271

Therapeutic Drug Monitoring of Psychotropics: Report of a Consensus Conference Organizers: P Riederer, G. Laux (Würzburg, Germany)

Although therapeutic drug monitoring (TDM) ofpsychotropic drugs has become a routine or is at least available on request in many psychiatric institutions, it seems that there es a lack of simple rules as to how to integrate TDM as a useful tool in the diagnostic and therapeutic c1inical strategies. Thirty-five years after the introduction of modem psychotropic agents there is still no c1early defined adequate, optimal dose of antidepressants and neuroleptics. In view of this with the help of progress in analytical laboratory methods, numerous studies have been done in recent years investigating the relationship between plasma level and therapeutic outcomel clinical efficacy (review: Guthrie et al., 1987). However, with the exception of lithium, TDM of psychotropics has been found to yield disappointing and contradictory results due to numerous methodological shortcomings. Therefore, it was considered necessary and useful to organize a first "state of the art conference" in Würzburg, Germany. Experts in c1inical pharmacology, biochemistry, chemistry and pharmacy tried to evaluate the "state ofthe art" together with psychiatrists in order to establish consensus regarding basic methodological and c1inical questions, and to encourage collaboration in future studies. Therefore, the first part ofthe conference consisted of presentations regarding personal experiences and methodological aspects of TDM. The second part dealt with intensive discussions ofTDM problems in c1inical practice. The details will be published elsewhere (Laux and Riederer, 1992). Here we give abrief report on recommendations for which consensus has been reached: I. SampIes to be used for analysis should consist of serum (and perhaps also plasma) that is as fresh as possible, which should have been collected into polypropylene (or possibly polystyrene) tubes after separation without the use of any interface gel. Sampies should be transported to the laboratory as soon as possible and, after centrifugation, should then be kept in the refrigerator (at 4 oe and in the dark) until they are analyzed. 2. Blood sampies should generally be taken prior to the morning dose, about 12 hours after the last administration. Suggested time intervals are: first value after about one week;

Pharmacopsychiat. 25 (1992) 271-272 © Georg Thieme Verlag Stuttgart· New York

second value after two to three weeks; third value determined just before discharge, or on the maintenance dose, in each case under steady-state conditions. In the case of non responders the level should be determined after increasing the dose. 3. Blood sampling should be performed under strict steadystate conditions, i. e., when four or five half-Iife intervals have elapsed. In the case of depot neuroleptics, blood sampIes should basically be taken prior to administration of the next dose. Where there is c1inical suspicion of a decline in effectiveness, or of an overdose, multiple determinations may be indicated. In certain cases it may be appropriate to measure Tmax. 4. For methodological and practical reasons it is not considered useful to carry out determinations on saliva. 5. As a rule, total blood levels will be measured, taking pathological albumin or ui-acid-glycoprotein values into consideration, and possibly also abnormal blood lipid values. Because of methodological difficulties, determination of the free fraction may be regarded essentially as a research investigation. 6. In general, a single determination is regarded as sufficient, but in the case of interfering peaks duplicate determinations are recommended. 7. It seems sensible to establish several different methods and to compare them with one another. It is recognized that different procedures may be applied to different c1inical investigations. Thus, immunological methods may increasingly be used for checking compliance, on suspicion to toxic effects, for an urgent result, or for economic reasons. However, chemical methods are preferred because established calibration curves are available. Immunological methods require validation; they may be used in individual cases and in situations involving single-drug treatment - otherwise the possible presence of other cross- reacting substances has to be taken into consideration. 8. The availability of internal standards is necessary (each laboratory's own therapeutic range); external quality control with the appropriate institutions is recommended. The establisment of a European quality control organisation is aimed for. 9. Each laboratory should prepare a catalog of methods and methodology to facilitate interlaboratory comparisons.

Received: Accepted:

10. 4. 1992 17. 7. 1992

Downloaded by: University of Pennsylvania Libraries. Copyrighted material.

Active participants: P. Baumann (Lausanne), U. Breyer-Pfaff (Tuebingen), K. Brosen (Odense), M. Cirsi (Würzburg), C. Hiemke (Mainz), K. Heininger (Cologne) U. Klotz (Stuttgart), B. Müller-Oerlinghausen (Berlin), W. E. Müller (Mannheim), M.-L. Rao (Sonn), A. Saria (Innsbruck), G. Schöllnhammer (Cologne), W. Sieghart (Vienna), F. Sjöqvist (Huddinge)

Pharmacopsychiat. 25 (1992)

10. Results should not be reported unaccompanied by any comment: a clinical pharmacologist or a clinician with a professional involvement in psychopharmacology should be responsible for the liaison between the individual case or individual patients, the doctor treating the patient, and the laboratory doing the analyses (Interpretation). 11. Regulations regarding the determination of psychopharmacological drugs should be specified for substances which are measured routinely and for those which are measured on request. 12. In future, all depressive patients should have their phenotype characterized, either with dextrometorphan, sparteine, or desmethylimipramine (lOmg). For this purpose patients should be free of all medication. It is recommended that phenotype characterization should be documented in some kind of patient record system ("passport"). 13. In future, no clinical studies should be undertaken without the monitoring of blood levels and the determination of the phenotype. 14. The possibility of drug interferences should be borne in mind, and such occurrences should be accurately documented. 15. The interchange of sampies between individuallaboratories is to be encouraged.

P Riederer, G. Laux References Guthrie, s., E. A. Lane, M. Linnoila: Monitoring of plasma drug concentrations in clinical psychopharmacology. In: Meltzer, H. Y. (ed.): Psychopharmacology: The Third Generation of Progress. Raven Press, New York (1987) 1323- 1338 Laux, G., P. Riederer (Hrsg.): Plasmaspiegelbestimmung von Psychopharmaka: Therapeutisches Drug Monitoring. Versuch einer ersten Standortbestimmung. Wiss. Verlagsgesellsch. Stuttgart 1992

Univ.-ProJ Dr. P Riederer Psychiatrische Klinik und Poliklinik Universitäts-Nervenklinik Klinische Neurochemie Füchsleinstraße 15 D-87oo Würzburg Germany Downloaded by: University of Pennsylvania Libraries. Copyrighted material.

272

Therapeutic drug monitoring of psychotropics: report of a consensus conference.

271 Therapeutic Drug Monitoring of Psychotropics: Report of a Consensus Conference Organizers: P Riederer, G. Laux (Würzburg, Germany) Although ther...
98KB Sizes 0 Downloads 0 Views