BIOLOGICAL APPROACHES TO MENTAL HEALTH A W.H.O. NEWSLETTER F. GARCIN Buebec, Canada M. GASTPAR Basel, Switzerland L. L. PRILIPEO Geneva, Switzerland C. RADOUCO-THOMAS Ruebec, Canada N. HOHACEK Zagreb, Yugoelavia W. BLJNNEY Irvine, Cal., USA T. CROW Harrow, Middlesex, H. HIPPIUS Munich, FRG A. A. LEEDS Rockville, MD, USA UK C. LEON G. PUCZINSKI Cali, Colombia Warsaw, Poland J. MENDLEWICZ N. SARTORIUS Brussels, Belgium Geneva, Switzerland D. MOUSSAOUI H. B. SETH1 Casablanca, Morocco Lucknow, India M. OLATAWURA M. E. VARTANIAN Ibadan, Nigeria Moscow, USSR P. PICHOT I. YAMASHITA Paris, France Sapporo, Japan The Newsletter is a means to bring information about WHO activities to those interested in biological approaches to mental health. It will include: i) summaries of original papers and critical reviews presented at scientific and technical meetings organized by WHO or at other selective meetings organized in collaboration with WHO ii) progress reports of WHO collaborating centres iii) short reports on WHO training activities, e.g.: training courses, workshops, travelling seminars iv) news and developments. The editors will also consider the inclL\sion of information relevant to biological investigations dealing with mental health and psychosocial problems, including those related to alcohol and drug abuse. The Newsletter will be published in English as a separate entity in the section "News and Intercommunications" of the Journal "Progress in Neuro- Psychopharmacology and Biological Psychiatry". The Newsletter will be available separately and will be distributed in-limited number of copies through WHO to persons involved in work in the above field. Additional copies can be obtained from WHO, Division of Mental Health (Dr. L. L. Prilipko, Editor), Geneva, Switzerland. Unsolicited contributions should be addressed to Dr. L. L. Prilipko at the above address so that they can be considered for publication. Authors should prepare their typescripts following the "Instructions to Contributors" of the Journal "Progress in Neuro-Psychopharmacology and Biological Psychiatry". It is planned to publish this Newsletter on Biological Approaches to Mental Health periodically. -_------_------_--------- * Opinions and views expressed by contributors do not necessarily represent the policies of the World Health Organization (WHO).
Transcript
BIOLOGICAL APPROACHES TO MENTAL HEALTH A W.H.O. NEWSLETTER
F. GARCIN Buebec, Canada M. GASTPAR Basel, Switzerland
L. L. PRILIPEO Geneva, Switzerland C. RADOUCO-THOMAS Ruebec, Canada
N. HOHACEK
Zagreb, Yugoelavia
W. BLJNNEY Irvine, Cal., USA T. CROW Harrow, Middlesex, H. HIPPIUS Munich, FRG A. A. LEEDS Rockville, MD, USA
UK
C. LEON G. PUCZINSKI
Cali, Colombia Warsaw, Poland J. MENDLEWICZ N. SARTORIUS Brussels, Belgium Geneva, Switzerland
D. MOUSSAOUI H. B. SETH1
Casablanca, Morocco Lucknow, India
M. OLATAWURA M. E. VARTANIAN
Ibadan, Nigeria Moscow, USSR P. PICHOT I. YAMASHITA
Paris, France Sapporo, Japan
The Newsletter is a means to bring information about WHO activities to those interested in biological approaches to mental health. It will include: i) summaries of original papers and critical reviews presented at
scientific and technical meetings organized by WHO or at other selective meetings organized in collaboration with WHO
ii) progress reports of WHO collaborating centres iii) short reports on WHO training activities, e.g.: training courses,
workshops, travelling seminars iv) news and developments.
The editors will also consider the inclL\sion of information relevant to biological investigations dealing with mental health and psychosocial problems, including those related to alcohol and drug abuse.
The Newsletter will be published in English as a separate entity in the section "News and Intercommunications" of the Journal "Progress in Neuro-
Psychopharmacology and Biological Psychiatry". The Newsletter will be available separately and will be distributed in-limited number of copies through WHO to persons involved in work in the above field. Additional copies can be obtained from WHO, Division of Mental Health (Dr. L. L. Prilipko, Editor), Geneva, Switzerland.
Unsolicited contributions should be addressed to Dr. L. L. Prilipko at the
above address so that they can be considered for publication.
Authors should prepare their typescripts following the "Instructions to Contributors" of the Journal "Progress in Neuro-Psychopharmacology and
Biological Psychiatry".
It is planned to publish this Newsletter on Biological Approaches to Mental
Health periodically.
-_------_------_--------- * Opinions and views expressed by contributors do not necessarily represent
the policies of the World Health Organization (WHO).
Biological approaches to mental health - A W.H.O. newsletter
EDITOHIAL NOTE
WHO’s Mental Health Programme has three major objectives which it hopes to achieve in cooperation with various countries around the world: first, to prevent or control mental and neurological disorders and psychosocial problems such as those related to alcohol and drug abuse; sencond, to ensure
broad utilization of mental health knowledge in general health care; and third, to facilitate appropriate management of psychological consequence of rapid socio-economic change.
The WHO Newsletter is intended to help in the achievement of the first of
these objectives: It is likely, however, that it will assist in the achievement of the other two objectives by improving our understanding of the
disease process, and of treatment techniques in general.
WHO has promoted the exchange of information and collaborative research in
this field over the last two decades and will continue doing 50 using the
Newsletter as well as other methods. Promoting collaboration and exchange of
information between institutes and individuals at the national and
international level are among the essential aims of the World Health
Organization as set forth in its mission.
Four issues have already been published between 1983 and 1987.
The general outline of issues consist of four parts:
Section 1: Research Protocols
Section 2: Reports from WHO Collaborating Centers
Section 3: Training & Teaching
Section 4: Other News and Developments.
We hope that this WHO Newsletter will become a useful tool in fulfilling
the above aims.
The Editors
RESEARCH PROTOCOLS COMPARISON OF ORAL AND INTRAVENOUS TREATMENT OF
DEPRESSIVE STATES
WHO Collaborative Study Division of Mental Health
Geneva, Switzerland
i. Introduction
Depressive disorders are a major public health problem because they are frequent, cause distress and suffering for patients and their families and result in severe socio-economic losses. With an estimated prevalence of 9% there are at least 100 million people in the world who are suffering from some form of depressive illness and who could benefit from qualified help.
Currently available oral treatment with antidepressant drugs usual 1 y involves a delay in onset of action and a lack of effect in 10-302 of the patients. Recent studies have shown that intravenous administration of antidepressants can overcome these shortcomings. The reason5 for this probably include the higher bioavailability of the drug, and the reduced influence of the liver first pass effect.
One of the important aims of the WHO mental health programme is the improvement of treatment technology in the field of mental health. In this effort WHO is undertaking an international collaborative multicentre study aiming to compare oral and intravenous treatment of depressive states.
What follows is the research protocol for this double-blind study comparing oral and intravenous treatment and using standardized assessment methods.
2. Description of the Research Protocol
A. Hypothesis
The purpose of this study is to answer the following questions:
1.
2.
3 .
4.
Does administration of an antidepressant such as maprotiline or clomipramine by intravenous infusion have an advantage over the administration of the same antidepressant orally? Does administration by intravenous infusion show greater therapeutic efficacy and/or a faster therapeutic action - measurable on the Clinical
Scale (CGI), Hamilton Psychiatric Hating Scale for 1 and Visual Analogue Scale (VAS) - than or-al
Global Impression Depression (H&M-D administration?
Similarily, do favourably to the antidepressant?
therapy-resistant depressed patients respond more intravenous than to the oral preparation of the same
Does administration by intravenous infusion produce a lower incidence and /or lesser severity of side effects - measurable by the Asberg Side Effect Rating Scale - than oral administration?
Are there transcultural differences in the therapeutic ratio (efficacy index) between the oral and intravenous administration of the same antidepressant?
. . . 111
iv Biological approaches to mental health- A W.H.O. newsletter
5. Are there transcultural differences in the atceptance of antidepressant treatment by intravenous route?
6. Does a Constant relationship exist between the steady state plasma level of the antidepressant and the clinical state? Does this relationship differ between the oral administration and the intravenous infusion groups? Can this difference be explained by the differences in steady state plasma levels or by the ratio between unchanged substance and i\ specific or all metabolites?
H. Desim
The study will follow a double-blind comparative design in which patients will be randomly assigned to one of the two parallel treatment groups, i.e. oral or intravenous infusion. Randomization will be carried out centrally for each center separately.
C. F'opulation
The experimental population will consist of 300 (including therapy- resistant) adult (18 to 65 years) in-patients of both sexes from 10 centres. Each centre contributes 30 "completed subjects" (see J below). Centres concentrating on therapy-resistant patients should use the following de+inition:
Therapy resistant in this study is defined as lack of a favourable therapeutic response to at least two consecutively administered treatments with two different antidepressant drugs, each taken for at least GI three week duration in dosages judged to be adequate in the culture.
c.1. Inclusion Criteria. The patient should fulfil the following:
a. Diagnosis of endogenous depression (ICD-9: 296.1 or 296.3) established on the basis o+ a semi-structured interview (WHO/SADD).
b. Having passed an observation period of three days without treatment with psychotropic drugs except lorazepam and chloralhydrate.
c. At least moderately severe depression with a minimum total score of 17 on the HAM-D at the end of the observation period.
C.2. Exclusion Criteria. Presence of any of the following items exclude
the patients:
a. Duration of depressive episode* longer than six months. This criterion does not apply to patients qualifying for admission to the therapy- resistant group.
b. Somatic diseases which may become aggravated (e.g., narrow angle glaucoma
or prostatic hypertrophy) or somatic diseases including history of
somatic diseases which increase the risk of serious side effects (e.g.,
cardiac, hepatic, renal).
c. Somatic disease that requires pharmacological treatment for Control.
t An episode is defined as a period of symptomatology preceded
30 days symptom-free period.
by at least a
Research protocols
d.
e.
f.
9.
h.
1.
J.
k.
1.
m.
D.
Epilepsy or potential risk for cerebral seizure on the basis of surface EEG (with provocation test).
Pregnancy based on positive pregnancy test.
Sexually active female with childbearing potential not practising birth control.
A secondary psychiatric diagnosis with the exception of ICD-9: 302, 305 and/or 312.
Diagnosis of mental retardation (based on clinical judgment).
History of alcohol and/or drug dependence within the past 5 years.
Immediate danger of suicide (based on clinical judgment).
Treatment with the drug which is being tested (clomipramine or maprotiline) within the six months prior to commencement of the clinical study for all patients or during the entire duration of the present episode* for patients in the therapy-resistant subpopulation.
Treatment with a MAO inhibitor drug within 14 days prior to commencement of active drug administration.
Electra-convulsive treatments within the present episode*.
Medication
The experimental medication will be supplied in form of tablets and ampoules with matching placebos identical in appearance, taste and smell. Each centre will use only one of the two active substances - maprotiline or clomipramine. Each tablet or ampoule will contain 25 mg of the active substance or inactive placebo.
Each participating centre will receive its entire medication sc~pply prior to commencement of the clinical investigation, packed for each experimental subject separately. Each package is assigned a unique number on the basis of the randomization list. Sealed information on the medication in the package received by the patient in question, in each period, will also be supplied; this information should only be revealed in case of clinical emergency (see G). Fit the time of termination of the study the list will be returned to WHO/HO.
E. Procedure
Patient5 who fulfil admission criteria will be randomly assigned to one of two treatment groups (6 or B). Subsequently each patient will undergo a 22- day clinical investigation with a 20-day treatment period. The 20-day treatment period is divided into two phases; intravenous + oral phase (10 days) and oral phase Cl0 days). The intravenous + oral phase is further subdivided into two (one low dose and one high dose) steps.
* fAn episode is defined as a period of symptomatology preceded by at least a 30 days symptom-free period.
vi Biological approaches to mentalheallh-A W.H.O. newsletter
Schematic presentation of the procedure is as follows:
1. Baseline assessments (Day 0)
2. Treatment period: 20 days (Days l-20) a. Intravenous + oral phase: 10 days (Days l-10)
- low dose step: 2 days (Days i-2) - high dose step: 8 days (Days 3-10)
b. Oral phase: 10 days (Days 11-20)
3. Final assessment (Day 21)
E.1. Treatment Period - Intravenous + Oral Phase. Both groups (A and 8) are administered an intravenous infusion on 10 consecutive days (Days l-10). During the low dose step (Days l-2), the infusion consists of two ampoules daily of either clomipramine (50 mg) or maprotiline (50 mg) or of placebo in 250 cc physiological saline (N&l 0.9%). During the high dose step (Days 3- 10), three ampoules daily of the same substance in a similar solution are administered. The infusion (both low dose and high dose) is administered in the morining over a period of 150 minutes, i.e. from 8:30 a.m. to 11:00 a.m. at a rate of 1.66 cc per minute. At the end of the infusion, the patient has to remain in the lying position for at least 30 minutes.
Simultaneously during the low dose step, patients will be taking one talbet of either clomipramine (25 mg) or maprotiline (25 mg) or placebo t.i.d. and during the high dose step two tablets of the same substance t.i.d.
E-2. Treatment Period - Oral F'hase. During the oral phase, all patients will be given active drug with the same number of talbets as during the high dose step intravenous + oral phase.
E.3. Schematic presentation of Treatments. Special attention should be
paid to ensure compliance with oral medication. The evening dose must be
administered before 8 p.m. It is very important that the evening treatments
be given at the same time each day. (Table 1)
Table 1
Schematic Presentation of Treatments
Phase
Intravenoul + oral
Oral
Days
l-2
3-10
11-20
Group CI
Intravenous
2 amp. active (50 mg)
3 amp. active (75 mg)
--
i-
Oral
1 tab. placebo t.i.d.
2 tab. placebo t.i.d.
2 tab. active t.i.d. (150 mg:
Group H
Intravenour
2 amp. placebo
3 amp.
placebo
5 Oral
1 tab. active t.i.d. (75 mg)
2 tat>. active
t.i.d. (150 mg)
2 tab. active t.i.d. (150 mg)
Research protocols vii
F. Concomitant Treatment
No concomitant medication with the exception of lorazepam and chloralhydrate is permissible during the entire course of the clinical investigation and the observation period (see C.1.b.).
It is not permissible to use the above drugs continuously, i.e. longer than on four consecutive days at a time and/or a total number of 16 days during 23 days, consisting of three days observation period and 20 days treatment period.
G. Emerqency
In ca5e of clinical emergency (i.e. an adverse effect with potentially hazardous consequences) where knowing the route of administration of the active drug is of critical importance for deciding about counter-measures, the relevant sealed information is to be consulted and the patient in question taken off the clinical investigation. Once the treatment for a given patient is revealed, the patient's initial(s) aa well as the date and reason should be marked on the list.
H. Assessments
Assessments are carried out from Day 0 (last day of observation period) to Day 21 (day after last drug administration) in the order in which they appear in the evaluation booklet (Table 2). They consist of psychiatric and physical examinations and vari OL~C~ testings on the basis of which the following data collection/assessemnt forms will be completed (see Table 3).
If an assessment cannot be carried out on due scheduled date during the oral phase, it will be permissible to carry it out on the preceding or .th e following day. Assessments during the intravenous + oral phase should be followed strictly according to the schedule. Table 3 gives a synopsis on the "Trial Plan" of "Intravenous and Oral Treatment of Depressive States".
I. Discontinuation
Premature discontinuation can be due to:
a. Treatment failure, i.e. emergency or requiring additional medication.
b. Early recovery.
C. Other reasons, e.g. at patient's request.
At the time o+ discontinuation (regular or premature) all asserjsment forms due on last assessment should be completed.
J. Acceptability
"Completed subjects" are defined as those patients who completed the 20-
days treatment period or those who were taken off the trial prematurely after the low dose step (Days i-2) due to treatment failure or early recovery (see 1-d. and 1-b.). They should not be replaced. Patients whose treatment was discontinued during the first two days of treatment or those leaving the trial for other (e.g. technical) reason5 (see 1.c.) will be r-eplaced. However, all data available will be analyzed.
k . Reliability
Implementation Of the study will be preceded by training sessions for
Hamilton Psychiatric Hating Scale for Depression (HN+D) 0,5,7,11,14,21
Schedule for Standardized Assessment of Patients with Depressive Disorder (WHO/SCIDD) 0,2i
Full WHO/SADD Schedule will be given on Day 0; WHO/SADD will be assessed on Day 21 with Section 2-Symptoms and Signs-only.
Clinical Global Impression Schedule (CGI) 0,3,7,11,14,21
Physical and Laboratorv Examinations
a. Orthostatic Hypotension Test
b. Pulse Rate/Blood Pressure
C. Hating Scale for Side Effects (Asberg)
d. Laboratory Routine (LFO
Transaminases, creatinine and whole blood counts. The results should be recorded in SI-Units.
e. Electroencephalography Test (EEG)
f. Electrocardiography Test (ECG)
0,5,10,20
0,3,5,7,9,11,14,21
0,3,7,11,14,21
0,11,21
0
0,5,10,20
08:00 Patient
08:00 Psychiatrist
Psychiatrist
08:00 Psychiatrist
15:00 Research Assistant
In the Hesearch morning Assistant before medication
08:00
08:0(l)
F'sychiatrist
Research Assistant
15:00
Research Assistant
Research Assistant
(continued on the next page)
Research protocols ix
Administrative Ratinq
a. Screening Form (SF 1 0 F'sychiatrist
b. Drug History Form (DHF) 0 Psychiatrist
c. Termination Record (TH) 21 Psychiatrist
08: 00 Fsychiatrist
Psychiatrist
F'har-macokinetic
Plasma Level5 (PL) 0,3,11,14,21
Blood samples are taken after an overnight fast for the determination of plasma.concentrations of the antidepressants.
Concomitant Medication
Drug Dosage Fiecord (DDR)
To be documented for each prescription of iorazepam and/orchloralhydrate.
investigators to become familiar with all evaluational instruments and to improve the levels of interrater agreement. Fieliability tests will be carried out three times: i.e. prior to, mid-way through and at about the time of termination of the clinical trial. Both levels of inter- and intrarater reliability will then be established.
L. Ethical Issues
Informed consent must be obtained from all patients included in the clinical trial. Infromed consent and the procedure regarding confidentiality will conform to local regulations. If "0 local regulations e:.: i st 7 the Helsinki regulations will be used. They should comply with the ethical requirements laid down by WHO's Secretariat Committee on Research Involving Human Subjects.
M. Analvsis
Analysis of data will be based on descriptive statistics, analysis of variance and co-variance, repeated measures model and group comparisons.
N. Return of Unused Treatments and Treatment Informatibn
At the end of the study, all unused treatments and sealed treatment informAtion (whether opened or not) should be returned to WHO/H@.
3. References
COLLINS, G. H. (1975) The u5e of parenteral and oral chlorimipramine (fkafranil) in the treatment of depressive states. Hrit. J. F'sychiat. 122: 189-190.
FERREY, G. and SFARTI, PI. (1980) Le traitement antiddpresseur par voie intraveineuse cornpar& au traitement par voie orale. Un essai en double aveugle de la quinupramine. L'Encephale vr: 59-68.
KIELHOLZ, P., TEHZANI, S., GASTPAR, M. (1979) Treatment for therapy
Biological approaches to mental health - A W.H.O. newsletter
KIELHOLZ, P. and ADAMS, C. (1982) Antidepreszve infusions-therapie. In:
Eine Standortbestimmung, P. Kielholz and C. Adams (Eds.), Thieme,
Stuttgart.
4. Appendix
Visual Analogue Scale for translation into local languages
Pharmacokinetic protocol
5. WHO Collaborating Centres
Lead Centre: Basel, Switzerland (Professor P. Kielholz)
Participating Centres: Bombay, India (Professor V.N. Bagadia)
Copenhagen, Denmark (Professor 0. Rafaelsen)
Lucknow, India (Professor B.B. Sethi)
Moscow, USSR (Professor M.E. Vartanian)
Nagasaki, Japan (Professor R. Takahashi)
Sapporo, Japan (Professor I. Yamashita)
Zagreb, Zagreb (Professor N. Bohacek)
TRAINING AND TEACHING
SEMINAR ON E(&O_L_O_G_IC_f%L, PSYCHIATRY_ @bJU_ F’SYCHCJPH~4MACOLGGY ------- --
Egypt, November 3-6, 1906 Health Organization (WHO), Head Ouarter
WHO Regional Office for the Eastern Mediterranean Department of Psychiatry of the Ain Shams University
Orqanininq Qmmittgg Scientific Director: Prof. P. Kielholz
Seengen, Switzerland Director of Administrative and Technical Matters: Dr. L. L. Prilipko
Geneva, Switzerland National Coordinator: Prof. Ahmed Okasha
Cairo, Egypt
Lea!Ghio!2 staff Invited Members: P. Eielholz. Il. Maj. D. Moussaoui, A. Okasha. 0. Rafaelsen,
H. Sethi WHO Staffmembers: L. L. Prilipko, N. N. Wig
rarticLeaot5 One of the most important aspects of the seminar was the active participation of a large number of Egyptian psychiatrists, neurologists and specialists in the basic sciences. The seminar was attended by more than 200 participants. It gave a very stimulating opportunity for foreign researchers and local scientists to exchange views. Seven high level scientists in the area of biological psychiatry and psychopharmacology gave 14 lectures. In spite of the shortage of time there was a very lively and productive discussion after each lecture whereby especially topics of local interest and local studies generated very active participation.
$ientif& &gqCa_m_m_g
I. Guidelines
The seminar provided participants with the following main guidelines:
d) Patients with therapy resistant depressions. A provisional description
of these conditions was provided and data from WHO collaborative studies about the efficacy and tolerability of infusion therapy with triciclic and tetraciclic antidepressants were presented. b) Patients with "mixed psychiatric syndrome". It was explained that so- called schizophrenic disorders represent heterogenious group syndromes. Possible more homogenious subtyped of these disorders were provisionally identified and indications were given about their treatment and prognosis. c) Patients with "atypical depression". The different definitons of this condition were reviewed and the possible therapeutic Lrsefulness of MAO inhibitors was emphasized.
2. GuideliDgg Fl!2oclt_ Dosa¶e_ of PSY~hg&X!El~~ Elruss SK! U_zS&!Zn_es_s of DetermiGaq&g gf rhe_hC cla_sma_ Levels
It was emphasized that Lithium is the only psychiatric drug for which measuring of the plasma levels on a routine basis is both feasible and useful for clinical purposes. It was suggested that the plasma level of Lithium for the prophylaxis of major affective disorders should be lower than that previously proposed (from 0.4 to 0.6 milliequivalent/l). It was reported
. . . Xl,,
xiv Biological approaches to mental health - A W.H.O. newsletter
that for tricyclic antidepressants and neuroleptics the relationship between plasma levels and clinical response is not consistently demonstrated. It was, however, stated that the dosage of this drug should be kept as low as possible in order to avoid adverse reactions, which may occasionally even include neuroleptic tardive dyskinesia.
The current state of knowledge about the advantages of the use of the "second
generation" antidepressants was reviewed. the possible usefulness of selective inhibitors of "A" coenzyme MAO (MAO + type A) was suggested. Although it was stressed that none of these drugs are at this time available.
Preliminary data were shown about the possible usefulness of phospholipids
and antioxydants in association with tricyclic antidepressants in order to improve the response to these last drugs or to speed up the onset of their
The use of some antiepileptic drugs such as carbamazepine and valproic
in bipolar affective patients was reviewed. The possible efficac
carbamazepine in agressive schizophrenic patients and hyperactive ch i
was suggested. It was emphasized that tryciclic antidepressants and
inhibitors exert, in anl:iolitic activity and may be useful in genera an::iety disorder and panic disorder with phobic avoidance.
acid
Y of ldren
MAO .lized
II. Round Tab 1 e
On the last day of the seminar a Hound Table discussion was held where the
current state of research in biological psychiatry was discussed as well as
its future prospects.
The Who would like to thank F'rof. A. Okasha of the Ain Shams University and
Dr. N. N. Wig of the WHO Regional Office for their part in the organization
of this course and their hospitality. Further Information: _-__-_- ---__-_---- Dr. L. L. F'rilipko, Senior Medical Office, Division of
Mental Health, WHO, Geneva, Switzerland.
OTHER NEWS AND DEVELOPMENTS
el~~~/Q~tg: Athens, Greece, October 27-91, 1986
Seo_n_s_!Kz: World Health Organization (WHO) Department of Psychiatry, Egintion Hospital, Athens University Medical School, Athens, Greece
1. Introduction
2. Reseat--h_ &tivities
2.1. Review of Completed Studies and Preparation of Reports for Publication 2.1.1. Biological Study of Alcohol Dependence Syndrome with Reference to
Ethnic Differences Lead Centre: Sapporo Participating Centres: &smara, Hasel, Casablanca, Lucknow, Manila, Mexico City, Moscow, Nederlands, Zagreb 2.1.2. Usage of Dexamethasone Suppression Test as a Biological Indicator of
Depressive Illness Lead Centre: Epsom Participating Centres: Ba5e1, Brussels, Budapest, Casablanca, Copenhagen, Irvine, Lucknow, Moscow, Munich, Nagasaki, Sapporo, Utrecht 2.1.3. Effects of Narcotic Antagonist Naloxone on Symptoms of Schizophrenia Lead Centre: Ijethesda Participating Centres: Lucknow, MOSCOW, Munich, Sapporo, Utrecht 2.1.4. Evaluations of Optimal Doses of a Neuroleptic by Measurement of Blood
Haloperidol Levels Lead Centre: Irvine Farticipating Centres: Casablanca, Lucknow, Moscow, Munirn, Sapporo 2.1.5. Comparison of Oral and Intravenous Treatment of Depressive States Lead Centre: Base1 Participating Centres: Bombay, Copenhagen, Lucknow, Moscow, Nagasaki, Sapporo, Zagreb
2.2. Review of Development in the Data collection Phase Since the Last Meeting
2.2.1. Validity of Imipramine Platelets Binding Sites as a Biological Plarker of Endogenous Depression
Lead Centre: Copenhagen Participating Centres: Athens, Baeel, Brussels, Munich, Milan/Naples, Paris, Tokyo 2.2.2. Biological Markers of Violent and Non-Violent Lead Centre: Brussels Participating Centres: Basel, Lucknow, Milan/Naples, 2.2.3. Role of Hereditary, Clinical and Pharmacok
Prediction of Lithium Prophylactic Effect Lead Centre: Moscow
rvine, Lucknow, Moscow,
Suicidal Behaviout-
Utrecht netic Factors for the
Participating Centres: Brussels, Lucknow, Munich, Milan/Naples, Sapporo 2.2.4. Research in Chronobiology of Affective Disorders-Value of EEG ‘2.1 eep
Abnormalities as Biological Markers of Depressive Illness Lead Centre: Brussels Participating Centres: Athens, Copenhagen, Irvine, Munich, Mexico City, Milan/Naples, Sapporo, Tokyo, Zagreb
xvi Biological approaches to mental health-A W.H.O. newsletter
2.3. Review of Collaborative Studies in the Preparatory Phase 2.3.1. Acute and Prophylactic Treatment of Manic-Depressive Patients with
Carbamazepine Lead Centre: Irvine Participating Centres: Brussels, Lucknow, Montreal, Moscow, Milan/Naples, New York, Sappot-a, Tokyo, Zagreb 2.3.2. EEG/Evoked Potential Topography in Relationship to Major F'sychoses Lead Centt-e: Irvine Participating Centres: Clthens, Basel, Beijing, Brussels, Mexico City, Lucknow, Montreal, Moscow, Munich, Sapporo, Tokyo 2.3.3. Evaluation of Light Therapy as 0ntidepressant Trea Lead Centre: St-ussels Participating Centres: Flthens, Basel, Casablanca, Irvine, Munich, Naples, Sapporo, Zagreb 2.3.4. Pharmacotherpay of Depression in the Elderly Lead Centt-e: Milan/Naples Participating Centres: Athens, Basel, Beijing, Casab Epsom, Lucknow, Mexico City, Montreal, Moscow, Munich, Tokyo, Zagreb
ment of Depression
Lucknow, Montreal,
anca, Copenhagen, New York, Sapporo,
2 5. . 3. Evaluation of Haloperidol Decanoate in the Prevention of Relapse in Schizophrenic Fatients
Lead Centre: Irvine Participating Centres: &eel, Beijing, Brussels, Casablanca, Lucknow, Mexico City, Montreal, Moscow, New York, Sapporo 2.3.6. Comparative Study on Amitriptyline Blood Levels and E.C.T. Lead Centre: Zagreb 2. 3. 7. Investigation with Concordant and Disconcordant Twins Lead Centre: Athens 7 7 S_ L . ._. . Hormonal Markers of Substance Use Disorders Lead Centre: Utrecht and Quebec City 2.3.9. Combined Utilization of Phospholipids and Antidepresants for the
Treatment of Depressive Patients Lead Centre: Milan/Naples
7 (4. Wh-&n_&n_g ActivLQe_s
'1 3. . Review of Developments in 1985-1986 3.1.1. The participants of the meeting were informed about the output of a WHO Training Seminar in Psychopharmacology for South-East Asian Countries which was held in Dhaka, Bangladesh, from October 21 to November 7 .z. . 1.2. The participants in the meeting were informed
2; 1;;;.
collaboration with Ain Shams University, Cairo, Egypt, is organizing a *Vi: Travelling Seminar on Biological Psychiatry and Psychopahrmaclogy to be held in Cairo, November 3-6, 1906.
3.2. Fellowships The fellowship programme is under progress.
4. WuQ Scientifis symes__a
4.1. Review of Developments in 1986 WHO/CINP Collaboration. WHO and Collegium Internationale Neuro- Psychopahrmacologicum (CINP) organized a symposium on "Recent Findings in
World Helath Organization Multi-Centre Studies in Biological F'sychiatrv and
Psychopharmacology" at San Juan, F'uerto Rico, December 17, 1906. lhe
proceedings were published by Raven Press, New York.
43 . L. Plan of Work for Future Activities WHO/CINP Collaboration. The organization of a WHO Symposium within the
framework of the 16th CINP (August 15-19, 1980, in Munich) was discussed.
Flnother WHO symposium could be organi zed during the Vth World Congress of
Other news and developments xvii
Biological Psychiatry in Florence in 1989.
5. -z---- Evchanqe_ of Information +fivities
5.1. WHO Newsletter - "Biological Approaches to Mental Health" The fourth issue (Vol. 2, No. 2, 1987) of the WHO Newsletter - Biological Approaches to Mental Health has appeared in the journal "Progress in Neuropsychopharmacology and Biological Psychiatry" Vol. 11, No. 1, 1987.
5.2. WHO Expert Series in Biological Psychiatry The manuscript "Depot Neuroleptics was prepared by the Munich centre and submitted for publication. Two other manuscripts: Psychoneuroendocrinology of Aging by Montreal centre, Clinical and Biolgoical Aspects of Anxiety by Milan/Naples and Casablanca centres will be prepared for the next meeting. It was suggested that practicing psychiatrists in both developing and developed countries need a comprehensive up to date book on biological psychiatry for their daily practice.
5.3. Consensus Statements The text of the consensus statement on "Pharmacotherapy of Depressive Disorders" Was well accepted in general and several modifications were proposed to clarify various issues. After circulation among all centres, the final version will be published.
6. G_e_n_Ka_L Lzzue_n
It was discussed that information about ere-ccie&Len patterns of psvchotroe&g m_edicatio_n_ could be useful for further development of projects in the field of clinical psychopharmacology.
The participants welcomed the invitation of Professor Bohacek to hold the 1.3th Exchange of Visits of Investigators in Biological Psychiatry in Zagreb, Yugoslavia, October 9-13, 1987.
8. List of Anne-es -_-- -- ----R--
Annex I: List of participants to the 12th WHO Athens Meeting Annex II: Agenda of the above meeting Annex III: IVth Travelling Seminar in Biological Psychiatry and
Psychopharmacology Annex IV: Plan of work by WHO centres, 1986/1987
Further Information: Dr. L. I_. Prilipko, Senior Medical Office, Division of Mental Health, WHO, Geneva, Switzerland.
RECENT PUBLICATIONS WITHIN THE RANGE OF W.H.O. ACTIVITIES IN BIOLOGICAL PSYCHIATRY
HECH, F'., GASTPAK, M., MENDLEWICZ, J. and MELLEHUP, E. (1986, WHO Pilot Study on the Validity of the 3H-Imipramine Platelet Binding Sites as a Hiological Marker of Endogenous Depression. Clinical Neuropharmacology r, Suppl. 4: 440-441.
GASTPAH, M., NGO KHAC, T., GILSDOHF, U. and BAUMANN, P. (1986) Comparison of: Oral and Intravenous Treatment of Depressive States: Preliminary Results of a WHO Collaborative Study. Clinical Neuropharmacology 2, SUppl . 4: 434-436.
POTKIN, S. G., UHHANCHEC:, M. S., KIHCH, D. G. and HUNNEY, W. E. JR. (1986) Evaluation of Optimal Doses of a Neuroleptlc: Preliminary Results. Clinical Neuropharmacology S, Suppl. 4: 437-439.
COPPEN, A. , METCALF, M., HAHWOOD, J. et al. ilY87) The Dexamethasone Suppression Test in Depression. A Wor-ld Health Organlzatlon
Collaborative Study. British Journal of Psychiatry Ls@: 4S9-d+b2. YAMASHITA, I., OHMORI, 'T,, KOYAHA, T. and MORI, H. (1986) WHO Collaborative
study of Alcoholism with Reference to Ethnic Differences. Clinical Nei_~ropharmacology 9, Suppl. 4: L 44'7-44.5 .
Eur_t_h_er Lnformation: Dr. L. L. F'rllipko, Senior Medlcal Offlce, Division of- Mental Health, WHO, Geneva, Switzerland.
