental disorder, both from the point of view of the nervous and the organic mechanisms. The absence of lesions which are anatomically visible in the case of endogenous psychoses does not prove that there could not be, while the patient was alive, lesions recognizable according to biological criteria through the use of neurophysiological and biochemical techniques. The creation and the diminution of psychiatric syndromes by the use of psychotropic drugs is evidence in favour of such a concept.

Psychotropic drugs are at the same time encephalotropic drugs which act on psychic functions to the extent that these functions are cerebral. It goes without saying that the psychic function cannot be localized in a centre, but the mechanics for its functioning requires the bringing into play of a specialised cerebral device with multiple connections. Neurophysiology has already discovered certain key pieces in this function, especially since information about the role of the base of the brain in mental life was added to the classical ideas about the role of its upper layer. So far as it is possible to see on an encephalic chart the cerebral targets which are selected by the different psychotropic agents, this evidence lends support to the topographic systematization of mental syndromes arrived at by other experimental methods.

The hypothesis of the neurophysiological and biochemical mechanism of psychosis has given rise to experiments to produce artificial psychoses by the administration of psychopharmacological agents. These experiments raise a preliminary question: Are artificial psychoses analogous to, or are they identical with natural psychoses? Analogy or identity - it is in these terms that Moreau de Tours posed the problem in 1845 in his work "Le haschish et l'aliénation mentale". His conclusion was in favour of the identity of artificial syndromes with natural ones whereas other workers had found in favour of analogy.

Artificial psychoses produced by dysleptic drugs (hallucinogenics) are acute exogenous psychoses, the symptomatology of which, varying according to the agent and the person to which it is administered, oscillates between two poles: on the one hand the confuso-oneiric syndrome and on the other hand the syndrome of depersonalisation. These acute exogenous psychoses provoked by experimental means, are not different from acute exogenous syndromes observed in clinical practice, and it is often difficult to distinguish them from certain endogenous psychoses. In order to see how difficult it is to make a diagnosis in this respect it would suffice to ask an experienced psychiatrist to examine a person who he does not know has been given LSD. He is likely to make a very wide-ranging diagnosis, with possible reservations about schizophrenia.

It is quite true that the dysleptic drugs at the moment are not capable of reproducing the characteristic schizophrenic process, but taking into account the many forms that atypical artificial psychoses can take, and also the many aspects of schizophrenia in its early stages, and if a comparison is made, not between a schizophrenic seizure and a chronic state of schizophrenia, but between a schizophrenic seizure engendered artificially and a natural schizophrenic seizure, then it would appear that there are certain resemblances between two kinds of schizophrenia, one artificially created and the other endogenously created. What is more, in schizophrenic patients certain syndromes can be reduced by the same chemiotherapy as can be applied in experimental psychoses (e.g. the neuroleptic cure), though this is only true if the treatment is not applied briefly and in a passing manner as in the case of an acute schizophrenic state, but massively and continuously as in treating a chronic schizophrenic condition. Do not these therapeutic analogies suggest analogies which are pathogenic? The words of Hippocrates come to mind "In truth, it is treatment which reveals the nature of disease ".

Alongside the research on biochemical substrata underlying psychoses, in other words, the biochemical lesion associated with this condition, much work is being carried out principally on the metabolism of the biogenic amines and evidence has been brought to light that in schizophrenics and in their families there are compounds (?) that do not occur in normal subjects. Psychiatry has a direct interest in the development of biochemical genetics because heredity is the principal causative factor in mental pathology.

At present the results obtained in the field of psychochemistry are fragmentary. This is not surprising considering the pioneer state of experiments on neuronic mediators and intracerebral metabolism. This is a science in the making, but enough work has already been done to open for psychiatry horizons that were hitherto unknown. It is to the credit of psychopharmacology that is has given an impetus to numerous researches in cerebral biochemistry, which science in its place is a necessary extension of psychopharmacology.

No matter how powerful the biological movement in psychiatry becomes, other methods of treatment should not be neglected. It would be absurd for the psychiatrist to be so enamoured of psychopharmacology as to deprive his patient of the great benefits of psychotherapy and sociotherapy. Psychiatry must not reduce itself to a medical system based on chemical preparations. In mental therapy the doctor-patient relationship is important, and the quality of the relationship plays a large part in the cure, whatever the methods of treatment employed. It is quite true that there might be a disagreement about theory, but in practice the doctor's first duty is to find a cure by all the means at his disposal.

An aspect of great interest to psychopharmacology is the use of drugs in psychotherapy which permit the pharmacodynamic exploration of the conscious and the subconscious in techniques involving narco-analysis, the Weck analysis and dream-analysis. The narco-analysis by barbiturates would appear to be opposed to Weck analysis which uses amphetamines but there is often a great interest in combining the action of these two agents, e.g. sodium-amobarbital and methylamphetamine in the subnarcosis developed by amphetamine administration. This method is so useful in the clinic in making diagnoses that I personally always prescribe it as a routine examination in the same way as I would psychometry or electro-encephalography. From the point of view of treatment the amphetamine subnarcosis can sometimes give spectacular results as in traumatic neuroses, but more often it can only play a contributory role and should be used from time to time at certain stages in psychotherapy both in cases of neuroses as well as psychoses.

As for dream-analysis through the agency of oneirogenics, above all LSD 25 and psilocybin, this also is a valid experimental and therapeutic method.

The techniques of re-education and social rehabilitation by means of work, play, art and professional and cultural influences have come to assume a considerable importance in psychiatry. Sir Aubrey Lewis wrote some years ago that if a choice had to be made between abandoning all the new psychotropic drugs or the various social techniques, including rehabilitation used in psychiatry, it is the drugs that would have to go.

Happily chemiotherapy and socio-therapy are not opposed but they complement and support each other in reducing turbulence, agressiveness, negativism and, generally speaking, all the dangerousness of mental patients. Chemiotherapy has greatly favoured the application of techniques of re-education and social rehabilitation. The era of the psychotropic drugs which has often been called the age of tranquillizers is only at its beginning and the results already obtained permit much optimism. Considering all the work now being carried out it seems that tranquillizers do not have the same effect on those who take them and those who study them : they calm the former while stimulating the latter and constantly present new problems to them. More than in providing answers, the exploration of the world of psychotropic drugs raises questions which cause a fertile disquiet, without which there would be neither search nor discovery.