Skip to main content Accessibility help

Acute tryptophan depletion and Lewy body dementias

  • Janet L. Mace (a1), Richard J. Porter (a2), John C. Dalrymple-Alford (a3) (a4), Chris Collins (a5) and Tim J. Anderson (a4) (a6)...



Studies using acute tryptophan depletion (ATD) to examine the effects of a rapid reduction in serotonin function have shown a reduction in global cognitive status during ATD in Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the severe cholinergic loss evident in dementia with Lewy bodies (DLB) and Parkinson's disease and dementia (PDD), we predicted that a reduction of global cognitive status during ATD would be greater in these conditions than in AD.


Patients having DLB or PDD underwent ATD in a double-blind, placebo-controlled, randomized, counterbalanced, crossover design.


While the study intended to test 20 patients, the protocol was poorly tolerated and terminated after six patients attempted, but only four patients – three with DLB and one with PDD – completed the protocol. The Modified Mini-Mental State Examination (3MSE) score was reduced in all three DLB patients and unchanged in the PDD and dementia patient during ATD compared with placebo.


This reduction in global cognitive function and the poor tolerability may fit with the hypothesis that people with dementia with Lewy bodies have sensitivity to the effects of reduced serotonin function.


Corresponding author

Correspondence should be addressed to: Professor R. J. Porter, Department of Psychological Medicine, University of Otago, Christchurch, PO Box 4345 Christchurch, New Zealand. Phone: +64 3 372 0400; Fax: +64 3 372 0407. Email:


Hide All
Bohnen, N. I., Kaufer, D. I., Hendrickson, R., Constantine, G. M., Mathis, C. A. and Moore, R. Y. (2007). Cortical cholinergic denervation is associated with depressive symptoms in Parkinson's disease and parkinsonian dementia. Journal of Neurology, Neurosurgery, and Psychiatry, 78, 641643.
Bohnen, N. I. et al. (2003). Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study. Archives of Neurology and Psychiatry, 60, 17451748.
Emre, M. et al. (2007). Clinical diagnostic criteria for dementia associated with Parkinson's disease. Movement Disorders, 22, 16891707; quiz 1837.
Hoehn, M. M. and Yahr, M. D. (1967). Parkinsonism: onset, progression and mortality. Neurology, 17, 427442.
Mace, J. L., Porter, R. J., Dalrymple-Alford, J. C. and Anderson, T. J. (2010a). The effects of acute tryptophan depletion on mood in patients with Parkinson's disease and the healthy elderly. Journal of Psychopharmacology, 24, 615619.
Mace, J. L., Porter, R. J., Dalrymple-Alford, J. C., Wesnes, K. A. and Anderson, T. J. (2010b). Effects of acute tryptophan depletion on neuropsychological and motor function in Parkinson's disease. Journal of Psychopharmacology, 24, 14651472.
Mace, J. L., Porter, R. J., Dalrymple-Alford, J. C., Wesnes, K. A. and Anderson, T. J. (2011). The effects of acute tryptophan depletion on neuropsychological function, mood and movement in the healthy elderly. Journal of Psychopharmacology, 25, 13371343.
McKeith, I. G. et al. (1996). Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology, 47, 11131124.
Nelson, H. E. (1982). National Adult Reading Test Manual, Windsor: NFER-Nelson.
Porter, R. J., Bourke, C. and Gallagher, P. (2007). Neuropsychological impairment in major depression: its nature, origin and clinical significance. Australian and New Zealand Journal of Psychiatry, 41, 115128.
Porter, R. J., Lunn, B. S. and O'Brien, J. T. (2003). Effects of acute tryptophan depletion on cognitive function in Alzheimer's disease and in the healthy elderly. Psychological Medicine, 33, 4149.
Porter, R. J., Lunn, B. S., Walker, L. L., Gray, J. M., Ballard, C. G. and O'Brien, J. T. (2000). Cognitive deficit induced by acute tryptophan depletion in patients with Alzheimer's disease. American Journal of Psychiatry, 157, 638640.
Porter, R. J., Phipps, A. J., Gallagher, P., Scott, A., Stevenson, P. S. and O'Brien, J. T. (2005). Effects of acute tryptophan depletion on mood and cognitive functioning in older recovered depressed subjects. American Journal of Geriatric Psychiatry, 13, 607615.
Price, L. H., Malison, R. T., McDougle, C. J., McCance-Katz, E. F., Owen, K. R. and Heninger, G. R. (1997). Neurobiology of tryptophan depletion in depression: effects of m-chlorophenylpiperazine (mCPP). Neuropsychopharmacology, 17, 342350.
Scholtissen, B., Verhey, F. R., Adam, J. J., Prickaerts, J. and Leentjens, A. F. (2006). Effects of acute tryptophan depletion on cognition, memory and motor performance in Parkinson's disease. Journal of the Neurological Sciences, 248, 259265.
Teng, E. L. and Chui, H. C. (1991). Manual for the Administration and Scoring of the Modified Mini-Mental State (3MS) test., Los Angeles: University of Southern California School of Medicine.
Tiraboschi, P. et al. (2002). Early and widespread cholinergic losses differentiate dementia with Lewy bodies from Alzheimer disease. Archives of General Psychiatry, 59, 946951.
Walker, M. P. et al. (2000). The clinician assessment of fluctuation and the one day fluctuation assessment scale. Two methods to assess fluctuating confusion in dementia. British Journal of Psychiatry, 177, 252256.
Young, S. N. (2013). Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects. Journal of Psychiatry and Neuroscience, 38, 294305.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

International Psychogeriatrics
  • ISSN: 1041-6102
  • EISSN: 1741-203X
  • URL: /core/journals/international-psychogeriatrics
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed