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.     

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.     

Major depression and agoraphobia in patients with angiographically normal coronary arteries and panic disorder

Patients with panic disorder and/or agoraphobia appearing in psychiatric settings report rates for lifetime major depression between 24% and 91%. Between 40% and 90% of patients with panic disorder in psychiatric populations report concomitant agoraphobia. A recent study of panic disorder subjects appearing in an outpatient cardiology clinic confirmed the strong link between panic and depression but found only a weak association between panic disorder and agoraphobia. In order to test the reliability of these outpatient cardiology findings, the authors studied major depression and agoraphobia in patients with angiographically normal coronary arteries and panic disorder. Twelve of the 32 (37.5%) panic disorder subjects reported a lifetime history of major depression (nine current, three past only). Only two of the 32 (six percent) reported any phobic avoidance. This study confirms the previous findings which suggest that major depression is common in cardiology populations with panic disorder and that phobic avoidance is uncommon in this group.     

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.     

Biologic tests in psychiatry

Neurobiologic research has discovered a number of abnormalities that might serve as biologic markers for specific psychiatric disorders. Tests for these markers could aid in differential diagnosis and in the choice and monitoring of treatment. Tests with potential clinical utility in affective illness (unipolar and bipolar depression and mania), panic disorder, and schizophrenia are discussed.     

Age at onset, precipitating events, sex distribution, and co-occurrence of anxiety disorders.

178 outpatients were administered to a structured interview evaluating diagnostic, illness history, and sociodemographic data of DSM-III-R anxiety disorders. Patients with panic disorder with agoraphobia were a more severely ill subgroup than patients with panic disorder without agoraphobia. Simple and social phobia had the earliest age at onset, panic disorder the latest age at onset. Conjugal stress was the most frequent event preceding the onset of the anxiety disorders. Female patients showed more severe impairment suffering more frequently from concomitant phobic avoidance, generalized anxiety, and depression compared to male patients.     

Comorbid psychiatric disorders in late life depression.

In late life depression, common comorbid psychiatric disorders are alcohol use, anxiety, and personality disorders. Elderly depressed patients are three to four times more likely to have an alcohol use disorder compared with nondepressed elderly subjects, with a prevalence of 15%-30% in patients with late life major depression. While the presence of a comorbid alcohol use disorder may worsen the prognosis for geriatric depression, limited data suggest that successful treatment of depression combined with reducing alcohol use leads to the best possible outcomes. Most studies show that the overall prevalence of anxiety disorders, particularly panic disorder and obsessive-compulsive disorder, is low in geriatric depression, but generalized anxiety disorder may not be uncommon. It remains unclear if the presence of a comorbid anxiety disorder impacts on the treatment and prognosis of late life major depression. Personality disorders occur in 10%-30% of patients with late life major depression or dysthymic disorder, particularly in patients with early onset depressive illness. Cluster C disorders, including the avoidant, dependent, and obsessive-compulsive subtypes predominate, while Cluster B diagnoses, including borderline, narcissistic, histrionic and antisocial, are rare. Overall, the research database on comorbid psychiatric disorders in major and nonmajor late life depression is relatively sparse. Since comorbid psychiatric disorders affect clinical course and prognosis, and may worsen long-term disability in late life depression, considerably more research in this field is needed.     

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.     

Phenomenology and course of psychiatric disorders associated with combat-related posttraumatic stress disorder.

OBJECTIVE: Studies indicate that chronic combat-related posttraumatic stress disorder (PTSD) is frequently associated with other psychiatric disorders. Questions regarding the nature and interrelationships of these conditions require clarification. The purpose of this study was to address primary and secondary illness relationships by focusing on the specific phenomenology and course of illness onset of PTSD comorbidity. METHOD: In order to minimize confounding factors, only outpatients without recent substance use disorders were included. Sixty subjects who had been exposed to severe combat stress including veterans of Vietnam and veterans of World War II or Korea, 15 of whom were former prisoners of war, received structured assessments over serial evaluations. RESULTS: PTSD was the most prevalent lifetime disorder followed by major depression, panic disorder, generalized anxiety disorder, and phobic disorder or symptoms. Endogenous-appearing features overlapping other clinical populations were common; however, some specific symptom patterns also were suggestive of traumatic influence. Unlike generalized anxiety disorder and past substance use, the mean onset of phobias, major depression, and panic disorder, respectively, occurred later than PTSD. CONCLUSIONS: These observations suggest that persistent conditions related to PTSD progress toward symptoms that are increasingly autonomous in their pattern of occurrence.     

Overview and clinical presentation of generalized anxiety disorder.

1. To distinguish GAD from panic disorder is not difficult if a patient has frequent, spontaneous panic attacks and agoraphobic symptoms, but many patients with GAD have occasional anxiety attacks or panic attacks. Such patients should be considered as having GAD. An even closer overlap probably exists between GAD and social phobia. Patients with clear-cut phobic avoidant behavior may be distinguished easily from patients with GAD, but patients with social anxiety without clear-cut phobic avoidant behavior may overlap with patients with GAD and possibly should be diagnosed as having GAD and not social phobia. The cardinal symptoms of GAD commonly overlap with those of social phobia, particularly if the social phobia is more general and not focused on a phobic situation. For example, free-floating anxiety may cause the hands to perspire and may cause a person to be shy in dealing with people in public, and thus many patients with subthreshold social phobic symptoms have, in the authors' opinion, GAD and not generalized social phobia. The distinction between GAD and obsessive-compulsive disorder, acute stress disorder, and posttraumatic stress disorder should not be difficult by definition. At times, however, it may be difficult to distinguish between adjustment disorder with anxious mood from GAD or anxiety not otherwise specified, particularly if the adjustment disorder occurs in a patient with a high level of neuroticism or trait anxiety or type C personality disorder. Table 2 presents features distinguishing GAD from other psychiatric disorders. 2. Lifetime comorbid diagnoses of other anxiety or depression disorders, not active for 1 year or more and not necessitating treatment during that time period, should not effect a diagnosis of current GAD. On the other hand, if concomitant depressive symptoms are present and if these are subthreshold, a diagnosis of GAD should be made, and if these are full threshold, a diagnosis of MDD should be made. 3. If GAD is primary and if no such current comorbid diagnosis, such as other anxiety disorders or MDD, is present, except for minor depression and dysthymia, or if only subthreshold symptoms of other anxiety disorders are present, GAD should be considered primary and treated as GAD; however, patients with concurrent threshold anxiety or mood disorders should be diagnosed according to the definitions of these disorders in the DSM-IV and ICD-10 and treated as such. 4. Somatization disorders are now classified separately from anxiety disorders. Some of these, particularly undifferentiated somatization disorder, may overlap with GAD and be diagnostically difficult to distinguish. The authors believe that, as long as psychic symptoms of anxiety are present and predominant, patients should be given a primary diagnosis of GAD. 5. Two major shifts in the DSM diagnostic criteria for GAD have markedly redefined the definition of this disorder. One shift involves the duration criterion from 1 to 6 months, and the other, the increased emphasis on worry and secondary psychic [table: see text] symptoms accompanied by the elimination of most somatic symptoms. This decision has had the consequence of orphaning a large population of patients suffering from GAD that is more transient and somatic in its focus and who typically present not to psychiatrists but to primary care physicians. Therefore, clinicians should consider using the ICD-10 qualification of illness duration of "several months" to replace the more rigid DSM-IV criterion of 6 months and to move away from the DSM-IV focus on excessive worry as the cardinal symptom of anxiety and demote it to only another important anxiety symptom, similar to free-floating anxiety. One also might consider supplementing this ICD-10 criterion with an increased symptom severity criterion as, for example, a Hamilton Anxiety Scale of 18. Finally, the adjective excessive, not used in the definition of other primary diagnostic criteria, such as depressed mood for MDD, should be omitted (Table 3). 6. One may want to consider the distinction of trait (chronic) from state (acute) anxiety, but whether the presence of some personality characteristics, particularly anxious personality or Cluster C personality and increased neuroticism, as an indicator of trait [table: see text] anxiety is a prerequisite for anxiety disorders; occurs independently of anxiety disorders; or is a vulnerability factor that, in some patients, leads to anxiety symptoms and, in others, does not, is unknown. 7. Symptoms that some clinicians consider cardinal for a diagnosis of GAD, such as extreme worry, obsessive rumination, and somatization, also are present in other disorders, such as MDD. (ABSTRACT TRUNCATED)     

Panic disorder and mortality

Evidence so far indicates two sources for excess mortality in panic disorder--suicide and cardiovascular morbidity. The risk for eventual suicide may rival that for primary depression, but the predictors and the necessary antecedents probably differ. The lapse between diagnosis and suicide may be larger for panic disorder, and complications such as secondary depression and substance abuse may be necessary. There are few well-established predictors for primary depression despite many relevant studies. The risk for suicide in panic disorder is barely recognized, and established predictors are accordingly remote. One study has demonstrated excess cardiovascular mortality among males with panic disorder, and another from the same center has provided weak support. Only one additional study has provided the necessary detail as to sex and cause, and those findings were quite supportive, although the subjects may have been mixed diagnostically. There are numerous feasible explanations for excess cardiovascular mortality in panic disorder and even some reason to believe that successful treatment might lessen it. To so advise patients would be not only premature at this point but unnecessary and countertherapeutic--unnecessary because these patients are motivated by discomfort to seek treatment and countertherapeutic because cardiovascular morbidity is what many of these patients pathologically fear. Rather, the findings suggest focus for future study. The initial findings of excess cardiovascular morbidity in males badly need replication, as do the more recent findings of Kahn et al. Likewise, animal models may reveal some of the pathophysiologic mechanisms at work. It is hoped that these efforts will converge in the not-too-distant future.     

Clinical characteristics of unipolar disorder and bipolar disorder according to the lifetime presence of recurrent panic attacks

Objectives:  The frequent comorbidity of panic and affective disorders has been described in previous studies. However, it is not clear how panic disorder comorbidity in unipolar disorder and bipolar disorder is related to illness course.
Methods:  We compared lifetime clinical characteristics of illness and items of symptomatology in samples of individuals with bipolar I disorder (n = 290) and unipolar disorder (n = 335) according to the lifetime presence of recurrent panic attacks.
Results:  We found significant differences in clinical course of illness characteristics that were shared across the unipolar and bipolar samples according to the lifetime presence of panic attacks. We also found a number of differences according to the presence of panic attacks that may be specific to the diagnostic group.
Conclusions:  Distinguishing patients who have mood disorder diagnoses, especially bipolar I disorder, according to the lifetime presence of panic attacks may not only be of use in clinical practice, but may also be informative for aetiological research, such as molecular genetic studies.     

Simultaneous panic and depressive disorders: clinical and sleep EEG correlates

Panic and depressive symptoms occur simultaneously in many depressed patients. To study the frequency of this association and to determine whether patients with simultaneous panic and major depression differed from those with only major depressive disorder (MDD) in clinical features and in sleep electroencephalographic (EEG) variables, we evaluated a total sample of 336 patients with MDD. Fifty-eight (17%) had both panic and MDD; 50 had complete data and were matched for age and severity of illness with other patients having only MDD. Patients with simultaneous panic and depression had significantly higher ratings for psychic and somatic anxiety, and rapid eye movement (REM) latencies approximating normal values. Patients with only MDD (without panic disorder) rated significantly higher in guilt feelings and had shorter REM latencies. Our results suggest that the simultaneous occurrence of panic and depression is relatively frequent, is accompanied by differences in sleep EEG variables, and may have implications for treatment.     

Moderating effects of major depression on patterns of comorbidity in patients with panic disorder

Given the high rate of co-occurring major depression in patients with panic disorder, it is unclear whether patterns of comorbidity in individuals with panic disorder reported in the literature are associated with panic disorder or with the presence of major depression. Subjects were 231 adult subjects with panic disorder and major depression (n=102), panic disorder without comorbid major depression (n=29), major depression without comorbid panic disorder (n=39), and neither panic disorder nor major depression (n=61). Subjects were comprehensively assessed with structured diagnostic interviews that examined psychopathology across the life cycle. Panic disorder, independently of comorbidity with major depression, was significantly associated with comorbid separation anxiety disorder, simple phobia, obsessive-compulsive disorder, generalized anxiety disorder, and agoraphobia. Major depression, independently of comorbidity with panic disorder, was significantly associated with comorbidity with psychoactive substance use disorders and childhood disruptive behavior disorders. Overanxious disorder was associated with both panic disorder and major depression. Major depression has important moderating effects on patterns of comorbidity of panic disorder in referred adults.     

Social phobic symptoms in patients with panic disorder: practical and theoretical implications

Of 35 patients with DSM-III-R diagnoses of panic disorder, 16 also received diagnoses of social phobia, and 15 of these 16 reported past episodes of major depression. Only nine of the 19 panic patients without social phobia had histories of depression. The panic patients with histories of depression had significantly higher self-ratings of social anxiety and avoidance, but not agoraphobic fear and avoidance, than those without histories of depression. Panic disorder and social phobia may coexist in many cases, and the presence of social phobia may be associated with a higher morbid risk for major depression in this population.     

Inflammatory bowel disease: psychiatric status of patients before and after disease onset

Compared to normal controls, individuals with Crohn's Disease manifest an increased prevalence of anxiety, depression and panic disorder occurring at any time in their life. Only panic disorder had an excess prevalence in Crohn's disease relative to community dwelling normals prior to the time of disease onset. Individuals with ulcerative colitis did not demonstrate an increased prevalence of psychiatric disorder before or after disease onset. The results suggest that there is a higher prevalence of psychiatric disorder in patients with Crohn's Disease relative to the normal population and that a small but significant percentage of individuals with Crohn's Disease may have a psychiatric disturbance which predates their medical illness.     

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.     

Bipolar II and unipolar comorbidity in 153 outpatients with social phobia

Previous studies on social phobia (SP) have focused largely on comorbidity between SP and major depression. Less attention has been devoted to the comorbidity between SP and bipolar disorder. In this retrospective study, we investigated family history, lifetime comorbidity, and demographic and clinical characteristics among 153 outpatients who met DSM-III-R diagnostic criteria for SP. Information regarding axis I diagnoses was obtained using the Structured Clinical Interview for DSM III-R (SCID-UP-R). Social phobic symptoms and the severity of the illness were assessed by the Liebowitz Social Anxiety Scale (LSAS) and the Liebowitz Social Phobic Disorders Rating Scale, Severity (LSPDRS). Patients completed the Hopkins Symptom Checklist (HSCL 90). Fourteen patients (9.1%) satisfied DSM-III-R criteria for lifetime bipolar disorder not otherwise specified (NOS) (bipolar II), while 71 (46.4%) had unipolar major depression and 68 (44.4%) had no lifetime history of major mood disorders. Comorbid panic disorder/agoraphobia (PDA), obsessive-compulsive disorder (OCD), and alcohol abuse were reported more frequently in the bipolar group than in the other two subgroups. Unipolar patients showed higher rates of comordid PDA and OCD compared with SP patients without mood disorders. Severity and generalization of the SP symptoms, prevalent interactional anxiety, multiple comorbidity, and alcohol abuse appeared to be the most relevant consequences of SP-bipolar coexistence. In a significant minority of cases, protracted social anxiety may hypothetically have represented, along with inhibited depression, the dimensional opposite of gregarious hypomania.     

Predictors of the development of phobic avoidance

BACKGROUND: Panic disorder and agoraphobia are closely linked. There are indications that uncontrolled panic attacks often lead to the rapid development of phobic avoidance, but our ability to predict which individuals with panic will develop avoidance has been limited. The purpose of this study was to identify independent predictors of the development of phobic avoidance and the time course of that development. METHOD: We conducted a secondary analysis of survey data from the community-based Panic Attack Care-Seeking Threshold Study. The presence of panic attacks was confirmed in 97 randomly selected adults from randomly selected households screened using the Structured Clinical Interview of DSM-III-R (SCID). The presence of limited and extensive phobic avoidance was measured using the SCID, while rapidity of development (lag time) was measured as the difference between onset of panic and onset of avoidance. Predictors considered included panic characteristics, psychiatric comorbidity, cognitive appraisal, family characteristics, illness attitudes, symptom perceptions, and coping style. RESULTS: Thirty-six subjects (37%) had at least mild phobic avoidance, with 81% (N = 29) of those developing the avoidance less than 1 year after the onset of panic attacks. The development of phobic avoidance was associated with the presence of panic disorder (beta = 1.36), the number of comorbid psychiatric disorders (beta = 0.69), and the number of family members and/or friends available to discuss health concerns (beta = 0.87). Further progression to agoraphobia was predicted by the presence of depersonalization during panic attacks (beta = 0.50). Rapid onset of avoidance (panic avoidance lag time < 1 year) was predicted by the perception that depersonalization is a life-threatening symptom (beta = 1.56). CONCLUSION: The development of phobic avoidance is closely linked to panic attacks and often develops soon after panic onset. Full-blown panic disorder and psychiatric comorbidity are important in this development. Depersonalization is also key to the development of avoidance and the rapidity of the development.     

Sleep electroencephalographic coherence abnormalities in individuals at high risk for depression: a pilot study.

BACKGROUND: Sleep electroencephalographic (EEG) studies of individuals with major depressive disorder have identified several microarchitectural features associated with the illness. These abnormalities are also found in clinically remitted individuals, raising the question of whether they are vulnerability markers of depression. This study evaluated the sleep EEG in high-risk individuals to see if abnormalities are present in the sleep EEG prior to the onset of illness. METHODS: A total of 26 subjects (13 males and 13 females) were recruited for study on the basis of 1) having a parent or grandparent treated for major depressive or bipolar affective disorder and 2) having no history of personal psychiatric illness. Polysomnographic data were collected and compared with gender- and age-matched healthy control subjects with no personal or family history of psychiatric illness. The primary outcome measures were interhemispheric and intrahemispheric coherence. RESULTS: Period analysis of the sleep EEG showed that beta-delta coherence was lower bilaterally in male high-risk subjects. Right-hemispheric theta-delta coherence was also lower in male high-risk subjects, with female high-risk subjects evidencing lower beta coherence. CONCLUSIONS: Sleep-EEG abnormalities associated with major depressive disorder are present in never mentally ill individuals at high risk for the illness. These markers may be useful in the prediction of illness and in family genetic studies of mood disorders.