Effects of Tryptophan Depletion in Drug-Free Depressed Patients Who Responded to Total Sleep Deprivation

Neumeister, Alexander; Praschak-Rieder, Nicole; Heßelmann, B.; Vitouch, Oliver; Rauh, Manfred; Barocka, Arnd; Tauscher, Johannes; Kasper, Siegfried

doi:10.1001/archpsyc.55.2.167

Cited by 63 publications

(28 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The timescales in the two studies, however, are not comparable and make it difficult to come to this conclusion. The positive effects of tryptophan depletion in the Neumeister et al (1998) study occurred almost 24 h later rather than 7.5 h later as in our study. After 24 h, subjects in our study who had an increase in their HRSD scores had already returned to their pre-TFD levels.…”

Section: Discussionsupporting

confidence: 61%

“…The other two studies by Delgado et al (1991Delgado et al ( , 1999 with partially remitted patients do not list the HRSD scores but have very similar inclusion criteria regarding the HRSD scores. One final interpretation is suggested by Neumeister et al (1998), which showed that tryptophan depletion prevented depressive relapses in patients who responded favorably to sleep deprivation after the recovery night of sleep. This study suggests that tryptophan depletion may actually decrease depressive symptoms in some people.…”

Section: Discussionmentioning

confidence: 99%

“…In another study by Leyton et al (2000), however, medication-free, remitted patients with a family history of psychiatric disorders had significantly greater mood-lowering responses to TFD than remitted patients without the family history. Most surprisingly, in a study by Neumeister et al (1998), TFDs in patients who responded to total sleep deprivation prevented depressive relapse after the recovery night in most patients.The current study examines the effects of the antidepressant bupropion on sleep and of a TFD on partially remitted depressed outpatients being treated with bupropion. Bupropion's mechanism of action as an antidepressant is not completely understood.…”

mentioning

confidence: 92%

See 2 more Smart Citations

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Evans

Golshan

Kelsoe

et al. 2002

Neuropsychopharmacology

View full text Add to dashboard Cite

Serotonin has been implicated in both sleep and mood regulation. When central serotonin was depleted with a tryptophan-free amino acid drink (TFD),Serotonin (5-hydroxytryptamine; 5-HT) has long been implicated in the pathophysiology of depression as well as in the sleep and mood abnormalities associated with depression (Maes and Meltzer 1995). Specifically, deficiencies in 5-HT levels or in cellular responses to 5-HT neurotransmission are thought to be involved in depression. In support of this idea, deficiencies in 5-HT neurotransmission in various projections from the raphe nucleus can at least partially explain many of the common abnormalities seen in depression such as a depressed mood, decreased interest and pleasure, decreased appetite, and insomnia (Stahl 2000). Also commonly seen in depression are reduced rapid eye -Colin 1982;McCarley 1982;Jones 1991;Luebke et al. 1992).The rate of 5-HT synthesis is limited by the availability of its amino acid precursor, tryptophan. Rapid depletion of plasma tryptophan levels by administration of a tryptophan-free amino acid drink (TFD) depletes central 5-HT levels (Biggio et al. 1974;Moja et al. 1988). See Moore et al. (2000) for a recent review of the TFD literature.Consistent with the hypothesis that 5-HT inhibits REM sleep, Bhatti et al. (1998) found that a TFD decreased REM latency and increased REM% in normal male subjects. Voderholzer et al. (1998) found a significant increase in RD in 12 healthy subjects after TFD administration but saw no other significant REM changes. A study by Moore et al. (1998) found reduced RL and stage 2 percent (S2%) and increased REM% and RD after TFD administration in fully remitted depression patients on selective serotonin reuptake inhibitors (SSRIs). Additionally, in four patients treated with the monoamine oxidase inhibitor (MAOI), phenelzine, Landolt et al. (2000) showed increased REM time and REM% after TFD administration.With regard to mood, TFD studies have had mixed results when tested in normal subjects. One TFD study showed normal males having significantly increased scores on a depression scale, the Multiple Affect Adjective Checklist (MAACL), after TFD administration (Young et al. 1985). Benkelfat et al. (1994) also found decreased mood on the Profile of Mood States (POMS) in six out of 20 of his healthy male subjects with a multigenerational history of affective disorder. Additionally, Klaassen et al. (1999) found that TFD administration lowered mood in both subjects with and without a family history of affective disorders with the mood changes being significantly more evident in those with a family history. Ellenbogen et al. (1996) showed that healthy female subjects had significantly lower scores after a TFD on four of six scales on the bipolar form of the POMS including the depression scale. However, Ellenbogen et al. (1999) showed that normal females with a multi-generational family history of major affective disorders had no lowering of mood in response to a TFD. Quintin et al. (2001) showed a decline in mood as m...

show abstract

Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 92%

See 1 more Smart Citation

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Evans

Golshan

Kelsoe

et al. 2002

Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

“…Variable effects on mood have been reported in depressed patients treated with electroconvulsive therapy (Cassidy et al 1997), in depressed and bipolar patients euthymic following one night of total sleep deprivation (Neumeister et al 1998a), or in seasonal affective disorder patients treated with bright light therapy (Lam et al 1996;Neumeister et al 1997Neumeister et al , 1998bLenzinger et al 1999). Cases of RTDinduced full clinical relapse (meeting Delgado et al (1990) criteria) are rare.…”

Section: Does Rtd Reverse Other Beneficial Treatments In Mood Disorders?mentioning

confidence: 99%

Clinical and Physiological Consequences of Rapid Tryptophan Depletion

Moore

Landolt

Seifritz

et al. 2000

Neuropsychopharmacology

184

121

View full text Add to dashboard Cite

We review here the rapid tryptophan depletion (RTD) methodology and its controversial association with depressive relapse. RTD has been used over the past decade to deplete serotonin (5-hydroxy-tryptamine, or 5-HT) in humans and to probe the role of the central serotonin system in a variety of psychiatric conditions. Its current popularity was stimulated by reports that RTD reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) KEY WORDS : 5-HT; Serotonin; Tryptophan-free drink; Major depressionSerotonin (5-hydroxy-tryptamine, or 5-HT) is involved in many physiologic and behavioral systems and clinical disease states. Much of the information available on the function of serotonin comes from pharmacological agents which mimic or amplify endogenous serotonergic neurotransmission, such as serotonin agonists or SSRIs. Historically, methods to functionally deplete serotonin have been problematic. Even previous approaches that have been moderately successful in experimental animals -such as the 5-HT synthesis inhibitor, parachloro-phenylalanine (PCPA); the neurotoxin 5-6-dihydroxy-tryptamine; or various lesions to the serotonergic raphe nuclei of the brainstem -have been non-specific, rife with secondary effects, or clearly inapplicable to humans (e.g., Engelman et al. 1967;Koella et al. 1968;Jouvet et al. 1967). The advent of rapid tryptophan depletion (RTD) as a method to deplete central serotonin has been met with enthusiasm because of its reversibil- NO . 6 ity, its relative lack of side effects, and its merit in elucidating the pathophysiology of various psychiatric conditions. This paper reviews the RTD methodology and its reported ability to induce a depressive relapse in euthymic patients, and other physiological and clinical effects. RAPID TRYPTOPHAN DEPLETION Availability of Tryptophan and Serotonin SynthesisRTD is based on the current understanding of the 5-HT biosynthetic pathway, in which the first step is generally considered to be the rate-limiting one. The first step entails the hydroxylation of the amino acid TRP (by the enzyme TRP hydroxylase, or TRP-H) into the intermediate product 5-hydroxy-tryptophan, or 5-HTP. 5-HTP is then decarboxylated into 5-HT. Under normal conditions, TRP-H is about 50% saturated with TRP. Increasing or decreasing the availability of TRP correlates highly with the amount of 5-HT produced (e.g., Lin et al. 1969;Schaechter and Wurtman 1990). Because the body cannot synthesize TRP, reducing dietary intake of TRP reduces TRP levels in plasma and diminishes its transport from plasma into the brain.In humans, TRP depletion is accomplished by consuming a TRP-free amino acid drink (e.g., Delgado et al. 1990;Biggio et al. 1974). This drink contains 15 amino acids in the same proportion as in human milk, except that TRP, aspartic acid, and glutamic acid are omitted (see Table 1). Within a matter of hours (4 to 12), plasma TRP declines to 10-50% of baseline levels (Delgado et al. 1990(Delgado et al. , 199...

show abstract

“…Sleep deprivation's efficacy may be amplified by 5-HT enhancing drugs (Wirz-Justice et al 1976;Benedetti et al 1997;Smeraldi et al 1999) and appears to be related with a functional polymorphism within the promoter of the serotonin transporter gene (Benedetti et al 1999). Interestingly, tryptophan depletion does not reverse sleep deprivation's antidepressant effects but rather prevents depressive relapse after one night of recovery sleep (Neumeister et al 1998). …”

Section: Antidepressant Action Of Sleep Deprivationmentioning

confidence: 99%

Contribution of Sleep Physiology to Depressive Pathophysiology

Seifritz

2001

Neuropsychopharmacology

View full text Add to dashboard Cite

Effects of Tryptophan Depletion in Drug-Free Depressed Patients Who Responded to Total Sleep Deprivation

Cited by 63 publications

References 52 publications

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Clinical and Physiological Consequences of Rapid Tryptophan Depletion

Contribution of Sleep Physiology to Depressive Pathophysiology

Contact Info

Product

Resources

About