- Email: [email protected]
Lessons from the Hampshire Depression Project
CORRESPONDENCE
COMMENTARY
CORRESPONDENCE Lessons from the Hampshire Depression Project Sir—In their excellent article C Thompson and colleagues (Jan 15, p 185) 1 described a randomised, controlled study of the effects of a clinical-practice guideline and practice-based education on the detection and outcome of depression in primary care. They concluded that no improvements in the recognition or recovery from depression could be achieved. We are beginning similar research projects, supported by the German Ministry of Research. One subproject is the evaluation of a suicide-preventative awareness programme consisting of an education programme for general practitioners (GPs) in combination with a media campaign directed at the general public. Another subproject is a large, controlled, randomised, double-blind study of five different treatments for depression in patients being treated in general practice. Having read the article by Thompson and colleagues, we felt obliged to reconsider our projects. However, we think that their sobering results do not justify generally pessimistic conclusions about the efficacy of large-scale programmes to combat depression and suicide. In their clinical-practice guideline Thompson and colleagues recommended tricyclic antidepressants (TCAs) as a first-line treatment for depression in a primary-care setting, with the advice to aim for a dose of 150 mg. We question whether this is really the best recommendation for this population. The introduction of serotonin-reuptake inhibitors (SSRIs), which are less toxic, have milder side effects and are easier to administer than TCA, has made it possible for depression to be treated more successfully in a primary care setting.2 Thus we would recommend that a compound from the SSRI-group, with a low potential for interaction with other medication (low potential for inhibition of cytochrome P 450 enzymes), should be used as a first-line treatment for depression in a primary care setting. Patient compliance must also be considered in this context. Was the compliance of the patients assessed? Treatment with a TCA at a high dose
THE LANCET • Vol 355 • May 6, 2000
could have been accompanied by tolerability complications, causing patients to stop treatment and reject a change to another antidepressant compound. If this did indeed occur, then it could be one explanation for the poor outcome of the intervention with respect to the recovery from depression. Compliance was controlled in the Norwegian naturalistic treatment study of depression, done in general practice, by counting pills and by measuring drug-plasma concentrations.3 We believe that alerting GPs, patients, and their relatives to the problem of compliance is crucial for the success of a large-scale programme. Thus, we are producing a videotape for patients and their relatives. This videotape, which will be handed out by GPs, gives short and simple information about depression, its biological correlates, and the rational basis of treatment, including practical aspects of antidepressant medication. The projects “Suicide preventive awareness program” and the “Treatment of minor and subthreshold depression” are exclusively financed by the German Ministry of Education and Research (BMBF).
*Verena Henkel, David Althaus, Ulrich Hegerl Department of Clinical Neurophysiology, Psychiatric Hospital of the Ludwig-MaximiliansUniversity Munich, 80336 Munich, Germany (e-mail: [email protected]) 1
2
3
Thompson C, Kinmonth AL, Stevens L, et al. Effects of a clinical-practice guideline and practice-based education on detection and outcome of depression in primary care: Hampshire Depression Project randomised controlled trial. Lancet 2000; 355: 185–91. Montano CB. Recognition and treatment of depression in a primary care setting [suppl]. J Clin Psychiatry 1994; 55: 18–34. Malt UF, Robak OH, Madsbu HP, Bakke O, Loeb M. The Norwegian naturalistic treatment study of depression in general practice (NORDEP)-I: randomised double blind study. BMJ 1999; 318: 1180–84.
Sir—In the Hampshire Depression Project Thompson and colleagues1 have given us food for thought in how best are we to manage depression in primary care. Here is a large, welldesigned, randomised, controlled trial testing the assumption that educating GPs in the recognition and
management of depression among their patients will lead to an increase in numbers being diagnosed and treated successfully. So why did the findings prove negative? There would appear to be few flaws in the study design. Limitations are discussed by the investigators. However, recruitment of practices was based upon self-selection (60 recruited from 224 eligible practices). We learn nothing of those practices choosing to decline. Does acceptance of participation in a research process signify greater motivation and interest among its participants thereby reducing the power of the intervention? One of the two study end-points was improvement in depression. This was assessed by serial hospital anxiety and depression (HAD) scales. While accepting this to be an appropriate rating scale, there are difficulties in using a threshold score of 8–10 as a measure of depression. Dowell and Biran2 used the HAD as a screening tool in a primary care population. The prevalence of probable caseness for anxiety and depression rose from 28% when an HAD threshold of 11 was used to 51% at a threshold of 8. Within the admittedly different context of an intervention study, this could still have implications. Inclusion of study participants scoring 8–10 may have weakened the power of the intervention. The study’s educational intervention was based on existing guidelines on depression management. But Kendrick questions the place of such guidelines.3 And are GPs who appear not to follow these guidelines really “failing” their patients? Numerous studies have confirmed that GPs miss psychological illness when it first presents. Naturalistic studies of detection and its effect on the course of depressive illness have produced mixed findings. In one study, unrecognised cases of depression in primary care were shown to have less severe depression and do better than recognised (more severely depressed) cases at 1 year.4 Is under-recognition therefore a serious problem? Once recognised, this heterogeneous illness often fails to conform to the pattern seen in secondary care (and
1641
CORRESPONDENCE
that which informs guidelines). In practice, GPs are frequently faced with a distressed patient, fearful of the label of depression, wary of the assurances that antidepressant medication is not addictive, and concerned about job security in the face of an inability to work (through the illness or side effects of medication). We are told we are overprescribing serotonin-reuptake inhibitors in minor depression and using subtherapeutic doses of tricyclic antidepressants in major depression. Our patients fail to comply with our prescriptions. Some who do stay the course experience a return of symptoms. The GP refers to a practice counsellor, because this seems to be what the patient wants, but this referral will not alter the intractable social disturbances which, for many, hinder recovery.5 How much of this behaviour is evidence-based? The management of depression in the context of a continuum of psychological distress is complex and the processes by which we, as GPs, negotiate compliance with follow-up and medication with our patients require much more research. These issues do not sit easily within the framework of clinical guidelines. Guidelines will continue to fail to have an impact until we look further at the natural history of depression in the community, address the wider social issues, and seek the perspective of the patients we are endeavouring to treat. Then, perhaps, we will have a more valuable tool to evaluate. Lorrie Symons Department of General Practice and Primary Care, Guy’s, King’s and St Thomas’ School of Medicine, London SE11 6SP, UK (e-mail: [email protected]) 1
2
3
4
5
Thompson C, Kinmonth AL, Stevens L, et al. Effects of clinical-practice guideline and practice-based education on detection and outcome of depression in primary care: Hampshire Depression Project randomised controlled trial. Lancet 2000; 355: 185–91. Dowell AC, Biran LA. Problems in using the hospital anxiety and depression scale for screening patients in general practice. Br J Gen Pract 1990; 40: 27–28. Kendrick T. Why can’t GPs follow guidelines on depression? BMJ 2000; 320: 200–01. Goldberg D, Privett M, Ustun B, et al. The effects of detection and treatment on the outcome of major depression in primary care: a naturalistic study in 15 cities. Br J Gen Pract 1998; 48: 1840–44. Goldberg D, Bridges K, Cook D, et al. The influence of social factors on common mental disorders: destabilisation and restitution. Br J Psychiatry 1990; 156: 704–13.
Author’s reply Sir—The different approach of the above correspondents illustrated the gulf between the medical model
1642
(Venera Henkel and colleagues) and the social approach (Lorrie Symons) to depression in primary care. We believe that the truth lies somewhere in the middle. Depression is heterogeneous. It is clearly influenced by social factors, but when the patient has a major depressive disorder antidepressants can make a difference. For the patient with an average depression being treated in primary care the size of the difference that medical interventions can make (including psychological treatments) is still in dispute. By definition GPs who take part in research are different to those who do not. However, these GPs were otherwise representative in their ability to recognise depression at baseline. The practices in our study were widely dispersed across the county of Hampshire, UK, so the intervention group was unlikely to have covertly educated the control group. Several external educators were kept away from the control group during the study. We recorded the GPs’ participation in training programmes accredited by the Post Graduate Education Authority, and are fairly sure there was no significant contamination. The ability of HAD to identify depression and anxiety is not relevant to our results, because we were interested in operationally defined cases as well as sub-threshold symptoms that are known to cause much disability.1 This is consistent with Symons’ argument. However, we also repeated the analysis at the more specific threshold of 11 on the D scale with no difference in study outcome. At this stage dichotomous analyses do not do justice to the complexity of the data. There is no evidence that compliance is worse in depression than in most other chronic illnesses so Symons should not despair. Psychiatrists are interested in behaviour and so are more aware of compliance as an issue than most other physicians. Compliance interventions can be tested—we have tested two2,3— and can be as easily incorporated into guidelines as any other health-care intervention. We adopted tricyclic antidepressants as the recommended first-line antidepressant on the basis of best evidence available, which is used in widely disseminated UK guidelines.4 Costs must be considered in a Clinical Practice Guideline that aims to be widely deliverable and if we were starting the project again we might choose generic fluoxetine as the recommended first-line treatment,
were it not for the fact that we have now analysed the effect of education on antidepressant choice. The educated GPs did increase prescriptions of tricyclic antidepressants and this occurred alongside (but may not have caused) the strong trend to increased recovery at 6 weeks, which we reported in the paper. This suggests, at least, that recommending tricyclic antidepressants as first line for certain patients does not retard recovery. Chris Thompson Community Clinical Sciences Research Division, University of Southampton, Royal South Hants Hospital, Southampton, SO14 0YG, UK 1
2
3
4
Olfson M, Broadhead WE, Weissman MM, et al. Sub-threshold psychiatric symptoms in a primary care group practice. Arch Gen Psychiatry 1996; 53: 880–86. Peveler R, George C, Kinmonth A-L, Campbell M, Thompson C. Effect of antidepressant drug counselling and information leaflets on adherence to drug treatment in primary care: randomised controlled trial. BMJ 1999; 319: 612–15. Thompson C, Peveler RC, Stevenson D, McKendrick L. Compliance with antidepressant medication in the treatment of major depressive disorder in primary care: a randomised comparison of fluoxetine and a tricyclic antidepressant. Am J Psychiatry (in press). Paykel ES, Priest RG. Recognition and management of depression in general practice. BMJ 1992; 305: 1198–202.
Enterolactone and coronary events Sir—Meri Vanharanta and colleagues (18/25 Dec, p 2112)1 report a lower risk of acute coronary events in middleaged men with high serum concentrations of the lignan enterolactone, when compared with those with lower serum enterolactone concentrations. This reduced risk observed in univariate analysis was also noted in multivariate analysis, after adjustment for nine predictive risk factors for coronary heart disease, including the presence of diabetes mellitus. However, we are surprised by the definition of diabetes Meri Vanharanta and colleagues chose to follow. In their study, diabetes was defined by a previous diagnosis or fasting blood-glucose concentration of at least 6·7 mmol/L. This definition does not comply at all with either the previous2 or current diagnostic criteria recommended by WHO or the American Diabetes Association.3 Moreover, the definition used differs also from the one used in previous studies in the same cohort.4 Because
THE LANCET • Vol 355 • May 6, 2000
COMMENTARY
CORRESPONDENCE Lessons from the Hampshire Depression Project Sir—In their excellent article C Thompson and colleagues (Jan 15, p 185) 1 described a randomised, controlled study of the effects of a clinical-practice guideline and practice-based education on the detection and outcome of depression in primary care. They concluded that no improvements in the recognition or recovery from depression could be achieved. We are beginning similar research projects, supported by the German Ministry of Research. One subproject is the evaluation of a suicide-preventative awareness programme consisting of an education programme for general practitioners (GPs) in combination with a media campaign directed at the general public. Another subproject is a large, controlled, randomised, double-blind study of five different treatments for depression in patients being treated in general practice. Having read the article by Thompson and colleagues, we felt obliged to reconsider our projects. However, we think that their sobering results do not justify generally pessimistic conclusions about the efficacy of large-scale programmes to combat depression and suicide. In their clinical-practice guideline Thompson and colleagues recommended tricyclic antidepressants (TCAs) as a first-line treatment for depression in a primary-care setting, with the advice to aim for a dose of 150 mg. We question whether this is really the best recommendation for this population. The introduction of serotonin-reuptake inhibitors (SSRIs), which are less toxic, have milder side effects and are easier to administer than TCA, has made it possible for depression to be treated more successfully in a primary care setting.2 Thus we would recommend that a compound from the SSRI-group, with a low potential for interaction with other medication (low potential for inhibition of cytochrome P 450 enzymes), should be used as a first-line treatment for depression in a primary care setting. Patient compliance must also be considered in this context. Was the compliance of the patients assessed? Treatment with a TCA at a high dose
THE LANCET • Vol 355 • May 6, 2000
could have been accompanied by tolerability complications, causing patients to stop treatment and reject a change to another antidepressant compound. If this did indeed occur, then it could be one explanation for the poor outcome of the intervention with respect to the recovery from depression. Compliance was controlled in the Norwegian naturalistic treatment study of depression, done in general practice, by counting pills and by measuring drug-plasma concentrations.3 We believe that alerting GPs, patients, and their relatives to the problem of compliance is crucial for the success of a large-scale programme. Thus, we are producing a videotape for patients and their relatives. This videotape, which will be handed out by GPs, gives short and simple information about depression, its biological correlates, and the rational basis of treatment, including practical aspects of antidepressant medication. The projects “Suicide preventive awareness program” and the “Treatment of minor and subthreshold depression” are exclusively financed by the German Ministry of Education and Research (BMBF).
*Verena Henkel, David Althaus, Ulrich Hegerl Department of Clinical Neurophysiology, Psychiatric Hospital of the Ludwig-MaximiliansUniversity Munich, 80336 Munich, Germany (e-mail: [email protected]) 1
2
3
Thompson C, Kinmonth AL, Stevens L, et al. Effects of a clinical-practice guideline and practice-based education on detection and outcome of depression in primary care: Hampshire Depression Project randomised controlled trial. Lancet 2000; 355: 185–91. Montano CB. Recognition and treatment of depression in a primary care setting [suppl]. J Clin Psychiatry 1994; 55: 18–34. Malt UF, Robak OH, Madsbu HP, Bakke O, Loeb M. The Norwegian naturalistic treatment study of depression in general practice (NORDEP)-I: randomised double blind study. BMJ 1999; 318: 1180–84.
Sir—In the Hampshire Depression Project Thompson and colleagues1 have given us food for thought in how best are we to manage depression in primary care. Here is a large, welldesigned, randomised, controlled trial testing the assumption that educating GPs in the recognition and
management of depression among their patients will lead to an increase in numbers being diagnosed and treated successfully. So why did the findings prove negative? There would appear to be few flaws in the study design. Limitations are discussed by the investigators. However, recruitment of practices was based upon self-selection (60 recruited from 224 eligible practices). We learn nothing of those practices choosing to decline. Does acceptance of participation in a research process signify greater motivation and interest among its participants thereby reducing the power of the intervention? One of the two study end-points was improvement in depression. This was assessed by serial hospital anxiety and depression (HAD) scales. While accepting this to be an appropriate rating scale, there are difficulties in using a threshold score of 8–10 as a measure of depression. Dowell and Biran2 used the HAD as a screening tool in a primary care population. The prevalence of probable caseness for anxiety and depression rose from 28% when an HAD threshold of 11 was used to 51% at a threshold of 8. Within the admittedly different context of an intervention study, this could still have implications. Inclusion of study participants scoring 8–10 may have weakened the power of the intervention. The study’s educational intervention was based on existing guidelines on depression management. But Kendrick questions the place of such guidelines.3 And are GPs who appear not to follow these guidelines really “failing” their patients? Numerous studies have confirmed that GPs miss psychological illness when it first presents. Naturalistic studies of detection and its effect on the course of depressive illness have produced mixed findings. In one study, unrecognised cases of depression in primary care were shown to have less severe depression and do better than recognised (more severely depressed) cases at 1 year.4 Is under-recognition therefore a serious problem? Once recognised, this heterogeneous illness often fails to conform to the pattern seen in secondary care (and
1641
CORRESPONDENCE
that which informs guidelines). In practice, GPs are frequently faced with a distressed patient, fearful of the label of depression, wary of the assurances that antidepressant medication is not addictive, and concerned about job security in the face of an inability to work (through the illness or side effects of medication). We are told we are overprescribing serotonin-reuptake inhibitors in minor depression and using subtherapeutic doses of tricyclic antidepressants in major depression. Our patients fail to comply with our prescriptions. Some who do stay the course experience a return of symptoms. The GP refers to a practice counsellor, because this seems to be what the patient wants, but this referral will not alter the intractable social disturbances which, for many, hinder recovery.5 How much of this behaviour is evidence-based? The management of depression in the context of a continuum of psychological distress is complex and the processes by which we, as GPs, negotiate compliance with follow-up and medication with our patients require much more research. These issues do not sit easily within the framework of clinical guidelines. Guidelines will continue to fail to have an impact until we look further at the natural history of depression in the community, address the wider social issues, and seek the perspective of the patients we are endeavouring to treat. Then, perhaps, we will have a more valuable tool to evaluate. Lorrie Symons Department of General Practice and Primary Care, Guy’s, King’s and St Thomas’ School of Medicine, London SE11 6SP, UK (e-mail: [email protected]) 1
2
3
4
5
Thompson C, Kinmonth AL, Stevens L, et al. Effects of clinical-practice guideline and practice-based education on detection and outcome of depression in primary care: Hampshire Depression Project randomised controlled trial. Lancet 2000; 355: 185–91. Dowell AC, Biran LA. Problems in using the hospital anxiety and depression scale for screening patients in general practice. Br J Gen Pract 1990; 40: 27–28. Kendrick T. Why can’t GPs follow guidelines on depression? BMJ 2000; 320: 200–01. Goldberg D, Privett M, Ustun B, et al. The effects of detection and treatment on the outcome of major depression in primary care: a naturalistic study in 15 cities. Br J Gen Pract 1998; 48: 1840–44. Goldberg D, Bridges K, Cook D, et al. The influence of social factors on common mental disorders: destabilisation and restitution. Br J Psychiatry 1990; 156: 704–13.
Author’s reply Sir—The different approach of the above correspondents illustrated the gulf between the medical model
1642
(Venera Henkel and colleagues) and the social approach (Lorrie Symons) to depression in primary care. We believe that the truth lies somewhere in the middle. Depression is heterogeneous. It is clearly influenced by social factors, but when the patient has a major depressive disorder antidepressants can make a difference. For the patient with an average depression being treated in primary care the size of the difference that medical interventions can make (including psychological treatments) is still in dispute. By definition GPs who take part in research are different to those who do not. However, these GPs were otherwise representative in their ability to recognise depression at baseline. The practices in our study were widely dispersed across the county of Hampshire, UK, so the intervention group was unlikely to have covertly educated the control group. Several external educators were kept away from the control group during the study. We recorded the GPs’ participation in training programmes accredited by the Post Graduate Education Authority, and are fairly sure there was no significant contamination. The ability of HAD to identify depression and anxiety is not relevant to our results, because we were interested in operationally defined cases as well as sub-threshold symptoms that are known to cause much disability.1 This is consistent with Symons’ argument. However, we also repeated the analysis at the more specific threshold of 11 on the D scale with no difference in study outcome. At this stage dichotomous analyses do not do justice to the complexity of the data. There is no evidence that compliance is worse in depression than in most other chronic illnesses so Symons should not despair. Psychiatrists are interested in behaviour and so are more aware of compliance as an issue than most other physicians. Compliance interventions can be tested—we have tested two2,3— and can be as easily incorporated into guidelines as any other health-care intervention. We adopted tricyclic antidepressants as the recommended first-line antidepressant on the basis of best evidence available, which is used in widely disseminated UK guidelines.4 Costs must be considered in a Clinical Practice Guideline that aims to be widely deliverable and if we were starting the project again we might choose generic fluoxetine as the recommended first-line treatment,
were it not for the fact that we have now analysed the effect of education on antidepressant choice. The educated GPs did increase prescriptions of tricyclic antidepressants and this occurred alongside (but may not have caused) the strong trend to increased recovery at 6 weeks, which we reported in the paper. This suggests, at least, that recommending tricyclic antidepressants as first line for certain patients does not retard recovery. Chris Thompson Community Clinical Sciences Research Division, University of Southampton, Royal South Hants Hospital, Southampton, SO14 0YG, UK 1
2
3
4
Olfson M, Broadhead WE, Weissman MM, et al. Sub-threshold psychiatric symptoms in a primary care group practice. Arch Gen Psychiatry 1996; 53: 880–86. Peveler R, George C, Kinmonth A-L, Campbell M, Thompson C. Effect of antidepressant drug counselling and information leaflets on adherence to drug treatment in primary care: randomised controlled trial. BMJ 1999; 319: 612–15. Thompson C, Peveler RC, Stevenson D, McKendrick L. Compliance with antidepressant medication in the treatment of major depressive disorder in primary care: a randomised comparison of fluoxetine and a tricyclic antidepressant. Am J Psychiatry (in press). Paykel ES, Priest RG. Recognition and management of depression in general practice. BMJ 1992; 305: 1198–202.
Enterolactone and coronary events Sir—Meri Vanharanta and colleagues (18/25 Dec, p 2112)1 report a lower risk of acute coronary events in middleaged men with high serum concentrations of the lignan enterolactone, when compared with those with lower serum enterolactone concentrations. This reduced risk observed in univariate analysis was also noted in multivariate analysis, after adjustment for nine predictive risk factors for coronary heart disease, including the presence of diabetes mellitus. However, we are surprised by the definition of diabetes Meri Vanharanta and colleagues chose to follow. In their study, diabetes was defined by a previous diagnosis or fasting blood-glucose concentration of at least 6·7 mmol/L. This definition does not comply at all with either the previous2 or current diagnostic criteria recommended by WHO or the American Diabetes Association.3 Moreover, the definition used differs also from the one used in previous studies in the same cohort.4 Because
THE LANCET • Vol 355 • May 6, 2000