DÄ internationalArchive23/2008Depression and Quality of Life in Patients With Amyotrophic Lateral Sclerosis

Original article

Depression and Quality of Life in Patients With Amyotrophic Lateral Sclerosis

Dtsch Arztebl Int 2008; 105(23): 397-403. DOI: 10.3238/arztebl.2008.0397

Lulé, D; Häcker, S; Ludolph, A; Birbaumer, N; Kübler, A

Introduction: There is increasing debate on the issue of whether to facilitate the end-of-life decisions of severely disabled paients with diseases such as amyotrophic lateral sclerosis (ALS). Our two studies were intended to explore the emotional state and quality of life of patients with ALS.
Methods: Two studies were performed to investigate depression and the quality of life in ALS patients: one was a longitudinal study, the other a comparison of ALS patients to normal control subjects.
Results: These studies found no correlation between physical disability in ALS and either depression or the quality of life. The rate of depression was found to be inversely related to educational status. A satisfactory quality of life without depressive manifestations seems to be possible in any stage of ALS. In ALS patients the quality of life was comparable with healthy controls.
Discussion: The rationale for not providing life-sustaining treatment to severely disabled patients is that a poor quality of life is expected after such treatment. Our studies have shown, however, that ALS patients can experience a satisfactory quality of life even if they are severely physically impaired, including in the terminal phase.

Dtsch Arztebl Int 2008; 105(23): 397–403
DOI: 10.3238/arztebl.2008.0397
Key words: depression, respiratory insufficiency, amyotrophic lateral sclerosis, assisted suicide, quality of life
LNSLNS Conversations with patients and their relatives, physicians, and nurses reveal that these other persons often possess no accurate knowledge of the actual emotional situation of patients with severe impairment of motor function in general, or, more specifically, of patients with amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). Ganzini and Block (1) suspect that this is due to a psychological defense mechanism: healthy people have difficulty imagining the feelings and experiences of a severely impaired patient. They generally assume that the patient's quality of life is poor (2). Despite this lack of sure knowledge, however, decisions about life-terminating measures are often made, or at least strongly influenced, by physicians and relatives (3, 4). Evidence suggests that, in the Netherlands today, one in five ALS patients dies either by euthanasia or by assisted suicide (5). In Germany, too, there are increasingly loud calls for a liberalization of the law regarding active euthanasia, particularly as it applies to ALS patients in the terminal stage, in order to shorten what is considered to be a period of suffering (e1). A study of the actual quality of life and affective state of ALS patients thus seems to be urgently necessary. The object of the present investigation was to find out whether ALS patients suffer from depressive mood disorders, and whether their quality of life becomes poorer over the course of their illness. The test results of ALS patients were compared with those of normal control subjects and those of other groups of patients without any severe motor impairment. This study is intended to shed light on the question of what life with a severe motor impairment is actually like.

Methods
In the first segment of the study (I), ALS patients in all stages of the disease were investigated with respect to their affective state (depressive symptoms) and subjectively experienced quality of life (SQL) at the time points T1 and T2 (T2 was 80 to 100 days after T1 for each patient; 39 patients were evaluated at T1, 30 at T2). Possible depressive symptoms were registered with the ALS Depression Inventory (ADI-12) (6, 7), an instrument for measuring the patient's self-reported affective state. The possible values on this scale range from 12 (no evidence of depressive symptoms) to 48 (most severe depression possible); values above 28 correspond to clinically relevant depressive symptoms (DS). The SQL was assessed with the aid of the Schedule for the Evaluation of Individual Quality of Life – Direct Weighting (SEIQoL-DW). The proband is asked to name five specific areas which have an influence on his or her quality of life (no = 0, yes = 1), and then to assign a weighting, in percent, to each of the areas that were stated to influence the quality of life and to rate his or her satisfaction in each of the five areas on a seven-point scale (again expressed in percent). On the basis of these data, the SEIQoL Index Score (SIS) is calculated (e2, 8) (see additional information in the e-supplement). Furthermore, functional impairments were assessed with the ALS Functional Rating Scale (ALSFRS) (e3), ranging from 0 (locked-in state) to 40 (no functional impairment). For the purposes of this article, an ALSFRS score above 15 is considered to correspond to a mild or moderately severe physical impairment, while a score of 15 or below is considered to correspond to a severe impairment. Furthermore, information was obtained about how many years the patient attended school and the time elapsed since the diagnosis (table 1 gif ppt). In a second segment of the study (II), another group of ALS patients was compared to normal control subjects with respect to their subjectively experienced quality of life (SQL), as assessed with the SEIQoL-DW (e2). These patients' functional impairments were registered with the ALSFRS, and data were collected on the time elapsed since their diagnosis.

Statistical analysis
Pearson correlations were calculated to test the linear correlation between depressive symptoms (ADI-12, metric) and the metric scales of functional impairment (ALSFRS), the time elapsed since diagnosis, the patient's highest educational attainment, and the quality of life (SIS).

A chi-square test was performed to detect any significant differences between the two groups in the frequencies of observed characteristics (i.e., identification of areas with an important influence on life quality) as assessed by the documentation of two independent variables, which were considered dichotomous (DS clinically relevant when ADI-12 >28, no clinically relevant DS when ADI-12 <28; mild to moderate physical impairment when ALSFRS >15, severe physical impairment when ALSFRS <15).

Differences between two independent variables with respect to a dependent variable were tested for significance with Student's t test. Group differences in the information supplied about quality of life (SIS) with respect to the intersubject factor "ventilation group" (ventilated or non-ventilated) were evaluated in this way. On the other hand, differences among several independent variables with respect to a single dependent variable were tested for significance with univariate variance analysis. Group differences in the information supplied about quality of life (SIS, identification and satisfaction ratings of determinants of life quality) with respect to the intersubject factor "ALS patients vs. normal controls" were evaluated in this way.

The statistical analysis was performed with SPSS (Statistical Package for the Social Sciences) for Windows, version 14.0. The significance level was tested with two tails and at p = 0.05. The strength of effects was rated with η2. The data were analyzed both exploratively and in hypothesis-guided fashion (independence of depression/SQL and physical impairment).

Results
Study I: emotional state and quality of life of ALS patients over the course of the illness

Self-reported emotional state – 28% of the ALS patients (T1 11/39) had clinically relevant depressive symptoms (ADI-12 >28) (table 1).

Interactions of the self-reported emotional state – At time T1, ALS patients displayed no correlation between their depressive symptoms (ADI-12) and the extent of their physical impairment (ALSFRS: r = –0.017, p = 0.920) (figure 1 gif ppt) or the time elapsed since diagnosis (months: r = 0.18, p = 0.267).

In ALS patients (T1), depressive symptoms (ADI-12) were significantly correlated with shorter schooling (r = –0.41, p = 0.005).

Subjectively experienced quality of life (SQL), SIS – ALS patients reported, both at time T1 and at time T2, that they were experiencing a quality of life comparable to that reported by other chronically ill patients without severe motor impairment (SIS; no quantitative comparison is possible here because of a lack of original data in the literature) (e4, e5) (table 1).

Patient-reported determinants of SQL – ALS patients with DS (T1 11/39 ADI-12 >28) named health (9/11, χ2 = 6.72, p = 0.010, η2 = 0.42) and mobility (6/11, χ2 = 4.07, p = 0.044, η2 = 0.32) as areas determining their quality of life significantly more commonly than did ALS patients without DS (T1 28/39 ADI-12 = 28; health named by 10/28, mobility by 6/28). ALS patients without DS were significantly more likely to name personal well-being as a determinant of their quality of life (8/28, χ2 = 3.95, p = 0.047, η2 = 0.32) (table 2 gif ppt); no ALS patient with DS did so.

Markedly physically impaired ALS patients (T1 16/39 ALSFRS < 15) named communication (7/16, χ2 = 5.93, p = 0.029, η2 = 0.39) and medical care (10/16, χ2 = 9.36, p = 0.002, η2 = 0.49) as areas determining their quality of life significantly more commonly than did patients with only mild or moderately severe impairment (T1 23/39 ALSFRS >15; communication named by 0/23, medical care named by 0/23).

Interactions of the subjectively experienced quality of life (SQL) – In ALS patients (T1), there was a significant negative correlation of the SQL (SIS) with ADI-12 depression scores (ADI-12; r = –0.36, p = 0.027). The lower the depression score, the higher the quality of life.

ALS patients were found, over the course of the disease (T2), to develop a significant correlation between the subjectively experienced quality of life (SIS) and the extent of their physical impairment (ALSFRS; r = –0.43, p = 0.021). The sign of the correlation was, however, negative: the more severe the physical impairment was, the better the subjectively experienced quality of life.

Ventilated patients (T1; invasively and non-invasively ventilated patients, 17/39; SIS) showed no significant differences in SQL to non-ventilated patients (22/39; SIS; t = –0.75, p = 0.461). Over the course of the disease (T2), ventilated patients (13/30; SIS) had a significantly higher subjectively experienced quality of life than non-ventilated ALS patients (17/30; SIS; t = 2.20, p = 0.035).

Study II: the quality of life of ALS patients compared with that of normal controls

Subjectively experienced quality of life (SQL), SIS – In the second segment of the study (II), which involved a different group of ALS patients with mild to moderately severe physical impairment compared to normal control subjects, no statistically significant difference in quality of life was found between these two groups (SIS, variance test variable F = 0.11, p = 0.745, η2 <0.01) (table 3 gif ppt).

Patient-reported determinants of the subjectively experienced quality of life – ALS patients (II) were significantly more likely to name friends and social environment as determinants of their quality of life than were the normal control subjects (for naming: F = 4.03, p = 0.050, η2 = 0.07) (table 4 gif ppt) but significantly less likely to name their occupation or financial status (for naming: F = 8.29, p = 0.006, η2 = 0.12). ALS patients were significantly more satisfied with the area "family" than the normal control subjects (satisfaction: F = 16.78, p <0.001, η2 = 0.26), although ALS patients were significantly less satisfied with their health than the normal control subjects (satisfaction: F = 8.79, p = 0.005, η2 = 0.18).

Discussion
ALS and emotional state
The prevalence of depressive symptoms in patients with ALS has been reported with a great deal of variability among studies, with values ranging from 0% (9) to 44% (10, e6). In the present study, 28% of patients with ALS had clinically relevant depressive symptoms; this figure is consistent with rates reported in the majority of the other studies (mid-range values, 24% to 28% (1113). The few studies in which depression was diagnosed by means of a DSM-IV structured clinical interview (e7) consistently showed prevalences in the range of 9% to 11% (1114) (this corresponds to the 11% value that we found in the same ALS patients that constituted the T1 group in the present study [7]). Thus, the prevalence of DSM-IV-defined depression is slightly higher among ALS patients than in the general population (4% to 5%) (e8), yet lower than among patients with multiple sclerosis (17% to 46%) (e9, e10). The discrepancies among the different prevalences of depression among ALS patients that were reported in different studies is attributable, among other things, to the fact that the clinical interview according to DSM-IV registers not only the patient's momentary affective state, but also any history of earlier depressive episodes that occurred prior to the diagnosis ALS; the ADI-12, on the other hand, which we used as a screening test in the present study, measures the self-reported momentary affective state and is therefore less specific and generally yields markedly higher rates of depression.

In our study, we found no correlation between depressive symptoms and the extent of physical impairment, or the time since diagnosis, in patients with ALS. The same has been shown in other studies (6, 12, 1517). For carcinoma patients, however, an association between depressive symptoms and the extent of physical impairment has been observed (e11). A significant correlation was found between the educational level of ALS patients and the severity of their depressive symptoms; the more years the patients had spent in school, the lower their depression scores. A possible reason for this correlation is the greater ability of better educated persons to develop functional coping strategies. The observed lack of a rise in the depression rate as the functional impairment worsens and the elapsed time from the diagnosis of the illness lengthens refutes the commonly voiced notion that emotional stress and depressive mood must necessarily become worse as the physical disease progresses. The fact is that depressive episodes can occur in any stage of ALS and be amenable to pharmacological and psychotherapeutic treatment (18). There is no empirical basis for the fatalistically postulated correlation of ALS with depression (12).

ALS and the quality of life
In multiple studies, ALS patients have reported experiencing a sometimes quite surprisingly high subjective quality of life despite their marked physical impairment (6, 12). In the present study, too, the mean subjective quality of life among ALS patients was in the range of 66% to 72% and thus comparable to that of normal control subjects. Few or no correlations were found between these patients' subjective quality of life and their degree of physical impairment or the length of time elapsed since the diagnosis was made (7, 12, 15, 16, 17, 19). In the present study, in fact, the subjective quality of life actually rose over time as the patients' physical impairment worsened. Ventilated patients had a better SQL than non-ventilated ALS patients. This may be explained as a result of the beneficial symptomatic effects of ventilation, including lessening daytime fatigue. Our data suggest that even patients in an advanced stage of ALS can subjectively experience a high quality of life.

The subjective quality of life of ALS patients in our studies lay in a range comparable to that of chronically ill patients without any severe motor impairment, as determined in a number of other studies (SQL ca. 70%) (e4, e12, e13). In contrast, carcinoma patients in an advanced stage of disease attain SQL values (<60%) (20, e14) that are significantly lower than those of ALS patients when directly compared with them (20) and that continue to decline as the disease produces progressive physical impairment (e11, e15).

These data permit the conclusion that ALS patients, compared to patients with other diseases that do not regularly produce severe paralysis (figure 2 jpg ppt), may surprisingly enjoy a subjectively experienced quality of life that is comparable or significantly higher. At present, we can only speculate on the possible causes of this special position of ALS patients relative to others.

Among the ALS patients in this study, depression was associated with a negative subjective quality of life, confirming the well-known close relationship of the affective state and the quality of life (6). Depressed ALS patients seem to define their quality of life to a greater extent as a function of external experiences that are no longer accessible to them, such as health and mobility. For non-depressed ALS patients, on the other hand, internal areas such as personal well-being seem to be more important. These areas can remain intact even as the disease progresses.

In accordance with the data presented here, Neudert et al. have confirmed that ALS patients shift their priorities with respect to quality of life to center them more on social aspects (8). In our study, ALS patients named their friends and social environment as determinants of their quality of life significantly more often than their occupation and financial status. Moreover, they were significantly more satisfied with their families. As ALS progressed, certain areas became increasingly important for these patients' subjective quality of life while the physical impairment worsened. Severely impaired ALS patients named communication and medical care significantly more often as determinants of the quality of life than did mildly to moderately impaired patients, who, in fact, did not name these areas at all. These data suggest that ALS patients develop successful adaptive strategies with respect to the needs and priorities corresponding to their living conditions in each stage of the disease.

Some possible limitations of the present study might include a lack of representativeness of the populations and the small sample sizes in the two different segments of the study (I and II). Questioning of very severely physically impaired patients can hardly be performed on much larger study populations than these. Patients lacking contact to the outpatient ALS clinic were presumably underrepresented in this study, as were patients lacking the interest to participate. Despite these qualifications, the surprising finding remains that neither the subjective quality of life nor depression is correlated to any significant extent with the patient's physical impairment. The studies presented here and the related findings reported in the literature have implications for the management of patients with ALS, including with respect to the euthanasia debate.

Conclusion
The results reported here with respect to the subjective quality of life and depressive symptoms in ALS patients in both the earlier and the later stages of the disease contradict the widespread opinion that patients with severe physical impairment necessarily suffer to an extreme degree. The decision not to undergo life-prolonging treatment is due to the fear of loss of autonomy and control and to the worry that a lack of mobility and impaired communication will lead to social isolation (1). Moreover, it is often assumed that severely paralyzed patients have a low quality of life, particularly when they are dependent on life-sustaining treatment (2). The fact that ventilated ALS patients reported enjoying a significantly higher quality of life than non-ventilated ones contradicts this notion as well. Many useful therapeutic measures are available, including invasive ventilation and communication devices that give the patient a greater measure of autonomy, improving the quality of life (e17, e18) by generating a feeling of control over one's own fate (e16). It seems likely that information is often inadequately communicated and the available treatment modalities are often underutilized (1). Depression usually goes untreated (12, 14), because it is viewed as a normal accompaniment of a fatal illness. If the results of this study were to be thoroughly discussed with ALS patients and their families, and if all therapeutic options were to be presented to them, including the possibility of cessation of invasive ventilation and artificial feeding, it may be that more patients would opt to continue treatment than is currently the case (21, 26, e16). It can be assumed that excellent palliative care would markedly reduce the number of requests for an accelerated death (1, 23).

The authors hope that these empirical data on the emotional state of severely impaired patients will serve as firmer scientific ground for future discussions of physician-assisted suicide (PAS), and that they will pave the way for further studies that share the goal of putting the emphasis on the patient's perspective.

Conflict of interest statement
The authors declare that no conflict of interest exists as defined by the guidelines of the International Committee of Medical Journal Editors.

Informed Consent and Ethical Approval
The research subjects participating in these studies consented in writing to their participation. The studies were approved by the Ethics Committees of the Universities of Ulm and Tübingen.

Acknowledgements
We thank Ertan Altintas (II, questioning of ALS patients; University of Ulm), Eva-Maria Braun (I), and Claudia Zickler (I T2, questioning of ALS patients; University of Tübingen) for their support in patient recruiting, data acquisition, and data analysis.

Manuscript received on 6 July 2007; revised version accepted on 18 April 2008.

Translated from the original German by Ethan Taub, M.D.


Corresponding author
Prof. Dr. med. Albert Ludolph
Neurologische Klinik der Universität Ulm im
Rehabilitationskrankenhaus Ulm (RKU)
Oberer Eselsberg 45
89081 Ulm, Germany
albert.ludolph@rku.de
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Abteilung Neurologie, Universität Ulm: Dr. rer. nat. Lulé, Prof. Dr. med. Ludolph; Institut für Medizinische Psychologie und Verhaltensneurobiologie, Eberhard-Karls-Universität Tübingen: Dr. rer. nat. Lulé, Dipl.-Psych. Häcker, Prof. Dr. phil. Birbaumer, PD Dr. rer. nat. Kübler; National Institutes of Health (NIH), NINDS, Human Cortical Physiology, Section Bethesda, USA: Prof. Dr. phil. Birbaumer; Clinical and Health Psychology Research Centre, School of Human and Life Sciences, Roehampton University, London, UK: PD Dr. rer. nat. Kübler
1. Ganzini L, Block S: Physician-assisted death – a last resort? N Engl J Med 2002; 346: 1663–5. MEDLINE
2. McDonald ER, Hillel A, Wiedenfeld SA: Evaluation of the psychological status of ventilatory-supported patients with ALS/MND. Palliat Med 1996; 10: 35–41. MEDLINE
3. Moss AH, Casey P, Stocking CB, Roos RP, Brooks BR, Siegler M: Home ventilation for amyotrophic lateral sclerosis patients: outcomes, costs, and patient, family, and physician attitudes. Neurology 1993; 43: 438–43. MEDLINE
4. Borasio GD, Voltz R: Discontinuation of mechanical ventilation in patients with amyotrophic lateral sclerosis. J Neurol 1998; 245: 717–22. MEDLINE
5. Veldink JH, Wokke JH, van der Wal G, Vianney de Jong JM, van den Berg LH: Euthanasia and physician-assisted suicide among patients with amyotrophic lateral sclerosis in the Netherlands. N Engl J Med 2002; 346: 1638–44. MEDLINE
6. Kubler A, Winter S, Ludolph AC, Hautzinger M, Birbaumer N: Severity of depressive symptoms and quality of life in patients with amyotrophic lateral sclerosis. Neurorehabil Neural Repair 2005; 19: 182–93. MEDLINE
7. Hammer EM, Häcker S, Hautzinger M, Meyer TD, Kübler A: Validity of the ALS-Depression-Inventory (ADI-12) – A new screening instrument for depressive disorders in patients with amyotrophic lateral sclerosis. J Affect Disord 2008 Feb 7 (Epub ahead of print). MEDLINE
8. Neudert C, Wasner M, Borasio GD: Patients' assessment of quality of life instruments: a randomized study of SIP, SF-36 and SEIQoL-DW in patients with amyotrophic lateral sclerosis. J Neurol Sci 2001; 191: 103–9. MEDLINE
9. Bungener C, Piquard A, Pradat PF, Salachas F, Meininger V, Lacomblez L: Psychopathology in amyotrophic lateral sclerosis: a preliminary study with 27 ALS patients. Amyotroph Lateral Scler Other Motor Neuron Disord 2005; 6: 221–5. MEDLINE
10. Lou JS, Reeves A, Benice T, Sexton G: Fatigue and depression are associated with poor quality of life in ALS. Neurology 2003; 60: 122–3. MEDLINE
11. Ganzini L, Johnston WS, Hoffman WF: Correlates of suffering in amyotrophic lateral sclerosis. Neurology 1999; 52: 1434–40. MEDLINE
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