Practical Therapeutics
Drugs 18; 392-397 (1979) 0012 -6667 f7 9! 1100-0392/$0 1.'::/)/0 1;) ADIS Press A ustra l(l$l(l Pty Ltd. A~ right s reserved.
Principles of Use of Psychotropic Drugs
in Children
John S. W erry Department 01 Psychiatry , Universi ty of Auckland School 01 Medic ine. Aucklar.d
The use of psychotrop ic dr ugs in children is likely to have a substantiv e and durable therapeutic ro le only where the centra l nervous system is functioning abnormally . Ot herwi se. chemical intervention simply distorts normal funct ion and. with the exception of severe stress situations or in short term use. is likely to have effects which will make its application unacceptable. The overuse of psychotrop ic medicatio n in children will only lead to the erroneous conclusion that the child's pro blems lie entirely within himself and that the solution is medical rather than social and political. Such is the complexity of the assessment process and the time it requires. the prescribing of psychotropic drugs in children. ideally, should be based only on a specialist opinion.
I . Im portance ofan Obj ective Diagnosis A lot of the criticism of psychotrop ic dr ug use in children centr es on the ability of doctors to diagnose by objective scientific criteria, rather than those dictated by personal or social imperative. In this regard ,
considerable effort has been made in the last few years to improve method s of diagnosis. These include: 1. Development of norms for various sympto m rating scales, most notably Conners' Teacher Questionnaire. 2. Cross checking of ratings by parents. teachers. doctors and observers. 3. Objective methods of measurement of symptomatology such as mechanical devices for motor activity. EEG procedures and other psychophysiological procedures. behaviour observa tions, neuro logical measu res and biochemical estimations. 4. Development of a stan dard set of measures for demographic. background and anamnestic data. However , there is still a reluctance on the part of child psychiatr ists to move in the direction of laboratory measures. and at present, most clinical use of psychotherapeut ic drugs in children becomes a matter of using very crude diagnostic or symptomatic signposts and subm itt ing the drug to an empirical trial to see if it suits the child concerned.
PrinCIples c t Use of Psychotropic D, ugs on Children
2. Some Principles of Prescribing Psy chotherapeutic Drugs Dru gs should never be regarded as definitive treatment in themselves any more than the converse view that because another treatment may produce some change in the patient, there is no place for drug therapy. Before commencing treatment, a specialist opinion should be sought, if at all possible. If the decision is made that drugs may be indicated, it is prudent to obtain an untreated baseline as many children will respond to simple reassurance, particularly where anxiety is a prominent symptom. In addition, children's problems generally have a strong tendency to improve 'spontaneously',
2.1 Use of Placebos One useful tactic to detect this nonspecific improvement is to commence medication with a placebo. In studies with hyperactive children, an improvement rate of between 18 and 45 % has been achieved with placebo, though the degree is usually rat her small. A placebo may also be usefully employed at a later stage of treatment to see if the child still needs the active medication.
2.2 Use Low Doses Initially When commencing medication, the lowest dose possible should be used. A useful guide is to use half the minimum recommended dose initially as previous stud ies have suggested that many recommended doses, part icularly for stimu lants, may be too high for some children. The dose is then increased with close monitoring for clinical and adverse effects; this requires close co-operation with teachers and parents and some standardised system of examination. In general, psychotherapeutic drugs are long acting drugs, so that serious accumulation can develop if the dosage is increased more frequently than at 4 to 5 day intervals. The important exception to this is the
393
stimulants, but it perhaps bears repeating that the benzcdiazepines such as diazepam are not short acting drugs and their plasma half-lives and those of their active metabolites may be as long as 24 to 72 hours.
2.3 Assessment of Clinical Effects A battery of widely accepted though still rather crude measures of children's behavioural, emotional and cognitive states now exist, These include the various Conners' Rating Scales, the Continuous Performance Test, the Actometer and other measures of motor activity, all of which are suitable for measuring treatment effects and particularly drug effects. However, for practical reasons many clinicians will continue to rely primarily on clinical impressions derived from parents, teachers, children, and their own observations, though in the latter respect it is important to note that these are virtually useless for detecting anything except overdosage and adverse effects. This is because the whole situation in a doctor's office is so contrived that the child's behaviour is highly atypical. The clinical global impression in which improvement is rated on a simple 7-point scale remains one of the simplest and best measures in psychopharmacology, although obviously it does not indicate in what particular way the child has improved. Most of the children seen by child psychiatrists for whom drugs may be indicated, present because of problems with social behaviour, and one may easily overlook the fact that drugs have important influences upon general nervous system function including such cognitive functions as attention, memory and learning. Some attempt to assess these effects is highly desirable since a quieter child is nearly always perceived as an improved child, yet this improvement may be at the expense of mental alertness. A good teacher or parent will very quickly detect mental dulling or improvement in alertness, and both these sources of information should be used regularly. Children on long term medication should have their response to medication and the continuing
39'
Pnoootes 01 Use 0 1 Psvchoteopc Drugs on Children
necessity for it checked at least once a year by either stopping the drug or , preferably, by substitution of a placebo. 'Drug holidays' should be encouraged to prevent both side effects and the development of tolerance. Many children (though by no means all) are, for example, able to go without stimulant drugs particularly on weekends and holidays.
Table I.
rrccetcos for
psychotropic drug s in children
Indicationls)
Drug group
1. Stimula nts (0 .3 to 1.Omg/ kg daily me thylphenidate)
Hyperlr.inesis
2. Antipsycho tics (no maximum dos e}
HyperlIIdren
'95
idase inhibitors are extremely infrequent. results are questionable. and they are in general more dangerous drugs. Wh ile the antidepressants have been shown to be 3.2 Antipsychotic:s of some value in hyperkinetic children, their response Antipsychotic drugs can be useful in disorders is generally less regular and less marked than that of mar ked by psychomotor excitation including hy- the stimulants and side effects are more troublesome. perkinesis. In hyperkinesis. however. they are not as How they work in hyperkinesis is unclear, but their useful as the stimulants; while both types of dru gs effecton cogruuve function suggests that it is by some quieten hyperkinetic children. the antipsychotics do action analogous to that of the stimulants, rather than so by exerting a general depressant effect. The by their often associated sedative effects. Similarly, widespread use of these drugs as anxiolytics can be the nature of their effect in enuresis is also unclear, although recent work has suggested an a-adrenergic supported even less in children than in adults. Side effects are much as would be expected from action. Their use as true antidepressants is this group of drugs. except that dystonias are more unestablished, largely because the delineation of a common in children, and a short lived extrapyramidal true depressive syndrome in children has remained rebound syndrome may occur in psychotic children elusive. after withdrawal of antipsychotic:s. The most popular Side effects of the tricyclics include the usual drug in this group is probably thioridazine becauseof autonomic blocking effects. weight loss. irritability. its strong sedative action and relative absence of ex- and tearfulness. Dosage is a controversial issue since. tra pyramidal side effects. Its most imponant side when used in the hyperkinetic syndrome, it has been effects. apart from anticholinergic ones. are seizures considerably higher (sometimes well over 200mg a and retinitis pigmentosa. neither of which are likely day) than that used in the symptomatic suppression of to appear in clinical dosages of less than 400 to enuresis where the dose has not usually exceeded 50 500 mg/ day. The use of antipsychotics in which ex- to 75mg. These higher doses can produce much more trapyramidal rather than anticholinergic side effects serious side effects, notably seizures and cardiotoxic predominate (e.g . trifluoperazine. fluphenazine and effects. haloperidoll should be avoided except where there are There is no reason to suspect any substantial difspecial indications for their use (such as with ference in therapeutic effect between the various tri fluphenazine decanoate and haloperidol in Gilles de la cyclics, though side effects such as sedation may Tourette syndrome), or where the dosage can be kept differ. Dosage for all is similar. One should probably well below that which produces extrapyramidal begin with about Img/kg and in increasing the dose, symptoms. This is because of the increasingly com- it is important to remember that these are long acting mono very distressing, and basically untreatable syn- drugs with rates of elimination measured in days or drome of tardive dyskinesia (usually presenting as even weeks. It is a good policy not to exceed 100mg choreoathetotic movements of the lips and tongue) daily except in exceptional cases. and in such cases. thought to be due to postsynaptic sensitisation to ECG monitoring is essential. The use of tricyclic antidepressants in paediatric dopamine. the transm ission of which is blocked by pharmacotherapy should be regarded as still being exthese drugs. ploratory and requiring close medical surveillance. Current use for enuresis is particularly indefensible 3.3 Antidepressant Drugs since cures are rare. tolerance and escape from supDiscussion here will be restricted to the tricyclic pression of enuresis the rule. and minor side effects compounds since controlled trials of monoamine ox- common.
doctors only on the recommendation of a paediatrician or child psychiatrist.
396
PrincIples of Use o f Psvcboteopic Drugs in Children
3.4 Anxiolytics and Sedatives
It is widely held that this group of drugs make some children (especially psychotic and hyperkinetic children) worse, and there is as yet no evidence to suggest they have a useful role in minor disturbances marked by disturbed sleep and anxiety. Both the benzodiazepine and antihistamine groups of drugs are widely used in children by family physicians but the lack of evaluation of their effects and properly defined indications is a significant gap in our knowledge. In general, dosage ceilings have not yet been established and manufacturers' recommended doses err on the conservative side. If they are to be used, it is suggested that the dosage be increased every 4 to 5 days ll use. an objective diagnosis is impor_ tant. Appropriate diagnostic me thods include: II ) Use of symptom ratirlg scales
b) Cross c hecking of rating s by parent s. teachers and other observers cl Direct measurement 01 sym ptoms le.g. EEG proce dures. biochemical estimat ion s, et c.) dl Consideration of social condition s and background ef Seek specialist opinio n whene ver in doubt
3. Assess need for drug therapy :
al Obtain untreated baseline data bl Many children respond to simple reassurance (part icularly where anxiety promine nt ) cl Condition may we~ improve 'spontaneously' d) Tria l of placebo may prove worthwhile
4. If drug treatment indicated. select appropriate therapy (see table Il 5. Commence with low doses initially {half minimum recom mended l: increase dose with close monitoring for Clinical and adverse effects 6. ContinlJll regular caref ul surveillanc e for adverse effects. both Ofl physiologica l syste ms and on cognitive f unction. mood and social behaviou r 7. If long term therapy indicated . assess response and con tinuing need for treatme nt at least once a year by e;lher stopping therapy or use of placebo 8. Encourage regular 'd rug holiday s' to prevent side. effects arid development of tolerance
largely that of another stimulant. Tr ials with lithium in hyperkinetic children have not been encouraging. Exclusion of certain foods and additives from the diet is the most recently introduced therapy for hyperkinesis. However, preliminary data from properly controlled studies suggests tha t this treatment is probably ineffective, cumbersome and involves a slight nutritional risk if inadequately supervised.
397
P""clples 01 Use o f PsVChotrOplc Dlu gs in Chddren
4. Assessmenl of Adverse Effects Careful medical surveilla nce in paediatr ic pharm acotherapy is vital. One must be prepared to conduct a shortened physical examination , including some routine interrogation of all body systems (not merely those at which treatment is aimed) at regular intervals. The child's height and weight shou ld be plotted on a growth chart, and other phys ical systems, particularly the nervous system, quickly screened. Blood tests need be done only if there are clear indications of toxic effects. Serious side effects of psychotherapeuti c dru gs are fortunately infrequent in children, but minor side effects are not and these are frequently overlooked if the clinician fails to interrogate the parents and child properly or to make routin e physical examinations. Occasionally one will encounter a child who undergoes a significant personality change which, even when it represents a significant improveme nt, is understa ndably unacceptable to parents. This depends on the drug but more particularly on the child, since the same drug may produce diametrically opposed effects on mood. self image and comfort level in different children, as has been noted with the stimulants and the antidepressants. It is particularly important to look for these effects since it is quite possible for a
child to be improved in behaviour yet made miserable by medication.
5. Conclusions Only the stimulants have a well tested place in paediatric psychopharmacology and then only on specialist approval. Most other drugs still require further careful study before definitive statements about their usefulness and safety can be made, though the antidepressants and anti psychotics may have a wort hy role. There rema in many unanswered questions such as the degree to wh ich stimulants influence long term prognosis and the effect of changes in cognitive function and on academic achievement . While it is indisputab ly true that some doctors do, and always will. misprescribe or overprescribe psychotherapeutic drugs in children, this is no more an argument against such treatm ent when properly indicated and supervised than it is against any other useful yet overprescribed treatment such as penicillin or vitamin Bll . Aut hOr's address : Profe;sor i, S , W'-' !)'. Department of Psycbiarry . Un iversity of Auckla nd School of Med icine. Private Bag. Au(klrllld (New Zealandl.
Drugs 18; 392-397 (1979) 0012 -6667 f7 9! 1100-0392/$0 1.'::/)/0 1;) ADIS Press A ustra l(l$l(l Pty Ltd. A~ right s reserved.
Principles of Use of Psychotropic Drugs
in Children
John S. W erry Department 01 Psychiatry , Universi ty of Auckland School 01 Medic ine. Aucklar.d
The use of psychotrop ic dr ugs in children is likely to have a substantiv e and durable therapeutic ro le only where the centra l nervous system is functioning abnormally . Ot herwi se. chemical intervention simply distorts normal funct ion and. with the exception of severe stress situations or in short term use. is likely to have effects which will make its application unacceptable. The overuse of psychotrop ic medicatio n in children will only lead to the erroneous conclusion that the child's pro blems lie entirely within himself and that the solution is medical rather than social and political. Such is the complexity of the assessment process and the time it requires. the prescribing of psychotropic drugs in children. ideally, should be based only on a specialist opinion.
I . Im portance ofan Obj ective Diagnosis A lot of the criticism of psychotrop ic dr ug use in children centr es on the ability of doctors to diagnose by objective scientific criteria, rather than those dictated by personal or social imperative. In this regard ,
considerable effort has been made in the last few years to improve method s of diagnosis. These include: 1. Development of norms for various sympto m rating scales, most notably Conners' Teacher Questionnaire. 2. Cross checking of ratings by parents. teachers. doctors and observers. 3. Objective methods of measurement of symptomatology such as mechanical devices for motor activity. EEG procedures and other psychophysiological procedures. behaviour observa tions, neuro logical measu res and biochemical estimations. 4. Development of a stan dard set of measures for demographic. background and anamnestic data. However , there is still a reluctance on the part of child psychiatr ists to move in the direction of laboratory measures. and at present, most clinical use of psychotherapeut ic drugs in children becomes a matter of using very crude diagnostic or symptomatic signposts and subm itt ing the drug to an empirical trial to see if it suits the child concerned.
PrinCIples c t Use of Psychotropic D, ugs on Children
2. Some Principles of Prescribing Psy chotherapeutic Drugs Dru gs should never be regarded as definitive treatment in themselves any more than the converse view that because another treatment may produce some change in the patient, there is no place for drug therapy. Before commencing treatment, a specialist opinion should be sought, if at all possible. If the decision is made that drugs may be indicated, it is prudent to obtain an untreated baseline as many children will respond to simple reassurance, particularly where anxiety is a prominent symptom. In addition, children's problems generally have a strong tendency to improve 'spontaneously',
2.1 Use of Placebos One useful tactic to detect this nonspecific improvement is to commence medication with a placebo. In studies with hyperactive children, an improvement rate of between 18 and 45 % has been achieved with placebo, though the degree is usually rat her small. A placebo may also be usefully employed at a later stage of treatment to see if the child still needs the active medication.
2.2 Use Low Doses Initially When commencing medication, the lowest dose possible should be used. A useful guide is to use half the minimum recommended dose initially as previous stud ies have suggested that many recommended doses, part icularly for stimu lants, may be too high for some children. The dose is then increased with close monitoring for clinical and adverse effects; this requires close co-operation with teachers and parents and some standardised system of examination. In general, psychotherapeutic drugs are long acting drugs, so that serious accumulation can develop if the dosage is increased more frequently than at 4 to 5 day intervals. The important exception to this is the
393
stimulants, but it perhaps bears repeating that the benzcdiazepines such as diazepam are not short acting drugs and their plasma half-lives and those of their active metabolites may be as long as 24 to 72 hours.
2.3 Assessment of Clinical Effects A battery of widely accepted though still rather crude measures of children's behavioural, emotional and cognitive states now exist, These include the various Conners' Rating Scales, the Continuous Performance Test, the Actometer and other measures of motor activity, all of which are suitable for measuring treatment effects and particularly drug effects. However, for practical reasons many clinicians will continue to rely primarily on clinical impressions derived from parents, teachers, children, and their own observations, though in the latter respect it is important to note that these are virtually useless for detecting anything except overdosage and adverse effects. This is because the whole situation in a doctor's office is so contrived that the child's behaviour is highly atypical. The clinical global impression in which improvement is rated on a simple 7-point scale remains one of the simplest and best measures in psychopharmacology, although obviously it does not indicate in what particular way the child has improved. Most of the children seen by child psychiatrists for whom drugs may be indicated, present because of problems with social behaviour, and one may easily overlook the fact that drugs have important influences upon general nervous system function including such cognitive functions as attention, memory and learning. Some attempt to assess these effects is highly desirable since a quieter child is nearly always perceived as an improved child, yet this improvement may be at the expense of mental alertness. A good teacher or parent will very quickly detect mental dulling or improvement in alertness, and both these sources of information should be used regularly. Children on long term medication should have their response to medication and the continuing
39'
Pnoootes 01 Use 0 1 Psvchoteopc Drugs on Children
necessity for it checked at least once a year by either stopping the drug or , preferably, by substitution of a placebo. 'Drug holidays' should be encouraged to prevent both side effects and the development of tolerance. Many children (though by no means all) are, for example, able to go without stimulant drugs particularly on weekends and holidays.
Table I.
rrccetcos for
psychotropic drug s in children
Indicationls)
Drug group
1. Stimula nts (0 .3 to 1.Omg/ kg daily me thylphenidate)
Hyperlr.inesis
2. Antipsycho tics (no maximum dos e}
HyperlIIdren
'95
idase inhibitors are extremely infrequent. results are questionable. and they are in general more dangerous drugs. Wh ile the antidepressants have been shown to be 3.2 Antipsychotic:s of some value in hyperkinetic children, their response Antipsychotic drugs can be useful in disorders is generally less regular and less marked than that of mar ked by psychomotor excitation including hy- the stimulants and side effects are more troublesome. perkinesis. In hyperkinesis. however. they are not as How they work in hyperkinesis is unclear, but their useful as the stimulants; while both types of dru gs effecton cogruuve function suggests that it is by some quieten hyperkinetic children. the antipsychotics do action analogous to that of the stimulants, rather than so by exerting a general depressant effect. The by their often associated sedative effects. Similarly, widespread use of these drugs as anxiolytics can be the nature of their effect in enuresis is also unclear, although recent work has suggested an a-adrenergic supported even less in children than in adults. Side effects are much as would be expected from action. Their use as true antidepressants is this group of drugs. except that dystonias are more unestablished, largely because the delineation of a common in children, and a short lived extrapyramidal true depressive syndrome in children has remained rebound syndrome may occur in psychotic children elusive. after withdrawal of antipsychotic:s. The most popular Side effects of the tricyclics include the usual drug in this group is probably thioridazine becauseof autonomic blocking effects. weight loss. irritability. its strong sedative action and relative absence of ex- and tearfulness. Dosage is a controversial issue since. tra pyramidal side effects. Its most imponant side when used in the hyperkinetic syndrome, it has been effects. apart from anticholinergic ones. are seizures considerably higher (sometimes well over 200mg a and retinitis pigmentosa. neither of which are likely day) than that used in the symptomatic suppression of to appear in clinical dosages of less than 400 to enuresis where the dose has not usually exceeded 50 500 mg/ day. The use of antipsychotics in which ex- to 75mg. These higher doses can produce much more trapyramidal rather than anticholinergic side effects serious side effects, notably seizures and cardiotoxic predominate (e.g . trifluoperazine. fluphenazine and effects. haloperidoll should be avoided except where there are There is no reason to suspect any substantial difspecial indications for their use (such as with ference in therapeutic effect between the various tri fluphenazine decanoate and haloperidol in Gilles de la cyclics, though side effects such as sedation may Tourette syndrome), or where the dosage can be kept differ. Dosage for all is similar. One should probably well below that which produces extrapyramidal begin with about Img/kg and in increasing the dose, symptoms. This is because of the increasingly com- it is important to remember that these are long acting mono very distressing, and basically untreatable syn- drugs with rates of elimination measured in days or drome of tardive dyskinesia (usually presenting as even weeks. It is a good policy not to exceed 100mg choreoathetotic movements of the lips and tongue) daily except in exceptional cases. and in such cases. thought to be due to postsynaptic sensitisation to ECG monitoring is essential. The use of tricyclic antidepressants in paediatric dopamine. the transm ission of which is blocked by pharmacotherapy should be regarded as still being exthese drugs. ploratory and requiring close medical surveillance. Current use for enuresis is particularly indefensible 3.3 Antidepressant Drugs since cures are rare. tolerance and escape from supDiscussion here will be restricted to the tricyclic pression of enuresis the rule. and minor side effects compounds since controlled trials of monoamine ox- common.
doctors only on the recommendation of a paediatrician or child psychiatrist.
396
PrincIples of Use o f Psvcboteopic Drugs in Children
3.4 Anxiolytics and Sedatives
It is widely held that this group of drugs make some children (especially psychotic and hyperkinetic children) worse, and there is as yet no evidence to suggest they have a useful role in minor disturbances marked by disturbed sleep and anxiety. Both the benzodiazepine and antihistamine groups of drugs are widely used in children by family physicians but the lack of evaluation of their effects and properly defined indications is a significant gap in our knowledge. In general, dosage ceilings have not yet been established and manufacturers' recommended doses err on the conservative side. If they are to be used, it is suggested that the dosage be increased every 4 to 5 days ll use. an objective diagnosis is impor_ tant. Appropriate diagnostic me thods include: II ) Use of symptom ratirlg scales
b) Cross c hecking of rating s by parent s. teachers and other observers cl Direct measurement 01 sym ptoms le.g. EEG proce dures. biochemical estimat ion s, et c.) dl Consideration of social condition s and background ef Seek specialist opinio n whene ver in doubt
3. Assess need for drug therapy :
al Obtain untreated baseline data bl Many children respond to simple reassurance (part icularly where anxiety promine nt ) cl Condition may we~ improve 'spontaneously' d) Tria l of placebo may prove worthwhile
4. If drug treatment indicated. select appropriate therapy (see table Il 5. Commence with low doses initially {half minimum recom mended l: increase dose with close monitoring for Clinical and adverse effects 6. ContinlJll regular caref ul surveillanc e for adverse effects. both Ofl physiologica l syste ms and on cognitive f unction. mood and social behaviou r 7. If long term therapy indicated . assess response and con tinuing need for treatme nt at least once a year by e;lher stopping therapy or use of placebo 8. Encourage regular 'd rug holiday s' to prevent side. effects arid development of tolerance
largely that of another stimulant. Tr ials with lithium in hyperkinetic children have not been encouraging. Exclusion of certain foods and additives from the diet is the most recently introduced therapy for hyperkinesis. However, preliminary data from properly controlled studies suggests tha t this treatment is probably ineffective, cumbersome and involves a slight nutritional risk if inadequately supervised.
397
P""clples 01 Use o f PsVChotrOplc Dlu gs in Chddren
4. Assessmenl of Adverse Effects Careful medical surveilla nce in paediatr ic pharm acotherapy is vital. One must be prepared to conduct a shortened physical examination , including some routine interrogation of all body systems (not merely those at which treatment is aimed) at regular intervals. The child's height and weight shou ld be plotted on a growth chart, and other phys ical systems, particularly the nervous system, quickly screened. Blood tests need be done only if there are clear indications of toxic effects. Serious side effects of psychotherapeuti c dru gs are fortunately infrequent in children, but minor side effects are not and these are frequently overlooked if the clinician fails to interrogate the parents and child properly or to make routin e physical examinations. Occasionally one will encounter a child who undergoes a significant personality change which, even when it represents a significant improveme nt, is understa ndably unacceptable to parents. This depends on the drug but more particularly on the child, since the same drug may produce diametrically opposed effects on mood. self image and comfort level in different children, as has been noted with the stimulants and the antidepressants. It is particularly important to look for these effects since it is quite possible for a
child to be improved in behaviour yet made miserable by medication.
5. Conclusions Only the stimulants have a well tested place in paediatric psychopharmacology and then only on specialist approval. Most other drugs still require further careful study before definitive statements about their usefulness and safety can be made, though the antidepressants and anti psychotics may have a wort hy role. There rema in many unanswered questions such as the degree to wh ich stimulants influence long term prognosis and the effect of changes in cognitive function and on academic achievement . While it is indisputab ly true that some doctors do, and always will. misprescribe or overprescribe psychotherapeutic drugs in children, this is no more an argument against such treatm ent when properly indicated and supervised than it is against any other useful yet overprescribed treatment such as penicillin or vitamin Bll . Aut hOr's address : Profe;sor i, S , W'-' !)'. Department of Psycbiarry . Un iversity of Auckla nd School of Med icine. Private Bag. Au(klrllld (New Zealandl.
