Neuropathy Pain Strongest Predictor of Depression in Diabetes

Liam Davenport

August 02, 2016

Diabetes patients with peripheral neuropathic pain have a substantially increased risk of depression, say Italian researchers, who underscore the need for     depression to be considered when treating the diabetes complication.

Vincenza Spallone, MD, PhD, from the endocrinology unit, department of systems medicine, University of Rome Tor Vergata, Italy, and colleagues found that     painful diabetic polyneuropathy (DPN) was associated with a more than fourfold increased risk of depression, while painless DPN did not have a notable     mental-health impact.

In the paper, which was published online recently in    Diabetes & Vascular Disease Research, the authors say that the findings highlight the need for the "prompt" management of painful DPN, which     should take into account the risk of depression.

Moreover, Dr Spallone told Medscape Medical News that comorbidities can have an impact on the treatment of diabetes per se, as "there are a number     studies that document an impact on glycemic control, on patient adherence, and on the treatment on both pain and depression."

She added: "It is a complex network between diabetes, pain, depression, and also, for example, sleep disturbance…and it is necessary to target in an early     and appropriate way neuropathic pain and depression in addition to strategies for glycemic control and the control of cardiovascular risk factors."

Dr Spallone said that the first step is to diagnose any neuropathic pain and associated depression early using validated questionnaires. The second stage     is to treat the pain "according to the guidelines" and based on the patient's comorbidities.

As to the ideal choice of antidepressant for treating depression with neuropathic pain, she said that "we don't have conclusive evidence" for one drug over     another, with, for example, conflicting results from studies examining the use of duloxetine or pregabalin.

Despite this, Dr Spallone said that both the neuropathic pain and depressive symptoms need to be treated, "and for this we can, in some cases, use an     antidepressant that is also active on neuropathic pain." In other cases, an antidepressant can be added to analgesics.

In some patients, nonpharmacological strategies may be preferred, including psychosocial interventions. Psychiatric referral may also be required "in the     most severe cases and when there are alarm symptoms, like suicidal ideation and so on."

Female Gender and Painful Neuropathy Independent Predictors of Depression

To examine the impact of diabetes-related comorbidities on the prevalence of depression, the researchers prospectively studied 181 patients with type 1 or     2 diabetes with a mean age of 60.7 years, a mean diabetes duration of 14.5 years, and a mean HbA1c level of 7.2%. Of the patients, 106 were     male and 33 had type 1 diabetes.

The team used the Michigan Neuropathy Screening Instrument Questionnaire, the Michigan Diabetic Neuropathy Score, the Douleur Neuropathique en 4 (DN4)     Questions, the Charlson Comorbidity Index, and the Beck Depression Inventory (BDI)-II, alongside nerve conduction studies, to assess for the presence of     painless DPN, painful DPN, comorbidities, and depression.

They found that 46 (25.4%) patients met the criteria for painless DPN, while 25 (13.8%) patients had painful DPN and 110 (60.8%) had neither comorbidity.     Patients with DPN, whether painful or painless, were older, had a longer duration of diabetes, higher body mass index (BMI), were more likely to have     micro- and macrovascular disease, were less likely to be active and be high school graduates, and had higher Charlson Comorbidity Index scores than     patients without DPN.

Thirty-six (19.7%) of patients had mild, moderate, or severe depression. Depression was significantly more common in painless and painful DPN patients than     in those without DPN, at 26% and 44% vs 10%, respectively (P < .0001).

While patients with painful DPN were not significantly more likely to have depression than those with painless DPN, they had significantly higher BDI-II     scores than both those with painless DPN and those without DPN, at 14.8 vs 9.9 (P = .018) and 5.9 (< .0001), respectively. The     difference remained significant after researchers controlled for age, sex, BMI, and diabetes duration.

Multiple logistic regression analysis taking into account variables such as age, female sex, BMI, employment status, diabetes duration, HbA1c,     insulin treatment, systolic blood pressure, nephropathy, retinopathy, and Charlson Comorbidity Index showed that only female sex and painful DPN were     independent predictors of depression, at odds ratios of 5.86 (P = .005) and 4.56 (= .038), respectively.

Further analysis showed that BDI-II scores were significantly associated with female sex and Douleur Neuropathique en 4 Questions scores (P =     .005).

Noting that the Douleur Neuropathique en 4 Questions is one of the most commonly used screening tools for neuropathic pain, the team says: "When analyzing     which of the seven symptoms of DN4 was most likely to be associated with depression, the results were 'painful cold' and 'electric shocks,' whereas those     with the lowest odds for depression were 'tingling' and 'numbness.'

"This finding points to a prominent role of typical symptoms of neuropathic pain compared with other sensory- or function-loss symptoms."

Dr Spallone explained that there are two potential explanations for the association between painful DPN and depression.

She said: "The first thing is the obvious impact of chronic pain, in many cases very severe pain, on mood and quality of life.…The novelty of this study is     to show that neuropathic pain is the main predictor of depression, in a condition where depression can be also associated with diabetes in isolation."

She continued: "There is also the hypothesis that these two conditions might share some abnormalities, some neuroendocrine dysregulation processes, located     in the central nervous system; maybe in the hippocampus or thalamus."

Dr Spallone noted that, in recent years, neuroimaging studies have suggested that the central nervous system is involved in diabetic peripheral neuropathy     and "it's possible to hypothesize a crucial role for some mechanisms in the central nervous system in mounting and sustaining chronic neuropathic pain."

The authors report no relevant financial relationships.

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Diab Vasc Dis Res.     Published online June 22, 2016. Abstract

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