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

Abstract

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...

Enhancement of serotonergic and noradrenergic neurotransmission in the rat hippocampus by sustained administration of bupropion

“…In line with this, Cryan et al (2001Cryan et al ( , 2004 reported that the antidepressant-like effect of bupropion is primarily attributable to the NE system. Furthermore, although tryptophan depletion did not induce relapses in bupropion-remitted patients with depression, certain mood measures were decreased (Evans et al 2002). The time-dependent enhancement of 5-HT and NE transmission due to reduced responsiveness of terminal α 2 -adrenergic hetero-and autoreceptors, respectively, may contribute to the therapeutic action of bupropion in major depression.…”

Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies

“…13,61,71,72,79,85,98,118,119,123,124 Six studies included patients ( < 25% of total) with Bipolar I or II disorder. 15,98,99,108,117,124 In total, this were 14 patients. The reason that several apparently high-quality studies were rated as moderate in this review was due to the lack of presentation of the mood effects, which in those studies was not the primary outcome.…”

“…In remitted patients using AD decreased mood after ATD was especially seen in the first 5 months after the achievement of remission (pooled Hedges' g À0.55 (À0.90 to À0.21) Q res = 47.18, df = 2, P < 0.0001). 92,95,[99][100][101]105 In contrast, remitted patients without AD showed more decrease in mood after X2 months of remission (Hedges' g À1.65 (À2.60 to À0.69) Q res = 13.81, df = 2, P = 0.001) 67,92,93 (figure available on request).…”

“…Three of these studies were also included in the metaanalysis. 98,99,117 This involved 6 patients of the total of 265 patients (2.2%) in the concerning meta analytical comparisons. Therefore, we consider the possibility of bias by the inclusion of this etiologically different disorder unlikely.…”

Equivalent effects of acute tryptophan depletion on REM sleep in ecstasy users and controls

“…ATD has been shown to reduce concentrations of 5-HT in the cerebrospinal fluid (CSF) of animals (Moja et al 1989) and humans (Carpenter et al 1998;Williams et al 1999), with a maximal decrease in plasma tryptophan 5-7 h after intake of the amino acid mixture (Rubia et al 2005). ATD has been shown to have clear effects on several sleep parameters, especially REM sleep (Haynes et al 2004;Moore et al 1998;Evans et al 2002;Landolt et al 2003;Bhatti et al 1998;Riemann et al 2002;Voderholzer et al 1998).…”