Regular Paper
Psychother Psychosom 1992;58:46-53
B. Van Houdenhove D. Verstraeten p. onghena H .D ecuyper
Chronic Idiopathic Pain, . . ... . .. Mianserin and Masked Depression
University Psychiatric Center, and Faculty of Psychology and Education. K.U. Leuven. Belgium
KeyWords
Abstract
Chronic idiopathic pain Masked depression Antidepressants Mianserin Depressive disorder
In this study an attempt was made to provide controlled empirical evidence for the hypothesis that chronic idiopathic pain might be a specific form o f‘masked depression’. For this purpose, chronic pain patients supposed to be suffering from a ‘masked depression’ were compared to patients with organic pain and coexistent depression, patients with only organic pain, and patients with only depression, in a double-blind pla cebo-controlled therapeutic trial with mianserin. Although mianserin appeared to have effective antidepressant proper ties in this study, no pain improvement was found in any of the three chronic pain groups. These results challenge the val idity and clinical relevance of the ‘masked depression’ concept for chronic idiopathic pain.
Chronic pain which is not fully explicable by organic factors remains a diagnostic and therapeutic enigma. Different diagnostic la bels have been proposed for this condition, such as ‘psychogenic pain disorder’ [1], ‘chronic idiopathic pain’ [2] and most re
cently ‘somatoform pain disorder’ [3], From an etiopathogenetic point of view, some au thors have hypothesized that at least a sub group of these patients may suffer from a spe cific form of ‘masked depression’, i.e. a de pression that would manifest itself primarily in the form of pain complaints [4, 5]. This hypothesis appears to be empirically sup-
Prof. B. Van Houdenhove. Raadpleging Psychiatrie. U.Z. St. Rafael Capucijnenvoer 33 B-3000 Leuven (Belgium)
© 1992 S. Karger AG. Basel 0033-3190/92/ 058l-0046$2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 2/24/2018 1:40:59 PM
Introduction
trol conditions (a group with only depression, and a placebo condition) were included in the study. The study protocol was approved by the ethical committee of our University Hos pital.
Methods Subjects Fifty-nine outpatients, all suffering from moderate to severe pain lasting for more than 6 months (mean duration: 5.6 years) and/or from major depression, were recruited from the psychiatric consultation ser vice and the pain clinic of the University Hospital St. Rafael, K.U. Leuven, and also from the rhcumatologic and orthopedic services of the University Hospital PelIcnbcrg, K.U. Leuven. Different pain locations were represented, but the majority of the patients had pain in the musculoskeletal system. The inclusion criteria for the four groups were: (1) group A: patients with organically inexplicable chronic pain diagnosed as 'masked depression', i.e. pain judged to be etiologically related to depression, without prominent complaints of depressed mood or emotional distress but with ‘vital’ and/or vegetative signs of depression (mainly anergia, anhedonia. insom nia: patients were assigned to this category' by the first author): (2) group B: patients with chronic organic pain and coexistent major depression (DSM III-R: Hamil ton score > 20); (3) group C: patients with chronic organic pain without depression (Hamilton score < 10); (4) group D: patients with only major depres sion (DSM III-R; Hamilton score > 20). Assessments Depression was evaluated by the Hamilton Rating Scale for Depression (HAM) [23] and the Beck Depres sion Inventory (BDI) [24]; the latter scale was used during the follow-up. Pain was evaluated by the McGill Pain Questionnaire. Dutch version (MPQ) [25], Design Table 1 shows the design of the study. A wellknown antidepressant with sedative properties (mian serin) was given in a dose varying from 30 to 90 mg to all groups in a double-blind placebo-controlled cross over fashion: the sequence of treatment was counter balanced. The total duration of the study was 12 weeks. Twenty-four patients (41%) dropped out.
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ported by the high prevalence of depression (or neurovegetative signs of depression) in chronic pain [6, 7]; the high prevalence of pain symptoms in depression [8]; the fact that depression often precedes chronic pain [4]: the growing evidence of common biological mechanisms in chronic pain and depression (as suggested by the presence of biological markers for depression in chronic pain pa tients) [9-11]; the finding of common famil ial-genetic factors [12]: and last but not least, the reduction of some chronic pain problems by antidepressant medication [ 13, 14], Nevertheless, the conceptualization of chronic pain as 'masked depression’ has been severely criticized and, despite its widespread clinical use, especially in primary care [15, 16], it is still very controversial. Several au thoritative writers, indeed, consider the con cept vague and confusing [17, 18], and even assert that it makes thinking about chronic pain ‘harder instead of easier’ [19]. Moreover, some of the above-mentioned empirical stud ies show manifest methodological flaws [20] and have not always been confirmed by other authors [21 ]. Finally, it must be noted that the positive results of antidepressant therapy in chronic pain may be due to other modes of action, such as a pain-tolerance-enhancing ef fect (by alleviating a coexistent depression, or by causing a more general sedation), a direct influence on central pain-controlling mecha nisms, or even a placebo effect [22], The present study was designed to provide controlled empirical evidence for the hypoth esis that chronic idiopathic pain might be a form of ‘masked depression’. For this pur pose, the therapeutic effects of antidepressant medication in a group of chronic pain pa tients, clinically diagnosed as ‘masked depres sion’, were compared to the same treatment in a group of patients with organic pain and coexistent depression, and in a group with only organic pain. In addition, two other con
Table 1. Measurements during the study, and dose schema of mianserin/placebo or placebo/mianserin
Pretreatment (1 week)
First 6 weeks
Second 6 weeks
Day Dose, mg
pre 0
1 0
4 30
8 60
15 60
22 60 90
29 60 90
36 60 90
43 60 90
46 30
50 60
57 60
64 60 90
71 60 90
78 60 90
85 60 90
DSM-1II HAM BDI MPQ Second eff.
X X X X X
X X X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
Statistical Analysis
Univariate repeated measures analyses of variance [26] were carried out on the BDI and MPQ total scores, using the Statistical Analysis System PC Ver sion 6 Edition [27]. ‘Treatment’ and ‘Time’ acted as the within-subject variables, and ‘Group’ as the between-subject variable. The Treatment variable has 2 levels: mianserin and placebo; the Time variable has 7 levels: the different moments of assessment; and the Group variable has 4 levels: the 4 diagnostic groups. Pairwise comparisons were made using the RyanEinot-Gabriel-Welsch multiple range test (REGWQ) [28],
48
Results
The univariate repeated measures analysis of variance on the BDI showed a significant main effect on the Group, F(3,31) = 6.22, p < 0.01, and on the Time variable, F(6,186) = 5.89. p < 0.01. The mean BDI score in group C was significantly lower than the mean BDI scores in the other groups (REGWQ. p < 0.05) and there was a significant decrease in mean BDI scores over time (REGWQ, p < 0.05). These main effects, however, were to be appreciated in the light of the significant Time-Group and Treatment-Time interac tions. The significant Time-Group interaction, F(18,186) = 3.15. p < 0.01. showed that the evolution in mean BDI scores over time dif fered for the different groups. Pairwise com parisons, however, revealed no systematic up ward or downward trend in the different groups when the data were aggregated across treatments. The significant Treatment-Time interaction, F(6,186) = 2.60, p < 0.05, showed that the evolution in mean BDI scores over time was not the same for the mianserin and for the placebo condition. In the mian serin condition the mean BDI scores de creased significantly over time (REGWQ.
Van Houdenhove/Verstraeten/ Onghena/De Cuyper
‘Masked’ Depression
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mostly because of severe side effects (drowsiness). There were no indications for differential dropout in the different conditions, nor were there differences between the dropouts and the non-dropouts with re gard to the baseline measurements and the demo graphic variables. Thus. 35 patients (11 in group A; 8 in group B, C and D), 13 males and 22 females, with a mean age of 45.1 years and a medium to low socioeco nomic status were considered for statistical analysis. For the non-dropouts, the mean Hamilton scores of the different groups were: group A: 23.9 (SD: 12.5); group B: 27.6 (SD: 9.9); group C: 6.5 (SD: 4.0): group D: 29.2 (SD: 6.9). Pain locations in the masked depres sion group were: abdominal: 2; musculoskeletal sim ple: 2: musculoskeletal multiple: 4.
Table 3. Mean BDI score, standard error of the mean BDI score (SE) and REGWQ in the placebo con dition for the different moments of assessment (t 1—17)
Time
Mean
SE
REGWQ
Time
Mean
SE
tl t2 t3 t4 t5 t6 t7
17.03 16.63 14.83 15.34 13.51 13.37 12.86
2.00 1.77 1.70 1.75 1.56 1.46 1.55
X X XY XY Y Y Y
tl t2 t3 t4 t5 t6 t7
14.26 14.49 14.51 13.83 13.06 13.49 13.54
1.46 1.43 1.39 1.24 1.42 1.31 1.37
Means with the same letter (X or Y) are not signifi cantly different.
REGWQ: No means are significantly different.
p < 0.05), while in the placebo condition they did not (tables 2-4). Table 4 also shows that the antidepressive effect was most marked in group D. However, this interaction effect was not statistically significant. When the same analyses were carried out without group C, the same pattern of results arose. To be sure, the main effect on the Group variable disappeared, but the Treat ment-Time interaction remained significant. The univariate repeated measures analyses of variance on the MPQ scores showed no signif icant effects besides a significant main effect on the Group variable, F(3,31) = 6.13, p < 0.01. The mean pain scores in group D were significantly lower than the mean pain scores in the other groups (REGWQ. p < 0.05) but there were no significant increases or de creases in the mean MPQ scores over time, neither in the mianserin condition nor in the placebo condition (tables 5-7). Table 7 shows that on the average patients deteriorated on mianserin (and as compared to placebo), but these differences were not statistically signifi cant.
Table 4. Mean difference BDI score between the first moment of assessment and the last moment of assessment for the different groups in the mianserin and the placebo condition
A B C D
Mianserin
Placebo
1.01 4.35 2.16 10.23
1.39 -2.50 -0.80 2.22
A positive difference means improvement, a nega tive difference means deterioration.
When the same analyses were carried out without group D, the main effect on the Group variable disappeared and all the other effects remained nonsignificant. When the data were analyzed for each group separately, again no significant effects appeared. A clini cal analysis also revealed that there was no evidence for pain improvement in any of the individual cases.
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Table 2. Mean BDI score, standard error of the mean BDI score (SE) and REGWQ in the mianserin condition for the different moments of assessment (t 1— 17)
Table 6. Mean MPQ total score, standard error of the mean MPQ total score (SE) and REGWQ in the placebo condition for the different moments of assess ment (t I— 17)
Time
Mean
SE
Time
Mean
SE
tl t2 t3 t4 t5 t6 t7
12.71 14.60 12.77 14.69 13.60 14.40 14.37
2.15 2.29 2.24 2.26 2.26 2.23 2.31
tl t2 t3 t4 t5 t6 tl
13.63 14.06 13.51 15.43 12.43 12.60 12.74
2.13 2.13 2.13 2.14 2.16 2.19 2.17
REGWQ: No means are significantly different.
REGWQ: No means are significantly different.
Table 7. Mean difference MPQ score between the first moment of assessment and the last moment of assessment for the different groups in the mianserin and the placebo condition
Looking for a possible explanation of these results, and within the methodological limita tions of our study, we hypothesize that the lack of effect in the ‘masked depression' group might be connected with intrinsic definition problems of the concept itself, and its am biguous clinical application [29], In our opin ion. indeed, the concept actually refers to two different explanatory models, namely a prob lem of communication between the patient and his doctor, and a ‘deeper’ dynamical problem of somatization [30]. On the one hand, pain patients with a ‘masked depression’ may have an interper sonal problem of expression and communica tion of depressive mood. Specific familial or developmental-learning factors [31 ], sociocul tural idiosyncrasies [32] and the traits of alexithymia [33] may explain why these patients, who suffer from a true depressive illness, do not spontaneously talk about their depressed mood (or even deny it), but instead complain of physical pain. For obvious reasons, the underlying mood disorder of these patients often remains unrecognized by their doctors [18]. Yet. when carefully interrogated, these
A B C D
Mianserin
Placebo
-5.23 -0.38 -5.26 0.95
2.07 5.35 -2.10 0
A positive difference means improvement, a nega tive difference means deterioration.
Discussion
The results of the present study demon strate that mianserin, despite its antidepres sant effect, had no analgesic effect in any of the chronic pain groups. Because of the ab sence of an antidepressant-mediated anal gesic effect in group A, more specifically, the validity of the ‘masked depression' concept for chronic idiopathic pain is not supported.
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Van Houdenhove/Verstraeten/ Onghena/De Cuyper
'Masked’ Depression
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Table 5. Mean MPQ total score, standard error of the mean MPQ total score (SE) and REGWQ in the mianserin condition for the different moments of assessment (t 1—17)
serin could not be demonstrated in our ‘masked depression' group. As a matter of fact, such an effect would only be demonstra ble in patients who suffer from a true underly ing depressive illness; somatizing patients, however, whose pain is not linked to the pres ence of an actual depressive state but is sup posed to play a substantial role in these pa tients’ psychic economy, will presumably re sist psychopharmacological therapy. In this perspective, we may speculate that the lack of an antidepressant-mediated analgesic effect in group A might be due to a (relative) pre dominance o f somatizing pain patients. Pos sibly. the overrepresentation of this type of patients in our study may have been pro moted by the recruitement from specialized, ‘tertiary care’ clinical settings, such as the pain clinic and the psychiatric consultation service [43]. As mentioned above, several alternative hypotheses about antidepressant-mediated analgesia were also taken into account in our study. However, due to the absence of an analgesic effect in groups B and C, these other potential modes of action (pain tolerance en hancement, sedation, interference with cen tral pain-controlling mechanisms, or placebo effect) are neither supported by the results. Nonetheless, it cannot be ruled out that the absence of any analgesic effect in this study might be due to serious methodological short comings. As a matter of fact, because of the small sample sizes (due to a high dropout rate), our statistical tests have low power. It must be noticed, however, that the power was high enough to detect an antidepressive effect and that an estimated analgesic effect size for our data would be negative (table 7). Further more, possible inadequacies of our pain as sessment (e.g. lack of sensitivity of the Dutch McGill scale) might also be responsible for the negative results.
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patients easily admit suffering from ‘vital’ and/or ‘vegetative’ signs of depression, which may put the clinician on the right diagnostic track (although the patients themselves gener ally attribute these symptoms to the long last ing burden of their pain). On the other hand, the ‘masking process’ may be equated with a ‘somatization process’ - considered here as a dynamical defence mechanism [34], In this context, it may be related to supposed intrapsychic links be tween pain and depression. According to sev eral psychodvnamically oriented authors, pain may indeed function as a ‘hysterical’ or ‘conversive’ somatization symptom which may prevent the breakthrough of a more se vere depression [35, 36], Furthermore, psy choanalytic theory stresses the fundamental parallelism between mental and physical pain, and the possible ‘displacement’ from the former to the latter [37, 38]. These intrapsy chic links largely correspond with the dynam ics of ‘pain-proneness’ which were originally described by Engel [39] and. in a further elab oration, connected with the ‘masked depres sion’ concept by Blumer and Heilbronn [4] and others [40] (this connection, however, has been rightly criticized, see ref. 30, 41). It must be added that somatizing pain patients too frequently present with ‘vital’ and/or vegeta tive signs of depression, which they consider as secondary to their pain as well. Thus, in line with Pilowsky and Bassett [42], it may be stated that making a clinical diagnosis of ‘masked depression’ in chronic pain patients is often an oversimplification. Clearly, it does not bear upon an unequivocal clinical entity, nor a simple etiopathogenetic mechanism, but it refers to a complex inter play of experiencing, attributing, expressing, communicating and recognizing depressed mood or emotional distress. If these basic assumptions are valid, it would become less surprising that a therapeutic effect of mian
In conclusion, the results of this study may call into question the validity and clinical rel evance of the ‘masked depression’ concept for patients suffering from chronic idiopathic pain. They arc in accordance with recent criti cism of the concept [17, 18], and empirically support the suggestion that in clinical practice as well as in further research this vague and ambiguous diagnostic category should be dropped [19]. Instead these results suggest
that it might be more fruitful to distinguish between pain patients who have an unrecog nized (but diagnosable and treatable) depres sive disorder, and those who somatize i.c. focus on physical pain as a means of dynami cal defence against severe emotional distress. This conceptual distinction could possibly contribute to a more specific delineation of the indications for antidepressant medication in chronic idiopathic pain.
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10
11
12
13
14
15 16
17
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‘Masked" Depression
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References
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38 Joffe WGW. Sandler J: On the con cept of pain, with special reference to depression and psychogenic pain. J Psychosom Res 1967; 11:69-75. 39 Engel GL: 'Psychogenic' pain and the pain-prone patient. Am J Med 1959:26:899-918. 40 Groen JJ: Das Syndrom des soge nannten ’unbehandelbaren Schmer zes'. Psychother Med Psychol 1984: 34:27-32. 41 Large R: DSM III diagnoses in chronic pain. Confusion or clarity? J Nerv Ment Dis 1986:174:295-303. 42 Pilowsky I. Bassett DL: Pain and depression. Br J Psychiatry' 1982; 141:30-36. 43 Pilowsky I. Chapman CR. Bonica JJ: Pain, depression and illness be havior in a pain clinic population. Pain 1977;4:183-192.
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26 Winer BJ: Statistical Principles in Experimental Design, ed 2. New York. McGraw-Hill. 1971. 27 SAS Institute: SAS/STAT Guide for Personal Computers. Version 6 ed. Cary, SAS, 1987. 28 Einot I. Gabriel KR: A study of the powers of several methods of multi ple comparisons. J Am Statist Assoc 1975:70:574-583. 29 Modai I. Bleich A. Cvgiclman G: Masked depression - an ambiguous entity. Psvchother Psychosom 1982: 37:235-240. 30 Van Houdenhove B: Interpersonal and psychodynamic links between pain and depression. Eur J Psychia try 1991:5:177-185. 31 Katon W. Kleinman A, Rosen G: Depression and somatization: A re view (Part 1). Am J Med 1982;72: 127-135.
Psychother Psychosom 1992;58:46-53
B. Van Houdenhove D. Verstraeten p. onghena H .D ecuyper
Chronic Idiopathic Pain, . . ... . .. Mianserin and Masked Depression
University Psychiatric Center, and Faculty of Psychology and Education. K.U. Leuven. Belgium
KeyWords
Abstract
Chronic idiopathic pain Masked depression Antidepressants Mianserin Depressive disorder
In this study an attempt was made to provide controlled empirical evidence for the hypothesis that chronic idiopathic pain might be a specific form o f‘masked depression’. For this purpose, chronic pain patients supposed to be suffering from a ‘masked depression’ were compared to patients with organic pain and coexistent depression, patients with only organic pain, and patients with only depression, in a double-blind pla cebo-controlled therapeutic trial with mianserin. Although mianserin appeared to have effective antidepressant proper ties in this study, no pain improvement was found in any of the three chronic pain groups. These results challenge the val idity and clinical relevance of the ‘masked depression’ concept for chronic idiopathic pain.
Chronic pain which is not fully explicable by organic factors remains a diagnostic and therapeutic enigma. Different diagnostic la bels have been proposed for this condition, such as ‘psychogenic pain disorder’ [1], ‘chronic idiopathic pain’ [2] and most re
cently ‘somatoform pain disorder’ [3], From an etiopathogenetic point of view, some au thors have hypothesized that at least a sub group of these patients may suffer from a spe cific form of ‘masked depression’, i.e. a de pression that would manifest itself primarily in the form of pain complaints [4, 5]. This hypothesis appears to be empirically sup-
Prof. B. Van Houdenhove. Raadpleging Psychiatrie. U.Z. St. Rafael Capucijnenvoer 33 B-3000 Leuven (Belgium)
© 1992 S. Karger AG. Basel 0033-3190/92/ 058l-0046$2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 2/24/2018 1:40:59 PM
Introduction
trol conditions (a group with only depression, and a placebo condition) were included in the study. The study protocol was approved by the ethical committee of our University Hos pital.
Methods Subjects Fifty-nine outpatients, all suffering from moderate to severe pain lasting for more than 6 months (mean duration: 5.6 years) and/or from major depression, were recruited from the psychiatric consultation ser vice and the pain clinic of the University Hospital St. Rafael, K.U. Leuven, and also from the rhcumatologic and orthopedic services of the University Hospital PelIcnbcrg, K.U. Leuven. Different pain locations were represented, but the majority of the patients had pain in the musculoskeletal system. The inclusion criteria for the four groups were: (1) group A: patients with organically inexplicable chronic pain diagnosed as 'masked depression', i.e. pain judged to be etiologically related to depression, without prominent complaints of depressed mood or emotional distress but with ‘vital’ and/or vegetative signs of depression (mainly anergia, anhedonia. insom nia: patients were assigned to this category' by the first author): (2) group B: patients with chronic organic pain and coexistent major depression (DSM III-R: Hamil ton score > 20); (3) group C: patients with chronic organic pain without depression (Hamilton score < 10); (4) group D: patients with only major depres sion (DSM III-R; Hamilton score > 20). Assessments Depression was evaluated by the Hamilton Rating Scale for Depression (HAM) [23] and the Beck Depres sion Inventory (BDI) [24]; the latter scale was used during the follow-up. Pain was evaluated by the McGill Pain Questionnaire. Dutch version (MPQ) [25], Design Table 1 shows the design of the study. A wellknown antidepressant with sedative properties (mian serin) was given in a dose varying from 30 to 90 mg to all groups in a double-blind placebo-controlled cross over fashion: the sequence of treatment was counter balanced. The total duration of the study was 12 weeks. Twenty-four patients (41%) dropped out.
47
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ported by the high prevalence of depression (or neurovegetative signs of depression) in chronic pain [6, 7]; the high prevalence of pain symptoms in depression [8]; the fact that depression often precedes chronic pain [4]: the growing evidence of common biological mechanisms in chronic pain and depression (as suggested by the presence of biological markers for depression in chronic pain pa tients) [9-11]; the finding of common famil ial-genetic factors [12]: and last but not least, the reduction of some chronic pain problems by antidepressant medication [ 13, 14], Nevertheless, the conceptualization of chronic pain as 'masked depression’ has been severely criticized and, despite its widespread clinical use, especially in primary care [15, 16], it is still very controversial. Several au thoritative writers, indeed, consider the con cept vague and confusing [17, 18], and even assert that it makes thinking about chronic pain ‘harder instead of easier’ [19]. Moreover, some of the above-mentioned empirical stud ies show manifest methodological flaws [20] and have not always been confirmed by other authors [21 ]. Finally, it must be noted that the positive results of antidepressant therapy in chronic pain may be due to other modes of action, such as a pain-tolerance-enhancing ef fect (by alleviating a coexistent depression, or by causing a more general sedation), a direct influence on central pain-controlling mecha nisms, or even a placebo effect [22], The present study was designed to provide controlled empirical evidence for the hypoth esis that chronic idiopathic pain might be a form of ‘masked depression’. For this pur pose, the therapeutic effects of antidepressant medication in a group of chronic pain pa tients, clinically diagnosed as ‘masked depres sion’, were compared to the same treatment in a group of patients with organic pain and coexistent depression, and in a group with only organic pain. In addition, two other con
Table 1. Measurements during the study, and dose schema of mianserin/placebo or placebo/mianserin
Pretreatment (1 week)
First 6 weeks
Second 6 weeks
Day Dose, mg
pre 0
1 0
4 30
8 60
15 60
22 60 90
29 60 90
36 60 90
43 60 90
46 30
50 60
57 60
64 60 90
71 60 90
78 60 90
85 60 90
DSM-1II HAM BDI MPQ Second eff.
X X X X X
X X X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
X X X
Statistical Analysis
Univariate repeated measures analyses of variance [26] were carried out on the BDI and MPQ total scores, using the Statistical Analysis System PC Ver sion 6 Edition [27]. ‘Treatment’ and ‘Time’ acted as the within-subject variables, and ‘Group’ as the between-subject variable. The Treatment variable has 2 levels: mianserin and placebo; the Time variable has 7 levels: the different moments of assessment; and the Group variable has 4 levels: the 4 diagnostic groups. Pairwise comparisons were made using the RyanEinot-Gabriel-Welsch multiple range test (REGWQ) [28],
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Results
The univariate repeated measures analysis of variance on the BDI showed a significant main effect on the Group, F(3,31) = 6.22, p < 0.01, and on the Time variable, F(6,186) = 5.89. p < 0.01. The mean BDI score in group C was significantly lower than the mean BDI scores in the other groups (REGWQ. p < 0.05) and there was a significant decrease in mean BDI scores over time (REGWQ, p < 0.05). These main effects, however, were to be appreciated in the light of the significant Time-Group and Treatment-Time interac tions. The significant Time-Group interaction, F(18,186) = 3.15. p < 0.01. showed that the evolution in mean BDI scores over time dif fered for the different groups. Pairwise com parisons, however, revealed no systematic up ward or downward trend in the different groups when the data were aggregated across treatments. The significant Treatment-Time interaction, F(6,186) = 2.60, p < 0.05, showed that the evolution in mean BDI scores over time was not the same for the mianserin and for the placebo condition. In the mian serin condition the mean BDI scores de creased significantly over time (REGWQ.
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mostly because of severe side effects (drowsiness). There were no indications for differential dropout in the different conditions, nor were there differences between the dropouts and the non-dropouts with re gard to the baseline measurements and the demo graphic variables. Thus. 35 patients (11 in group A; 8 in group B, C and D), 13 males and 22 females, with a mean age of 45.1 years and a medium to low socioeco nomic status were considered for statistical analysis. For the non-dropouts, the mean Hamilton scores of the different groups were: group A: 23.9 (SD: 12.5); group B: 27.6 (SD: 9.9); group C: 6.5 (SD: 4.0): group D: 29.2 (SD: 6.9). Pain locations in the masked depres sion group were: abdominal: 2; musculoskeletal sim ple: 2: musculoskeletal multiple: 4.
Table 3. Mean BDI score, standard error of the mean BDI score (SE) and REGWQ in the placebo con dition for the different moments of assessment (t 1—17)
Time
Mean
SE
REGWQ
Time
Mean
SE
tl t2 t3 t4 t5 t6 t7
17.03 16.63 14.83 15.34 13.51 13.37 12.86
2.00 1.77 1.70 1.75 1.56 1.46 1.55
X X XY XY Y Y Y
tl t2 t3 t4 t5 t6 t7
14.26 14.49 14.51 13.83 13.06 13.49 13.54
1.46 1.43 1.39 1.24 1.42 1.31 1.37
Means with the same letter (X or Y) are not signifi cantly different.
REGWQ: No means are significantly different.
p < 0.05), while in the placebo condition they did not (tables 2-4). Table 4 also shows that the antidepressive effect was most marked in group D. However, this interaction effect was not statistically significant. When the same analyses were carried out without group C, the same pattern of results arose. To be sure, the main effect on the Group variable disappeared, but the Treat ment-Time interaction remained significant. The univariate repeated measures analyses of variance on the MPQ scores showed no signif icant effects besides a significant main effect on the Group variable, F(3,31) = 6.13, p < 0.01. The mean pain scores in group D were significantly lower than the mean pain scores in the other groups (REGWQ. p < 0.05) but there were no significant increases or de creases in the mean MPQ scores over time, neither in the mianserin condition nor in the placebo condition (tables 5-7). Table 7 shows that on the average patients deteriorated on mianserin (and as compared to placebo), but these differences were not statistically signifi cant.
Table 4. Mean difference BDI score between the first moment of assessment and the last moment of assessment for the different groups in the mianserin and the placebo condition
A B C D
Mianserin
Placebo
1.01 4.35 2.16 10.23
1.39 -2.50 -0.80 2.22
A positive difference means improvement, a nega tive difference means deterioration.
When the same analyses were carried out without group D, the main effect on the Group variable disappeared and all the other effects remained nonsignificant. When the data were analyzed for each group separately, again no significant effects appeared. A clini cal analysis also revealed that there was no evidence for pain improvement in any of the individual cases.
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Table 2. Mean BDI score, standard error of the mean BDI score (SE) and REGWQ in the mianserin condition for the different moments of assessment (t 1— 17)
Table 6. Mean MPQ total score, standard error of the mean MPQ total score (SE) and REGWQ in the placebo condition for the different moments of assess ment (t I— 17)
Time
Mean
SE
Time
Mean
SE
tl t2 t3 t4 t5 t6 t7
12.71 14.60 12.77 14.69 13.60 14.40 14.37
2.15 2.29 2.24 2.26 2.26 2.23 2.31
tl t2 t3 t4 t5 t6 tl
13.63 14.06 13.51 15.43 12.43 12.60 12.74
2.13 2.13 2.13 2.14 2.16 2.19 2.17
REGWQ: No means are significantly different.
REGWQ: No means are significantly different.
Table 7. Mean difference MPQ score between the first moment of assessment and the last moment of assessment for the different groups in the mianserin and the placebo condition
Looking for a possible explanation of these results, and within the methodological limita tions of our study, we hypothesize that the lack of effect in the ‘masked depression' group might be connected with intrinsic definition problems of the concept itself, and its am biguous clinical application [29], In our opin ion. indeed, the concept actually refers to two different explanatory models, namely a prob lem of communication between the patient and his doctor, and a ‘deeper’ dynamical problem of somatization [30]. On the one hand, pain patients with a ‘masked depression’ may have an interper sonal problem of expression and communica tion of depressive mood. Specific familial or developmental-learning factors [31 ], sociocul tural idiosyncrasies [32] and the traits of alexithymia [33] may explain why these patients, who suffer from a true depressive illness, do not spontaneously talk about their depressed mood (or even deny it), but instead complain of physical pain. For obvious reasons, the underlying mood disorder of these patients often remains unrecognized by their doctors [18]. Yet. when carefully interrogated, these
A B C D
Mianserin
Placebo
-5.23 -0.38 -5.26 0.95
2.07 5.35 -2.10 0
A positive difference means improvement, a nega tive difference means deterioration.
Discussion
The results of the present study demon strate that mianserin, despite its antidepres sant effect, had no analgesic effect in any of the chronic pain groups. Because of the ab sence of an antidepressant-mediated anal gesic effect in group A, more specifically, the validity of the ‘masked depression' concept for chronic idiopathic pain is not supported.
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'Masked’ Depression
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Table 5. Mean MPQ total score, standard error of the mean MPQ total score (SE) and REGWQ in the mianserin condition for the different moments of assessment (t 1—17)
serin could not be demonstrated in our ‘masked depression' group. As a matter of fact, such an effect would only be demonstra ble in patients who suffer from a true underly ing depressive illness; somatizing patients, however, whose pain is not linked to the pres ence of an actual depressive state but is sup posed to play a substantial role in these pa tients’ psychic economy, will presumably re sist psychopharmacological therapy. In this perspective, we may speculate that the lack of an antidepressant-mediated analgesic effect in group A might be due to a (relative) pre dominance o f somatizing pain patients. Pos sibly. the overrepresentation of this type of patients in our study may have been pro moted by the recruitement from specialized, ‘tertiary care’ clinical settings, such as the pain clinic and the psychiatric consultation service [43]. As mentioned above, several alternative hypotheses about antidepressant-mediated analgesia were also taken into account in our study. However, due to the absence of an analgesic effect in groups B and C, these other potential modes of action (pain tolerance en hancement, sedation, interference with cen tral pain-controlling mechanisms, or placebo effect) are neither supported by the results. Nonetheless, it cannot be ruled out that the absence of any analgesic effect in this study might be due to serious methodological short comings. As a matter of fact, because of the small sample sizes (due to a high dropout rate), our statistical tests have low power. It must be noticed, however, that the power was high enough to detect an antidepressive effect and that an estimated analgesic effect size for our data would be negative (table 7). Further more, possible inadequacies of our pain as sessment (e.g. lack of sensitivity of the Dutch McGill scale) might also be responsible for the negative results.
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patients easily admit suffering from ‘vital’ and/or ‘vegetative’ signs of depression, which may put the clinician on the right diagnostic track (although the patients themselves gener ally attribute these symptoms to the long last ing burden of their pain). On the other hand, the ‘masking process’ may be equated with a ‘somatization process’ - considered here as a dynamical defence mechanism [34], In this context, it may be related to supposed intrapsychic links be tween pain and depression. According to sev eral psychodvnamically oriented authors, pain may indeed function as a ‘hysterical’ or ‘conversive’ somatization symptom which may prevent the breakthrough of a more se vere depression [35, 36], Furthermore, psy choanalytic theory stresses the fundamental parallelism between mental and physical pain, and the possible ‘displacement’ from the former to the latter [37, 38]. These intrapsy chic links largely correspond with the dynam ics of ‘pain-proneness’ which were originally described by Engel [39] and. in a further elab oration, connected with the ‘masked depres sion’ concept by Blumer and Heilbronn [4] and others [40] (this connection, however, has been rightly criticized, see ref. 30, 41). It must be added that somatizing pain patients too frequently present with ‘vital’ and/or vegeta tive signs of depression, which they consider as secondary to their pain as well. Thus, in line with Pilowsky and Bassett [42], it may be stated that making a clinical diagnosis of ‘masked depression’ in chronic pain patients is often an oversimplification. Clearly, it does not bear upon an unequivocal clinical entity, nor a simple etiopathogenetic mechanism, but it refers to a complex inter play of experiencing, attributing, expressing, communicating and recognizing depressed mood or emotional distress. If these basic assumptions are valid, it would become less surprising that a therapeutic effect of mian
In conclusion, the results of this study may call into question the validity and clinical rel evance of the ‘masked depression’ concept for patients suffering from chronic idiopathic pain. They arc in accordance with recent criti cism of the concept [17, 18], and empirically support the suggestion that in clinical practice as well as in further research this vague and ambiguous diagnostic category should be dropped [19]. Instead these results suggest
that it might be more fruitful to distinguish between pain patients who have an unrecog nized (but diagnosable and treatable) depres sive disorder, and those who somatize i.c. focus on physical pain as a means of dynami cal defence against severe emotional distress. This conceptual distinction could possibly contribute to a more specific delineation of the indications for antidepressant medication in chronic idiopathic pain.
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10
11
12
13
14
15 16
17
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