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Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects.
J Psychiatry Neurosci. 2000 Sep; 25(4):337-46.JP

Abstract

OBJECTIVE

Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine.

DESIGN

Randomized, double-blind, placebo-controlled trial.

PATIENTS

Thirty individuals with major depressive disorder.

INTERVENTIONS

Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo.

OUTCOME MEASURES

Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures.

RESULTS

During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness.

CONCLUSIONS

Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings.

Authors+Show Affiliations

Clarke Division, Centre for Addiction and Mental Health, Toronto, Ont. robert_levitan@camh.netNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11022398

Citation

Levitan, R D., et al. "Preliminary Randomized Double-blind Placebo-controlled Trial of Tryptophan Combined With Fluoxetine to Treat Major Depressive Disorder: Antidepressant and Hypnotic Effects." Journal of Psychiatry & Neuroscience : JPN, vol. 25, no. 4, 2000, pp. 337-46.
Levitan RD, Shen JH, Jindal R, et al. Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects. J Psychiatry Neurosci. 2000;25(4):337-46.
Levitan, R. D., Shen, J. H., Jindal, R., Driver, H. S., Kennedy, S. H., & Shapiro, C. M. (2000). Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects. Journal of Psychiatry & Neuroscience : JPN, 25(4), 337-46.
Levitan RD, et al. Preliminary Randomized Double-blind Placebo-controlled Trial of Tryptophan Combined With Fluoxetine to Treat Major Depressive Disorder: Antidepressant and Hypnotic Effects. J Psychiatry Neurosci. 2000;25(4):337-46. PubMed PMID: 11022398.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects. AU - Levitan,R D, AU - Shen,J H, AU - Jindal,R, AU - Driver,H S, AU - Kennedy,S H, AU - Shapiro,C M, PY - 2000/10/7/pubmed PY - 2001/2/28/medline PY - 2000/10/7/entrez SP - 337 EP - 46 JF - Journal of psychiatry & neuroscience : JPN JO - J Psychiatry Neurosci VL - 25 IS - 4 N2 - OBJECTIVE: Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Thirty individuals with major depressive disorder. INTERVENTIONS: Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo. OUTCOME MEASURES: Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures. RESULTS: During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness. CONCLUSIONS: Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings. SN - 1180-4882 UR - https://www.unboundmedicine.com/medline/citation/11022398/Preliminary_randomized_double_blind_placebo_controlled_trial_of_tryptophan_combined_with_fluoxetine_to_treat_major_depressive_disorder:_antidepressant_and_hypnotic_effects_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=11022398.ui DB - PRIME DP - Unbound Medicine ER -