Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy

Arch Gen Psychiatry. 2002 May;59(5):425-33. doi: 10.1001/archpsyc.59.5.425.


Background: Neurofunctional changes underlying effective antianxiety treatments are incompletely characterized. This study explored the effects of citalopram and cognitive-behavioral therapy on regional cerebral blood flow (rCBF) in social phobia.

Methods: By means of positron emission tomography with oxygen 15-labeled water, rCBF was assessed in 18 previously untreated patients with social phobia during an anxiogenic public speaking task. Patients were matched for sex, age, and phobia severity, based on social anxiety questionnaire data, and randomized to citalopram medication, cognitive-behavioral group therapy, or a waiting-list control group. Scans were repeated after 9 weeks of treatment or waiting time. Outcome was assessed by subjective and psychophysiological state anxiety measures and self-report questionnaires. Questions were readministered after 1 year.

Results: Symptoms improved significantly and roughly equally with citalopram and cognitive-behavioral therapy, whereas the waiting-list group remained unchanged. Four patients in each treated group and 1 waiting-list patient were classified as responders. Within both treated groups, and in responders regardless of treatment approach, improvement was accompanied by a decreased rCBF-response to public speaking bilaterally in the amygdala, hippocampus, and the periamygdaloid, rhinal, and parahippocampal cortices. Between-group comparisons confirmed that rCBF in these regions decreased significantly more in treated groups than control subjects, and in responders than nonresponders, particularly in the right hemisphere. The degree of amygdalar-limbic attenuation was associated with clinical improvement a year later.

Conclusions: Common sites of action for citalopram and cognitive-behavioral treatment of social anxiety were observed in the amygdala, hippocampus, and neighboring cortical areas, ie, brain regions subserving bodily defense reactions to threat.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amygdala / blood supply
  • Amygdala / diagnostic imaging
  • Brain / blood supply*
  • Brain / diagnostic imaging*
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / diagnostic imaging
  • Citalopram / pharmacology
  • Citalopram / therapeutic use*
  • Cognitive Behavioral Therapy*
  • Female
  • Hippocampus / blood supply
  • Hippocampus / diagnostic imaging
  • Humans
  • Limbic System / blood supply
  • Limbic System / diagnostic imaging
  • Male
  • Middle Aged
  • Oxygen Radioisotopes
  • Phobic Disorders / diagnostic imaging
  • Phobic Disorders / physiopathology
  • Phobic Disorders / therapy*
  • Regional Blood Flow / physiology
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Tomography, Emission-Computed
  • Treatment Outcome


  • Oxygen Radioisotopes
  • Serotonin Uptake Inhibitors
  • Citalopram