PMID- 9224903
OWN - NLM
STAT- MEDLINE
DCOM- 19970915
LR  - 20230320
IS  - 0940-1334 (Print)
IS  - 0940-1334 (Linking)
VI  - 247
IP  - 3
DP  - 1997
TI  - Serotonin syndrome and drug combinations: focus on MAOI and RIMA.
PG  - 113-9
AB  - Serotonin syndrome is a potentially life-threatening complication of 
      psychopharmacological drug therapy. The syndrome is produced most often by the 
      concurrent use of two or more drugs that increase brainstem serotonin activity 
      and is often unrecognized because of the varied and nonspecific nature of its 
      symptomatology. Serotonin syndrome is characterized by alterations in cognition, 
      behavior, autonomic nervous system function and neuromuscular activity. The 
      purpose of this study was to investigate the possibility that any serotomimetic 
      substance alone or in combination may give rise to serotonin syndrome, that this 
      condition is not confined to the use of newly introduced substances, and that the 
      newer reversible inhibitors of monoamine oxidase type A (RIMAs) are at decreased 
      risk for this phenomenon than older, classical (irreversible) monoamine oxidase 
      inhibitors (MAOI). This is a hypothesis-generating study based on a review of all 
      published cases of adverse effects arising in patients receiving serotomimetic 
      substances or combinations. A wide range of substances were involved in 226 cases 
      published worldwide since 1950 where there was any use of single or combined 
      serotomimetic treatments. Of the 226 cases, 105 fulfilled the Sternbach criteria 
      for serotonin syndrome. Some classes of drugs and individual substances were more 
      commonly represented. This may arise from product utilization patterns or from 
      the specific properties of the individual products. However, moclobemide, a RIMA, 
      was represented in only 9 of the 226 published cases and 3 of the 105 defined 
      serotonin syndromes, either in multi-drug combinations and/or in mixed drug 
      overdose. One explanation for the small number of cases involving RIMAs could be 
      the reversibility of these new products. In addition the small number of reports 
      on moclobemide could be an effect of its short availability in routine use during 
      the period of the literature review. We conclude that a spectrum of serotonergic 
      hyperactivity, through to a defined serotonin syndrome, may arise from the use or 
      combination of any serotomimetic substance, as this is a consequence of the 
      mechanism involved, rather than the use of any specific product such as the new 
      antidepressants. We further conclude that this condition is not confined to the 
      use of newly introduced substances and that the newer reversible inhibitors of 
      monoamine oxidase type A (RIMAs) may be at decreased risk for this phenomenon 
      than older, classical (irreversible) (MAOI). Given that a spectrum of 
      serotonergic hyperactivity was observed, this analysis prompts redefinition of 
      the currently accepted criteria for serotonin syndrome.
FAU - Hilton, S E
AU  - Hilton SE
AD  - Department of Drug Regulatory Affairs, F. Hoffmann-La Roche, Basel, Switzerland.
FAU - Maradit, H
AU  - Maradit H
FAU - Moller, H J
AU  - Moller HJ
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Germany
TA  - Eur Arch Psychiatry Clin Neurosci
JT  - European archives of psychiatry and clinical neuroscience
JID - 9103030
RN  - 0 (Benzamides)
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 0 (Receptors, Serotonin)
RN  - 333DO1RDJY (Serotonin)
RN  - PJ0Y7AZB63 (Moclobemide)
SB  - IM
MH  - Autonomic Nervous System Diseases/*chemically induced/diagnosis
MH  - Benzamides/administration & dosage/adverse effects
MH  - Brain Stem/*drug effects
MH  - Drug Therapy, Combination
MH  - Humans
MH  - Moclobemide
MH  - Monoamine Oxidase Inhibitors/administration & dosage/*adverse effects
MH  - Neuromuscular Diseases/*chemically induced/diagnosis
MH  - Receptors, Serotonin/*drug effects
MH  - Risk Factors
MH  - Serotonin/*metabolism
MH  - Substance-Related Disorders/*diagnosis
MH  - Syndrome
RF  - 49
EDAT- 1997/01/01 00:00
MHDA- 1997/01/01 00:01
CRDT- 1997/01/01 00:00
PHST- 1997/01/01 00:00 [pubmed]
PHST- 1997/01/01 00:01 [medline]
PHST- 1997/01/01 00:00 [entrez]
AID - 10.1007/BF03033064 [doi]
PST - ppublish
SO  - Eur Arch Psychiatry Clin Neurosci. 1997;247(3):113-9. doi: 10.1007/BF03033064.