Predictors of symptom resolution in panic disorder after one year of pharmacological treatment: a naturalistic study

OBJECTIVE: In this naturalistic and prospective study, patients with panic disorder (PD) were treated for one year 1) to verify the rate of patients achieving the resolution of full-symptom attacks, limited-symptom attacks, anticipatory anxiety, phobic avoidance and depression; and 2) to identify the predictors of symptom resolution for each domain. METHOD: One hundred patients with PD, according to DSM-IV criteria, participated in the study. In all patients, a baseline and a follow-up with monthly evaluations of SCL-90, Ham-A, Ham-D and panic diaries were carried out over a one-year period. All patients were treated with paroxetine or citalopram. RESULTS: Seventy-one patients completed the study, whereas the remaining 29 dropped out. Among completers, remission of full- and limited-symptom panic attacks was observed in 76 % of patients, whereas complete remission (resolution of panic attacks, anticipatory anxiety, phobic anxiety, and depression) was achieved by only 46 % of patients. Predictors of absence of symptom remissions were obsessive-compulsive disorder (OCD) and recurrent major depression (MD) comorbidity (for panic attacks), pre-treatment severity of anxious symptoms (for anticipatory anxiety), phobic anxiety (for phobic avoidance), and depressive symptoms (for depression). CONCLUSION: This naturalistic study shows that the high comorbidity of OCD and MD and the greater pre-treatment severity of anxious, phobic and depressive symptoms reduced the likelihood of achieving complete remission of symptoms in PD patients who completed the protocol, even though they were adequately treated with SSRI medication.     

The effects of pregnancy on preexisting panic disorder.

BACKGROUND: Limited evidence suggests that pregnancy may be associated with a reduction of panic and related symptoms. The authors investigate reported changes in panic symptoms during pregnancy. METHOD: Questionnaires asking about changes in panic and phobic avoidance symptoms during pregnancy were mailed to 129 women who had previously participated in our Anxiety Disorders Program over a 5-year period; all had diagnoses of panic disorder by DSM-III-R criteria. Reported here are responses from 22 of the women who experienced pregnancy after the onset of panic disorder. RESULTS: A majority of women (14 of 22) reported a decrease in panic symptoms during pregnancy, but significant variability in this phenomenon occurs between and within individuals. CONCLUSION: A subpopulation of women may experience improvement in panic symptoms during pregnancy, which has implications for management of these patients. Further research is needed to verify the existence of such a subpopulation and to determine an etiology.     

The long-term course of panic disorder--an 11 year follow-up

BACKGROUND: The purpose of this study was to assess the naturalistic long-term course of panic disorder over a period of 11 years. METHOD: Thirty DSM-III-R panic disorder patients, who had suffered from panic disorder for 6 years on average and who had taken part in an 8-week multicenter drug trial, were included in the intent-to-follow-up group to be reinterviewed 11 years after the end of the trial. At baseline and at follow-up the same instruments were used to assess frequency of panic attacks, level of phobic avoidance, and disabilities. Treatments received during the follow-up period and attempted suicides were assessed with a structured interview. Periods of well-being during the follow-up period were elicited retrospectively with a specifically designed longitudinal chart. RESULTS: Twenty-four patients could actually be reinterviewed after 11.3 years. While at baseline all patients had suffered from panic attacks and had been severely disabled on a number of measures, 66.7% had no panic attack during the year before follow-up. During the month before follow-up 87.5% had no panic attack, and 54% showed no or only mild phobic avoidance. In the areas of work and family life 90% showed no or only mild disabilities, whereas in the area of social life this percentage was lower (67%). Thirty-three percent of the patients were completely remitted according to a composite remission criterion. CONCLUSIONS: Panic disorder is not a uniformly chronic and progressing disorder. Over a period of 11 years there is a good chance of recovery from panic attacks and disabilities, and full remission is also possible.     

Secondary depression in panic disorder and agoraphobia. I. Frequency, severity, and response to treatment

Depressive symptomatology in 481 subjects with panic disorder and phobic avoidance was studied as part of an investigation of the efficacy of alprazolam in panic disorder. Subjects who had a major depressive episode (MDE) before the onset of their panic disorder were not included in the trial. With this exclusion criterion, 31% of subjects had a secondary MDE occurring after the onset of the panic disorder. The occurrence of secondary MDE was related to the length of time subjects were ill with panic disorder. Compared with the subjects without depression, those subjects with current MDE had higher scores on measures of anxiety and depression but not on the number of panic attacks per week. The presence of depression and the degree of phobic avoidance contributed independently to measures of the severity of the panic illness. Alprazolam was effective in reducing panic and depressive symptomatology in both depressed and nondepressed subjects with panic disorder. The presence of an MDE was not predictive of the outcome of treatment for the panic and phobic symptoms. Subjects with or without depression responded similarly to alprazolam.     

Clonazepam for the treatment of social phobia

Nine of 11 patients with social phobia of both the generalized and performance type responded to treatment with clonazepam in total daily doses ranging from 0.75 to 3 mg. Only 2 of these 9 had comorbid panic disorder; the benefit for social phobic symptoms appears independent of clonazepam's putative efficacy for panic disorder.     

Citalopram controls phobic symptoms in patients with panic disorder: randomized controlled trial

OBJECTIVE: To examine the effects of long-term treatment with citalopram or clomipramine on subjective phobic symptoms in patients with panic disorder. DESIGN: Double-blind, parallel-group, five-arm study. PATIENTS: Patients aged 18 to 65 years with panic disorder (DMS-III-R diagnosis) and with no major depressive symptoms. INTERVENTIONS: Four hundred and seventy-five patients were randomized to 8 weeks of treatment with either citalopram (10 to 15 mg per day; 20 to 30 mg per day; or 40 to 60 mg per day), clomipramine (60 to 90 mg per day) or placebo. Two hundred and seventy-nine patients continued treatment after the 8-week acute phase. OUTCOME MEASURES: Phobic symptoms were assessed using the Phobia Scale and the Symptom Checklist's (SCL-90) phobia-related factors. RESULTS: At all dosages, citalopram was more efficacious than placebo, with 20 to 30 mg generally being the most effective dosage. Citalopram (20 to 30 mg) generally decreased phobic symptoms significantly more than placebo after Month 3. Interpersonal sensitivity decreased when measured on the respective SCL-90 sub-scale. Alleviation of phobic symptoms generally continued to increase towards the end of the treatment. The effect of clomipramine was not as consistent. CONCLUSIONS: All active treatment groups, especially the group receiving 20 to 30 mg per day of citalopram, effectively controlled phobic symptoms in patients with panic disorder. Long-term treatment with citalopram further decreased phobic symptoms.     

Outcome of panic disorder. Relationship to diagnostic subtypes and comorbidity

Eighty-nine subjects with panic disorder, who had been naturalistically treated, and 46 nonanxious controls were followed up after 3 years. Although they remained symptomatic, most subjects with panic disorder reported relatively little distress or social maladjustment. The course of panic disorder was characterized by fluctuating anxiety and depressive symptoms. Panic subtypes (uncomplicated, limited phobic avoidance, and extensive phobic avoidance) and Axis I and II comorbidity (major depression and personality disorders) were highly predictive of symptoms and social adjustment after 3 years. Abnormal personality was, in fact, the strongest predictor of social maladjustment in both subjects with panic disorder and controls. The results showed that while panic disorder has a favorable outcome, the illness is a chronic one that may require continuing treatment. They also show that subtypes and comorbid disturbances are important predictors of outcome.     

Past and current thyroid function in subjects with panic disorder

Disturbances in thyroid function can result in symptoms similar to those occurring in patients with anxiety disorders, especially panic disorder. An association between thyroid illness and panic and phobic disorders has been suggested, but few studies have directly investigated this issue. To assess this possible relationship, the authors measured indices of thyroid function in 165 subjects who had a current DSM-III diagnosis of panic disorder, either with or without phobic avoidance. These subjects reported a higher prevalence of thyroid illness by history compared with the prevalence of thyroid illness in the general population; however, less than 1% of all subjects had current thyroid dysfunction. The presence of a major depressive episode (MDE) was unrelated to current thyroid function, although subjects with MDE reported a higher prevalence of thyroid disease by history. Indices of thyroid function were not correlated with the severity of panic attacks or phobias.     

Imipramine dose-response relationship in panic disorder with agoraphobia. Preliminary findings

At the end of a two-week single-blind placebo baseline, 43 patients with a diagnosis of panic disorder with agoraphobia without significant dysphoria-depression and with moderate to severe panic and phobic symptoms were assigned to, and 32 of them completed, a placebo-controlled (n = 7) dose-response study with three weight-adjusted imipramine hydrochloride dosages: 0.5 mg/kg/d (n = 10), 1.5 mg/kg/d (n = 9), and 3 mg/kg/d (n = 6). Eleven patients, three from the medium-dose and eight from the high-dose conditions, dropped out owing to side effects. No instructions or encouragement for self-directed exposure to phobic situations or other coping strategies with panic or fear were given throughout the trial. Compliance, as assessed by pill counts and by plasma tricyclic levels, was high. Results provided strong evidence for a positive dose-response relationship on panic and phobic symptoms and confirmed earlier suggestions (1) that imipramine without concurrent exposure possesses a significant antipanic and antiphobic effect, (2) that improvement correlates primarily with imipramine but not N-desmethylimipramine plasma levels, and (3) that side effects prevent optimum dose buildup in a substantial proportion of patients with this disorder.     

Psychiatric illness and irritable bowel syndrome: a comparison with inflammatory bowel disease

Structured psychiatric interviews and psychological self-report measures were administered to 28 patients with irritable bowel syndrome and 19 patients with inflammatory bowel disease. Significantly more of the patients with irritable bowel syndrome had lifetime diagnoses of major depression, somatization disorder, generalized anxiety disorder, panic disorder, and phobic disorder. They had significantly more medically unexplained somatic symptoms, and most had suffered from psychiatric disorders, particularly anxiety disorders, before the onset of their irritable bowel symptoms.     

The epidemiology of panic symptomatology and agoraphobic avoidance

In a random community survey of 1,498 urban adults age 18 to 64 years who were interviewed using the Diagnostic Interview Schedule (DIS), the lifetime prevalence of panic disorder was 2.2% +/- 0.4%. This was higher in women (3.4% +/- 0.7%) than in men (0.9% +/- 0.6%), and in those under the age of 45 years. Lifetime prevalence for panic attacks was 7.8% +/- 0.7%. Panic attacks and panic disorder had a similar distribution by age and sex, with higher rates in women than men, and also in the under 45 age groups. The panic symptomatology reported by those subjects with panic attacks was similar to that described by subjects meeting full criteria for panic disorder. The lifetime prevalence of phobic disorders was 10.7% +/- 0.9% and was more common in women (14.6% +/- 1.3%) than in men (6.8% +/- 1.3%). The lifetime prevalence of agoraphobia was 3.8% +/- 0.5%. The occurrence of panic attacks and phobic disorders were frequently related, and in agoraphobic subjects those with more severe agoraphobic avoidance reported more panic symptoms. Indeed, among agoraphobic subjects with at least moderate agoraphobic avoidance, nearly all had either panic attacks or major depression. Subjects with panic attacks and moderate agoraphobic avoidance compared with patients with panic attacks alone, especially when panic symptoms appear before the age of 15, are more likely to have grown up in a family where there was parental conflict, are more likely to have left school at a younger age and without school exams, and are likely to have had more symptoms of a childhood conduct disorder.     

Effect of pharmacological treatment on temperament and character in panic disorder

Temperament and character were evaluated in patients with panic disorder (PD) before and after 1 year of pharmacological therapy to verify whether personality characteristics change after treatment. Therefore, 65 PD patients and 71 healthy subjects participated in the study. All subjects were evaluated with the SCID-IV, the Temperament and Character Inventory (TCI), the SCL-90, the Ham-A and the Ham-D. Patients were treated with paroxetine or citalopram. The TCI was re-administered to the patients at the end of the study. At the end of the study, complete remission was achieved by 31 patients (R), whereas symptoms did not disappear in the remaining 34 patients (NR). Before treatment, NR patients showed higher levels of harm avoidance (HA) and lower levels of persistence (P), self-directedness (SD) and cooperativeness (C) than healthy controls. Only HA levels were higher than normal in R, although they were significantly lower in R than in NR patients. These differences persisted after treatment. However, in NR patients the levels of SD and C worsened, whereas the difference between R patients and controls in HA levels (higher in R patients than in controls) disappeared after controlling the effect of residual phobic anxiety (higher than normal in R patients). Our data suggest that the high levels of HA found after remission may depend on the subsyndromal residual phobic symptoms, observed in R patients. Moreover, the persistence of anxious symptoms may have worsened the low levels of SD and C observed before treatment in patients who did not achieve remission.     

Dependent personality disorder associated with phobic avoidance in patients with panic disorder

Eighty-eight panic disorder patients were divided into three groups according to the extent of their phobic avoidance (none, limited, or extensive). These groups were compared on three personality disorder instruments: the Structured Interview for DSM-III Personality Disorders, the Personality Diagnostic Questionnaire, and the Millon Clinical Multiaxial Inventory. Phobic patients were found to have significantly more dependent personality disorder and DSM-III third-cluster personality disorders than nonphobic patients. A subgroup of patients with social phobic symptoms was found to resemble the rest of the phobic group in terms of personality.     

Behavior therapy, supportive psychotherapy, imipramine, and phobias.

In a controlled outcome study of phobias, 111 adult patients (69% women, 31% men) received a course of 26 weekly treatment sessions consisting of (1) behavior therapy and imipramine hydrochloride (2) behavior therapy and placebo, or (3) supportive psychotherapy and imipramine. Patients were classified as agoraphobic, mixed phobic, or simple phobic. The great majority of patients in all groups showed moderate to marked global improvement (70% to 86%, depending on rater). In agoraphobics and mixed phobics (both groups experiencing spontaneous panic attacks), imipramine was significantly superior to placebo. There was no difference between behavior therapy and supportive therapy, both resulting in high improvement rates (76% to 100%, depending on rater). In simple phobic patients, there was a high rate of improvement with all treatment regimens (72% to 93%, depending on rater), with no significant difference between imipramine and placebo or between behavior therapy and supportive therapy. Of 88 moderately to markedly improved patients followed up for one year after completing treatment, 83% maintained their gains and 17% relapsed. No patients showed symptom substitution. Eighteen percent of the patients receiving imipramine hydrochloride showed marked stimulant side effects on from 5 to 75 mg/day.     

Agoraphobia with panic attacks. Development, diagnostic stability, and course of illness

A structured psychiatric interview was used to examine the symptom history of 55 patients meeting DSM-III criteria for agoraphobia with panic attacks and five patients meeting DSM-III criteria for panic disorder. Anticipatory anxiety and generalized anxiety occurred in over 80% of the patients, and these anxiety states together with panic attacks and phobic avoidances had courses that were chronic and unremitting. Major depression occurred in 70% of the patients and had an episodic course that differentiated it from the anxiety states. Other frequently reported disorders were childhood separation disorder (18%), alcoholism (17%), and obsessive compulsive disorder (17%). An initial nonspontaneous first panic attack and separation anxiety was associated with earlier onset and longer duration of agoraphobia and panic disorder. An inaccurate cognitive appraisal of the initial panic attack frequently led to the rapid development of subsequent agoraphobia. Caffeine consumption exacerbated anxiety in 54% of the patients and triggered panic attacks in 17%. Fifty-one percent of female agoraphobics experienced premenstrual exacerbation of anxiety symptoms.     

Comparing panic disorder uncomplicated and panic disorder with agoraphobia in cardiology patients with atypical or nonanginal chest pain

Thirty-eight cardiology patients with either atypical or nonanginal chest pain and current panic disorder were divided into two groups, those with agoraphobia (N = 8) and those without agoraphobia (N = 30). The agoraphobia group reported marginally longer duration of panic disorder (17.0 ± 21.1 years vs. 3.0 ± 3.2 years) and significantly more panic symptoms (10.6 ± 3 vs. 7.3 ± 2.2) during the last major attack. The agoraphobia group also scored significantly higher on measures of anxiety, depression, phobic avoidance, somatization, interpersonal sensitivity, and psychoticism and also scored higher on three of three global measures of distress. This agoraphobia group differed from previously reported agoraphobics with panic attacks in that they all had current panic disorder, while previously reported groups were categorized according to DSM-III, which required only a history of panic attacks. These findings suggest that patients who have current panic disorder and agoraphobia are more symptomatic. Of interest is the low proportion of agoraphobics compared to nonagoraphobics found in this panic disorder population.     

Application of electroconvulsive therapy in treatment of retinitis pigmentosa comorbid with major depressive disorder and panic disorder

A substantial proportion of retinitis pigmentosa (RP) patients have depression/anxiety and a phobic pathology that may be related to changes in melatonin secretion. We discuss electroconvulsive therapy (ECT) in a patient with RP comorbid with depression and panic disorder. A 51-year-old man was admitted because of major depression, panic disorder, and RP. Ultrabrief pulse (0.3 millisecond) right unilateral ECT was performed 9 times in total. The symptoms relieved, and patient tolerated the treatments well. Electroconvulsive therapy increases serum melatonin, providing therapeutic effects in depression. The application of ECT in this population therefore appears to be an alternative treatment.     

An examination of syndromal validity and diagnostic subtypes in social phobia and panic disorder.

BACKGROUND: We investigated whether patients with DSM-III-R panic disorder and patients with social phobia could be distinguished on the basis of selected demographic variables and by several commonly used anxiety and phobia rating scales. METHOD: Sixty-six patients with social phobia and 60 patients with panic disorder (42 with and 18 without agoraphobia) were studied. Subjects completed a battery of self-report measures that assessed phobic fears, avoidance, and related problems. RESULTS: Social phobic patients showed an earlier age at onset than the panic disorder group, and there was a trend for more social phobics to have never married. Social phobics reported significantly greater levels of social phobic avoidance and distress, fear of negative evaluation, and avoidance of social situations than the panic disorder patients who reported more overall anxiety and rated themselves as significantly more avoidant of situations involving exposure to public places and to blood or injury. Discriminant function analyses showed that social phobic and panic disorder patients can be reliably discriminated on these scales. CONCLUSION: The results of this study lend further support for the validity of the DSM-III-R nosologic distinctions between social phobia and panic disorder. Furthermore, generalized social phobia appears to be remarkably different from discrete social phobia on these measures. This study provides less support for considering panic disorder with agoraphobia to be distinct from panic disorder without agoraphobia.     

Generalized anxiety and generalized anxiety disorder: description and reconceptualization

One hundred eight patients complaining of anxiety were diagnosed using the Anxiety Disorders Interview Schedule and classified into the various anxiety disorder categories as well as major depression. Although patients with a primary diagnosis of generalized anxiety disorder were more chronic than were panic disorder patients, most patients in each category met the DSM-III criteria for generalized anxiety disorder with the exception of simple phobic patients. On the basis of these data, it would seem that generalized anxiety disorder is a residual category within the anxiety disorders, since generalized anxiety disorder symptoms are almost always present. But if one distinguishes anticipatory anxiety, which is often part of panic or phobic disorders, from generalized anxiety, an independent anxiety disorder category emerges. This category is characterized by apprehensive expectation or chronic worry focused on multiple life situations.