Abstract
The importance of somatic comorbidity in relation to recovery from depression has undergone little study despite estimates indicating that depressive patients with somatic disease are likely to increase in number as populations age [1]. Results from a large, observational, cross-sectional medical outcomes study [2] showed that subjects with current depressive disorder or with only depressive symptoms displayed poorer physical and social functioning when compared with healthy subjects. This difference was greatest when the depression group was compared with subjects having chronic physical conditions (hypertension, arthritis, back problems etc.). Only the group with coronary heart disease performed worse than the depression group. Furthermore, although the chronic medical categorisation was based on patient self-reports, it was found that depressive symptoms and chronic medical conditions had additive associations with poorer wellbeing [2].
In a follow-up study examining the course of depression in patients with and without histories of hypertension, myocardial infarction and diabetes mellitus type I, the authors [3] found that many of them suffered from persistent depression, especially those with a history of myocardial infarction. The limitation of this study was that the treatment provided was offered by 523 different general medical clinicians or mental health specialists and the treatment or care could not be controlled between groups with or without somatic disease. The design made it difficult to evaluate the results. Furthermore, the follow-up time varied from 1 to 2 years which can also affect the results.
Keitner et al. [4] studied the effects of inpatient treatment on patients with either depression alone (n = 37) or depression accompanied by somatic diseases (n = 41). The patients were studied while hospitalised and at 12 months after discharge from a psychiatric hospital. Their study found lower recovery rates in patients with depression and somatic disease than in those with depression alone. The limitation was that the treatment received after discharge could not be compared reliably between groups.
Somatic comorbidity has also been reported to result in longer periods of hospitalisation of depressed patients on psychiatric wards [5]. One review [6] suggested that depressive patients having somatic comorbidity (especially cancer, neurological disorders or cardiovascular disease) should be treated aggressively because comorbid somatic disease worsens the prognosis of depression and is associated with a poorer treatment outcome. It is important to note that the treatment suggestions were given for diseases which are chronic, severe and often fatal.
It may be life-threatening to have depressive symptoms. Koenig et al. [7] examined effects of depressive symptoms on after-discharge survival of hospitalised, medically ill male veterans (n = 1001). During an observation period of 9 years on average, patients with depressive symptoms were less likely to survive. Depressive symptoms were obtained by telephone interview of surviving family members. It was found that every one-point increase on the 12-item Brief Carroll Depression Rating Scale increased the risk of dying by 10%. Age did not significantly affect the association between depressive symptoms and mortality. This study had many confounding factors which could not be controlled for adequately and caution must therefore be exercised in assessing the results. Nevertheless, these findings are in line with those of the multicentre WHO study on psychological problems in general health care [8]. In non-elderly patients essentially disability-free at baseline, depressive illness resulted in a 1.8-fold increase in the risk of onset of physical disability during a 12-month follow-up and in a 2.3-fold increase in the risk of onset of social disability.
Recently, a Cochrane review has been published on the use of antidepressants on the physically ill [9]. Altogether, 18 studies were included covering 838 patients with a large range of physical diseases (multiple sclerosis, stroke, cancer, diabetes, heart disease, HIV etc.). Patients treated with antidepressants were significantly more likely to improve than those given placebo or no treatment. The authors concluded that the review provides evidence that use of antidepressants should at least be considered in those with both physical illness and depression.
In one study [10] patients with a history of high use of health care services and a control group were screened. Twenty patients classed as high users with a confirmed diagnosis of depression were treated with antidepressants by primary care physician for 6 months. Treatment resulted in significant reductions in depression and service use.
Somatic comorbidity would thus seem to be an important factor in depression. Critical assessment shows that it is not currently known whether depressive patients with somatic comorbidity should be treated differently from other types of depressive patients, while even less is known about outpatients with depression in this respect. There is a considerable body of literature showing that somatic disease can lead to depression, but less is known about the importance of somatic disease in depressive patients.
We therefore carried out a follow-up study on depressive outpatients to assess the significance of somatic comorbidity in relation to recovery from depression.
Method
All the patients were first referred for care to four outpatient units of the Department of Psychiatry, Kuopio University Hospital, which provides psychiatric services for a population of 200 000. Most outpatient psychiatric services are provided in the context of a regionally comprehensive psychiatric care model [11]. There are 50 doctors in the department and the total number of staff is over 400. Treatment methods such as drug treatment, individual psychotherapy and family therapy are used in a combination which the attending psychiatrist working with a multi-occupational staff assesses as the best for each individual patient.
The patients in this study were referred to the outpatient units by another department of same University Hospital (53%), the occupational health service (14%), general practitioners in public health centres (14%), private physicians (9%), or they arrived without referral (10%).
The patient was assessed as eligible for inclusion in this study if the treating doctor clinically diagnosed the patient to be suffering from depression according to ICD-10 guidelines [12]. The patient should have received one of the following diagnoses: any diagnosis in classes F32, F33 or F34; or one of following separate diagnoses: F31.3, F31.4, F31.5 or F41.2.
Patients were excluded if they had been previously diagnosed with central nervous system (CNS) diseases, severe somatic disease (recent myocardial infaraction, sequelae of stroke etc.), alcohol dependence or drug addiction, marked deficiency in cognitive capacity, or other serious mental disorders such as schizophrenia or other psychoses. Other somatic diseases were not regarded as criteria for exclusion if the patient was well looked after by the doctor responsible for treatment, the treatment balance achieved had been as good as possible and the somatic disease in question could be treatable. Thus, somatic comor-bidity in this study means specifically that the patient had at least one diagnosed and, in the short-term, nonfatal physical disease.
Those initially eligible for inclusion in the study numbered 128. Of these, eight patients (6%) declined to participate and four patients (3%) were subsequently excluded because of CNS disease (e.g. Alzheimer's disease). The final study population therefore consisted of 116 patients.
At baseline, diagnosis of depression was confirmed by means of semistructured SCID (Structured Clinical Interview for DSM-HI-R) [13], which was administered by an investigator (K. Haatainen) who had been trained in the use of the method. The interviewer had passed a 3-day clinical training course prior to this study achieving a total K of 0.78 against an experienced trainer in SCID diagnoses. It was also confirmed during the SCID interview that no organic factor or somatic disease had initiated and maintained the depressive syndrome.
All accompanying somatic diagnoses were verified by checking every patient's medical case records and referrals, but this was done 6 months after the initial interviews. The results included the following somatic diagnoses: musculoskeletal disease (n = 31, 81% had spondyloarthrosis), cardiovascular disease (n = 14, 79% had hypertension arterialis and 64% coronary heart disease), other single disease (n = 19, asthma, psoriasis, polyneuropathy, etc.) or a combination of several somatic diseases (n = 11). This two-phase checking was done in order to exclude the possibility that we could miss any somatic diagnosis or place such a patient in the depression-only group. Among the somatic comorbidity (SC) group, 71% of the patients had major depression, 12% dysthymia and 17% adjustment disorder. In the pure depression (PD) group, major depression was found in 88% and dysthymia in 12% of the patients.
Patients completed questionnaires relating to their sociodemographic background, subjective health status (‘How is your health at the moment?’ 1–2, good; 3–4, poor), financial status (‘How is your financial status at the moment?’ 1–2, good; 3–4, poor) and perceived social support (‘Do you receive enough support and understanding for your problems with those closest to you?’ 1–2, sufficient; 3–4, insufficient). Each of these variables was assessed using only one question. Inquiry was also made into previous suicide attempts (see Table 1). A patient's capacity for work was classified on the basis of an assessment made by the referring physician in accordance with the Finnish Sickness Insurance Act.
Background variables examined in depressive patients in relation to somatic comorbidity at the beginning of treatment
The questionnaire that the patients completed also included a life-satisfaction scale involving four items, with scores ranging from 4 to 20. Scores of 4–11 were considered to represent satisfaction with life, and scores of 12–20 represented dissatisfaction [14]. Alexithymic features were recorded using the 20-item Toronto Alexithymia Scale. Scores on this scale can range from 20 to 100. Those scoring over 60 are considered alexithymic [15,16]. The level of depression of each patient was assessed by means of the self-rated 21-item Beck Depression Inventory (BDI) scale (score range 0–63) [17]. It was also assessed separately by an investigator (K. Haatainen) using the Hamilton Depression Rating Scale (scores can range from 0 to 52) [18], and the levels of psychosocial functioning was rated using the Global Assessment of Functioning (GAF) Scale (scores can range from 1 to 100) [19]. All these ratings were carried out blind to SC categorisations, and the SC categorisation for this study was actually done only after the 6-month of follow-up.
Treatment received during the 6-month follow-up period was classified as follows: antidepressive medication used by patients was considered adequate if the length of treatment had exceeded 3 months and if the daily dose used had been within the therapeutic range deemed efficient according to the daily dosage (e.g. daily dose: tricyclics ≥ 150 mg, citalopram ≥ 20 mg, fluoxetine ≥ 20 mg and paroxetine ≥ 20 mg) [20]. Psychiatric ward treatment received during the follow up was recorded (yes or no). Patients were considered to have received psychotherapy if face-to-face treatment contacts had been planned, the length of treatment had exceeded 3 months, the length of face-to-face contact was 45 min or more in each session and the patient had visited the therapist at least three times per month. None of the authors participated in the treatment process of patients.
Approval for the study was obtained from the Ethics Committee of the Kuopio University Hospital and the University of Kuopio. All patients provided written consent before entering the study.
The χ-squared test was used to compare SC and PD groups with regard to class variables, and the Student's t-test or Mann-Whitney U-test for comparison of continuous variables depending on distribution of variables. Logistic regression analysis was undertaken to assess factors associated with alleviation of depression and to control for confounding factors.
Results
Patients in the SC group were older and less educated than those in the PD group, and their capacity for work and economic status were lower than that of the other patients. No statistically significant differences were observed in relation to the perceived social support received by the patients. Those with SC had a less favourable view of their health status than did the PD group (Table 1).
There were no differences between the groups in the means of the symptom scales at the start of treatment. Changes occurring during the 6-month follow-up period were statistically significant in both groups for all symptom scales. The differences between groups with respect to these changes were statistically significant only as regards Hamilton Scale scores (Table 2).
Results in relation to symptom scales at baseline and changes after 6 months of follow-up
Antidepressive medication was considered to be adequate by 82% of those in the SC group and 63% of those in the PD group (χ2 = 4.5, df = 1, p = 0.03) during the follow-up period. The corresponding percentages in relation to adequacy of psychotherapy were 23% and 55% (χ2 = 12.0, df = 1, p = 0.001), respectively. Twenty-two per cent of the SC patients and 12% of others (χ2 = 1.6, df = 1, p = ns) had been on a psychiatric ward during the follow-up period.
Scores for BDI indicated that 44% of SC patients and 42% of PD patients had recovered from depression (BDI score < 10 at time of follow up) (χ2 = 0.1, df = 1, p = ns).
Adequate antidepressive medication had been received by 66% of those with SC who had subsequently recovered and 93% of those who had not (χ2 = 8.5, df = 1, p = 0.04). Psychotherapy was received by 16% of those that recovered and 29% of those not recovering (χ2 = 1.9, df = 1, p = ns), and hospital treatment by 19% of those recovering and 24% of those not (χ2 = 0.33, df = 1, p = n.s.).
Of those with PD, 59% of those who had recovered and 67% of those who had not had received adequate antidepressive medication (χ2 = 0.26, df = 1, p = n.s.). The corresponding percentages for adequate psychotherapy were 59% versus 50% (χ2 = 0.31, df = 1, p = n.s.) and for hospital treatment 6% versus 17% (χ2 = 1.08, df = 1, p = n.s.).
Logistic regression analysis was done in order to assess whether any of the following factors were independently associated with recovery from depression (BDI score < 10 at time of follow-up): age (years), sex, education (secondary-school leaving or other), working ability (able or unable), subjective health status (good or poor) and somatic comorbidity (no comorbidity, or comorbidity such as musculo-skeletal disease, cardiovascular disease, some other single diagnosis or a combination of several diagnoses). The following factors (scored yes or no) were also included, first separately and then together: psychotherapy, adequate antidepressive medication and hospital treatment.
None of the above factors were found to be independently associated with recovery from depression defined by BDI in any of the analyses (data not shown).
Discussion
Our data suggest that somatic comorbidity impedes recovery from depression. Nevertheless, the difference between those with depression only and those with somatic comorbidity may be less marked than previous studies have suggested. Multivariate analyses of the BDI suggested that somatic comorbidity is not an independent variable preventing recovery from depression.
Our findings differ from many previous observations, but not from all [21]. One explanation for the differences in results might be that we excluded patients with major or fatal somatic diseases that could severely limit their recovery. Moreover, in the SC group the somatic disease was not in an acute phase and the treatment balance achieved may have affected our results.
Another explanation for differences in results might be that most of the earlier reports have either been observational or the patients were treated by general practitioners [3,4]. The psychiatric treatment offered at a specialised level may improve the outcome, especially in the group with somatic disease. However, we can not verify this suggestion with the data we obtained in this study.
Indeed, there are many reports showing the difference in treatment of depression between specialised level and primary care [22]. On the other hand, if general practitioners receive clear guidelines for the treatment of depression, the results achieved are good [23,24]; but if structured guidelines are not given, the motivation to identify and treat depression may even decrease during an educational program [25].
Somatic disease was established on the basis of interview and case histories, and a diagnosis of depression by means of SCID interviews. Distributions of psychiatric diagnoses in the SC and the PD groups were not identical. Although the drop-out rate was low, this study was limited by the relatively small sample size. It also decreased the statistical power to identify differences and we can not totally exclude the possibility of type 2 statistical error having occurred. No statistically significant difference was observed in the severity of depression between patients with and without somatic comorbidity at the start of treatment which might have served as a potential source of error. Moreover, our study design can be considered adequate since it exploited several standardised symptom scales for assessing treatment outcome.
However, a marked limitation of this study was its naturalistic, non-random design and caution is therefore advisable especially in assessing treatment associations. On the other hand, we studied the actual treatment provided which has received little attention in previous studies. In addition, some of the results of clinical trials may be difficult to introduce into clinical practice. One patient can have more than one somatic diagnosis and the severity of physical illness can vary. A Cochrane review showed that anti-depressant therapy may be beneficial for patients with physical disease who are also suffering depression [9]. However, comparison of that study with the present one is complicated by the fact that the Cochrane review included many severe and fatal diseases that were excluded in our study.
The Hamilton Scale score showed differences in outcome during follow up between groups, although the BDI score did not. The result may be due to a small, although statistically non-significant difference in Hamilton score between groups at baseline while no differences were found in the BDI score. An alternative explanation, which we consider to be more probable, is that the Hamilton scale includes, for example, three questions about sleeping difficulties while the BDI has only one. The Hamilton scale also includes two questions about somatic symptoms, but the BDI has none. Long-term somatic diseases, as in our sample, can lead, for example, to sleeping difficulties due to pain (in our sample 41% had musculoskeletal disease) and general somatic symptoms may not decrease due to treatment for depression.
There were no differences between the groups in relation to hospital treatment received during the follow-up period. Moreover, those with somatic comorbidity received adequate antidepressive medication slightly more often, but psychotherapy less frequently, than the others. Nevertheless, in the SC group adequate antidepressive medication was more common among those having not recovered than in those who had recovered. This finding suggests that the response to antidepressive drug treatment may be poor is some subgroups.
In conclusion, the treatment of depressive patients with somatic comorbidity should be planned individually, and therapeutic methods should be combined as required. The response obtained will probably be quite similar to that of patients with depression only.