Advertisement

Metabolic Brain Disease

, Volume 21, Issue 2–3, pp 230–241 | Cite as

A comparison of the effects of citalopram and moclobemide on resting brain perfusion in social anxiety disorder

  • J. M. WarwickEmail author
  • P. Carey
  • G. Van der Linden
  • C. Prinsloo
  • D. Niehaus
  • S. Seedat
  • P. Dupont
  • D. J. Stein
Original Paper

Abstract

Introduction: The serotonin specific reuptake inhibitor (SSRI) citalopram and the reversible mono-amine oxidase-A inhibitor (RIMA) moclobemide have both been used successfully for the treatment of social anxiety disorder (SAD). In this study we investigate the effects of these compounds on resting brain function using single photon emission computed tomography (SPECT).

Methods: Subjects meeting DSM-IV criteria for SAD underwent regional cerebral blood flow (rCBF) SPECT using Tc-HMPAO at baseline and after 8 weeks of treatment with either citalopram or moclobemide. Using statistical parametric mapping brain SPECT studies were analysed to determine the effects of treatment on rCBF, to compare the effects of citalopram and moclobemide, and to detect correlations between changes in rCBF and clinical response.

Results: Subjects received citalopram (n=17) or moclobemide (n=14) as therapy. Subjects in both treatment groups demonstrated a significant improvement of SAD symptoms as measured by the Liebowitz Social Anxiety Scale total score. All subjects demonstrated a decrease in rCBF in the insulae post therapy. Subjects receiving citalopram had decreased superior cingulate rCBF after therapy compared to those receiving moclobemide.

Conclusion: Both SSRI's and RIMA's decreased rCBF in the insulae during treatment of SAD; an effect that may be consistent with the role of these regions in processing internal somatic cues evoked by emotional stimuli. Citalopram had a greater effect on superior cingulate perfusion, an effect that is consistent with evidence of high levels of 5-HT transporters in this region.

Keywords

Social phobia SPECT Citalopram Moclobemide Insula Cingulate 

References

  1. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DCGoogle Scholar
  2. Ballenger JC (1998) Focus on social anxiety disorder. J Clin Psychiatry 59(suppl. 17):3Google Scholar
  3. Birbaumer N, Grodd W, Diedrich O, Klose U, Erb M, Lotze M, Schneider F, Weiss U, Flor H (1998) fMRI reveals amygdala activation to human faces in social phobics. Neuroreport 9:1223–1226PubMedGoogle Scholar
  4. Carey PD, Warwick J, Niehaus DJ, Van der Linden G, Van Heerden BB, Harvey BH, Seedat S, Stein DJ (2004) Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram. BMC Psychiatry 4:30PubMedCrossRefGoogle Scholar
  5. Chang LT (1978) A method for attenuation correction in radionuclide computed tomography. IEEE Trans Nucl Sci 25:638–643CrossRefGoogle Scholar
  6. Coplan JD, Lydiard RB (1998) Brain circuits in panic disorder. Biol Psychiatry 44:1264–1276PubMedCrossRefGoogle Scholar
  7. Deakin JWF et al (1991) J Psychopharmacol 5:305–315Google Scholar
  8. de Win MM, Habraken JB, Reneman L, van den Brink W, den Heeten GJ, Booij J (2005) Validation of [(123)I]beta-CIT SPECT to assess serotonin transporters in vivo in humans: a double-blind, placebo-controlled, crossover study with the selective serotonin reuptake inhibitor citalopram. Neuropsychopharmacology 30:996–1005PubMedCrossRefGoogle Scholar
  9. First MB, Spitzer RL, Gibbon M, Williams JBW (1996) Structured Clinical Interview for DSM-IV Axis I Disorders—Clinician Edition. Biometrics Research Department, New York State Research Institute, NYGoogle Scholar
  10. Friston KJ, Frith CD, Liddle PF, Frackowiak RS (1991) Comparing functional (PET) images: the assessment of significant change. J Cereb Blood Flow Metab 11:690–699PubMedGoogle Scholar
  11. Furmark T, Tillfors M, Marteinsdottir I, Fischer H, Pissiota A, Långström B, Fredrikson M (2002) Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioural therapy. Arch Gen Psychiatry 59:425–433.PubMedCrossRefGoogle Scholar
  12. Geday J, Hermansen F, Rosenberg R, Smith DF (2005) Serotonin modulation of cerebral blood flow measured with positron emission tomography (PET) in humans. Synapse 55:224–229PubMedCrossRefGoogle Scholar
  13. Graeff FG, Guimaraes FS, De Andrade TG, Deakin JF (1996) Role of 5-HT in stress, anxiety, and depression. Pharmacol Biochem Behav 54:129–141PubMedCrossRefGoogle Scholar
  14. Kent JM, Coplan JD, Lombardo I, Hwang D, Huang Y, Mawlawi O, Van Heertum RL, Slifstein M, Abi-Dargham A, Gorman JM, Laruelle M (2002) Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with [11C]McN 5652. Psychopharmacology 164:341–348PubMedCrossRefGoogle Scholar
  15. Kessler RM (2003) Imaging methods for evaluating brain function in man. Neurobiol Aging 24:S21–35PubMedCrossRefGoogle Scholar
  16. LeDoux J (1998) Fear and the brain: where have we been and where are we going? Biol Psychiatry 44:1229–1238PubMedCrossRefGoogle Scholar
  17. Liebowitz MR (1987) Social Phobia. Mod Probl Pharmacopsychiat 22:141–173Google Scholar
  18. Liebowitz MR, Schneier FR, Campeas R, Hollander E, Hatterer J, Fyer A, Gorman J, Papp L, Davies S, Gully R, Klein DF (1992) Phenelzine versus atenolol in social phobia: a placebo-controlled trial. Arch Gen Psychiatry 49:290–300PubMedGoogle Scholar
  19. Lorderbaum JP, Kose S, Johnson MR, Arana GW, Sullivan LK, Hamner MB, Ballenger JC, Lydiard RB, Brodrick PS, Bohning DE, George MS (2004) Neural correlates of speech anticipatory anxiety in generalised social phobia. Neuroreport 15:2701–2705Google Scholar
  20. Madsen PL, Vorstrup S, Schmidt JF, Paulson OB (1990) Effect of acute and prolonged treatment with propranolol on cerebral blood flow and cerebral oxygen metabolism in healthy volunteers. Eur J Clin Pharmacol. 39:295–297PubMedCrossRefGoogle Scholar
  21. Magee WJ, Eaton WW, Wittchen HU, McGonagle KA, Kessler RC (1996) Agoraphobia, simple phobia and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry 53:159–168PubMedGoogle Scholar
  22. Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry. 134:382–389PubMedGoogle Scholar
  23. New AS, Buchsbaum MS, Hazlett EA, Goodman M, Koenigsberg HW, Lo J, Iskander L, Newmark R, Brand J, O'Flynn K, Siever LJ (2004) Fluoxetine increases relative metabolic rate in prefrontal cortex in impulsive aggression. Psychopharmacology (Berl) 176:451–458CrossRefGoogle Scholar
  24. Nutt DJ, Bell CJ, Malizia AL (1998) Brain mechanisms of social anxiety disorder. J Clin Psychiatry 59(suppl. 17):4–9PubMedGoogle Scholar
  25. Roy-Byrne P, Fleishaker J, Arnett C, Dubach M, Stewart J, Radant A, Veith R, Graham M (1993) Effects of acute and chronic alprazolam treatment on cerebral blood flow, memory, sedation, and plasma catecholamines. Neuropsychopharmacology 8:161–169PubMedGoogle Scholar
  26. Schneider F, Weiss U, Kessler C, Muller-Gartner HW, Posse S, Salloum JB, Grodd W, Himmelmann F, Gaebel W, Birbaumer N (1999) Subcortical correlates of differential classical conditioning of aversive emotional reactions in social phobia. Biol Psychiatry 45:863–871PubMedCrossRefGoogle Scholar
  27. Sheehan D (1983) The anxiety disease, Scribners, New YorkGoogle Scholar
  28. Smith GS, Kramer E, Hermann CR, Goldberg S, Ma Y, Dhawan V, Barnes A, Chaley T, Belakhleff A, Laghrissi-Thode F, Greenwald B, Eidelberg D, Pollock BG (2002) Acute and chronic effects of citalopram on cerebral glucose metabolism in geriatric depression. Am J Geriatr Psychiatry 10:715–723PubMedCrossRefGoogle Scholar
  29. Stein DJ, Westenberg HGM, Liebowitz MR (2002) Social anxiety disorder and generalised anxiety disorder: serotoninergic and dopaminergic neurocircuitry. J Clin Psychiatry 63(suppl 6):12–19PubMedGoogle Scholar
  30. Stein MB, Leslie WD (1996) A brain single photon-emission computed tomography (SPECT) study of generalized social phobia. Biol Psychiatry 39:825–828PubMedCrossRefGoogle Scholar
  31. Tillfors M, Furmark T, Marteinsdottir I, Fischer H, Pissiota A, Långström B, Fredrikson M (2001) Cerebral blood flow in subjects with social phobia during stressful speaking tasks: a PET study. Am J Psychiatry 158:1220–1226PubMedCrossRefGoogle Scholar
  32. Tillfors M, Furmark T, Marteinsdottir I, Fredrikson M (2002) Cerebral blood flow during anticipation of public speaking in social phobia: a PET study. Biol Psychiatry 52:1113–1119PubMedCrossRefGoogle Scholar
  33. Van Ameringen M Mancini C, Szechtman H, Nahmias C, Oakman JM, Hall GBC, Pipe B, Farvolden P (2004) A PET provocation study of generalised social phobia. Neuroimaging 132:13–18PubMedCrossRefGoogle Scholar
  34. Van der Linden GJ, Stein DJ, Van Balkom AJ (2000) The efficacy of the selective serotonin reuptake inhibitors for social anxiety disorder (social phobia): a meta-analysis of randomised controlled trials. Int Clin Psychopharmacol 15(suppl. 2):S15–S23PubMedGoogle Scholar
  35. Van der Linden G, Van Heerden B, Warwick J, Wessels C, Van Kradenburg J, Zungu-Dirwayi N, Stein DJ (2000) Functional brain imaging and pharmacotherapy in social phobia: single photon emission computed tomography before and after treatment with the selective serotonin reuptake inhibitor citalopram. Prog Neuro-psychopharmacol and Biol Psychiat 24:419–438CrossRefGoogle Scholar
  36. Varnäs K, Halldin C, Hall H (2004) Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain. Hum Brain Mapp 22:246–260PubMedCrossRefGoogle Scholar
  37. Veit R, Flor H, Erb M, Hermann C, Lotze M, Grodd W, Birbaumer N (2002) Brain circuits involved in emotional learning in antisocial behaviour and social phobia in humans. Neuroscience Letters 328:233–236PubMedCrossRefGoogle Scholar
  38. Wittchen HU, Beloch E (1996) The impact of social phobia on quality of life. Int Clin Psychopharmacol 11(suppl. 3):15–23PubMedCrossRefGoogle Scholar
  39. Weiller E, Bisserbe J-C, Boyer P, Lepine JP, Lecrubier Y (1996) Social phobia in general health care: An unrecognised undertreated disabling disorder. Br J Psychiatry 168:169–174PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • J. M. Warwick
    • 1
    • 3
    Email author
  • P. Carey
    • 1
  • G. Van der Linden
    • 1
  • C. Prinsloo
    • 1
  • D. Niehaus
    • 1
  • S. Seedat
    • 1
  • P. Dupont
    • 2
  • D. J. Stein
    • 1
  1. 1.MRC Unit for Stress and Anxiety DisordersFaculty of Health Sciences, Stellenbosch UniversityCape TownSouth Africa
  2. 2.Nuclear MedicineKatolieke UniversiteitLeuvenBelgium
  3. 3.Nuclear MedicineTygerberg HospitalCape TownSouth Africa

Personalised recommendations