YONKERS, PANIC Am JDISORDER Psychiatry ZLOTNICK, 155:5, IN WOMEN ALLSWORTH, May 1998 AND MEN ET AL.

Is the Course of Panic Disorder the Same in Women and Men? Kimberly A. Yonkers, M.D., Caron Zlotnick, Ph.D., Jenifer Allsworth, A.B., Meredith Warshaw, M.S.S., M.A., Tracie Shea, Ph.D., and Martin B. Keller, M.D.

Objective: Panic disorder with or without agoraphobia has a chronic relapsing course. Factors associated with poor outcome include early onset of illness and phobic avoidance. Several, but not all, authors have found a worse clinical course for women. Using observational, longitudinal data from the Harvard/Brown Anxiety Disorders Research Program, the authors analyzed remission and symptom recurrence rates in panic patients with respect to sex. Method: Male and female patients (N=412) in an episode of panic with or without agoraphobia were assessed by structured interview and prospectively followed for up to 5 years. Data on remission, symptom recurrence, and comorbid psychiatric conditions for each sex were compared. Results: There were no significant differences between men and women in panic symptoms or level of severity at baseline. Women were more likely to have panic with agoraphobia (85% versus 75%), while men were more likely to have uncomplicated panic (25% versus 15%). The rates of remission for panic with or without agoraphobia at 5 years were equivalent in men and women (39%). Of the subjects who achieved remission, 25% of the women and 15% of the men reexperienced symptoms by 6 months. Recurrence of panic symptoms continued to be higher in women (82%) than men (51%) during the follow-up period and was not influenced by concurrent agoraphobia. Conclusions: This study extends previous findings by showing that not only are women more likely to have panic with concurrent agoraphobia, but they are more likely than men to suffer a recurrence of panic symptoms after remission of panic. (Am J Psychiatry 1998; 155:596–602)

A

nxiety disorders such as panic disorder and panic disorder with agoraphobia are common psychiatric illnesses. As the Epidemiologic Catchment Area data show (1), the lifetime prevalence rate for panic disorder in women is double that for men (2% versus 1%), and the rate for panic disorder with concurrent agoraphobia is even more disproportionate: 7.9% for women compared with 3.7% for men. Data from the National Comorbidity Survey (2) also demonstrate that the lifetime prevalence of DSM-III-R panic disorder for women (5%) is more than twice that for men (2%), but the 2:1 sex ratio is retained for panic disorder with agoraphoReceived Sept. 18, 1996; revision received Sept. 29, 1997; accepted Nov. 14, 1997. From the University of Texas Southwestern Medical Center at Dallas. Address reprint requests to Dr. Yonkers, University of Texas Southwestern Medical Center at Dallas, 5959 Harry Hines Blvd., Dallas, TX 75235-9101; [email protected] (e-mail). Supported in part by the Upjohn Company, by NIMH grant MH51415, and by NIMH grant MH-41115 from the Clinical Research Center Study of Neuropsychobiology in Affective Disorders to Dr. Yonkers. The authors thank the Quintiles Corporation for providing consultation services to this project. This manuscript has been reviewed by the Publications Committee of the Harvard/Brown Anxiety Disorders Research Program and has its endorsement.

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bia in the National Comorbidity Survey and in other community studies (3, 4). Aside from the variation in prevalence rates, only a few significant differences between men and women with either panic disorder or panic disorder with agoraphobia have been shown (5, 6). Some studies have found that women who have panic disorder with agoraphobia endorse slightly greater fear (7, 8), although other studies have found that men are more fearful, particularly regarding somatic concerns (9). A more consistent finding is the higher rate of alcoholism in men than in women suffering from panic disorder with agoraphobia (10–12). Finally, there is some suggestion that the clinical course and outcome of anxiety disorders, including panic disorder with agoraphobia and panic disorder, differ between men and women. In one naturalistic study of anxiety neurosis (defined according to the Feighner criteria [13]), women had more symptoms and higher medical care utilization at 4-year follow-up (14). A second observational study found that female sex predicted greater avoidance and panic after 1 year (15). No sex differences were found in a third study that reinterviewed subjects an average of 3 years after their participation in a treatment study (16). While cross-sectional studies can address a number of

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YONKERS, ZLOTNICK, ALLSWORTH, ET AL.

questions, they are limited in their evaluation TABLE 1. Definitions for Psychiatric Status Ratings Used in a Study of Panic Disorder in Women and Men of clinical course. Using a prospective design and short-interval follow-up interviews, our Psychiatric Definition for group has shown that panic disorder and Status Rating Panic Disorder Definition for Agoraphobia panic disorder with agoraphobia are chronic, 6 At least one panic Severe avoidance resulting in near or recurring illnesses. We found 1-year remisepisode per day total restriction to home or inability to sion rates of 37% for panic disorder and leave home unaccompanied 5 At least one panic Avoidance resulting in constricted life17% for panic disorder with agoraphobia episode per week style or fear endured with great anxiety (17), but among the patients who attained rebut less than one (e.g., able to leave house alone but mission, relapse was common. This illusper day unable to go more than a few miles trates the potential for varying results in outunaccompanied) come evaluations if a single cross-sectional 4 Persistent fear of Some avoidance and relatively normal panic lifestyle (e.g., travels unaccompanied point is designated. This may also bear on the when necessary, such as to work or to question of prevalence rates, since longer cushop, but otherwise avoids traveling mulative symptomatic periods, due to either alone) lower remission rates or a higher likelihood 3 Limited-symptom Moderate anxiety when in a phobic panic situation but no avoidance of symptom recurrence, would increase ap2 Sometimes feels on Slight anxiety in a phobic situation (or parent prevalence estimates. Given the mixed the verge of an anticipation of the situation) but no reports on differences between the sexes in attack but is able avoidance clinical course, we used prospectively colto control it lected data to test whether women would ex1 None of the above None of the above perience lower remission rates or greater relapse into symptoms compared with their Evaluation (22) was used to collect information on severity of sympmale counterparts. We also used these data to explore toms and medication treatment. possible sex differences in demographic characteristics All intake interviews were conducted in person or by telephone by and comorbidity. Since previous studies have failed to experienced clinical interviewers who underwent an initial 3- to 6find substantial differences between the sexes in demomonth training period. Ongoing monitoring for interrater reliability included review and comparison of raw data, with an interview sumgraphic characteristics or age at onset, we hypothesized mary and one videotaped interview per month. The latter was rated that there would be few differences in our study group. independently by other monitors, who also met to discuss ratings. We did hypothesize that our study group, similar to othThree substudies to assess interrater reliability, subject recall, and vaers, would show more comorbid alcohol abuse in men lidity of the Longitudinal Interval Follow-up Evaluation psychiatric but higher rates of co-occurring agoraphobia in women. status ratings were conducted with subjects already enrolled in the METHOD This report is based on data from the Harvard/Brown Anxiety Disorders Research Program. The methods used in the program have been described in detail elsewhere (17). The Harvard/Brown Anxiety Disorders Research Program is a prospective, naturalistic longitudinal study of patients with DSM-III-R-defined anxiety disorders. Entrance criteria for the study include at least one of the following DSMIII-R current or past diagnoses: panic disorder, panic disorder with agoraphobia, agoraphobia without panic disorder, generalized anxiety disorder, and social phobia. Subjects were at least 18 years of age and provided written informed consent. The exclusion criteria were organic mental disorder, schizophrenia, or psychosis within the last 6 months. Seven hundred eleven patients were recruited from private practices and teaching clinics of the psychiatry departments at Harvard Medical School, the University of Massachusetts, and Brown University. Five hundred twenty-seven subjects had a lifetime history of panic disorder or panic disorder with agoraphobia; 412 were in an episode of panic disorder or panic disorder with agoraphobia at intake and had at least one follow-up evaluation. Since data on course of panic were available only for the latter group, this set was used for the analysis in this report. The initial comprehensive evaluation of subjects included selected items from the Personal History of Depressive Disorders (18), the Structured Clinical Interview for DSM-III-R—Patient Version (SCID-P) (19) (nonaffective disorders section), and the Schedule for Affective Disorders and Schizophrenia—Lifetime Version (SADS-L) (20). Items from the SCID-P and SADS-L were combined to create the SCALUP (21). Follow-up was conducted at 6-month intervals for the first 2 years and annually after that point. The Longitudinal Interval Follow-up

Am J Psychiatry 155:5, May 1998

Harvard/Brown Anxiety Disorders Research Program (23). Median intraclass correlations (ICC) for psychiatric status ratings according to disorder were the following: for panic, 0.72 (range=0.62–0.88); for agoraphobia, 0.81 (range=0.49–0.98); for social phobia, 0.87 (range=0.75–0.89); for major depressive disorder, 0.80 (range=0.73– 0.93); and for Global Assessment Scale (GAS) score, 0.75 (range= 0.72–0.77). The long-term test-retest reliability of subjects’ retrospective recall over a 1-year period was found to be acceptable for panic (ICC range=0.62–0.80) and very good to excellent for all other index disorders and for major depressive disorder (ICC range=0.89–1.00). An independent external validity assessment comparing summed psychiatric status ratings with GAS scores found a significant inverse correlation of 0.57 (N=550, p=0.0001) (higher GAS scores reflect higher functioning, while higher psychiatric status rating scores are indicative of greater impairment).

Psychiatric Status Ratings At each interview, individuals were assigned a psychiatric status rating ranging from 1 to 6 (table 1) that corresponded to the number and frequency of symptoms and the degree of functional impairment experienced during each week of the study. Subjects were assigned a psychiatric status rating for panic and for agoraphobia if they experienced both. For this report, a subject’s status for each given week was assessed by taking the higher of the two ratings for panic and agoraphobia; for example, if a subject’s psychiatric status rating for panic was 5 and for agoraphobia was 4, the combined psychiatric status rating was 5. This gives a measure of whether the subject met the full DSM-III-R criteria (was in an episode), was asymptomatic (in remission), or was somewhere in-between (met partial criteria). To investigate possible differences missed by this simplification, panic psychiatric status ratings for the panic and agoraphobia groups were also compared separately.

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PANIC DISORDER IN WOMEN AND MEN

TABLE 2. Characteristics of Subjects in a Study of Panic Disorder in Women and Men Male Patients (N=132)

Variable

Age (years) Age at onset of panic disorder (years) Global Assessment Scale score at intake

Education Less than high school graduate High school graduate Some college College graduate Graduate school Works full timea Married History of hospitalization Made suicide gestures/attempts aSignificant

Female Patients (N=280)

Mean

SD

Mean

SD

41.7

11.5

39.6

12.2

28.8

11.6

27.9

11.6

59.6

9.7

59.5

11.3

N

%

N

%

10 38 28 30 26 75 72 48 8

8 29 21 23 20 57 55 36 6

20 71 96 59 34 101 148 82 27

7 25 34 21 12 36 53 29 10

difference between groups (χ2=15.78, df=1, p