Do panic disorder patients indiscriminately endorse somatic complaints?

207

Psychiatry Research, 291201-2I3 Elsevier

Do Panic Disorder Patients Indiscriminately Somatic Complaints?

Endorse

Raymond R. Go&z, Jack M. Gorman, Donald J. Dillon, Laszlo A. Papp, Eric Hollander, Abby J. Fyer, Michael R. Liebowitz, and Donald F. Klein Received

October

18, 1988; revised version received March 7, 1989; accepted April 23, 1989.

Abstract. Ehlers et al. (19866) and Margraf et al. (1986) suggested that panic disorder patients indiscriminately endorse somatic complaints and that their responses to lactate infusion are nonspecific. Their Symptom Questionnaire was composed of anxiety/panic/lactate infusion relevant symptoms, while the Somatic Control Scale was composed of “irrelevant” symptoms. In an attempt to address and in part replicate the above findings among panic disorder patients, we adopted the SCS of Margraf et al. (1986) for use with our Acute Panic Inventory, an instrument similar to their Symptom Questionnaire. Contrary to their reports, we did not find a tendency for panic patients to indiscriminately endorse somatic complaints. Only Acute Panic Inventory scores differed significantly across assessment points. Key Words. Panic disorder, lactate infusions,

somatic symptoms.

In a recent report on physiological and symptom responses to lactate infusion, Ehlers et al. (19866) found no differences between their group of 10 patients suffering from panic disorder/agoraphobia with panic attack and 10 normal control subjects in self-reported anxiety and heart rate. They reported a tendency for their patients to endorse somatic symptoms “indiscriminately” during lactate infusion. This was assessed by including a Somatic Control Scale (SCS) of seven symptoms deemed “irrelevant to lactate or anxiety experiences” within their Symptom Questionnaire (SQ). Their SQ comprised 53 adjectives or short phrases (inclusive of the SCS), including panic symptoms included in DSM-ZZZ(American Psychiatric Association, 1980), panic symptoms often reported in the literature, and symptoms related to catecholamine secretion and hypocalcemia. Symptoms were self-rated on a O-4 scale (ranging from “not at all” to “extremely”). Comparisons were carried out between a “usual attack” assessment obtained the day before the infusion and a “lactate” assessment obtained about 20 min after the lactate infusion was completed or stopped at the request of the subjects. Klein and Ross (1986) earlier discussed and Ehlers et al.

Raymond R. Goetz, Ph.D., is Research Scientist, Biological Studies Unit and HIV Center for Behavioral Studies; Jack M. Gorman, M.D., is Associate Professor of Psychiatry; Donald J. Dillon, Ph.D., is Assistant Professor of Psychology in Psychiatry; Laszlo A. Papp, M.D., is Assistant Professor of Clinical Psychiatry; Eric Hollander, M.D., is Assistant Professor of Clinical Psychiatry; Abby J. Fyer, M.D., is Assistant Professor of Clinical Psychiatry; Michael R. Liebowitz, M.D., is Associate Professor of Clinical Psychiatry; and Donald F. Klein, M.D., is Professor of Psychiatry, College of Physicians and Surgeons of Columbia University and the Department of Therapeutics, New York State Psychiatric Institute. (Reprint requests to Dr. R.R. Goetz, New York State Psychiatric Inst., 722 W. 168th St., New York, NY 10032, USA.) 0165-178 I /89/$03.50

@ 1989 Elsevier Scientific

Publishers

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Ltd.

(1986~) replied to a number of methodological aspects of the Ehlers report; however, neither group specifically addressed the Ehlers et al. SCS findings. Ehlers et al. (1986b) concluded that their data do not support the notion that panic patients have a specific “biological” response to lactate that differs from that of controls, but rather that they react to nonspecific physiological changes caused by lactate with diffuse somatic complaints. Margraf et al. (written personal communication to D.F.Klein, 1986) reported a retest reliability of 0.90 on a modified version of the SCS. This version included three additional items, making a total of 10 panic “irrelevant” items, each rated on a scale of O-4 (“not at all” to “extreme”). There was also a significant correlation between SCS score and “relevant” symptoms on the SQ (r < 0.60, n = 68). The SCS distinguished panic disorder patients from normal controls on a “usual” attack rating by correctly classifying 42 of 53 patients. These findings call into question the specificity of panic-like symptoms caused by lactate infusion. We tested this issue by incorporating the 10 panic “irrelevant” items (SCS) into our Acute Panic Inventory (API) (Dillon et al., 1987). Here, we attempt to replicate two findings reported by Ehlers et al. and Margraf et al., respectively: (1) the report that panic patients indiscriminately endorse somatic symptoms, and (2) the report of a positive correlation between the SQ and the SCS. In addition, we were interested in seeing if any changes occurred in these scales across a lactate infusion, and whether these changes differed between panic and nonpanic responses to the lactate infusion. Methods Subjects. The API and SCS were administered to 24 patients diagosed as having DSM-III panic disorder/agoraphobia with panic attack while the patients were undergoing lactate infusion studies. No normal controls were studied; thus, our ability to replicate the Ehlers et al. report was limited. Patients were 10 males and 14 females, between the ages of 22 and 56 years (mean age = 35.0, SD = 8.9 years). Patients were recruited by media presentations, advertisements, medical referrals, and word of mouth. All patients underwent physical exams and were deemed in good health. Patients were excluded if they had concurrent major depressive disorder or current psychoactive drug use that could not be discontinued at least 2 weeks before lactate infusion. Patients whose infusions were without procedural difficulties and who received the SCS have been included in this report. Procedural difficulties included extended infusions with lactate (22 min), the occurrence of panic during the preliminary saline placebo infusion, or i.v. infiltration. Procedure. The procedure used for sodium lactate infusion has been described in detail elsewhere (Liebowitz et al., 1984). In brief, the patient first receives a slow i.v. infusion of normal saline for 30 min. Then, under single-blind conditions, the infusion is switched to half-molar racemic sodium lactate (10 cc/ kg). This is continued for 20 minor until the patient experiences a panic attack, at which point the infusion is stopped. A panic attack response is identified on the basis of the attending psychiatrist’s observation of an abrupt escalation of fear and apprehension accompanied by the DSM-ZZZphysical symptoms of a panic attack (e.g., heart palpitations, shortness of breath, sweating, and faintness). Physical symptoms alone are not sufficient. The API, as used here, is a 29-item inventory of anxiety or lactate-related symptoms that are rated on a O-3 scale (0 = symptom not experienced, 1 = mild, 2 = moderate, 3 = severe). Similar to the SQ scale of Ehlers et al., the API contains DSM-III symptoms, and symptoms related to catecholamine secretion and hypocalcemia. The API can be administered in a matter of minutes and yields a maximum score of 87. In all cases, the assessments are performed by the staff psychiatrist or psychologist. We randomly incorporated the 10 items of the SCS into our API.

209 The SCS items include the panic “irrelevant” somatic complaints of toothache, sore throat, back pain, smell of smoke, burning eyes, itchiness, tunnel vision, swollen tongue, sweet taste in mouth, and burning ears. The API with the SCS items incorporated was administered serially throughout the procedure. Unlike the subjects studied by Ehlers et al., our patients responded verbally to the API-SCS and it was given at the following four specific time points during the experimental procedure: (1) A rating of the “usual” degree of symptoms during a typical panic attack is obtained the day before or the morning of the actual experimental infusion before setup. (2) A prelactate rating is done at the end of the saline infusion immediately before the start of the lactate infusion. (3) A rating is done at the IO-min point of the lactate infusion or at the point of panic if it occurred during the first 10 min. (4) A rating is made at the 20-min end point of the infusion or at the point of panic occurring at minutes 11 through 22. The termination API/ SCS assessment was defined as the rating at the point when the infusion was stopped either due to a complete 20-min infusion or the occurrence of panic. Statistical comparisons were performed across groups (as defined by a panic or a nonpanic response to the lactate infusion) using conventional two-tailed I tests. Paired t tests were performed within the two response groups across assessments. Comparisons were performed using total API and SCS scores separately. The A change scores for API and SCS were determined by subtracting the prelactate assessment from the termination scores. Spearman correlations were performed between API and SCS scores for each assessment point, at termination and for A change scores. The number of subjects varies due to missing data points; therefore, the n’s for each comparison are reported in the data tables.

Results Fourteen of the 24 patients (58%) experienced panic attacks during the lactate infusion. Seven of 10 males and 7 of 14 females panicked to lactate infusion. Mean (? SD) age of the panicking and nonpanicking groups did not differ (35.2 f 9.0 vs. 37.7 f 8.2 years). In the following analyses, the SCS and API data were handled separately. The panic and nonpanic groups did not differ in their total “usual” API score or in their total prelactate API score (see Table 1). Total API score at termination and the API change score (termination minus prelactate) did differ significantly (p < O.OOl), with the panicking subjects attaining levels 2-3 times higher than the nonpanicking subjects. However, the groups did not differ in any comparison of SCS scores. The API scores significantly increased across the infusion period from prelactate to the termination of the infusion in both panickers and nonpanickers, while the SCS scores did not significantly increase during the infusion period in either group. The paired t tests (within group/across assessment points [see Table 21) yielded expected differences in API scores for the “usual” vs. the prelactate assessments, and the prelactate vs. the termination assessments in both response groups. In the comparison of the “usual” vs. the termination API scores, both groups differed significantly across these assessments, indicating that neither group experienced anxiety or panic symptomatology during the lactate infusion to the degree that they do during their “usual” panic attack. SCS scores yielded no significant differences. To determine the relationship between total API and A API scores on the one hand and the total SCS and A SCS scores on the other, Spearman correlations were performed between the two scales. Only with regard to the “usual” API and SC scale assessments was a weak trend toward a correlation found (rho 0.38,~ < 0.08, n = 22). For the prelactate, termination, and panic point assessments, no discernible relationship between the two scales was found. q

210

Table 1. Acute Panic Inventory and Somatic Complaint Scale data compared across the panic response to lactate infusion Panickers Scales

Mean

Nonpanlckers

SD

n

Mean

49.0

10.5

14

40.4

14.8

9

1.63

0.12

9.6

5.0

14

8.0

6.2

10

0.69

NS

Termination

38.5

12.7

14

17.4

7.5

9

4.47

0.001

A Change

28.9

10.9

14

9.8

9.5

9

4.38

0.001

Usual

2.2

2.8

13

1.0

2.0

9

0.66

NS

Prelactate

0.69

0.95

13

0.22

0.67

9

1.28

NS

Termination

1.08

1.55

14

0.37

0.529

9

1.50

NS

A Change

0.38

1.50

13

0.12

0.99

9

0.43

NS

SD

n

t

R

API totals Usual Prelactate

SCS totals

Note. API = Acute Panic Inventory. SCS = Somatic Complaint Scale.

Table 2: Comparison of API and SCS totals and A change scores across assessment/within response groups API totals

SCS totals

Mean

SD

n

Usual vs. Prelactate

49.0 9.6

10.5 5.0

14

Usual vs. Termination

49.0 38.5

10.5 12.7

14

Prelactate vs. Termination

9.6 38.5

5.0 12.7

14

Usual vs.

40.4

14.8

9

Prelactate

8.3

6.4

Usual vs.

41.4

15.5

Termination

17.7

7.9

P

Mean

SD

n

2.2 0.7

2.8 0.9

13

If

2.2 1.1

2.8 1.6

13

f

0.7 1.1

0.9 1.6

14

f.

1.0

2.0

9

l

t

0.2

0.7

1.1

2.1

l

.

0.4

0.5

Panickers

Nonpanickers

Prelactate vs. Termination

7.9

6.5

17.4

7.5

8

9 *

0.2

0.7

0.4

0.5

Note. API = Acute Panic Inventory. SCS = Somatic Complaint Scale Paired

t

tests: * = p c 0.05; ** = p < 0.01.

8

9

P

211

The reported significant correlation between the SC scale and the Margraf et al. symptom scale predicts that we should lind a parallel increase between the SC scale and our API scale during lactate infusion. To test this, we performed a repeated measures analysis of variance (RM-ANOVA) to determine if there was a significant interaction between the scores on the two instruments (API and SC) across the prelactate and termination assessments in the two patient groups (panickers and nonpanickers). This yielded a highly significant (group x time x scale) interaction between the two scales (prelactate to termination), between the panicking and nonpanicking groups (F = 15.35; p < 0.001; df = 1, 19). This demonstrates nonparallel changes across the infusion period in the two instruments, again not supportive of Ehlers et al. (1986) or Margraf et al. (personal communication, 1986). An additional RM-ANOVA was performed adding sex as an independent measure to test for possible sex differences. There were no significant sex differences or interactions with any of the other factors. Discussion

Several criticisms should be discussed at the outset, particularly our lack of normal control data. We were not uncomfortable with this design as we felt we could adequately address the specific findings of Ehlers et al. that interested us. We wanted to address three issues-the level of SCS symptoms reported among the Ehlers et al. patients, and the API and SCS responses of patients to lactate infusion-and we hoped to demonstrate that the response of patients is discernibly different based upon the experience of a panic attack. Another problem involved missing data and the inconsistent n’s that we report. The missing data were always the result of either staff not getting a “usual rating” from the patients or the inability of a patient to answer the APIjSCS questions immediately after experiencing a panic attack. We decided to present all possible data and indicate where the n’s varied. We replicated one finding of Ehlers et al. in that our analysis of the valid symptoms (our API) in panic disorder patients indicates that lactate-induced panic attacks may not be as symptomatically severe as retrospectively (“usual panic rating”) rated spontaneous attacks. There are at least two explanations that could account for these findings. Either the panic disorder patients are overestimating the degree of symptomatology that they experience during a “usual” attack, or their “usual” attacks are in fact more severe than a lactate-induced attack. The presence of the laboratory staff almost certainly contributes to the latter explanation. Our results are inconsistent with those reported by Ehlers et al. in that our group of panic disorder patients did not report significant SCS symptomatology for their “usual rating,” and their endorsement of these items did not significantly increase as a result of lactate infusion, from prelactate to termination assessments. In contrast, they responded positively to panic-related items, such as palpitations, difficulty breathing, and sweating. Thus, we find no evidence that panic patients are “indiscriminate” in identifying symptoms during a rating of their “usual attack” or in response to lactate infusion or lactate-induced panic. Independent of the fact that we do not report normal control data here, our procedural design for the symptom and SC assessments did differ from those used in

212 the Ehlers et al. study. Our API and SCS were administered verbally by either an attending psychologist or psychiatrist, while Ehlers et al. administered the SQ and SCS as a self-report questionnaire. Our verbal administration raises the issue of objectivity and the possibility of a verbal inflection influencing the subjects to respond in a particular fashion. The assessments are performed in a very monotonous fashion with the SCS items having been randomly integrated among the 29 API items; nevertheless, the above possibility cannot be ruled out as an explanation for our inconsistent findings. In studies already published from our laboratory (Appleby et al., 1981; Liebowitz et al., 1981, 1984; Dillon et al., 1982) patients experiencing lactate-induced panic attacks consistently report a higher level of symptomatology, as assessed by the API, than nonpanicking patients and normal controls. Dillon et al. (1987) reported on the API data of 89 panic disorder patients and 26 normal controls during lactate infusions. They divided their patient group into panicking and nonpanicking subgroups, and further subgrouped the panicking patients into early (< 10 min to panic) and late (> 10 min but < 22 min) panickers. They reported both raw score and A score API differences among panicking and nonpanicking patients and normal controls. Early and late panickers also differed from each other. Dillon et al. (1987) further reported a high degree of sensitivity and specificity for A API scores in distinguishing lactate panickers from nonpanickers (patients and controls). An API A score > 13 identified 78% (43/ 55) of the panicking patients (sensitivity) while misidentifying none of the 26 normals as false-positives, yielding a specificity of 100%. Overall correct response group identification was 84%. If this same test is applied to the data presented here, a change in the API total 2 13 yielded a sensitivity of 83% (identifying 20124 accurately) and a kappa statistic of 0.66 (converted to Z score = 3.65, p < 0.001). Specificity was not a question that could be addressed as normal controls were not studied. The SCS, on the other hand, was insensitive in distinguishing panickers from nonpanickers in our laboratory. Among a group of patients suffering from panic disorder/ agoraphobia with panic attack, the report of anxiety-related symptoms on the API increased significantly in response to lactate infusions; no such changes were found for the nonspecific and irrelevant symptoms of the SCS. Our results are consonant with other findings that lactate infusion induces psychophysiologically valid panic attacks in some patients with panic disorder.

213

Acknowledgments. The authors acknowledge the support of the NIMH Mental Health Clinical Research Center Grant to Psychiatric Institute (MH-30906), NIMH grants MH-33422 and MH-37592 (Dr. Donald F. Klein), and a Research Scientist Development Award (MH00416) to Dr. Jack Gorman.

References American Psychiatric Association. DSM-III: Diagnostic and Statistical Manual of Mental Disorders. 3rd ed. Washington, DC: APA, 1980. Appleby, I.; Klein, D.F.; Sachar, E.J.; and Levitt, M. Biochemical indices of lactate-induced panic: A preliminary report. In: Klein, D.F., and Rabkin, J., eds. Anxiety: New Research and Changing Concepts. New York: Raven Press, 1981. Dillon, D.J.; Gorman, J.M.; Liebowitz, M.R.; Fyer, A.J.; and Klein, D.F. The measurement of lactate-induced panic and anxiety. Psychiatry Research, 20:97-105, 1987. Dillon, D.J.; Levitt, M.; Klein, D.F.; and Danielson, E. Some physiological, biochemical and psychological concomitants of lactate-induced panic. In: Maletesha, R.N., and Hartlage, L.C., eds. Neuropsychologyand Cognition. Vol. II. The Hague, Boston, London: Nijhoff, 1982. pp. 65 l-660. Ehlers, A.; Margraf, J.; and Roth, W.T. The authors reply. Psychiatry Research, 19:165-167, 1986a. Ehlers, A.; Margraf, J.; Roth, W.T.; Taylor, C.B.; Maddock, R.J.; Sheikh, J.; Kopell, M.L.; McClenahan, K.L.; Gossard, D.; Blowers, G.H.; Agras, W.S.; and Kopell, B.S. Lactate infusions and panic attacks: Do patients and controls respond differently? Psychiatry Research, 17:295-301, 19866. Klein, D.F., and Ross, D.C. Response of panic patients and normal controls to lactate infusions. (Letter) Psychiatry Research, 19:163-164, 1986, Liebowitz, M.R.; Fyer, A.J.; Gorman, J.M.; Dillon, D.; Appleby, 1.L.; Levy, G.; Anderson, S.; Levitt, M.; Palij, M.; Davies, SO.; and Klein, D.F. Lactate provocation of panic attacks: 1. Clinical and behavioral findings. Archives of General Psychiatry, 41~764-770, 1984. Liebowitz, M.R.; Fyer, A.J.; McGrath, P.J.; and Klein, D.F. Clonidine treatment of panic disorder. Psychopharmacology Bulletin, 171122-124, 1981. Margraf, J.; Ehlers, A.; and Roth, W.T. Sodium lactate infusions and panic attacks: Review and critique. Psychosomatic Medicine, 48~23-5 1, 1986.