The emergence of social phobia during clozapine treatment and its response to fluoxetine augmentation

J Clin Psychiatry. 1999 Dec;60(12):819-23. doi: 10.4088/jcp.v60n1203.


Background: The underlying neurochemical basis of social phobia has yet to be fully explained, but there are suggestions of serotonergic and dopaminergic dysfunction. The atypical neuroleptic clozapine has been reported to induce anxiety symptoms, probably owing to its effect on serotonergic pathways. We report 12 cases of schizophrenic patients who developed social phobia during clozapine treatment.

Method: Patients were assessed using the Structured Clinical Interview for DSM-III-R, Patient Version, Scale for the Assessment of Negative Symptoms, Scale for the Assessment of Positive Symptoms, the Liebowitz Social Phobia Scale, and the Brief Psychiatric Rating Scale. They were reevaluated after 12 weeks of cotreatment with clozapine and fluoxetine.

Results: In 8 of the 12 cases, symptoms responded (> or = 35% reduction in Liebowitz Social Phobia Scale score) with an adjunctive regimen of fluoxetine.

Conclusion: Data are discussed in light of neurochemical mechanisms and cognitive adaptations that could explain the onset of anxiety spectrum disorders (such as social phobia) in clozapine-treated schizophrenic subjects during remission of psychotic symptoms.

Publication types

  • Case Reports
  • Clinical Trial

MeSH terms

  • Adult
  • Ambulatory Care
  • Antipsychotic Agents / adverse effects*
  • Clozapine / adverse effects*
  • Clozapine / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Fluoxetine / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Male
  • Phobic Disorders / chemically induced*
  • Phobic Disorders / drug therapy
  • Phobic Disorders / psychology
  • Psychiatric Status Rating Scales
  • Schizophrenia, Paranoid / drug therapy*
  • Schizophrenia, Paranoid / psychology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Treatment Outcome


  • Antipsychotic Agents
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Clozapine