Alterations in brain tryptophan levels cause changes in brain serotonin synthesis, and this has been used to study the implication of altered serotonin levels in humans. In the acute tryptophan depletion (ATD) technique, subjects ingest a mixture of amino acids devoid of tryptophan. This results in a transient decline in tissue tryptophan and in brain serotonin. ATD can result in lower mood and increase in irritability or aggressive responding. The magnitude of the effect varies greatly depending on the susceptibility of the subject to lowered mood or aggressivity. Unlike ATD, tryptophan can be given chronically. Tryptophan is an antidepressant in mild to moderate depression and a small body of data suggests that it can also decrease aggression. Preliminary data indicate that tryptophan also increases dominant behavior during social interactions. Overall, studies manipulating tryptophan levels support the idea that low serotonin can predispose subjects to mood and impulse control disorders. Higher levels of serotonin may help to promote more constructive social interactions by decreasing aggression and increasing dominance.

The role of serotonin in human mood and social interaction: Insight from altered tryptophan levels

Objective:There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta-analysis) has been conducted.Method:A systematic search of PubMed, CINAHL, Cochrane Library, and Web of Science was conducted up to December 2015 for clinical trials using adjunctive nutrients for depression. Where sufficient data were available, a random-effects model analyzed the standard mean difference between treatment and placebo in the change from baseline to endpoint, combining the effect size data. Funnel plot and heterogeneity analyses were also performed.Results:Primarily positive results were found for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or et...

https://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.2016.15091228

Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses

Biochemistry of tryptophan in health and disease.

1. 1. An alteration in the brain serotonergic system in individuals with depression, and possibly mania, has been proposed on the basis that these patients have reduced 5-hydroxyindoleacetic acid levels in cerebrospinal fluid. 2. 2. Reduced brain serotonin concentrations have also been observed in some studies of suicides. 3. 3. Other investigations of serotonin-related functions in depressed patients have yielded equivocal results, although potentiation of the therapeutic effects of antidepressant drugs by L-tryptophan, and their reversal by p-chlorophenylalanine, are in agreement with animal pharmacological studies indicating that antidepressant drugs act in part via serotonergic mechanisms. 4. 4. The biochemical basis for the suggested serotonergic system alterations in the affective disorders remains unknown. 5. 5. Additional basic information is needed on (a) the storage, transport and synthesis of indoleamines, (b) adaptational mechanisms within the system and their relationships to other neurotransmitter systems, and (c) correlations with behavior in animals and man. 6. 6. Such studies may further our understanding of the role which the serotonergic system alterations may play in the affective disorders.

The brain serotonergic system in the affective disorders.

BACKGROUND: 5 Hydroxytryptophan (5-HTP) and tryptophan are so-called natural alternatives to traditional antidepressants, used to treat unipolar depression and dysthymia. OBJECTIVES: To determine whether 5-HTP and tryptophan are more effective than placebo, and whether they are safe to use to treat depressive disorders in adults. SEARCH STRATEGY: Trials were searched in computerized general (Medline, Psychlit, and Embase) and specialized databases (Cochrane Controlled Clinical Trials Register, Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trial Register); by checking reference lists of relevant articles; by handsearching relevant specialist journals; and by contacting relevant authors where appropriate. Publications in all languages were sought. SELECTION CRITERIA: Trials were included if they were randomized, included patients with unipolar depression or dysthymia, compared preparations of 5-HTP or tryptophan with placebo, and included clinical outcomes assessed by scales assessing depressive symptoms. DATA COLLECTION AND ANALYSIS: Data was extracted independently by the three reviewers, onto data collection forms. Inclusion criteria were applied to all potential studies independently and a coefficient of agreement (Kappa) was calculated for them. Disagreement was resolved by reaching consensus. Trial quality was scored according to risk of bias. Analysis for 5-HTP and tryptophan were combined due to the small number of included trials. MAIN RESULTS: 108 trials were located using the specified search strategy. Of these, only two trials, involving a total of 64 patients, were of sufficient quality to meet inclusion criteria. The available evidence suggests these substances were better than placebo at alleviating depression (Peto Odds Ratio 4.10; 95% confidence interval 1.28-13.15; RD 0.36; NNT 2.78). However, the evidence was of insufficient quality to be conclusive. REVIEWER'S CONCLUSIONS: A large number of studies appear to address the research questions, but few are of sufficient quality to be reliable. Available evidence does suggest these substances are better than placebo at alleviating depression. Further studies are needed to evaluate the efficacy and safety of 5-HTP and tryptophan before their widespread use can be recommended. The possible association between these substances and the potentially fatal Eosinophilia-Myalgia Syndrome has not been elucidated. Because alternative antidepressants exist which have been proven to be effective and safe the clinical usefulness of 5-HTP and tryptophan is limited at present

/pdf/tryptophan-and-5-hydroxytryptophan-for-depression-1u4sdo2ohr.pdf

Tryptophan and 5-hydroxytryptophan for depression.

Depressed patients (unipolar) were given one of the following combinations in an attempt to test aspects of the ‘amine hypothesis’ and to find a preferential therapy: (1) clomipramine; (2) clomipramine and tryptophan; (3) desipramine and clomipramine, and (4) desipramine and tryptophan. Treatment (2) should have given optimal potentiation of 5-HT neurones and (3) and (4) should have acted similarly on both serotoninergic and adrenergic pathways. In no group was there any evidence of accelerated recovery, indicating that the process of conversion to normal mood may be more complex than suggested by most versions of the amine hypothesis.

Tricyclic antidepressants and tryptophan in unipolar depression.

THE MANAGEMENT OF RESISTANT DEPRESSION DEAR Sia, Most patients who suffer from the depressive phase of affective illness remit spontaneously or respond to treatment readily, but in a very small number the illness appears to be relatively resistant to therapy. We would like to initiate discussion on this group, mainly because really intractable illness occurs in such a small proportion of depressed individuals that it is difficult to accumulate experience with a large sample. In those with the clinical picture of the depressive phase of unipolar or bipolar affective illness, charac terized by depression, diurnal variation of mood, loss of appetite and libido, early morning waking, diminished energy, interest and concentration, self blame, etc., there are no known means of distinguish ing those who will become â€ ̃¿ non-responders'. When such individuals are identified it is obvious that the initial diagnosis, together with any psychosocial factors, drugs, endocrine abnormalities, physical illness, etc. which may be hindering recovery, should be re-examined. Management is easier if the order of treatment caters in advance for the few patients who require a continuous and systematic series of therapies. The scheme tabulated gives two of the possible formats, but each new treatment is consi dered in the light of the needs and circumstances of the patient at the time. Both the timing and methods of therapy are ten tative. The position of bilateral electroconvulsive therapy (ECT) in the order of treatments poses particular difficulties, especially since Abrams (:972) has suggested that bilateral ECT is more effective than unilateral treatment. We have tended recently to replace unilateral with bilateral ECT for some patients and omit the second course of EC@, in which

Robyn Hewland

Papers

Tricyclic antidepressants and tryptophan in unipolar depression.

Correspondence: The management of resistant depression.