Tryptophan/Imipramine in Depression

Jensen, Knud; Fruensgaard, Kjeld; Ahlfors, U. G.; Pihkanen, T.; S, Tuomikoski; E, Ose; Dencker, S. J.; Lindberg, D.; Nagy, Ádám

doi:10.1016/s0140-6736(75)92151-0

Cited by 40 publications

(11 citation statements)

References 10 publications

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“…The same explanation might be offered for the increase of tryptophan only in the brain caused by tricyclic antidepressants, bearing in mind that for some of them a serotonergic component has already been described (Carlsson et al} 1969a-c). This further confirms that tryptophan levels can modulate the activity of tricyclic antidepres sants (Jensen et al, 1975).…”

Section: Resultssupporting

confidence: 74%

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Effect of Different Psychoactive Drugs on Serum and Brain Tryptophan Levels

Valzelli¹,

Bernasconi²,

Coen³

et al. 1980

Neuropsychobiology

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A considerable amount of evidence indicates that the brain tryptophan level depends on circulating tryptophan. Changes of tryptophan concentration have also been described to modify the activity of benzodiazepines and tricyclic antidepressants. In the present study, a series of psychoactive drugs have been preliminarily screened for their activity on brain and plasma tryptophan levels. The results obtained suggest that tryptophan may be involved to varying extents in the activity of different psychoactive compounds.

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Section: Resultssupporting

confidence: 74%

“…Further, decreased or increased serum tryptophan has been seen to change benzo diazepine and tricyclic antidepressant activity (Billingsley and Kubena, 1976;Jensen et al, 1975) . In vitro experiments have recently shown that benzodiazepines increase trypto phan uptake by brain slices (Höckel et al, 1977).…”

Section: Introductionmentioning

confidence: 99%

Effect of Different Psychoactive Drugs on Serum and Brain Tryptophan Levels

Valzelli¹,

Bernasconi²,

Coen³

et al. 1980

Neuropsychobiology

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“…It has been suggested to be as effective as ECT (Coppen, Shaw, Herzberg & Maggs, 1967) and no better than placebo (Carroll, Mowbray & Davies, 1970;Murphy, Baker, Goodwin, Miller, Kotin & Bunney, 1974). Whilst one recent study has indicated that the efficacy of tryptophan is similar to that of imipramine (Jensen, Fruensgaard, Ahlfors, Pihkanan, Tuomikoski, Ose, Dencker, Lindberg & Nagy, 1975) another has suggested that its value alone is small, but that it potentiates other antidepressant drugs such as chlorimipramine or monoamine oxidase inhibitors (d'Elia, Hanson & Raotma, 1978).…”

Section: Introductionmentioning

confidence: 99%

Metabolism of an oral tryptophan load. I: Effects of dose and pretreatment with tryptophan.

Ar¹,

Aronson²,

Curzon³

et al. 1980

Brit J Clinical Pharma

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The Royal Hallamshire Hospital, Sheffield. 1 The metabolism of three oral doses of L-tryptophan (50, 25 and 10 mg/kg) in healthy young males has been investigated. 2 There was a linear relationship between both peak height and area under curve of the total plasma tryptophan concentrations whilst the relationship between these parameters and plasma free tryptophan was hyperbolic. 3 Before the tryptophan load about 85% of plasma tryptophan was bound to albumin. As plasma tryptophan concentrations increased there was a hyperbolic increase in free tryptophan. Scatchard analysis revealed 1.4 binding sites/molecule albumin with a dissociation constant (Kd) of 57.9 ,uM. Following administration of L-tryptophan (50 mg/kg) twice daily for 7 days there was no alteration in the number of binding sites but the dissociation constant (Kd) had decreased to 30.9 ,uM. 4 L-Tryptophan (50 mg/kg twice daily for 7 days) markedly increased both basal plasma total and free tryptophan. However following a further load the total tryptophan curve was comparable to that seen after acute administration. The plasma free tryptophan curve was lowered relative to that seen after an acute dose. 5 Increasing the tryptophan dose shortened the plasma half-life and decreased the volume of distribution and the rate of clearance. Longer term tryptophan administration had no significant effect on plasma half-life or volume of distribution but did decrease the rate of plasma clearance. 6 The plasma kynurenine concentration increased with increasing tryptophan dose and basal concentrations increased markedly after longer term tryptophan administration. 7 Tryptophan administration either acutely or chronically produced little change in urinary tryptophan or 5-hydroxyindole acetic acid excretion. Urinary kynurenine and indole acetic acid excretion increased with increasing doses of tryptophan. 8 Data are discussed in relation to the administration of L-tryptophan for the treatment of depression.

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“…Reports of L-tryptophan being as effective as imipramine as an antidepressant have been published by Coppen et al, 15 Kline and Shah, 16 Broadhurst, 17 and Jensen et al 18 The last study demonstrated that the reduction of depressive symptoms was more rapid in the imipramine group, though side effects were less frequent in tryptophan recipients. No significant antidepressant effect of L-tryptophan was reported in the studies of Bowers, 19 Carroll et al, 20 Bunney et al, 21 and Murphy et al 22 Several of these studies, pro and con, were singleblind trials or had a small sample size.…”

Section: Use As An Antidepressantmentioning

confidence: 98%

L-Tryptophan in Psychiatric Practice

Pakes¹

1979

Drug Intelligence & Clinical Pharmacy

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The amino acid L-tryptophan is being prescribed more and more for the treatment of depression. Since L-tryptophan is a precursor to serotonin and crosses the blood brain barrier, it is believed by some investigators to be most effective in depressions secondary to serotonin deficiency. Several studies using L-tryptophan with and without concomitant tryptophan pyrrolase inhibitors, decarboxylase and hydroxylase cofactors, or decarboxylase inhibitors, have indicated its usefulness in combatting depression, but other studies have found it to be of value only as an ancillary drug therapy with tricyclic antidepressants and especially with monoamine oxidase inhibitors. The drug's sedative side effect has prompted several studies which indicate it has some value as a hypnotic agent. L-tryptophan has also been reported to be useful in acute mania, although its mechanism of action in this condition is not well understood. Side effects to L-tryptophan use are minimal, but long-term adverse effects are in question, as certain tryptophan metabolites have been implicated as being in excess in bladder and breast cancers. The greatest utility of L-tryptophan is probably as a concomitant agent with MAO inhibitors, and in depressions that have not responded to tricyclic antidepressants, MAO inhibitors alone, or electroconvulsive therapy.

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Tryptophan/Imipramine in Depression

Cited by 40 publications

References 10 publications

Effect of Different Psychoactive Drugs on Serum and Brain Tryptophan Levels

Effect of Different Psychoactive Drugs on Serum and Brain Tryptophan Levels

Metabolism of an oral tryptophan load. I: Effects of dose and pretreatment with tryptophan.

L-Tryptophan in Psychiatric Practice

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