Anxious and depressive symptoms and their correlation with pain severity in patients with peripheral neuropathy

Abstracts

INTRODUÇÃO: As neuropatias periféricas incluem disfunções sensitivo-motoras e quadros de dor crônica que podem propiciar a eclosão de transtornos psiquiátricos, como a ansiedade e a depressão. Este estudo visa estimar a frequência de sintomas ansiosos e depressivos entre pacientes com neuropatia periférica, correlacionando-os com a intensidade da dor. MÉTODO: Estudo de corte transversal realizado em ambulatório docente assistencial de neurologia entre abril de 2006 e março de 2007. Foram utilizados como instrumentos de avaliação a Escala Hospitalar de Ansiedade e Depressão e a Escala Analógica Visual de Dor para avaliação da dor. A amostra foi composta por 54 pacientes. RESULTADOS: Constatou-se uma frequência de 68,5% (n = 37) de sintomas ansiosos e 51,9% (n = 28) de sintomas depressivos. Dor intensa foi relatada por 57,4% dos pacientes. Houve correlação positiva entre a intensidade da dor e a de sintomas ansiosos e depressivos (p ≤ 0,05). Presença de cefaleia, trauma e história familiar de doença psiquiátrica também estava associada positivamente aos sintomas ansiosos e depressivos. CONCLUSÕES: Os resultados demonstram uma elevada frequência de sintomas ansiosos e depressivos em pacientes com neuropatia periférica, havendo uma correlação positiva com a gravidade da dor.

Ansiedade; depressão; dor; medição da dor; doenças do sistema nervoso periférico

ORIGINAL ARTICLE

*

Israel Soares Pompeu de Sousa Brasil^I; Milena Pereira Pondé^II

^IMedical Student. Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.

^IIAssociate professor, Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.

Correspondence

ABSTRACT

INTRODUCTION: Peripheral neuropathies include sensory-motor dysfunctions and chronic pain that may trigger psychiatric disorders such as anxiety and depression. The objective of the present study was to estimate the frequency of anxious and depressive symptoms among patients with peripheral neuropathies, correlating them with pain severity.

METHODs: Cross-sectional study conducted in an outpatient neurology clinic between April 2006 and March 2007. The Hospital Anxiety and Depression Scale and the Pain Visual Analogue Scale were used to evaluate pain. The sample included 54 patients.

RESULTS: We found a frequency of 68.5% (n = 37) of anxious symptoms and 51.9% (n = 28) of depressive symptoms. Severe pain was reported by 57.4% of the patients. There was a positive correlation between pain severity and anxious and depressive symptoms (p ≤ 0.05). Headache, trauma and family history of psychiatric disease were also associated with anxious and depressive symptoms.

CONCLUSIONS: Our findings demonstrate a high frequency of anxious and depressive symptoms in patients with peripheral neuropathies. Such symptoms are positively correlated with pain severity.

Keywords: Anxiety, depression, pain, pain measurement, peripheral nervous system diseases.

Introduction

The association between mental disorders and physical diseases is caused both by psychosocial and biological factors. Among the psychosocial factors, the most relevant are frustration in terms of fulfillment of desires and needs, worsening of intrapsychic conflicts, inappropriate defense mechanisms, loss of self-esteem, change in body image, and social isolation.¹ The alteration in the sleep-wake cycle and the use of drugs and procedures that affect the central nervous system are some of the biological factors.¹ Mental disorder can be associated with physical problems, and organic changes may result in psychic disorders. Depression and phobic anxiety, for instance, can be associated with a higher risk of myocardial infarction.² In addition, adjustment reactions are common in inpatients,³ and depression and emotional lability often affect people with cerebrovascular diseases.⁴

There are two psychiatric disorders that play an important role in the relationship established between organic and psychiatric factors. Anxiety, which is frequently associated with new and unknown situations, such as the onset of a disease, has a high prevalence rate in institutions that provide primary health care: 13.8% in Spain; 19.2% in Canada and 21.8% in the USA.⁵ Depression may be confounded with the underlying organic disease, since suffering and functional disability favor the occurrence of symptoms like insomnia, fatigue and loss of libido, even when there is not a diagnosis of depression.⁶ The most common symptoms of depression in patients with physical diseases are loss of interest in people, pessimism, indecision, irritability, anhedonia, insomnia, low self-esteem, and hopelessness.^7-9

The onset of diseases involving the peripheral nerves is within this context, since it involves a wide range of symptoms, including chronic pain and sensory-motor disorders. In a study including patients with diabetic neuropathy, the authors found that 60.4% of the patients had anxiety and 50.6% had depression, and the symptoms were proportional to pain intensity.¹⁰ Depressive symptoms, measured using the Hospital Anxiety and Depression Scale, were associated with the neuropathy.¹¹ Neuropathic pain, which is present in most peripheral neuropathies, can be a causal or aggravating factor of psychiatric symptoms. The presence of acute pain may also trigger an anxious response, leading to a lower pain threshold.¹² There is high comorbidity of psychiatric disorders and chronic pain. Mood disorders were found in 21.7% of the sample of patients who had chronic pain.¹³ The prevalence rates of pain in depression cohorts and the prevalence rates of depression in pain cohorts are higher than in those cohorts in which such conditions are evaluated separately.¹⁴ Multiple pain sites are also associated with mood disorders and anxiety.¹⁵ Comorbidities, such as diabetes, heart disease and cancer, are also risk factors that have been proved to play an important role in the disability caused by chronic painful conditions,¹⁶ therefore potentializing the depressive and anxious symptomatology. It has not been defined in the literature which disorder represents a higher risk, even though anxiety disorders seem to be more strongly associated with pain complaints than mood disorders.¹⁷

Based on this information, the objectives of the present study are to identify the frequency of anxious and depressive symptoms in low-income patients with peripheral neuropathy and to correlate the patients' pain severity with the intensity of psychiatric symptoms.

Method

A cross-sectional study was carried out from April 2006 to March 2007 involving patients with peripheral neuropathy who were treated at the outpatient clinic of peripheral neuropathies of Foundation of Neurology and Neurosurgery Institute of Brain (Fundação de Neurologia e Neurocirurgia Instituto do Cérebro — Salvador, state of Bahia, Brazil). This is a teaching institution that provides free health care to low-income people. We included all patients aged ≥ 18 years old who attended the service during data collection, provided written consent and had unimpaired cognitive functions to answer the questionnaire. Those patients who were not suspected of having peripheral neuropathy, were younger than 18 years old and refused to participate in the research were excluded.

The following assessment instruments were used: sociodemographic data collection record, information about the underlying disease and medical history, the Hospital Anxiety and Depression Scale and the Pain Visual Analog Scale. The Hospital Anxiety and Depression Scale was chosen because it does not include somatic symptoms, which could confound the diagnosis of mood disorder or anxiety disorder.¹⁸ Its Portuguese version was validated for outpatients, resulting in a sensitivity rate of 74.2% and a specificity rate of 74% for the anxiety subscale, whereas the rates for the depression subscale were 85.7% of sensitivity and 72.4% of specificity.¹⁹ The cutoff point for both scales was 8, and this cutoff point was used in the present study. The questionnaires were orally administered to the whole sample, since there were illiterate patients. The Pain Visual Analog Scale was used to assess pain severity. On this scale, 0 (zero) indicates no pain and 10 means unbearable pain. It is a simple and easily administered method to measure pain severity, in addition to being compatible with the educational level of the population studied. Scoring was classified into three categories, similarly to the procedure used in the study by Tölle et al.:²⁰ from 1 to 3, mild pain; from 4 to 7, moderate pain; and from 8 to 10, severe pain. Patients were interviewed by the researcher, a medical student trained to administer the questionnaire.

This study was approved by the Research Ethics Committee of Foundation for the Development of Sciences of Bahia (Fundação Bahiana para Desenvolvimento das Ciências), under the protocol no. 25/2006, and it was financially supported by the Foundation for Research Support of the State of Bahia (Fundação de Amparo à Pesquisa do Estado da Bahia - FAPESB). All patients included in the study received and signed the written consent form.

For data analysis, the Statistical Package for the Social Sciences (SPSS), version 12.0, was used. For the descriptive analysis, the descriptive statistical parameters were used according to the usual measures of central tendency (mean, median, mode) and dispersion (range, variance, standard deviation and coefficient of variation), as well as calculation of simple and relative frequencies. For continuous variables with normal distribution, we used the Student's t test; for the frequencies of categorical variables, the chi-square test and Fisher's exact test were used. Linear regression analysis was performed in order to correlate the intensity of anxiety and depression symptoms with pain severity. The significance level was set at 5%.

Results

Sixty-eight patients were approached to comprise the sample, and 54 of them met the inclusion criteria. Among the 14 patients excluded, two were younger than 18 years old, seven did not have diseases classified as peripheral neuropathy (three with myopathy, three with myelopathy and one with trigeminal neuralgia of possible central cause), one had topographic underlying disease to be clarified, one had advanced Alzheimer's disease and three refused to participate in the study.

Table 1 summarizes the sociodemographic and clinical data. The mean age of the group was 44.5±10.4 years old, and 74% of the patients were younger than or 50 years old. Most patients (90.7%) had a monthly income of at most three minimum salaries (minimum salary of R$ 350.00 at the time of data collection), and the majority of them (85.2%) did not work (unemployed, dismissed or retired). Regarding the clinical data, the most frequent peripheral neuropathies were the radiculopathies (41.5%) and the carpal tunnel syndrome (30.2%). Most of the sample was comprised of chronic patients: the mean duration of the disease was 5.2±4.3 years, and 38.9% had the disease for longer than 5 years. Comorbidities were found in 83.3% of the patients: headache was mentioned by 29.6% of the sample; hypertension by 24%; and 22.2% reported to be smokers. Psychiatric care was provided to 20.4% of the patients; among them, 63.6% reported depression as the reason for psychiatric treatment. Tricyclic antidepressants (amitriptyline or nortriptyline) were used by 68.5% of the patients; 19% used non-steroidal anti-inflammatory drugs; 17.1% used vitamin complexes; 13.3% used muscle relaxants; and 13.3% used anticonvulsants. Polypharmacy was detected in 70.3% of the patients, and the mean number of drugs used by patients was 2.4±1.2.

The score ≥ 8 on the anxiety subscale of the Hospital Anxiety and Depression Scale (HAD-A) was reached by 68.5% of the sample, with a mean score of 9.4±4.6. Anxious symptoms were more frequent among patients in the age group between 31 and 50 years; patients with lesions caused by trauma; patients who complained of headache; those who had family history of psychiatric disorder; patients who had severe pain; and those who had depressive symptoms (p ≤ 0.05) (Table 2). On the other hand, 51.9% of the patients had scores ≥ 8 on the depression subscale (HAD-D), with a mean score of 8.2±4.3. The depressive symptoms were more frequent among the same groups of patients associated with the anxiety symptoms (31-50 years old; trauma; headache; family history of psychiatric disorder; severe pain), besides those who reached the cutoff point for anxious symptoms (p ≤ 0.05) (Table 2).

Table 2 - Click to enlarge

Almost half of the patients (46.3%) had concomitant anxiety and depression symptoms. The mean score of anxious symptoms among these patients was 13.1±3, and it was significantly higher when compared to the score of patients with anxious symptoms alone (p < 0.001). The mean score of depressive symptoms was 11.38±2.2, and there was not a significant difference in comparison to the score of those patients who had only depressive symptoms.

In terms of the pain severity measured by the Pain Visual Analog Scale, 5.6% of the sample reported no pain; 9.3% had mild pain (1 to 3 on the Pain Visual Analog Scale); 27.8% had moderate pain (4 to 6 on the Pain Visual Analog Scale) and 57.4% reported severe pain (7 to 10). Severe pain, regarding no pain/mild pain/moderate pain, was more frequently reported by the patients who had anxious or depressive symptoms, and among those who had both types of symptoms concomitantly (p ≤ 0.05) (Table 3).

Table 3 - Click to enlarge

The simple linear regression analysis, using the pain score as a dependent variable, suggested that pain severity presents a difference of 0.25 for each increased or reduced anxiety point, and a difference of 0.27 for each depression point under the same conditions. The determination coefficient (r² = 0.19) was similar both for anxiety and depression (p ≤ 0.05). The impact of pain on the presence of anxious (Figure 1) and depressive symptoms (Figure 2) can be demonstrated by the increasing mean score on each subscale, which was found in different categories of pain severity. There was an increasing curve for both conditions (p ≤ 0.05).

Discussion

Patients with peripheral neuropathy can suffer both due to the functional disability and pain caused by the disease. Presence of anxiety and/or depression can have a negative impact on the natural history of this disease. In the present study, we estimated a frequency of 68.5% of anxiety symptoms and 51.9% of depression symptoms among patients with peripheral neuropathy. Such a finding is higher than the findings of studies involving clinical patients in general.^6,13,21,22 In comparison with studies that approached specific neuropathies, these values remain higher.^12,23 A study that assessed patients with diabetic neuropathy, using a study design similar to the one used in the present study, estimated very similar prevalence rates: 60.4% for anxiety and 50.6% for depression.¹⁰ It is important to consider that the sample investigated in the present study involved a low-income population. Most of the patients had a monthly family income of at most 3 minimum salaries, were not working, and some had significant comorbidities.

Almost half of the patients in the present study had both depressive and anxious symptoms. The association between anxiety and depression is well-known and common, mainly in the depressive patients who seek medical care. Knowing how to recognize an anxiety disorder in a depressive patient is extremely important for a more efficient therapeutic management.²⁴ The same caution regarding the diagnosis and treatment must be used for bipolar disorders, which can be associated with anxiety disorders in many cases. In these cases, a previous control with mood stabilizers before the use of antidepressants to treat the anxiety symptoms is recommended with the purpose of avoiding the manic state induced by antidepressants.²⁵

Family history of psychiatric disease is positively associated with the presence of anxious and depressive symptoms. Genetic factors that may explain the occurrence of repeated cases of anxiety and/or depression in families have been studied, as well as the presence of anxious symptoms associated with depressive symptoms in the same patient. Studies conducted with twins have suggested a possible genetic etiology for the association. It is important to bear in mind that specific environmental factors can favor the outburst of both symptomatologies in certain familial contexts.²⁶

The complaint of headache as a comorbidity is positively associated with the presence of depressive and anxious symptoms — a finding that is in agreement with other studies.^18,27 We suggest that the close relationship between headache (specifically the one caused by tension) and depression is originated by a dysfunction in the serotoninergic pathways, which is present in both conditions. It is also important to consider the anxiogenic factor typical of the fear of having a more severe disease (such as brain tumor, cerebrovascular disease), which was reported by many patients who had severe headache.²⁷

The relationship of anxiety and depression with neuropathic pain is already known, and the evaluation of the depressive state is more frequent in the literature.^10-12,28-30 In the present study, we found a positive correlation between pain severity and anxiety and depression symptoms, suggesting that the therapeutic intervention for anxiety and depression symptoms can be even more necessary in patients with more severe pain. Both anxiety and depression can play a central role as facilitators of painful afferences, participating in the pathogenesis of pain.²⁴ The study on the physiopathology of depression associated with pain detects a close relationship between mood regulation and perception of pain. An important role is attributed to the disorders of serotoninergic and noradrenergic neurotransmission, as well as to the neuropeptides such as opioids and substance P. Brain structures, like the amygdala, the anterior cingulate cortex and the prefrontal cortex, are of main significance in this process. The action of dual-action antidepressants in such disorders results from this pathogenesis.³¹

The presence of posttraumatic neuropathies is also positively associated with anxiety and depression symptoms. The sudden functional loss or disability of a limb due to trauma can be involved in this phenomenon, which is even worse when the patient is young and has to stop working. The presence of anxiety and depression or the pain severity were not significantly correlated with age, sex, marital status, educational level, religion, monthly family income, disease duration and hypertension, alcoholism or smoking in the present study.

Some limitations of this study must be mentioned. The cross-sectional design does not allow for the definition of causal relations between the presence of pain and anxiety and depression symptoms. The small size of the sample made it impossible to perform a multivariate analysis; therefore, we could not assess the behavior of the variables among the different peripheral neuropathies. A more detailed evaluation of the psychiatric state and other clinical variables (such as quality of life and quality of sleep) could not be carried out in the present study. The oral reading of the questionnaire by the researcher might have caused answer bias, since there is not spontaneity and authenticity, which are enhanced when the individuals answer the questionnaire by themselves.

In spite of the limitations, our results suggest that peripheral neuropathies are associated with a high prevalence of anxious and depressive symptoms and that neuropathic pain severity can have an influence on the intensity of the psychiatric symptoms. These patients must be approached in a special manner, focusing on specific clinical data such as headache, family history of psychiatric disease, presence or absence of trauma and pain severity. Psychotherapy and pharmacotherapy need to be more deeply studied and should be recommended for such patients. There are few studies about the use of psychotherapy in the treatment of anxiety and depression disorders in patients with chronic pain. General practitioners and specialists need to know how to recognize such disorders and define a specific treatment or refer the patient to a specialized health care institution. We hope that the data provided by further studies can help to define routines for the adequate evaluation and treatment of the patient with peripheral neuropathy, therefore reducing the risk of complications and increasing the therapeutic efficacy.

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*

Bolsa de Iniciação Científica da Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) - protocolo nº 0452/2006.

Publication Dates

• Publication in this collection
  24 Aug 2009
• Date of issue
  2009

History

• Accepted
  18 Dec 2008
• Received
  19 Sept 2008