Q
1998 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 1998 Volume 2 Pages 41 -45
41
Psychiatric disorder in essential dyspepsia SHAILESH KUMAR,’ RAKESH KHANNAR,~ BR WJRA3AND J BOSE3
Int J Psych Clin Pract Downloaded from informahealthcare.com by McMaster University on 11/03/14 For personal use only.
’Institute of Psychiatry, London; ’Eaglehawk, Australia; and 3Calcutta Medical College, India
Correspondence Address Dr Shaifesh Kumar, DPM, MRCPsych, Consultant Psychiatrist, Roturua Hospital, Private bag 3023, Roturua, New Zealand Tel: +64 7349 7971 Fa: +64 7349 7883
We wanted to examine the prevalence of psychiatric morbidity in patients diagnosed as having essential dyspepsia, as well as the short-term course of dyspeptic symptoms, following drug treatment of the psychiatric condition. Seventy-four patients with essential dyspepsia presenting to the gastro-enterology outpatient department of a medical college were investigated for the presence of psychiatric disorder. The response to an open trial of pharmucotherapy in 50 patients with a psychiatric disorder and no other demonstrable pathology was assessed. These patients met the criteria for a DSM-III-R diagnosis, most commonly major depressive disorder (26) or generalized anxiety disorder (10). The mean age of those with a psychiatric disorder alone was signijicantly higher than that of those with another demonstrable pathology. With treatment, 16 patients with no demonstrable pathology other than psychiatric disorder (depression: 12; anxiety: 4) showed improvement over a period of 6 weeks in psychiatric as well as dyspepsia ratings. The difference was however statistically significant only for the group with major depressive disorder. We concluded that, despite dijferences in the characteristics of the population studied, a psychiatric diagnosis is associated with at least a proportion of cases with essential dyspepsia and emerges as a likely explanation. (Int J Psych Ctin Pract 1998 2: 41-45) Keywords
Received 7 October 1997; accepted for publication 12 FebruaIy 1998
dyspepsia non-ulcer dyspepsia Generalized Anxiety Disorder Hamilton Anxiety Rating Scale
INTRODUCTION
D
yspepsia is a very common symptom. However, there is no consensus as regards its definition, classification and management. The management of patients with dyspeptic symptoms involves not only the investigation, identification and treatment of those most likely to have organic dyspepsia (due to peptic ulcer, reflux oesophagitis, gastric carcinoma, or cholelithiasis), but also the identification and treatment of those in whom an organic cause is unlikely. Various authors have used different terms, including non-ulcer dyspepsia, functional dyspepsia, unexplained dyspepsia and dyspepsia of unknown origin, to describe subtypes of dyspepsia. The. definitions given by Talley et all were used for this study and their equivalent terms are described in Table 1. A type of dyspepsia termed non-ulcer dyspepsia (NUD) has been extensively studied. The relevance of non-ulcer dyspepsia (NUD) becomes readily apparent when one considers the morbidity caused, the number of man-days lost and the cost of treatment that the condition entails. In
essential dyspepsia Major Depressive Disorder Hamilton Depression Rating Scale
Sweden alone, with a population of only eight million, the condition was estimated to account for an annual loss of $280 million in 1985.’ The study of NUD is plagued by the complex relationship between peptic ulceration and symptom formation. Many subjects with peptic ulcer are asymptomatic, while others with symptoms typical of peptic ulcer may have a normal endoscopy, but could well have other pathologies to explain the symptom f~rmation.~ About 20% of cases with NUD are still reported to have no discernible cause?.’ This subgroup of cases, termed ‘essential’ dyspepsia (ED)‘.’ or ‘unexplained dy~pepsia’,~ has attracted increasing clinical interest . Psychological factors have been hypothesized to play a contributory role in NUD and ED6-’ because of their potential to influence gut secretion, motility and vascularity? Patients with dyspepsia of unknown origin were found to have significantly more symptoms of anxiety and tension and higher scores for trait tension and hostility than those with peptic ulcer.’ Patients with functional dyspepsia had more anxiety, neuroticism and depression than healthy adults.’ Patients were not
42
S Kumar et a1
Table 1 Terms and definitions (from Talley et all) TfTltI
Equivalent renns
Int J Psych Clin Pract Downloaded from informahealthcare.com by McMaster University on 11/03/14 For personal use only.
Dyspepsia
Non-Ulcer Dyspepsia
Functional dyspepsia
Essential
Dyspepsia of unknown
Dyspepsia
Origin,
unexplained dyspepsia
Definition usedfor study Any pain, discomfort, or referable to the upper alimentary tract which m a y be intermittent or continuous, has been present for 1 month or more, and is not precipitated by exertion and not relieved within 5 minutes by rest. Dyspepsia in which clinical evaluation reveals no obvious structural cause, and panendoscopy of the upper gastrointestinal tract finds no evidence of acute or chronic ulceration, oesophagitis or malignancy. NUD in which gallstones have been excluded radiologically, the imtable bowel syndrome and gastrooesophageal reflux have been excluded by objective clinical criteria, and no other disorders are present to explain the symptoms.
matched with their controls for age and sex in both these studies?.’ Alexander and Tantry reported higher trait anxiety in the NUD group.” Bennett et a1 found the presence of highly threatening stressors to be far more predictive of NUD status,” while Hui et a1 reported NUD patients to have a higher negative perception of major life events.12 Platz et a1 found a higher prevalence of dependency- independency conflict among subjects with dy~pepsia.’~ Others have reported patients with ED and dyspeptic disease to be similar in terms of psychological distress, but previous consultations for abdominal or other somatic complaints were more common in the former group.14 Several investigators have reported a high prevalence of depression and anxiety in NUD. Magni et a1 from Italy reported dyspepsia of unknown origin to be associated with a high prevalence (86.7%) of DSM-111 psychiatric diagnosis, particularly anxiety disorders (66.7%).15Kane et al, in a retrospective follow-up study of patients having motility studies for chest pain and gastro-intestinal (GI) sympt o m , found GI symptoms compatible with the diagnosis of NUD to be strongly associated with a psychiatric diagnosis.16Comparison of those with and without known heart disease revealed that a substantial number of patients in both groups fulfilled criteria for GAD ( > 70%),panic
disorder ( > 30%) or major depression ( >35%). Conditions such as excessive gastric acid secretion, disturbance of pyloro-duodenal motility, different types of foods, psychological factors, consumption of non-steroidal anti inflammatory drugs (NSAID), tobacco and alcohol consumption and Helicobucter pylon infection have been suggested to explain the pathogenesis of dyspepsia.’ The contribution of these factors to the pathogenesis of subtypes of dyspepsia has not been widely investigated. Many of these factors are dependent on the characteristics of the population studied. Few studies have looked specifically at the contribution of psychiatric disorders to the aetiology of ED, even though the effects of psychological factors on the GI system are well documented. Moreover, the problem has not been systematically studied in developing countries, including India. The present study is aimed at investigating the prevalence of psychiatric morbidity in patients diagnosed as having essential dyspepsia, and the short-term course of dyspeptic symptoms following an open trial of pharmacotherapy for the psychiatric condition. The criteria for dyspepsia, non-ulcer dyspepsia, and essential dyspepsia proposed by Talley et al’ were used for this study. Details of antral biopsy and gastric motility studies have not been included.
MATERIAL AND METHOD SUBJECTS A total of 276 patients with dyspepsia attending the gastroenterology Outpatients Department of a Medical College Hospital in Eastern India were screened. Following an initial gastro-enterology assessment, 110 of these patients were diagnosed to be suffering from acptdchronidhealed peptic ulceration and were excluded. Of the remaining 166 Table 2 The study population
Exclusion criteria Total GI patients Non-PUD Non-GI reflux Non-biliry diseases Non-NSAlD>Uweek Completed study Psychiatric
n
140 116 83 74 50
% of total % o j total usingn.1276 &ngn=83
60 51 42 30 18
89 60
6
19
Int J Psych Clin Pract Downloaded from informahealthcare.com by McMaster University on 11/03/14 For personal use only.
Psychiatric disorder in essential dyspepsia
patients, clinical history revealed gastro-oesophageal reflux in 26, biliary tract disease in 24, irritable bowel syndrome in 15, and ‘excessive’ NSAID consumption (defined for the purpose of study as more than two tablets of an NSAID per week for at least 4 consecutive weeks) in 18 cases. These cases (n = 83) were excluded. The remaining 83 patients were diagnosed to be suffering from essential dyspepsia, according to the definition used, and were included within the study. Informed consent for investigations, psychiatric evaluation, and treatment was taken from every patient. Nine patients dropped out at various stages of subsequent investigations and only 74 completed the study. None of these 74 patients had a history of alcohoVsubstance abuse.
STUDY I Psychiatric Interview A consultant psychiatrist UB) with extensive teaching and clinical experience interviewed all 74 patients, and 66 of their informants, for 40-50 min. All interviews were carried out in Bengali, the native langiage of the interviewer as well as that of all the subjects. Cases were diagnosed according to DSM-111-R criteria.” They were then investigated by the gastro-enterologist (BH) as follows: Gastro-enterologic assessment All the 74 patients with an established diagnosis of ED then underwent a full gastro-enterologic assessment to identify cases with a demonstrable organic pathology that could explain the dyspeptic symptoms. Antral biopsy A repeat endoscopy was done. Two antral biopsy specimenswere taken 2 cm from the pylorus by a senior endoscopist (BH) who was blind to the results of previous investigations. The specimens were examined histologically and microbiologically as described by Coghlan et a1.l’
Gastric motility and emptying time The ultrasonogram method described by Holt et all9 was used for this purpose, with a slight modification: mutton broth was used instead of beef, as consumption of beef is taboo for Hindus, and is generally refused on religious grounds. The 50% emptying time was measured. None of the patients in the study popubtion had undergone partial gastrectomy.
STUDY I1 At the end of the assessments, 50 of the 74 patients were
found to have a psychiatric diagnosis, while 24 had other demonstrable pathology (Helicobacter pylon or dysmotility) but no psychiatric diagnosis. Out of the 50 cases with a psychiatric diagnosis, 17 had concomitant Helicobacter pylon’ infection, eight had dysmotility, and nine had both (Helicobacter pylon infection plus dysmotility). In 16 cases there was no demonstrable pathology, other than a
43
psychiatric diagnosis. These 16 constituted the sample for the second part of the study. Scoring Out of these 16 patients, 12 had a diagnosis of major depressive disorder (MDD).and four of generalized anxiety disorder (GAD). The patients with MDD were rated on the 17-item Hamilton Depression Rating Scale,” and those with GAD were rated on the Hamilton Rating Scale for Anxiety21 before treatment (week 01, and at the end of 1, 2 , 4 , and 6 weeks of treatment, at approximately 10 am each time. The rater (SK) was blind to the treatment received by the patient. At each evaluation they were also rated on a 5-point dyspepsia rating scale (DRS) developed for the purpose of study (Appendix I). Treatment Patients with MDD were prescribed the tricyclic antidepressants (TCA), imipramine (n = 9) or amitryptiline (n = 3). The TCAs were prescribed in a single bedtime dose of 75 mdday, with biweekly increments up to 225 mdday, depending on the clinical response as measured by followup interviews. The assessor (JB) was blind to the scores on the Hamilton Rating Scales for Depression and A e e t y . The mean dose of TCAs received was 170.8k41.9 mg/&y. Some patients experienced the usual side-effects of TCAs, though none was severe enough to cause impairment in functioning or warrant discontinuation of treatment. Cases with GAD were prescribed alprazolam, which was started at a dose of 0.25 mg twice daily, and gradually increased to a maximum daily dose of 1.75 mg (mean dose 1.25& 0.39 mg).
STATISTICS Categorical data were analysed using the X2-test, with Yates’ correction, while continuous variables were analysed by using the t-test.
RESULTS Seventy-four cases with ED (30 men, 44 women) completed the study protocol. Fifty (67.6%)had a DSM111-Rpsychiatric diagnosis. MDD was the commonest (26), followed by GAD (lo), hypochondriasis (6), dysthymia (5) and personality disorder (3). Thirty-four cases had an associated organic condition as well as the psychiatric diagnosis, while 16 had only a psychiatric diagnosis. These two groups were compared (Table 3). The mean age of those with a psychiatric diagnosis alone was significantly higher than that of those with a psychiatric diagnosis plus another condition (38.6k 11.4 vs 27.6k 6.5 years, t = 4.35, df = 48, P
1998 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 1998 Volume 2 Pages 41 -45
41
Psychiatric disorder in essential dyspepsia SHAILESH KUMAR,’ RAKESH KHANNAR,~ BR WJRA3AND J BOSE3
Int J Psych Clin Pract Downloaded from informahealthcare.com by McMaster University on 11/03/14 For personal use only.
’Institute of Psychiatry, London; ’Eaglehawk, Australia; and 3Calcutta Medical College, India
Correspondence Address Dr Shaifesh Kumar, DPM, MRCPsych, Consultant Psychiatrist, Roturua Hospital, Private bag 3023, Roturua, New Zealand Tel: +64 7349 7971 Fa: +64 7349 7883
We wanted to examine the prevalence of psychiatric morbidity in patients diagnosed as having essential dyspepsia, as well as the short-term course of dyspeptic symptoms, following drug treatment of the psychiatric condition. Seventy-four patients with essential dyspepsia presenting to the gastro-enterology outpatient department of a medical college were investigated for the presence of psychiatric disorder. The response to an open trial of pharmucotherapy in 50 patients with a psychiatric disorder and no other demonstrable pathology was assessed. These patients met the criteria for a DSM-III-R diagnosis, most commonly major depressive disorder (26) or generalized anxiety disorder (10). The mean age of those with a psychiatric disorder alone was signijicantly higher than that of those with another demonstrable pathology. With treatment, 16 patients with no demonstrable pathology other than psychiatric disorder (depression: 12; anxiety: 4) showed improvement over a period of 6 weeks in psychiatric as well as dyspepsia ratings. The difference was however statistically significant only for the group with major depressive disorder. We concluded that, despite dijferences in the characteristics of the population studied, a psychiatric diagnosis is associated with at least a proportion of cases with essential dyspepsia and emerges as a likely explanation. (Int J Psych Ctin Pract 1998 2: 41-45) Keywords
Received 7 October 1997; accepted for publication 12 FebruaIy 1998
dyspepsia non-ulcer dyspepsia Generalized Anxiety Disorder Hamilton Anxiety Rating Scale
INTRODUCTION
D
yspepsia is a very common symptom. However, there is no consensus as regards its definition, classification and management. The management of patients with dyspeptic symptoms involves not only the investigation, identification and treatment of those most likely to have organic dyspepsia (due to peptic ulcer, reflux oesophagitis, gastric carcinoma, or cholelithiasis), but also the identification and treatment of those in whom an organic cause is unlikely. Various authors have used different terms, including non-ulcer dyspepsia, functional dyspepsia, unexplained dyspepsia and dyspepsia of unknown origin, to describe subtypes of dyspepsia. The. definitions given by Talley et all were used for this study and their equivalent terms are described in Table 1. A type of dyspepsia termed non-ulcer dyspepsia (NUD) has been extensively studied. The relevance of non-ulcer dyspepsia (NUD) becomes readily apparent when one considers the morbidity caused, the number of man-days lost and the cost of treatment that the condition entails. In
essential dyspepsia Major Depressive Disorder Hamilton Depression Rating Scale
Sweden alone, with a population of only eight million, the condition was estimated to account for an annual loss of $280 million in 1985.’ The study of NUD is plagued by the complex relationship between peptic ulceration and symptom formation. Many subjects with peptic ulcer are asymptomatic, while others with symptoms typical of peptic ulcer may have a normal endoscopy, but could well have other pathologies to explain the symptom f~rmation.~ About 20% of cases with NUD are still reported to have no discernible cause?.’ This subgroup of cases, termed ‘essential’ dyspepsia (ED)‘.’ or ‘unexplained dy~pepsia’,~ has attracted increasing clinical interest . Psychological factors have been hypothesized to play a contributory role in NUD and ED6-’ because of their potential to influence gut secretion, motility and vascularity? Patients with dyspepsia of unknown origin were found to have significantly more symptoms of anxiety and tension and higher scores for trait tension and hostility than those with peptic ulcer.’ Patients with functional dyspepsia had more anxiety, neuroticism and depression than healthy adults.’ Patients were not
42
S Kumar et a1
Table 1 Terms and definitions (from Talley et all) TfTltI
Equivalent renns
Int J Psych Clin Pract Downloaded from informahealthcare.com by McMaster University on 11/03/14 For personal use only.
Dyspepsia
Non-Ulcer Dyspepsia
Functional dyspepsia
Essential
Dyspepsia of unknown
Dyspepsia
Origin,
unexplained dyspepsia
Definition usedfor study Any pain, discomfort, or referable to the upper alimentary tract which m a y be intermittent or continuous, has been present for 1 month or more, and is not precipitated by exertion and not relieved within 5 minutes by rest. Dyspepsia in which clinical evaluation reveals no obvious structural cause, and panendoscopy of the upper gastrointestinal tract finds no evidence of acute or chronic ulceration, oesophagitis or malignancy. NUD in which gallstones have been excluded radiologically, the imtable bowel syndrome and gastrooesophageal reflux have been excluded by objective clinical criteria, and no other disorders are present to explain the symptoms.
matched with their controls for age and sex in both these studies?.’ Alexander and Tantry reported higher trait anxiety in the NUD group.” Bennett et a1 found the presence of highly threatening stressors to be far more predictive of NUD status,” while Hui et a1 reported NUD patients to have a higher negative perception of major life events.12 Platz et a1 found a higher prevalence of dependency- independency conflict among subjects with dy~pepsia.’~ Others have reported patients with ED and dyspeptic disease to be similar in terms of psychological distress, but previous consultations for abdominal or other somatic complaints were more common in the former group.14 Several investigators have reported a high prevalence of depression and anxiety in NUD. Magni et a1 from Italy reported dyspepsia of unknown origin to be associated with a high prevalence (86.7%) of DSM-111 psychiatric diagnosis, particularly anxiety disorders (66.7%).15Kane et al, in a retrospective follow-up study of patients having motility studies for chest pain and gastro-intestinal (GI) sympt o m , found GI symptoms compatible with the diagnosis of NUD to be strongly associated with a psychiatric diagnosis.16Comparison of those with and without known heart disease revealed that a substantial number of patients in both groups fulfilled criteria for GAD ( > 70%),panic
disorder ( > 30%) or major depression ( >35%). Conditions such as excessive gastric acid secretion, disturbance of pyloro-duodenal motility, different types of foods, psychological factors, consumption of non-steroidal anti inflammatory drugs (NSAID), tobacco and alcohol consumption and Helicobucter pylon infection have been suggested to explain the pathogenesis of dyspepsia.’ The contribution of these factors to the pathogenesis of subtypes of dyspepsia has not been widely investigated. Many of these factors are dependent on the characteristics of the population studied. Few studies have looked specifically at the contribution of psychiatric disorders to the aetiology of ED, even though the effects of psychological factors on the GI system are well documented. Moreover, the problem has not been systematically studied in developing countries, including India. The present study is aimed at investigating the prevalence of psychiatric morbidity in patients diagnosed as having essential dyspepsia, and the short-term course of dyspeptic symptoms following an open trial of pharmacotherapy for the psychiatric condition. The criteria for dyspepsia, non-ulcer dyspepsia, and essential dyspepsia proposed by Talley et al’ were used for this study. Details of antral biopsy and gastric motility studies have not been included.
MATERIAL AND METHOD SUBJECTS A total of 276 patients with dyspepsia attending the gastroenterology Outpatients Department of a Medical College Hospital in Eastern India were screened. Following an initial gastro-enterology assessment, 110 of these patients were diagnosed to be suffering from acptdchronidhealed peptic ulceration and were excluded. Of the remaining 166 Table 2 The study population
Exclusion criteria Total GI patients Non-PUD Non-GI reflux Non-biliry diseases Non-NSAlD>Uweek Completed study Psychiatric
n
140 116 83 74 50
% of total % o j total usingn.1276 &ngn=83
60 51 42 30 18
89 60
6
19
Int J Psych Clin Pract Downloaded from informahealthcare.com by McMaster University on 11/03/14 For personal use only.
Psychiatric disorder in essential dyspepsia
patients, clinical history revealed gastro-oesophageal reflux in 26, biliary tract disease in 24, irritable bowel syndrome in 15, and ‘excessive’ NSAID consumption (defined for the purpose of study as more than two tablets of an NSAID per week for at least 4 consecutive weeks) in 18 cases. These cases (n = 83) were excluded. The remaining 83 patients were diagnosed to be suffering from essential dyspepsia, according to the definition used, and were included within the study. Informed consent for investigations, psychiatric evaluation, and treatment was taken from every patient. Nine patients dropped out at various stages of subsequent investigations and only 74 completed the study. None of these 74 patients had a history of alcohoVsubstance abuse.
STUDY I Psychiatric Interview A consultant psychiatrist UB) with extensive teaching and clinical experience interviewed all 74 patients, and 66 of their informants, for 40-50 min. All interviews were carried out in Bengali, the native langiage of the interviewer as well as that of all the subjects. Cases were diagnosed according to DSM-111-R criteria.” They were then investigated by the gastro-enterologist (BH) as follows: Gastro-enterologic assessment All the 74 patients with an established diagnosis of ED then underwent a full gastro-enterologic assessment to identify cases with a demonstrable organic pathology that could explain the dyspeptic symptoms. Antral biopsy A repeat endoscopy was done. Two antral biopsy specimenswere taken 2 cm from the pylorus by a senior endoscopist (BH) who was blind to the results of previous investigations. The specimens were examined histologically and microbiologically as described by Coghlan et a1.l’
Gastric motility and emptying time The ultrasonogram method described by Holt et all9 was used for this purpose, with a slight modification: mutton broth was used instead of beef, as consumption of beef is taboo for Hindus, and is generally refused on religious grounds. The 50% emptying time was measured. None of the patients in the study popubtion had undergone partial gastrectomy.
STUDY I1 At the end of the assessments, 50 of the 74 patients were
found to have a psychiatric diagnosis, while 24 had other demonstrable pathology (Helicobacter pylon or dysmotility) but no psychiatric diagnosis. Out of the 50 cases with a psychiatric diagnosis, 17 had concomitant Helicobacter pylon’ infection, eight had dysmotility, and nine had both (Helicobacter pylon infection plus dysmotility). In 16 cases there was no demonstrable pathology, other than a
43
psychiatric diagnosis. These 16 constituted the sample for the second part of the study. Scoring Out of these 16 patients, 12 had a diagnosis of major depressive disorder (MDD).and four of generalized anxiety disorder (GAD). The patients with MDD were rated on the 17-item Hamilton Depression Rating Scale,” and those with GAD were rated on the Hamilton Rating Scale for Anxiety21 before treatment (week 01, and at the end of 1, 2 , 4 , and 6 weeks of treatment, at approximately 10 am each time. The rater (SK) was blind to the treatment received by the patient. At each evaluation they were also rated on a 5-point dyspepsia rating scale (DRS) developed for the purpose of study (Appendix I). Treatment Patients with MDD were prescribed the tricyclic antidepressants (TCA), imipramine (n = 9) or amitryptiline (n = 3). The TCAs were prescribed in a single bedtime dose of 75 mdday, with biweekly increments up to 225 mdday, depending on the clinical response as measured by followup interviews. The assessor (JB) was blind to the scores on the Hamilton Rating Scales for Depression and A e e t y . The mean dose of TCAs received was 170.8k41.9 mg/&y. Some patients experienced the usual side-effects of TCAs, though none was severe enough to cause impairment in functioning or warrant discontinuation of treatment. Cases with GAD were prescribed alprazolam, which was started at a dose of 0.25 mg twice daily, and gradually increased to a maximum daily dose of 1.75 mg (mean dose 1.25& 0.39 mg).
STATISTICS Categorical data were analysed using the X2-test, with Yates’ correction, while continuous variables were analysed by using the t-test.
RESULTS Seventy-four cases with ED (30 men, 44 women) completed the study protocol. Fifty (67.6%)had a DSM111-Rpsychiatric diagnosis. MDD was the commonest (26), followed by GAD (lo), hypochondriasis (6), dysthymia (5) and personality disorder (3). Thirty-four cases had an associated organic condition as well as the psychiatric diagnosis, while 16 had only a psychiatric diagnosis. These two groups were compared (Table 3). The mean age of those with a psychiatric diagnosis alone was significantly higher than that of those with a psychiatric diagnosis plus another condition (38.6k 11.4 vs 27.6k 6.5 years, t = 4.35, df = 48, P
