Elsevier

Biological Psychiatry

Volume 56, Issue 7, 1 October 2004, Pages 503-509
Biological Psychiatry

Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorder

https://doi.org/10.1016/j.biopsych.2004.07.006Get rights and content

Background

Tryptophan depletion studies have suggested that central serotonin (5-hydroxytryptamine, 5-HT) function mediates the therapeutic effect of selective serotonin reuptake inhibitors (SSRIs) in depression and panic disorder. The present study tested the hypothesis that temporary reduction in central 5-HT transmission, through acute tryptophan depletion, could reverse the therapeutic effect of the SSRIs in social anxiety disorder (SAD) patients.

Methods

Fourteen patients with SAD who showed sustained clinical improvement with SSRI treatment underwent tryptophan depletion in a double-blind, placebo-controlled, crossover design, over 2 days 1 week apart. At the peak time of depletion, the participants also underwent three behavioral challenges: autobiographical script, verbal task, and neutral script. Psychological outcome was assessed with the Spielberger State Anxiety Inventory (STAI) Form Y-1 and visual analog scales (VAS) measuring anxiety, depression, and somatic symptoms.

Results

Anxiety was significantly increased on the depletion day compared with the control day, both on the STAI Form Y-1 and composite VAS score. Furthermore, there was a significant depletion × time interaction, explained mainly by the anxiogenic effect of the autobiographical script. In contrast, the verbal and the neutral tasks failed to differentiate between depletion and placebo.

Conclusions

Tryptophan depletion induced significant increase of anxiety in treated SAD patients, which was more prominent during the recital of an autobiographical script. This finding supports the notion that SSRIs improve social anxiety by increasing 5-HT availability. The autobiographical script seems to be a more robust challenge test for SAD than the stressful verbal task.

Section snippets

Subjects and treatment

Prospective subjects were recruited from a tertiary anxiety disorders outpatient clinic that accepts referrals from community mental health teams and general practitioners, as well as self-referrals in response to local media awareness campaigns. An experienced clinician (MA, SH, SA, CB, or JN) made the diagnosis of social anxiety disorder (generalized type), according to DSM-IV criteria (American Psychiatric Association 1994) and by means of a semi-structured interview (Mini International

Characteristics of the sample

Fourteen patients (9 male, 5 female) completed the study, with a mean (SD) age of 39.9 (11.2) years (range: 21–58 years). Mean duration of treatment was 7.8 months (range: 4–12 months). The mean dose of paroxetine (12 patients) at the time of depletion was 32.5 (9.65) mg/day (range: 20–50 mg/day). Two patients were treated with citalopram: one received 30 mg/day and the other 40 mg/day. Five subjects had a history of depression and one of dysthymia, but none was depressed during the treatment

Discussion

In this study, we explored the importance of 5-HT in mediating the clinical effect of SSRIs in the treatment of SAD, using the TD technique. The main finding was that levels of anxiety, as measured with STAI Form Y-1 and VAS, were significantly increased on the TD day compared with the control day, thus indicating that the therapeutic effect of SSRIs in SAD depends on the availability of 5-HT. The increase in state anxiety observed in this study was clinically significant and considerable by

References (48)

  • Diagnostic and Statistical Manual of Mental Disorders

    (1994)
  • D. Baldwin et al.

    Paroxetine in social phobia/social anxiety disorderRandomised, double-blind, placebo-controlled study. Paroxetine Study Group

    Br J Psychiatry

    (1999)
  • L.C. Barr et al.

    Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors

    Arch Gen Psychiatry

    (1994)
  • A.T. Beck et al.

    Beck Depression Inventory Manual

    (1987)
  • D.C. Beidel

    Social anxiety disorder: Etiology and early clinical presentation

    J Clin Psychiatry

    (1998)
  • C. Bell et al.

    Tryptophan depletion and its implications for psychiatry

    Br J Psychiatry

    (2001)
  • C. Bell et al.

    Does 5-HT restrain panic?A tryptophan depletion study in panic disorder patients recovered on paroxetine

    J Psychopharmacol

    (2002)
  • S. Blomhoff et al.

    Randomised controlled general practice trial of sertraline, exposure therapy and combined treatment in generalised social phobia

    Br J Psychiatry

    (2001)
  • A.J. Bond et al.

    The use of analogue scales in rating subjective feelings

    Br J Med Psychol

    (1974)
  • L.L. Carpenter et al.

    Tryptophan depletion during continuous CSF sampling in healthy human subjects

    Neuropsychopharmacology

    (1998)
  • K.M. Connor et al.

    Psychometric properties of the Social Phobia Inventory (SPIN)New self-rating scale

    Br J Psychiatry

    (2000)
  • E.W. Cook et al.

    Emotional imagery and the differential diagnosis of anxiety

    J Consult Clin Psychol

    (1988)
  • D.M. Fresco et al.

    The Liebowitz Social Anxiety Scale: A comparison of the psychometric properties of self-report and clinician-administered formats

    Psychol Med

    (2001)
  • W. Guy

    ECDEU Assessment Manual for Psychopharmacology: Publication ADM 76–338

    (1976)
  • Cited by (0)

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