ABSTRACT

Objective

To investigate the frequency of anxiety and depression and their association with clinical features of amyotrophic lateral sclerosis.

Methods

This is a cross-sectional and descriptive study including a consecutive series of patients with sporadic amyotrophic lateral sclerosis according to Awaji’s criteria. Patients underwent clinical and psychiatric assessment (anxiety and depression symptoms).

Results

We included 76 patients. The men/women ratio was 1.6:1. Participants’ mean age at disease onset was 55 years (SD±12.1). Sixty-six patients (86.8%) were able to complete psychiatric evaluation. Clinically significant anxiety was found in 23 patients (34.8%) while clinically significant depression was found in 24 patients (36.4%). When we compared patients with and without depression a significant difference was seen only in the frequency of anxiety symptoms (p<0.001). We did further analysis comparing subgroups of patients classified according to the presence or not of anxiety and or depression, without any significant difference regarding sex, age at onset, initial form, disease duration or functional measures. A positive correlation between anxiety and depressive symptoms was found (p<0.001).

Conclusion

Anxiety and depressive symptoms were highly correlated and frequent in patients with amyotrophic lateral sclerosis. In addition, anxiety and depression were not associated with disease duration and presentation, sex, age at onset, and functional score.

Amyotrophic lateral sclerosis/diagnosis; Depression; Anxiety

RESUMO

Objetivo

Investigar a frequência de ansiedade e depressão e sua associação com aspectos clínicos da esclerose lateral amiotrófica.

Métodos

Estudo transversal e descritivo de uma série consecutiva de pacientes com esclerose lateral amiotrófica esporádica conforme os critérios de Awaji. Os pacientes foram submetidos à avaliação clínica e psiquiátrica (sintomas depressivos e ansiosos).

Resultados

Foram incluídos 76 pacientes. A relação homem/mulher foi de 1,6:1. A média de idade de início dos sintomas foi de 55 anos (DP±12,1). Foram capazes de completar a avaliação psiquiátrica 66 (86,8%) pacientes. Ansiedade clinicamente significativa foi encontrada em 23 pacientes (34,8%), enquanto depressão clinicamente significativa foi encontrada em 24 pacientes (36,4%). Ao comparar os pacientes com e sem depressão, houve diferença significativa apenas na frequência de sintomas de ansiedade (p<0,001). Posteriormente, foram comparados subgrupos de pacientes categorizados em relação à presença ou não de ansiedade e/ou depressão, sem diferença significativa em relação a sexo, idade de início dos sintomas, forma inicial, duração da doença ou na escala funcional. Foi encontrada correlação positiva entre os sintomas de ansiedade e depressão (p<0,001).

Conclusão

Sintomas de ansiedade e depressão são frequentes em pacientes com esclerose lateral amiotrófica e estiveram altamente correlacionados. Ansiedade e depressão não foram associadas com duração da doença, forma inicial, sexo, idade de início dos sintomas e pontuação na escala funcional.

Esclerose amiotrófica lateral/diagnóstico; Depressão; Ansiedade

INTRODUCTION

Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration leading to progressive muscle paresis and functional disability, with a mean survival of 3 to 5 years.(¹1. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, et al. Amyotrophic lateral sclerosis. Lancet. 2011;377(9769):942-55. Review.) Non-motor symptoms may be seen including depression and anxiety.(¹1. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, et al. Amyotrophic lateral sclerosis. Lancet. 2011;377(9769):942-55. Review.,²2. Kurt A, Nijboer F, Matuz T, Kübler A. Depression and anxiety in individuals with amyotrophic lateral sclerosis: epidemiology and management. CNS Drugs. 2007;21(4):279-91. Review.) The prevalence of depression and anxiety is highly variable among published studies, and may be present in up to 44 and 30% of patients, respectively.(²2. Kurt A, Nijboer F, Matuz T, Kübler A. Depression and anxiety in individuals with amyotrophic lateral sclerosis: epidemiology and management. CNS Drugs. 2007;21(4):279-91. Review.) There is evidence indicating that functional disability and depression are linked, and that depression reduces the quality of life of patients with ALS.(³3. Rabkin JG, Goetz R, Factor-Litvak P, Hupf J, McElhiney M, Singleton J, Mitsumoto H; Als Cosmos Study Group. Depression and wish to die in a multicenter cohort of ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(3-4):265-73.) However, some studies failed to confirm the association between the severity of anxiety and depressive symptoms, and functional disability in ALS.(⁴4. Atassi N, Cook A, Pineda CM, Yerramilli-Rao P, Pulley D, Cudkowicz M. Depression in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011; 12(2):109-12.,⁵5. Chen D, Guo X, Zheng Z, Wei Q, Song W, Cao B, et al. Depression and anxiety in amyotrophic lateral sclerosis: correlations between the distress of patients and caregivers. Muscle Nerve. 2015;51(3):353-7.)

This study investigated clinical features and anxiety/depressive symptoms in Brazilian patients with ALS. We hypothesized that the presence of anxiety and depression would be related to a more significant functional impairment.

OBJECTIVE

To investigate the frequency of anxiety and depression and their association with clinical features of amyotrophic lateral sclerosis.

METHODS

This is a cross-sectional study of consecutive patients diagnosed with probable or definite sporadic ALS according to Awaji’s criteria(⁶6. de Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, et al. Eletrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol. 2008;119(3): 497-503. Review.) conducted from May 2013 to November 2015. All patients signed the written consent.

The protocol included standardized questions regarding clinical features of ALS, the Hospital Anxiety and Depression Scale (HADS)(⁷7. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361-70.,⁸8. Botega NJ, Bio MR, Zomignani MA, Garcia Jr C, Pereira WA. [Mood disorders among medical in-patients: a validation study of the hospital anxiety and depression scale (HAD)]. Rev Saude Publica. 1995;29(5):355-63. Portuguese.) and the ALS Functional Rating Scale Revised (ALSFRS-R).(⁹9. Guedes K, Pereira C, Pavan K, Valerio BC. Cross-cultural adaptation and validation of als Functional Rating Scale-Revised in Portuguese language. Arq Neuropsiquiatr. 2010;68(1):44-7.) A total score on HADS for depression above 8 is highly indicative of clinically significant depression (i.e. probable depression); the same criteria was applied for anxiety.(⁸8. Botega NJ, Bio MR, Zomignani MA, Garcia Jr C, Pereira WA. [Mood disorders among medical in-patients: a validation study of the hospital anxiety and depression scale (HAD)]. Rev Saude Publica. 1995;29(5):355-63. Portuguese.)

The study was approved by the human research Ethics Committee of both Universidade Federal de Minas Gerais, CAAE: 19599813.0.0000.5149 and Fundação Hospitalar do Estado de Minas Gerais, protocol number 002B/2014.

Statistical analysis

We performed non-parametric tests (Mann-Whitney, χ² and Spearman) using Statistical Package for the Social Sciences (SPSS), version 22.0. A p value <0.05 was considered statistically significant.

RESULTS

Seventy-six patients were selected for the study. The clinical parameters are summarized at table 1. Forty-seven patients (61.8%) were men (men/women ratio: 1.6:1). Considering the initial presentation, 78% of cases were spinal and 22% were bulbar.

Sixty-six patients (86.8%) completed the HADS (Table 2). The others did not fulfill the scale due to refusal (n=4) or severe disability (n=6). Probable anxiety was confirmed in 23 (34.8%) patients; probable depression was found in 24 (36.4%) patients. Of 66 patients, 65% were men, 50 (75%) had spinal and 16 (24%) had bulbar initial presentation. Fifteen (23%) had anxiety and depression, 9 (14%) had only depression, 8 (12%) had only anxiety, while 34 (51%) had none of these symptoms. Thirty patients were current using antidepressants to treat depressive state and/or pain, insomnia or excessive salivation. Eleven of 24 patients with depression (45.8%) were using effective doses of antidepressants.

When we compared subgroups of patients according to the presence or not of probable depression, there was a statistical difference regarding the score on HADS for anxiety (Table 3). No significant difference was found regarding sex and initial form.

We did further analysis comparing subgroups of patients categorized according to the presence or not of anxiety and or depression, and no significant difference regarding ALSFRS-R scores, sex, age at onset, disease duration and initial form emerged.

There was no correlation between HADS scores for anxiety or depression and ALSFRS-R scores. A positive correlation between anxiety and depressive symptoms was found (r=0.67; p<0.001).

DISCUSSION

To the best of our knowledge, this is the first study assessing psychiatric symptoms in ALS patients from South America. The frequency of depression (zero to 44%) and anxiety (zero to 30%) in ALS varies significantly across the studies.(²2. Kurt A, Nijboer F, Matuz T, Kübler A. Depression and anxiety in individuals with amyotrophic lateral sclerosis: epidemiology and management. CNS Drugs. 2007;21(4):279-91. Review.,³3. Rabkin JG, Goetz R, Factor-Litvak P, Hupf J, McElhiney M, Singleton J, Mitsumoto H; Als Cosmos Study Group. Depression and wish to die in a multicenter cohort of ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(3-4):265-73.,⁴4. Atassi N, Cook A, Pineda CM, Yerramilli-Rao P, Pulley D, Cudkowicz M. Depression in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011; 12(2):109-12.) Our rates (around 35%) are within the range reported in the literature.

The assessment of psychiatric symptoms in ALS may be hampered by several factors, including assessment tools(¹⁰10. Ferentinos P, Paparrigopoulos T, Rentzos M, Zouvelou V, Alexakis T, Evdokimidis I. Prevalence of major depression in ALS: comparison of a semi-structured interview and four self-report measures. Amyotroph Lateral Scler. 2011; 12(4):297-302.) and severity of the disease,(³3. Rabkin JG, Goetz R, Factor-Litvak P, Hupf J, McElhiney M, Singleton J, Mitsumoto H; Als Cosmos Study Group. Depression and wish to die in a multicenter cohort of ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(3-4):265-73.,¹¹11. Rabkin JG, Albert SM, Del Bene ML, O’Sullivan I, Tider T, Rowland LP, et al. Prevalence of depressive disorders and change over time in late-stage ALS. Neurology. 2005;65(1):62-7.) partly explaining the discrepancy among studies. Moreover, the use of antidepressants, that is frequent in ALS for different reasons,(²2. Kurt A, Nijboer F, Matuz T, Kübler A. Depression and anxiety in individuals with amyotrophic lateral sclerosis: epidemiology and management. CNS Drugs. 2007;21(4):279-91. Review.

3. Rabkin JG, Goetz R, Factor-Litvak P, Hupf J, McElhiney M, Singleton J, Mitsumoto H; Als Cosmos Study Group. Depression and wish to die in a multicenter cohort of ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(3-4):265-73.-⁴4. Atassi N, Cook A, Pineda CM, Yerramilli-Rao P, Pulley D, Cudkowicz M. Depression in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011; 12(2):109-12.,¹²12. Rabkin JG, Wagner GJ, Del Bene M. Resilience and distress among amyotrophic lateral sclerosis patients and caregivers. Psychosom Med. 2000; 62:271-9.) may have influenced the frequency and/or severity of depressive and anxiety symptoms.

Interestingly, despite the use of antidepressants, psychiatric symptoms are prominent, indicating persistence of symptoms even with treatment.(²2. Kurt A, Nijboer F, Matuz T, Kübler A. Depression and anxiety in individuals with amyotrophic lateral sclerosis: epidemiology and management. CNS Drugs. 2007;21(4):279-91. Review.,³3. Rabkin JG, Goetz R, Factor-Litvak P, Hupf J, McElhiney M, Singleton J, Mitsumoto H; Als Cosmos Study Group. Depression and wish to die in a multicenter cohort of ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(3-4):265-73.,¹²12. Rabkin JG, Wagner GJ, Del Bene M. Resilience and distress among amyotrophic lateral sclerosis patients and caregivers. Psychosom Med. 2000; 62:271-9.) It remains to be defined whether these patients respond differently to antidepressants and which factors are associated to clinical response.

Contrary to our hypothesis, we did not find significant association between symptoms of anxiety/depression and functional disability. The absence of association between depression and disease duration or functional score in ALS were reported in some studies,(⁴4. Atassi N, Cook A, Pineda CM, Yerramilli-Rao P, Pulley D, Cudkowicz M. Depression in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011; 12(2):109-12.,⁵5. Chen D, Guo X, Zheng Z, Wei Q, Song W, Cao B, et al. Depression and anxiety in amyotrophic lateral sclerosis: correlations between the distress of patients and caregivers. Muscle Nerve. 2015;51(3):353-7.) but other authors did find this association.(³3. Rabkin JG, Goetz R, Factor-Litvak P, Hupf J, McElhiney M, Singleton J, Mitsumoto H; Als Cosmos Study Group. Depression and wish to die in a multicenter cohort of ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(3-4):265-73.) Methodological issues, including differences in the selection criteria of patients and in the choice of the functional and psychiatric scales may account for these distinct findings. The controversial findings in literature hamper a precise conclusion about this subject. Further studies could help to clarify this data.

Based on the absence of significant difference in clinical features between subgroups, it is possible that these psychiatric symptoms may be due to other reasons not related to motor and functional impairment. It also remains to be elucidated why anxiety and depression symptoms were highly correlated in ALS. Limitations of the study include sample size, bias of the use of antidepressants and intrinsic limitations of the HADS.

CONCLUSION

The frequency of anxiety and depression in amyotrophic lateral sclerosis was elevated, and was not associated with disease duration, sex, presentation form and functional score. There was a high correlation between anxiety and depression symptoms in amyotrophic lateral sclerosis.

REFERENCES

Publication Dates

History