Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action

Delgado, Pedro L.; Miller, Helen; Salomon, Ronald M.; Licinio, Júlio; Krystal, John H.; Moreno, Francisco; Heninger, George R.; Charney, Dennis S.

doi:10.1016/s0006-3223(99)00014-1

Cited by 264 publications

(149 citation statements)

References 29 publications

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“…One major difference with Delgado et al (1990Delgado et al ( , 1999) is that 69 of the 71 patients included in this reanalysis had shown improvement for at least one month (mean: 18.3 months). In contrast, subjects enrolled in the Delgado studies were clinically stable for only two to four weeks and were on antidepressant medication not longer than 10 weeks.…”

Section: Tryptophan Depletion As a Model Of Ssri Antidepressant Mechamentioning

confidence: 71%

“…The dependent variable was the change from baseline on the ATD session (standardized post score minus standardized pre score), minus the change from baseline after control testing. Since there is convincing evidence that the effect is highest in SSRI treated patients (Delgado et al 1990(Delgado et al , 1999, the type of antidepressant treatment was forced into the regression equation as the first predictor. Next, the following variables were entered stepwise: gender, number of prior depressive episodes, duration of remission, current antidepressant medication use, remission status, chronicity of illness (single episode vs. recurrent episodes) and duration of remission.…”

Section: Correlates and Predictors Of Mood Effects Of Atdmentioning

confidence: 99%

“…The recurrence of symptoms appears to be highest in subjects treated with a selective serotonin reuptake inhibitor (SSRI) (Delgado et al 1990(Delgado et al , 1994(Delgado et al , 1999.…”

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confidence: 99%

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Predictors of Mood Response to Acute Tryptophan Depletion A Reanalysis

Booij

Does

Benkelfat

et al. 2002

Neuropsychopharmacology

166

134

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Acute tryptophan depletion (ATD) induces depressive symptoms in 50-Acute tryptophan depletion (ATD) is a technique used to study serotonin (5-hydroxytryptamine; 5-HT) brain function in mood disorders. In this paradigm, 5-HT function is temporarily lowered by deprivation of its precursor L -Tryptophan (Trp), an amino acid essential for 5-HT synthesis. It has been suggested that behavioral response to ATD might be informative about the pathophysiology of clinical depression and the mechanisms mediating antidepressant efficacy.A number of studies have demonstrated that ATD temporarily induces depressive symptoms in remitted depressive patients treated with antidepressant medication (Delgado et al. 1990; Spillman et al. 2001). The recurrence of symptoms appears to be highest in subjects treated with a selective serotonin reuptake inhibitor (SSRI) (Delgado et al. 1990(Delgado et al. , 1994(Delgado et al. , 1999.However, not all patients react to ATD; even in SSRItreated patients, ATD exacerbates symptoms in 50-60% of investigated patients (Van der Does 2001a). This raises the question of what factors determine response to ATD. It has been argued that induced depressive

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Section: Tryptophan Depletion As a Model Of Ssri Antidepressant Mechamentioning

confidence: 71%

Section: Correlates and Predictors Of Mood Effects Of Atdmentioning

confidence: 99%

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Predictors of Mood Response to Acute Tryptophan Depletion A Reanalysis

Booij

Does

Benkelfat

et al. 2002

Neuropsychopharmacology

166

134

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“…Delgado et al (1990Delgado et al ( , 1991Delgado et al ( , 1999 found that 53-80% of partially remitted depressed patients on SSRIs suffered a "depressive relapse" after administration of a TFD. Another 10 patients on SSRIs in a study by Spillman et al (2001) had significantly increased scores on the 6-item HRSD, the Hamilton Anxiety Rating Scale, and the Symptom Questionnaire Somatic Symptoms and Anxiety in response to a TFD.…”

Section: Serotonin Has Been Implicated In Both Sleep and Mood Regulatmentioning

confidence: 99%

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

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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...

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“…Among women, the short-repeat promotor variant of the 5-HT transporter gene is associated with higher 5-HIAA levels, but in males with lower levels (Williams et al, 2003). Currently, the most common class of effective antidepressant drugs are selective 5-HT reuptake inhibitors (SSRIs) that enhance serotonergic neurotransmission by blocking reuptake (Delgado et al, 1999). Approximately 70% of prescribed SSRIs are given to women (Kessler et al, 1994;Kessler, 2003).…”

Section: Introductionmentioning

confidence: 99%

Sex Differences in the Regulation of Serotonergic Transmission and Behavior in 5-HT Receptor Knockout Mice

Jones

Lucki

2005

Neuropsychopharmacol

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Few studies have examined the relationship between genetics, stress, and sex-linked differences in neurotransmitter systems. Examining serotonin (5-HT) receptor knockout mice on stress-induced behavioral depression, female 5-HT 1B receptor knockout mice demonstrated significantly reduced immobility than either male 5-HT 1B receptor knockout mice or male and female wild-type mice on the tail suspension test (TST) and forced swimming test. The behavioral phenotype was identified as likely due to a disinhibition of 5-HT release, because depletion of 5-HT with parachlorophenylalanine selectively reduced immobility of female 5-HT 1B receptor knockout mice in the TST. In contrast, male and female 5-HT 1A receptor knockout mice demonstrated reduced immobility compared with control mice, but the depletion of 5-HT with PCPA did not reverse the antidepressant-like phenotype. Microdialysis studies confirmed significantly higher baseline levels of hippocampal 5-HT in female, but not male, 5-HT 1B receptor knockout mice. Both male and female 5-HT 1B receptor knockout mice demonstrated augmented dialysate responses to fluoxetine. Also, both male and female 5-HT 1B receptor knockout mice demonstrated reductions of immobility in the TST after treatment with fluoxetine. Therefore, female 5-HT 1B receptor knockout mice demonstrate a sex-linked disinhibition of 5-HT release that sustained higher baseline levels of hippocampal 5-HT and behavioral vulnerability to 5-HT depletion.

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Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action

Cited by 264 publications

References 29 publications

Predictors of Mood Response to Acute Tryptophan Depletion A Reanalysis

Predictors of Mood Response to Acute Tryptophan Depletion A Reanalysis

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

Sex Differences in the Regulation of Serotonergic Transmission and Behavior in 5-HT Receptor Knockout Mice

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