Natural course of depression

Given the number of effective treatments that are available for poststroke depression (see Chapter 20), it is increasingly difficult to conduct studies on the natural course of this disorder. Several studies, however, were conducted prior to publication of the current treatment studies. In addition, most of these pretreatment studies examined the course of poststroke depression in the setting of "usual care." Thus, in these studies, a minority of patients were treated with antidepressants by their primary care physician. Since effective treatment, however, must produce more rapid improvement of symptoms than would naturally occur over time, it is essential to study the natural course of poststroke depressive disorders. Our data on the natural course of depressive disorder is based on longitudinal studies in which patients received "usual care" and the vast majority were not given antidepressant treatment. We have studied the natural course of poststroke depression in two studies and several other groups have conducted similar investigations (Morris et al. 1990; House et al. 1991; Astrom et al. 1993a; Burvill et al. 1995; Pohjasvaara et al. 2001).

Our first longitudinal study of acute stroke patients was reported in 1983 (Robinson et al. 1983). A consecutive series of 103 patients admitted to the hospital with acute stroke, and diagnosed for depression using diagnostic and statistical manual (DSM-III) criteria were prospectively studied over a 2-year period. We have recently examined diagnostic outcomes using DSM-IV criteria in a larger group of 215 patients (i.e., the 103 previously described patients, who were re-diagnosed with DSM-IV criteria, plus a new group of 112 patients). These data have not previously been published. Follow-up was obtained for 142 of these patients (3 months n = 75, 6 months n = 78, 12 months n = 69, 24 months n = 70).

The diagnostic outcomes are displayed in Fig. 8.1. Diagnoses included DSM-IV "mood disorder due to stroke with major depression-like episode" or "minor depression" (research criteria) which required depression or anhedonia plus one other major depression symptom but fewer than the five total symptoms

(see Chapter 5). The findings from this larger group were generally consistent with those found in the initial group of 103. Of the 27 patients (19% of the overall group) with major depression in-hospital, 18% had no depressive diagnosis at 3 months, (38% still had major depression, and 44% had developed minor depression). Major depression, nevertheless, continued to persist in about half of the cases during the first 6 months (i.e., at 6 months, 47% of the original 27 patients still had major depression). There was a marked decrease in frequency of major depression, however, between 6 and 12 months poststroke. At 12 months, only 11% of the original group still had major depression and at 24 months, none of the original group had major depression. In contrast, the 2-year outcome for in-hospital minor depression showed a more persistent rate of major and minor depression (Fig. 8.1). Although more than half of the minor depressions had remitted by 3-month follow-up, about a quarter of the patients had developed major depression. Throughout the 2-year follow-up more than half of the patients with in-hospital minor depression continued to have either major or minor depression. In fact, at 24-month follow-up, a significantly higher frequency of depression (major or minor) was found in patients with in-hospital minor depression (i.e., 65% had major or minor depression) than among patients with in-hospital major depression (i.e., only 22% had minor depression [p < 0.01]). In addition, about one third of the non-depressed patients developed major or minor depression at follow-up (Fig. 8.1). Thus, our new data indicate that major poststroke depression has a mean duration of 5.6 months, while minor depression has a mean duration of 9.4 months. Furthermore, a significant number of non-depressed patients developed major or minor depression after the acute stroke period. Of the 79 patients not depressed at the initial evaluation, 11 (13.9%) developed major depression, and an additional 18 (22.8%) developed minor depression (Fig. 8.1).

Morris et al. (1990) evaluated 56 patients in an Australian rehabilitation hospital at 8 weeks poststroke and again at 15 months. Only 2 of 7 major depressions (29%) and 2 of 14 minor depressions (14%) persisted throughout that entire time period (Fig. 8.2). The mean duration of major depression was 39.0 ± 31.8 (SD) weeks based on patients' reports of the time of remission, while the mean duration of minor depression was 12.2 ± 18.2 (SD) weeks.

House et al. (1991) examined a community sample of 128 patients, who were identified by their family physician as having had a first stroke. The present state examination was conducted on 89 patients at 1 month poststroke, on 119 patients at 6 months (i.e., 30 patients were seen for the first time at 6 months) and 112 patients at 12 months poststroke. Although the diagnostic status of the 10 patients (11%) with major depression at 1 month was not reported at 6 months, two patients continued to have major depression at both 6 months and 1 year. Using the

50 40

ra cp

0 20

10 0

1 60

6 12 In-hospital major depression

6 12 In-hospital minor depression

6 12 Months since index stroke n

In-hospital non-depressed

□ No depression □ Minor depression □ Major depression

Figure 8.1 Diagnostic outcome at 3, 6, 12, and 24-month follow-up for 142 patients based on their in-hospital diagnoses of DSM-IV major depression (n = 27). DSM-IV minor depression (n = 36) or no mood disorder (n = 79). Among the patients with in-hospital major depression (a) note the increase in the non-depressed group at 12 and 24 months. This is not seen in the minor depression patients (b) About 25% of the initially non-depressed patients (c) were found to have a depressive diagnosis at follow-up.

Beck depression inventory (BDI) as a measure of depression, 6 of 14 patients who scored 13 or more at 1 month continued to score 13 or more at 6-month follow-up.

Burvill et al. (1995) conducted psychiatric interviews using a modified version of the present state exam at 4 months following stroke in 248 patients as part of a community based study of stroke. At 12 months following stroke, 234 of these

50 n

Robinson et al. (unpublished data)

Morris et al. (1990)

Astrom et al. (1993)

Burvill et al. (1995)

□ Major depression □ Minor depression

Figure 8.2 The percent of patients with an initial assessment diagnosis of major poststroke depression who continued to have a diagnosis of major depression, or had changed to a diagnosis of minor depression at 1-year follow-up. Note the number of chronic cases varies between studies probably reflecting a mixture of etiologies among the group with in-hospital major poststroke depression. The mean frequency of persistent major depression at 1-year follow-up across all studies was 26%.

patients were reassessed. Of 42 patients with major depression at 4 months, 29% continued to have major depression at 1-year follow-up and 17% now had minor depression (10% had developed agoraphobia, and 9% anxiety or emotional lability). Only 35% were without a diagnosis (Fig. 8.2). Among patients with minor depression at 4 months, 27% continued to have minor depression and 14% now had major depression at 1 year. Only 46% had no diagnosis.

Astrom et al. (1993b) also examined 80 patients with a first stroke and followed them for three years. At the initial in-hospital evaluation, 19 of 76 patients (25%) who could be assessed had major depression. One year later, 10 of 25 patients (40%) who developed major depression in-hospital or at 3 months continued to have major depression. Furthermore, 8 of these 10 patients survived to the 3-year follow-up, and 6 (75%) of them continued to be depressed. The latest study was done by Berg et al. (2003) in which 46% of patients with Beck depression scores above 9 at the acute or 2 month evaluation continued to have these scores at 12- or 18-months follow-up. As shown in Fig. 8.2, all of the longitudinal studies have found that most major depressions spontaneously improve by 1 year following stroke. However, using pooled data from across all of the studies cited, 26% of patients with acute poststroke major depression continued to have major depression 1 year later while 41% of patients with acute poststroke minor depression continued to have minor or major depression at 1-year follow-up. Thus, the duration of depression was greater than a year in a substantial number of patients and the duration of major depression in some patients was more than 3 years.

Another question related to the course of depression following stroke is whether these depressions may recur after treatment or spontaneous remission? The answers to questions such as what percentage of poststroke depressed patients have recurrent depressions, whether recurrent depressions occur more frequently over time, whether recurrent depressions last as long as initial depressions, or whether there is a relationship between the type or location of brain injury and the frequency or duration of recurrent depressions have not been determined. There are, however, many examples of recurrent depression after brain injury.

The following case history gives an example of a recurrent depressive disorder following stroke.

CASE STUDY

Mrs. A. was a 35-year-old woman who had been the regional director of marketing for a national company. Deadlines, frequent travel, and sales quotas were all part of her high pressured work. She developed hypertension during her first pregnancy but in spite of this kept up her hectic work schedule. While on a business trip during this pregnancy, however, she suffered a stroke which caused mild weakness of her right side as well as an aphasia characterized by difficulty producing speech but intact comprehension (i.e., non-fluent aphasia). These motor and language impairments were relatively mild and cleared up within several months after the stroke.

When I first saw her, she was about 6 months poststroke and was convinced that there was still something wrong with her as a result of the stroke. She had never experienced prolonged depressive symptoms prior to the stroke. Several physicians had told her there was nothing physically wrong with her and all she needed to do was to get back to work. She did not appear depressed when I first met her. She was talkative and her thoughts and speech were not slowed as frequently occurs in depression. She was not tearful or suicidal. She did, however, feel depressed and had loss of interest, concentration, and motivation. She had returned to work for a couple of hours a day but was unable to concentrate well enough to accomplish even the simple tasks. She had lost interest and pleasure in virtually all of her work or social activities. She no longer had the ambition to climb the corporate hierarchy. She also had sleep disturbance with early morning awakening, loss of appetite and weight, decreased sexual interest, and decreased energy. Her response to antidepressant treatment was dramatic. Between 4 and 6 weeks after beginning nortriptyline, her mood had greatly improved, she returned to work, and was able to concentrate and experience interest and pleasure in her work. Over a period of 2 to 3 months, she changed from somebody who was virtually immobilized vocationally and socially by depression to an effective, energetic woman. She also had a return of some of her previous ambition although she still did not have the same drive to reach the top of the corporate hierarchy as she had prior to the stroke.

After 9 months of taking nortriptyline, she wanted to discontinue her medications because she felt that she had fully recovered and did not want to continue taking medication which produced a dry mouth and constipation. The medication was tapered over a period of about 6 weeks and then stopped. She remained well approximately one year but then had a recurrence of the same symptoms that I initially observed. She was uninterested in work, had no feeling of pleasure in any of her usual activities, was unable to concentrate or attend to the demands of work or home, had difficulty sleeping, lost her appetite, and felt depressed. These symptoms again subsided after restarting her antidepressant medication which she continued to take for another year. After that year, she again insisted on stopping her antidepressant medication. Over the next 2 years of follow-up, she remained free of depressive symptoms but it is clear from her previous history that the possibility of another recurrence of depression still exists.

Recurrence of depression is clearly an issue which requires further research. In primary depression, the likelihood of recurrence is dependent upon the number of prior episodes and time since the previous depression. Whether these factors are also important in predicting recurrence of poststroke depression needs to be examined. Questions such as how long patients should prophylactically take antidepressants or whether treatment influences the likelihood of recurrence need to be answered before important patient management decisions can be made.

In summary, several follow-up studies have consistently demonstrated two findings. First, the majority of poststroke major depressions are over by 12 months poststroke. Remissions of depression occur even without treatment. It is noteworthy that a natural course of approximately 9 months has been observed in primary depression (i.e., depression in patients with no brain lesion) (Rennie 1942). The finding by Morris et al. (1990) of 39 weeks mean duration for poststroke major depression suggests a similarity between primary and poststroke major depression. Secondly, there are a group of poststroke depressions which do not remit within a year and become chronic major depressions. This probably reflects the fact that major and minor depressions include a mix of different etiologies. Patients who develop chronic poststroke depression may have a premorbid vulnerability, such as a personality trait or family history of mood disorder that leads to prolonged depression. These prolonged depressions, however, did not correlate significantly with severity of poststroke physical impairment. Other patients may have no such vulnerability and hence depressions of significantly shorter duration.

Whatever the cause of these chronic depressions, identification of the clinical correlates and effective treatment for these disorders are important goals of research into poststroke mood disorders.

REFERENCES

Astrom, M., Adolfsson, R., and Asplund, K. Major depression in stroke patients: a 3-year longitudinal study. Stroke (1993a) 24:976-982.

Astrom, M., Olsson, T., and Asplund, K. Different linkage of depression to hypercortisolism early versus late after stroke: A 3-year longitudinal study. Stroke (1993b) 24:52-57.

Berg, A., Psych, L., Palomaki, H., et al. Poststroke depression - an 18-month follow-up. Stroke (2003) 34(1):138-143.

Burvill, P. W., Johnson, G. A., Jamrozik, K. D., et al. Prevalence of depression after stroke: the Perth Community Stroke Study. Br J Psychiatr (1995) 166:320-327.

House, A., Dennis, M., Mogridge, L., et al. Mood disorders in the year after first stroke. Br J Psychiatr (1991) 158:83-92.

Morris, P. L. P., Robinson, R. G., and Raphael, B. Prevalence and course of depressive disorders in hospitalized stroke patients. Int J Psychiatr Med (1990) 20:349-364.

Pohjasvaara, T., Vataja, R., Leppavuori, A., et al. Depression is an independent predictor of poor long-term functional outcome post-stroke. Eur J Neurol (2001) 8(4):315-9.

Rennie, T. A. C. Prognosis in manic-depressive psychoses. Am J Psychiatr (1942) 98:801-814.

Robinson, R. G., Starr, L. B., Kubos, K. L., et al. A two year longitudinal study of post-stroke mood disorders: findings during the initial evaluation. Stroke (1983) 14:736-744.

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