Intended for healthcare professionals


A meta-analysis of the association between adherence to drug therapy and mortality

BMJ 2006; 333 doi: (Published 29 June 2006) Cite this as: BMJ 2006;333:15

Tryptophan, serotonin and treatment adherence

Dr.S.H. Simpson et al. evaluated the relation between adherence to
drug therapy and placebo and mortality. For participants with good
adherence to therapy, the risk of mortality was about half of that of
participants with poor adherence. From the meta-analysis data,
drug/placebo adherence increases mortality by approximately half. Authors
conclude that good adherence to drug therapy is associated with positive
health outcomes. Surprisingly this was true in the verum and the placebo

Indeed, adherence to drug therapy may be a surrogate marker for overall
healthy behaviour. It could also be linked with tumour biology and its
interaction with the immune system: activation of tryptophan degrading
enzyme indoleamine (2,3)-dioxygenase (IDO) is induced during inflammation
and immune activation (1). And lower free tryptophan concentrations in
serum/plasma was found to be associated with reduced survival expectation
in patients with HIV infection, with cardiovascular risk and also in
various forms of cancer, e.g., colorectal cancer and malignant melanoma (2
-4). Reduced tryptophan availability influences production of
neurotransmitter 5-hydroxy tryptamine (serotonin), which is also involved
in memory and cognitive function (5). Higher tryptophan and serotonin
levels may allow patients better adhere to the instructions by the
physician and, vice versa, better adherence to treatment may serve as an
indirect marker of a less disturbed tryptophan metabolism and serotonin

Dietmar Fuchs

Division of Biological Chemistry, Biocentre, Innsbruck Medical University,
6020 Innsbruck, Austria

1. Schroecksnadel K, Wirleitner B, Winkler C, Fuchs D. Monitoring
tryptophan metabolism in chronic immune activation. Clin Chim Acta
2006;364: 82-90.

2. Fuchs D, Moeller AA, Reibnegger G, Werner ER, Werner-Felmayer G,
Dierich MP, et al. Increased endogenous interferon-gamma and neopterin
correlate with increased degradation of tryptophan in human
immunodeficiency virus type 1 infection. Immunol Lett 1991;28:207-12.

3. Brandacher G, Perathoner A, Ladurner R, Schneeberger, S, Obrist P,
Winkler C, et al. Prognostic value of Indoleamine 2,3- dioxygenase
expression in colorectal cancer: impact on tumor-infiltrating T-cells.
Clin Cancer Res 2006;12:1144-51.

4. Weinlich G, Murr C, Richardsen L, Winkler C, Ueberall F, Fuchs D.
Decreased serum tryptophan concentration predicts poor prognosis in
malignant melanoma patients. Dermatology (in press)

5. Mitchell ES, Neumaier JF. 5-HT6 receptors: a novel target for
cognitive enhancement.
Pharmacol Ther 2005;108:320-33.

Competing interests:
None declared

Competing interests: No competing interests

30 June 2006
Dietmar Fuchs
Biocentre at Medical University
Innsbruck, Austria