title: The clinical-familial correlates and naturalistic outcome of panic-disorder-agoraphobia with and without lifetime bipolar II comorbidity.
abstract: BACKGROUND
  Much of the literature on panic disorder (PD)-bipolar disorder (BP) comorbidity concerns BP-I. This literature emphasizes the difficulties encountered in pharmacologic treatment and outcome when such comorbidity is present. The present report explores these issues with respect to BP-II.
  
  
  METHODS
  The sample comprised 326 outpatients (aged 34.5 +/- 11.5 years old; 222 females) with Diagnostic and Statistical Manual of Mental Disorders 3rd edn, revised (DSM-III-R) PD-agoraphobia; among them 52 subjects (16%) were affected by lifetime comorbidity with BP-II. Patients were evaluated by means of the Structured Clinical Interview for DSM-IV (SCID), the Panic-Agoraphobia Interview, and the Longitudinal Interview Follow-up Examination (Life-Up) and treated according to routine clinical practice at the University of Pisa, Italy, for a period of 3 years. Clinical and course features were compared between subjects with and without BP-II. All patients received the clinicians' choice of antidepressants and, in the case of the subsample with BP-II, mood stabilizers (for example, valproate, lithium) were among the mainstays of treatment.
  
  
  RESULTS
  In comparison to patients without bipolar comorbidity, those with BP-II showed a significantly greater frequency of social phobia, obsessive-compulsive disorder, alcohol-related disorders, and separation anxiety during childhood and adolescence. Regarding family history, a significantly greater frequency of PD and mood disorders was present among the BP-II. No significant differences were observed in the long-term course of PD or agoraphobic symptoms under pharmacological treatment or the likelihood of spontaneous pharmacological treatment interruptions.
  
  
  CONCLUSIONS
  Although the severity and outcome of panic-agoraphobic symptomatology appear to be similar in patients with and without lifetime bipolar comorbidity, the higher number of concomitant disorders in our PD patients with BP-II does indicate a greater complexity of the clinical picture in this naturalistic study. That such complexity does not seem to translate into poorer response and outcome in those with comorbid soft bipolarity probably reflects the fact that we had brought BP-II under control with mood stabilizers. We discuss the implications of our findings as further evidence for the existence of a distinct anxious-bipolar diathesis.
authors.affiliation: Institute of Behavior Sciences G. De Lisio, Carrara, Italy. cristina.toni@virgilio.it
authors.forename: Cristina
authors.initials: C
authors.lastname: Toni
authors.forename: Giulio
authors.initials: G
authors.lastname: Perugi
authors.forename: Franco
authors.initials: F
authors.lastname: Frare
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tusini
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Fountoulakis
authors.forename: Kareen K
authors.initials: KK
authors.lastname: Akiskal
authors.forename: Hagop S
authors.initials: HS
authors.lastname: Akiskal