Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects.
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.


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
Thirty individuals with major depressive disorder.


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


METHODS
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.
Levitan
R D
RD
Clarke Division, Centre for Addiction and Mental Health, Toronto, Ont. robert_levitan@camh.net
Shen
J H
JH
Jindal
R
R
Driver
H S
HS
Kennedy
S H
SH
Shapiro
C M
CM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D008297:Male; D012720:Severity of Illness Index; D014364:Tryptophan / Q000627:therapeutic use*
D000928:Antidepressive Agents; D006993:Hypnotics and Sedatives; D005473:Fluoxetine; D014364:Tryptophan