The AMÜP Study for Drug Surveillance in Psychiatry - a Summary of Inpatient Data

From 1979 to 1989 the AMÜP study (AMÜP = Arzneimittelüberwachung in der Psychiatrie) was conducted in two psychiatric hospitals in Germany with the aim to provide a systematic and standardized assessment of all adverse reactions to psychotropic drugs under conditions of routine practice. A total of 60.7 % of patients experienced at least one adverse drug reaction (ADR) with probable or definite causality during their stay in the hospital; 37.1 % of patients exhibited ADRs that had some therapeutic impact on further treatment. ADRs that led to drug discontinuation were observed in 8.6 %. This rate ranged from 9.5 to 5.1 % for haloperidol and perazine, the most common neuroleptics at that time; sedating antidepressants (AD) rated lower than non-sedating (amitriptyline 5.1 %, clomipramine 10.4 %). Lithium salts, antiparkinson drugs, and benzodiazepines were associated with considerably lower rates of ADRs than neuroleptics or antidepressants. Severe ADRs occurred in 1.4 % of exposed patients (e. g., toxic delirium, grand mal seizures, malignant neuroleptic syndrome, or agranulocytosis).

The AMÜP data suggest that administration of psychotropic drugs in psychiatric hospitals at that time was a safe, but also inconvenient treatment for many patients due to a wide range of bothersome side effects that compromised patient compliance. The data can serve as a reference base for comparisons with newer compounds introduced to the market over the last decade such as serotonin reuptake inhibitors (SSRIs) and other new AD, atypical neuroleptics, or other new generation psychotropic drugs.

References

• 1 Ananth J V, Ban T A, Lehmann H E, Rivzi F A. An adverse reaction unit: results and functions.  Am J Psychiat. 1971;  127 1339-1344
• 2 Brenner P M, Wolf B, Grohmann R, Rüther E. Benzodiazepine dependence - aetiological factors, time course, consequences and withdrawal symptomatology: a study of five cases.  Drug Alcohol Depend. 1988;  22 253-261
• 3 Bürke H, Grohmann R, Rüther E. Drug surveillance/drug monitoring in psychiatric outpatient treatment: Prescription of psychotropic drugs. diagnosis and adverse drug reaction - 3 years.  Pharmacopsych. 1988;  21 293-294
• 4 Casey D E. Neuroleptic-induced acute extrapyramidal syndromes and tardive dyskinesia.  Psychiatr Clin North Am. 1993;  16 589-610
• 5 Dirschedl P, Hasford J. Drug monitoring of psychiatric patients: Mathodological aspects.  Pharmacopsych. 1985;  18 27-28
• 6 Dirschedl P, Grohmann R, Schmidt L G. Reliability of adverse drug reactions assessment.  Pharmacopsych. 1986;  19 292-293
• 7 Dirschedl P, Grohmann R. Exploring heterogeneous risk structures: Comparison of a bootstrapped model selection and nonparametric classification technique. In: Jöckel KH, Rothe G, Sendler W [eds] Bootstrapped and related techniques. Trier, FRG. 1990. proceedings. Springer Berlin Heidelberg New York Tokyo; 1992: 189-195
• 8 Gerz H J, Schmidt L G. Low Melanin content of substantia nigra in a case of neuroleptic malignant syndrome.  Pharmacopsch. 1991;  24 93-95
• 9 Grohmann R, Hippius H, Müller-Oerlingheusen B. et al . Assesment of adverse drug reactions in psychiatric hospitals.  Eur J Clin Pharmacol. 1984;  26 727-734
• 10 Grohmann R, Dirschedl P, Scherer J, Schmidt L G, Wunderlich O. Reliability of adverse drug reaction assessment in psychiatric inpatients.  Eur Arch Psychiatry Neurol Sci. 1985;  235 158-163
• 11 Grohmann R, Dirschedl P, Rennig E, Scherer J, Schmidt L G. Methodological problems in assessment of adverse drug reactions with drug combinations.  Pharmacopsychiat. 1986;  19 300-301
• 12 Grohmann R, Rüther E, Sassim N, Schmidt L G. Adverse effects of clozapine.  Psychopharmacology. 1989;  99 101-104
• 13 Grohmann R, Schmidt L G, Spieß-Kiefer C, Rüther E. Agranulocytosis and significant leucopenia with neuroleptic drugs: results from the AMÜP program.  Psychopharmacol. 1989;  99 109-112
• 14 Grohmann R, Schmidt L G, Rühter E. Drug surveillance in psychiatric patients in the FRG. In: Bunney EW, Hippius H, Laakmann G, Schmauss M. [eds] Proceedings of the 16th C.I.N.P.-Congress. Springer Berlin Heidelberg New York Tokyo; 1990: 590-597
• 15 Grohmann R, Ströbel C, Rüther E, Dirschedl P, Helmchen H, Hippius H, Müller- Oerlinghausen B, Schmidt L G, Wolf B. Adverse psychic reactions to psychotropic drugs - a report from the AMÜP-study.  Pharmacopsychiat. 1993;  26 84-93
• 16 Grohmann R, Rüther E, Schmidt L G [Hrsg] . Unerwünschte Wirkungen von Psychopharmaka - Ergebnisse der Amüp-Studie. Springer Verlag Berlin; 1994
• 17 Grohmann R, Rüther E, Engel R R, Hippius H. Assessment of adverse drug reactions in psychiatric inpatients with the AMSP drug safety program: methods and first results for tricyclic antidepressants and SSRI.  Pharmacopsychiat. 1999;  32 21-28
• 18 Hurwitz N. Predisposing factors in adverse reactions to drugs.  Brit Med J. 1969;  1 536-539
• 19 Hurwitz N, Wade O. Intensive hospital monitoring of adverse reactions to drugs.  Brit Med J. 1969;  1 531-536
• 20 Jick H, Miettinen O S, Shapiro S, Lewis G P, Siskind V, Slone D. Comprehensive drug surveillance.  JAMA. 1970;  213 1455-1460
• 21 Kewitz H. Unerwünschte Wirkungen von Arzneimitteln: Mechanism. Erfassung. Bedeutung.  Internist. 1978;  19 357-365
• 22 Lenz W. Thalidomide embryopathy in Germany 1959 - 1961. Riss New York; 1985: 77-83
• 23 Miller R R, Greenblatt D J [Eds.]. Drug effects in hospitalized patients. Experiences of the Boston Collaborative Drug Surveillance Program 1966 - 1075. John Wiley and sons New York; 1976
• 24 Müller-Oerlinghausen B, Schmidt L G, Grohmann R. Does drug monitoring in psychiatry provide meaningful information on the problem of cardiotoxicity of psychotropic drugs?.  Arzneimittelforschung. 1982;  32 889-890
• 25 Novartis: Leponex Fachinformation 6. Juni 2002. 
• 26 Grohmann R, Engel R R, Rüther E, Hippius H. The AMSP Drug Safety Program: Methods and Global Results.  Pharmacopsychiat. 2004;  37 Suppl 1 S4-11
• 27 Sassim N, Grohmann R. Adverse drug reactions with clozapine and simultaneous applications of benzodiazepines.  Pharmacopsychiat. 1988;  21 306-307
• 28 Schmidt L G, Grohmann R, Helmchen H. et al . Adverse drug reactions.  Acta psychiatr scand. 1984;  70 77-89
• 29 Schmidt L G, Müller-Oerlinghausen B. Drug safety in psychiatry - an objective for drug monitoring in phase IV.  Pharmacopsychiat. 1984;  17 152-156
• 30 Schmidt L G, Schüssler G, Linden M, Müller-Oerlinghausen B. Impact of adverse drug reactions on treatment of psychiatric outpatients.  Pharmacopsychiatry. 1985;  17 40-41
• 31 Schmidt L G, Dirschedl P, Grohmann R, Scherer J, Wunderlich O, Müller-Oerlinghausen B. Consistency of assessment of adverse drug reactions in psychiatric hospitals: A comparison of an algorithmic and empirical approach.  Eur J Clin Pharmacol. 1986;  30 199-204
• 32 Schmidt L G, Grohmann R, Müller-Oerlinghausen B, Ochsenfahrt H. Tolerability and safety of antidepressant drugs in psychiatric in- and out-patients assessed by two drug surveillance systems.  Pharmacopsychiat. 1986;  19 288-289
• 33 Schmidt L G, Grohmann R, Müller-Oerlinghausen B, Ochsenfahrt H, Schönhofer P S. Adverse drug reactions of first and second generation antidepressants - a critical evaluation of drug surveillance data.  Br J Psychiatry. 1986;  148 38-43
• 34 Schmidt L G, Czerlinsky H, Stöckel M. Longitudinal assessment of psychotropic drug use in acutely-ill psychiatric inpatients.  Int J Clin Pharmacol Ther Toxicol. 1987;  25 244-250
• 35 Schmidt L G, Lammers V, Stöckel M, Müller-Oerlinghausen B. Recent trends in prescribing psychotropic drugs at a psychiatric university hospital in Germany [1981 - 1984].  Pharmacopsychiat. 1988;  21 126-130
• 36 Schmidt L G, Grohmann R, Strauss A, Spiess-Kiefer C, Lindmeier D, Müller-Oerlinghausen B. Epidemiology of toxic delirium due to psychotropic drugs in psychiatric hospitals.  Compreh Psychiat. 1987;  28 242-249
• 37 Seidl L G, Thornton G F, Cluff L E. Epidemiological studies of adverse drug reation.  Am J Publ Health. 1965;  55 1190
• 38 Spieß-Kiefer C, Grohmann R, Schmidt L G, Rüther E. Severe and life-threatening adverse reactions to psychotropic drugs.  Pharmacopsychiat. 1988;  21 290-292
• 39 Swett C P, Shader R I. Cardiac side effects and sudden death in hospitalized psychiatric patients. Dis Nerv Syst 1977: 69-72
• 40 Swett C. Patterns of drug use in psychiatric inpatient wards.  J Clin Psychiat. 1979;  40 464-468
• 41 Von Oefele K, Rüther E. Adverse drug reaction monitoring in long-term psychiatric inpatients.  Pharmacopsychiatry. 1985;  18 33-34
• 42 Von Oefele K, Grohmann R, Rüther E. Adverse drug reactions in Combined Tricyclic and MAOI Therapy.  Pharmacopsychiat. 1986;  19 243-244
• 43 Wastl R, Grohmann R, Rüther E. Frequency of increased serum liver-enzyme levels under treatment with neuroleptics.  Pharmacopsychiatry. 1986;  19 290-291
• 44 Wolf B, Conradty M, Grohmann R, Rüther E, Witzgall H, Londong V. A case of immune complex hemolytic anemia. thrombocytopenia. and acute renal failure associate with Doxepin use.  J Clin Psychiatry. 1989;  50 99-100
• 45 Wolf B, Grohmann R, Biber D, Brenner P M, Rüther E. Benzodiazepine abuse and dependence in psychiatric inpatients.  Pharmacopsychiatry. 1989;  22 54-60
• 46 Wolf B, Grohmann R, Schmidt L G, Rüther E. Psychiatric admissions due to adverse drug reactions.  Compr Psychiatry. 1989;  30 534-545