OBJECTIVES: A combination of antidepressants with the cognitive-behavioural therapy showed effectiveness in treatment-resistant patients with panic disorder. This prospective study intended to establish how childhood adverse experiences, self-stigma, dissociation, and severity of psychopathology influence the effectiveness of combined cognitive-behavioural therapy and pharmacotherapy in patients with treatment-resistant panic disorder. METHODS: One hundred and ten patients were included into the study and one hundred five subjects finished the study. After admission, the subjects were assessed during the first two days of hospitalization. Rating scales were administered before the beginning of the cognitive behavioural therapy (measurement-1) and at the end of the treatment which was after six weeks (measurement-2). Patients with panic disorder were treated using a combination of group cognitive-behavioural therapy and antidepressants. The usual antidepressant dosage range was used. Before admission to intensive cognitive behavioural therapy program, the patients were unsuccessfully treated by antidepressants for minimum 3 months, which defined them as pharmacoresistant. RESULTS: Hospitalized pharmacoresistant patients with panic disorder improved significantly throughout the 6-week intensive CBT program in all measurements that assessed the overall severity of the disorder, the degree of general anxiety and depression and the severity of specific symptoms of panic disorder and agoraphobia. The rate of improvement was negatively related to sexual abuse in childhood, presence of comorbid personality disorder, and positively with the severity of the disorder at the beginning, and the level of self-stigma at the beginning of treatment. Improvement in symptoms correlates significantly with decreasing of dissociation during the treatment.severity of depressive symptoms. The earlier development of the disorder is linked to higher score in childhood adverse events, higher level of dissociation and pathological dissociation, and higher level of self-stigma. CONCLUSIONS: Our prospective study discovers importance of the role of adverse childhood experiences, self-stigma, dissociation and comorbid personality disorder in effectiveness of combined cognitive-behavioural therapy and pharmacotherapy treatment in patients with treatment-resistant panic disorder.