Abstract
Background: Brain serotonin (5-HT) content is dependent on plasma levels of the essential
amino acid, tryptophan (TRP). We have previously reported that rapid TRP depletion
more frequently reversed the antidepressant response to monoamine oxidase inhibitors
and 5-HT reuptake inhibitors than to desipramine (DMI). This study further investigates
the relationship of relapse during TRP depletion to antidepressant type in nonrefractory,
depressed patients randomly assigned to treatment with either DMI or fluoxetine (FLU).
Methods: Fifty-five drug-free depressed (DSM-III-R) patients were randomly assigned
to antidepressant treatment with either DMI or FLU. All patients were either treatment
naive (n = 34) or had previously received successful antidepressant treatment (n = 21). During the treatment phase, 35 patients had therapeutic responses by predetermined
criteria (DMI 18/25; FLU 17/23) and 30 of these (15 DMI responders and 15 FLU responders)
went on to TRP depletion testing. Patients received two 2-day test sessions involving
administration of similar amino acid drinks. One session led to rapid TRP depletion
and the other did not. Behavioral ratings [Hamilton Depression Scale (HDRS)] and plasma
for TRP levels were obtained prior to, during, and after testing. Relapse was defined
as a 50% increase in HDRS with total ≤ 17.
Results: Total and free TRP decreased 70% to 80% 5 hours after the TRP-free drink.
While 8/15 FLU responders relapsed, only 1/15 of the DMI responders relapsed. No patient
experienced significant depressive symptoms during control testing.
Conclusions: Rapid depletion of plasma TRP transiently reverses the antidepressant
response in many patients on FLU but not DMI. Depressive relapse during TRP depletion
appears to be more related to antidepressant type than to patient variables since
patients were randomly assigned to the two treatments. Antidepressant response to
FLU appears to be more dependent on 5-HT availability than that of DMI, suggesting
that antidepressants mediate their therapeutic effects through different mechanisms.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Diagnostic and Statistical Manual of Mental Disorders. 3rd Ed, revised. American Psychiatric Association, Washington, DC1987
- Liquid-chromatographic determination of serotonin and tryptophan in whole blood and plasma.Clin Chem. 1981; 27: 775-776
- Tryptophan depletion in stable lithium-treated patients with bipolar disorder in remission.Arch Gen Psychiatry. 1995; 52: 154-155
Berman RM, Delgado PL, Miller HL, Price LH, Heninger GR, Charney DS. Correlates of depressive relapse in medicated depressed subjects undergoing acute tryptophan depletion. Presented at the 26th Annual Meeting of the Society for Neuroscience, Washington, DC, November, 1996.
- Current advances in the treatment of depression.TIPS. 1994; 15: 220-226
- A role for the serotonin system in the mechanism of action of antidepressant treatments.J Clin Psychiatry. 1990; 51: 14-20
- Norepinephrine in depressive reactions.Arch Gen Psychiatry. 1965; 13: 483-494
Carpenter LL, Anderson G, McDougle CJ, Kirwin PD, Price LH, Heninger GR (1997): Tryptophan depletion during continuous CSF sampling via indwelling lumbar catheter in healthy human subjects. Presented at the 150th Annual Meeting of the American Psychiatric Association, NR #72, San Diego, CA, May 19, 1997.
- Eosinophilia-myalgia syndrome and l-tryptophan containing products—New Mexico, Minnesota, Oregon, and New York.MMWR. 1989; 38: 785-788
- The biochemistry of affective disorders.Br J Psychiatry. 1967; 113: 1237-1264
- Influence of plasma tryptophan on brain 5HT synthesis and serotonergic activity.in: Haber B Gabay S Serotonin Current Aspects of Neurochemistry and Function. Plenum Press, New York1981: 207-219
- Relationships between plasma, CSF and brain tryptophan.J Neural Transm. 1979; 15: 93-105
- Neuroendocrine challenge studies in affective disorders.in: Horton R.W Katona C Biological Aspects of Affective Disorders. Academic Press, London1991: 146-190
- Serotonin function and the mechanism of antidepressant action.Arch Gen Psychiatry. 1990; 47: 411-418
- Neuroendocrine and behavioral effects of dietary tryptophan restriction in healthy subjects.Life Sci. 1989; 45: 2323-2332
- Monoamines and the mechanism of antidepressant action.Psychopharmacol Bull. 1993; 29: 389-396
- Norepinephrine and serotonin in antidepressant action.in: Briley M Antidepressant Therapy at the Dawn of the Third Millennium. Martin Dunitz LTD, London1997: 141-163
Delgado PL, Moreno FA, Gelenberg AJ, Potter R (1997): Sequential catecholamine and 5-HT depletion in mirtazapine-treated depressives. Presented at the 36th Annual Meeting of the American College of Neuropsychopharmacology, Waikoloa, HI, December 8, 1997.
- Neurochemistry of affective disorders.in: Paykel E.S Handbook of Affective Disorders. 2nd ed. Churchill Livingstone, London1992
- Rapid serotonin depletion as a provocative challenge test for patients with major depression.Psychopharmacol Bull. 1991; 27: 321-330
- A molecular and cellular theory of depression.Arch Gen Psychiatry. 1997; 54: 597-606
- Effects of the diet on brain neurotransmitters.Metabolism. 1977; 26: 207-223
- Noradrenergic modulation of central serotonergic neurotransmission.Int Clin Psychopharmacol. 1995; 10: 11-17
- Effects of ingestion of disproportionate amounts of amino acids.Physiol Rev. 1970; 50: 428-548
- Effect of altered tryptophan availability on tissue and extracellular serotonin in the rat.in: Rollema J Westerink B Drijshout W.J Monitoring Molecules in Neuroscience. Krits Repro, Meppel, Netherlands1991: 259-261
- Initiation and adaptation.Am J Psychiatry. 1996; 153: 151-162
- Effects of acute tryptophan depletion in seasonal affective disorder in remission with light therapy.Arch Gen Psychiatry. 1995; 53: 41-44
- Intensification of the central serotonergic processes as a possible determinant of the thymoleptic effect.Lancet. 1969; 1: 132-136
- Reliability and validity of the symptoms of major depressive illness.Arch Gen Psychiatry. 1986; 43: 451-456
- Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression.Arch Gen Psychiatry. 1996; 53: 117-128
- Dose-response decrease in plasma tryptophan and in brain tryptophan and serotonin after tryptophan-free amino acid mixtures in rats.Life Sci. 1989; 44: 971-976
Moreno FA, McGavin C, Malan P, et al (1997): CSF monoamine metabolites during tryptophan depletion. Presented at the 36th Annual Meeting of the American College of Neuropsychopharmacology, Waikoloa, HI, December 10, 1997.
- Current status of the indoleamine hypothesis of the affective disorders.in: Lipton M.A DiMascio A Killam K.F Psychopharmacology A Generation of Progress. Raven Press, New York1978: 1235-1247
- Effects of tryptophan depletion on drug-free patients with seasonal affective disorder during a stable response to bright light therapy.Arch Gen Psychiatry. 1997; 54: 133-138
- Differences between males and females in rates of serotonin synthesis in human brain.Proc Natl Acad Sci U S A. 1997; 94: 5308-5313
- Effects of desipramine and fluvoxamine treatment on the prolactin response to l-tryptophan.Arch Gen Psychiatry. 1989; 46: 625-631
- The amino acid requirements of man.J Biol Chem. 1954; 206: 421-430
- The catecholamine hypothesis of affective disorders.Am J Psychiatry. 1965; 122: 509-522
- Overview.Am J Psychiatry. 1985; 142: 1017-1031
- Parachlorophenylaline reversal of tranylcypromine effects in depressed patients.Arch Gen Psychiatry. 1976; 33: 811-891
- Use of synthesis inhibitors in defining a role for biogenic amines during imipramine treatment in depressed patients.Psychopharmacol Comm. 1975; 1: 239-249
- A test of possible cognitive and environmental influences on the mood lowering effect of tryptophan depletion in normal males.Psychopharmacology. 1987; 91: 451-457
- Tricyclic antidepressants—blood level measurements and clinical outcome.Am J Psychiatry. 1985; 142: 155-162
Williams WA, Hommer DW, Shoaf S, Goldman DS, Geyer C, Linnoila MI. Behavioral and biological effects of acute depletion of plasma tryptophan in patients with alcoholism and normal volunteers. Presented at the 150th Annual Meeting of the American Psychiatric Association, New Research Abstracts, NR #165, May 19, 1997.
- Biochemical aspects of tryptophan depletion in primates.Psychopharmacology. 1989; 98: 508-511
- Plasma tryptophan response curve and its relation to tryptophan requirements in young adult men.J Nutrition. 1971; 101: 45-60
- Tryptophan intake, spacing of meals, and diurnal fluctuations of plasma tryptophan in men.Am J Clin Nutrition. 1969; 22: 1563-1567
- Tryptophan depletion causes a rapid lowering of mood in normal males.Psychopharmacology. 1985; 87: 173-177
Article info
Publication history
Accepted:
January 11,
1999
Received in revised form:
January 4,
1999
Received:
August 26,
1998
Identification
Copyright
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
