Decision-making in diabetes mellitus type 1.

Decreased treatment adherence in patients with diabetes mellitus type 1 (type 1 DM) may reflect impairments in decision-making and underlying associated deficits in working memory and executive functioning. Other factors, including comorbid major depression, may also interfere with decision-making. The authors sought to review the clinically relevant characteristics of decision-making in type 1 DM by surveying the literature on decision-making by patients with type 1 DM. Deficiencies in decision-making in patients with type 1 DM or their caregivers contribute to treatment nonadherence and poorer metabolic control. Animal models of type 1 DM reveal deficits in hippocampal-dependent memory tasks, which are reversible with insulin. Neurocognitive studies of patients with type 1 DM reveal lowered performance on ability to apply knowledge to solve problems in a new situation and acquired scholarly knowledge, psychomotor efficiency, cognitive flexibility, visual perception, speed of information-processing, and sustained attention. Other factors that might contribute to poor decision-making in patients with type 1 DM, include "hypoglycemia unawareness" and comorbid major depression (given its increased prevalence in type 1 DM). Future studies utilizing novel treatment strategies to help patients with type 1 DM make better decisions about their disease may improve their glycemic control and quality of life, while minimizing the impact of end-organ disease.

Stress, depression, and coronary artery disease: modeling comorbidity in female primates.

Depression and coronary heart disease (CHD) are leading contributors to disease burden in women. CHD and depression are comorbid; whether they have common etiology or depression causes CHD is unclear. The underlying pathology of CHD, coronary artery atherosclerosis (CAA), is present decades before CHD, and the temporal relationship between depression and CAA is unclear. The evidence of involvement of depression in early CAA in cynomolgus monkeys, an established model of CAA and depression, is summarized. Like people, monkeys may respond to the stress of low social status with depressive behavior accompanied by perturbations in hypothalamic-pituitary-adrenal (HPA), autonomic nervous system, lipid metabolism, ovarian, and neural serotonergic system function, all of which are associated with exacerbated CAA. The primate data are consistent with the hypothesis that depression may cause CAA, and also with the hypothesis that CAA and depression may be the result of social stress. More study is needed to discriminate between these two possibilities. The primate data paint a compelling picture of depression as a whole-body disease.

Sequential multiple-assignment randomized trial design of neurobehavioral treatment for patients with metastatic malignant melanoma undergoing high-dose interferon-alpha therapy.

BACKGROUND: Interferon-alpha therapy, which is used to treat metastatic malignant melanoma, can cause patients to develop two distinct neurobehavioral symptom complexes: a mood syndrome and a neurovegetative syndrome. Interferon-alpha effects on serotonin metabolism appear to contribute to the mood and anxiety syndrome, while the neurovegetative syndrome appears to be related to interferon-alpha effects on dopamine. PURPOSE: Our goal is to propose a design for utilizing a sequential, multiple assignment, randomized trial design for patients with malignant melanoma to test the relative efficacy of drugs that target serotonin versus dopamine metabolism during 4 weeks of intravenous, then 8 weeks of subcutaneous, interferon-alpha therapy. METHODS: Patients will be offered participation in a double-blinded, randomized, controlled, 14-week trial involving two treatment phases. During the first month of intravenous interferon-alpha therapy, we will test the hypotheses that escitalopram will be more effective in reducing depressed mood, anxiety, and irritability, whereas methylphenidate will be more effective in diminishing interferon-alpha-induced neurovegetative symptoms, such as fatigue and psychomotor slowing. During the next 8 weeks of subcutaneous interferon therapy, participants whose symptoms do not improve significantly will be randomized to the alternate agent alone versus escitalopram and methylphenidate together. RESULTS: We present a prototype for a single-center, sequential, multiple assignment, randomized trial, which seeks to determine the efficacy of sequenced and targeted treatment for the two distinct symptom complexes suffered by patients treated with interferon-alpha. LIMITATIONS: Because we cannot completely control for external factors, a relevant question is whether or not 'short-term' neuropsychiatric interventions can increase the number of interferon-alpha doses tolerated and improve long-term survival. CONCLUSIONS: This sequential, multiple assignment, randomized trial proposes a framework for developing optimal treatment strategies; however, additional studies are needed to determine the best strategy for treating or preventing neurobehavioral symptoms induced by the immunotherapy interferon-alpha.

Platelet thromboxane A2 secretion in patients with major depression responsive to electroconvulsive therapy.

OBJECTIVE: To determine a) whether clinical response to electroconvulsive therapy (ECT) is associated with decreased platelet activation in patients with major depressive disorder (MDD) and b) if any medical/demographic characteristics predict response to ECT or changes in platelet activation. Increased platelet activation may underlie the increased risk of coronary artery disease (CAD) in patients with MDD. METHODS: Before their first and sixth ECT treatments, study patients (n = 44) completed the Beck Depression Inventory (BDI) to assess the severity of depressive symptoms. Activity of the platelet thromboxane (TBX) A(2) pathway was assessed by measuring the morning spot urinary concentrations of 11-dehydroxy-thromboxane B(2) (11-D-TBX B(2)), a major metabolite of platelet-derived TBX A(2). RESULTS: Multivariate logistic regression analyses revealed that improvement on the BDI was significantly more likely in patients without a history of hypertension (p = .02) and in patients who were prescribed a greater number of "platelet-altering" medications (p = .03). During a course of ECT, a decrease in urinary 11-D-TBX B(2) was significantly more likely to occur in ECT nonresponders (p = .01) and younger patients (p = .02). CONCLUSIONS: Clinical response to ECT coadministered may not be associated with decreases in platelet-derived TBX. Future studies will confirm which somatic "antidepression" treatments offer optimal thrombovascular benefits for depressed patients with multiple risk factors for, or clinically evident, cerebral disease or CAD.

Ethnic heterogeneity in glucoregulatory function during treatment with atypical antipsychotics in patients with schizophrenia.

OBJECTIVE: Atypical antipsychotics induce weight gain and are linked to increased diabetes risk, but their relative impact on factors that elevate disease risk are unknown. METHODS: We performed a 6-month, randomized, double-blind study to evaluate the effects of risperidone and olanzapine in patients with schizophrenia. At baseline and weeks 6 and 24, we quantified: (1) total adiposity by DEXA, (2) visceral adiposity by abdominal CT, and (3) insulin sensitivity (SI) and (4) pancreatic function ("disposition index", DI) by intravenous glucose tolerance test. RESULTS: At baseline, groups (risperidone: n=28; olanzapine: n=31) were overweight or obese by body mass index (risperidone: 28.4+/-5.4, olanzapine: 30.6+/-7.0kg/m2). Both drugs induced weight gain (p<0.004). Total adiposity was increased by olanzapine at 6 weeks (p=0.0006) and by both treatments at 24 weeks (p<0.003). Visceral adiposity was increased by olanzapine and risperidone by 24 weeks (p<0.003). S(I) did not deteriorate appreciably, although a downward trend was observed with risperidone. Given known ethnic differences in adiposity and S(I), we performed secondary analysis in African American and Hispanic subjects. In this subset, olanzapine expanded both total and visceral adiposity (p<0.02); no increase was observed with risperidone. There were modest downward trends for SI with both treatments. By week 24, olanzapine-treated subjects exhibited diminished DI (p=0.033), indicating inadequate pancreatic compensation for insulin resistance. CONCLUSIONS: This is the first prospective study in psychiatric patients that quantified antipsychotic effects on the multiple metabolic processes that increase diabetes risk. Results indicate that ethnic minorities may have greater susceptibility to antipsychotic-induced glucoregulatory complications.

Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress.

OBJECTIVE: The authors sought to determine innate immune system activation following psychosocial stress in patients with major depression and increased early life stress. METHOD: Plasma interleukin (IL)-6, lymphocyte subsets, and DNA binding of nuclear factor (NF)-kB in peripheral blood mononuclear cells were compared in medically healthy male subjects with current major depression and increased early life stress (N=14) versus nondepressed male comparison subjects (N=14) before and after completion of the Trier Social Stress Test. RESULTS: Trier Social Stress Test-induced increases in IL-6 and NF-kappaB DNA-binding were greater in major depression patients with increased early life stress and independently correlated with depression severity, but not early life stress. Natural killer (NK) cell percentages also increased following stress. However, there were no differences between groups and no correlation between NK cell percentage and stress-induced NF-kappaB DNA-binding or IL-6. CONCLUSIONS: Male major depression patients with increased early life stress exhibit enhanced inflammatory responsiveness to psychosocial stress, providing preliminary indication of a link between major depression, early life stress and adverse health outcomes in diseases associated with inflammation.

A double-blind, multicenter, parallel-group study of paroxetine, desipramine, or placebo in breast cancer patients (stages I, II, III, and IV) with major depression.

OBJECTIVE: This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer, stages I-IV. METHOD: In a double-blind, placebo-controlled study, 35 female outpatients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were randomly assigned to treatment with paroxetine (N=13), desipramine (N=11), or placebo (N=11) for 6 weeks. Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score. RESULTS: Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group. An unusually high rate of response (defined as >or=50% improvement in the HAM-D score) in the placebo group was observed (55% [N=6]); adverse events precipitated patient discontinuation in the active treatment groups (9% [N=1] for desipramine, 15% [N=2] for paroxetine) similar to that in the placebo-treated patients (18% [N=2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic) was also similar between groups. CONCLUSION: The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment. Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance.

Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) Platelet Substudy.

BACKGROUND: Depression after acute coronary syndromes (ACSs) has been identified as an independent risk factor for subsequent cardiac death. Enhanced platelet activation has been hypothesized to represent 1 of the mechanisms underlying this association. Selective serotonin reuptake inhibitors (SSRIs) are known to inhibit platelet activity. Whether treatment of depressed post-ACS patients with SSRIs alters platelet function was not known. Accordingly, we serially assessed the release of established platelet/endothelial biomarkers in patients treated with sertraline vs placebo in the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART). METHODS AND RESULTS: Plasma samples (baseline, week 6, and week 16) were collected from patients randomized to sertraline (n=28) or placebo (n=36). Anticoagulants, aspirin, and ADP-receptor inhibitors were permitted in this study. Platelet factor 4, beta-thromboglobulin (betaTG), platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane B2, 6-ketoprostaglandin F1a, vascular cell adhesion molecule-1, and E-selectin were measured by ELISA. Treatment with sertraline was associated with substantially less release of platelet/endothelial biomarkers than was treatment with placebo. These differences attained statistical significance for betaTG (P=0.03) at weeks 6 and 16 and for P-selectin (P=0.04) at week 16. Repeated-measures ANOVA revealed a significant advantage for sertraline vs placebo for diminishing E-selectin and betaTG concentrations across the entire treatment period. CONCLUSIONS: Treatment with sertraline in depressed post-ACS patients is associated with reductions in platelet/endothelial activation despite coadministration of widespread antiplatelet regimens including aspirin and clopidogrel. The antiplatelet and endothelium-protective properties of SSRIs might represent an attractive additional advantage in patients with depression and comorbid coronary artery and/or cerebrovascular disease.

Depression, alterations in platelet function, and ischemic heart disease.

Platelets, the smallest corpuscular component of human blood, are central to various crucial biologic pathways in the human body. Diminished platelet function is thought to contribute to the increased risk of ischemic heart disease in patients with major depressive disorder, and to the increased morbidity and diminished survival of depressed patients after an index myocardial infarction. We reviewed both recent studies that evaluated platelet function in various patient groups and recent information regarding the potential beneficial effects of selective serotonin reuptake inhibitors on platelet reactivity.

Relationship of depression to diabetes types 1 and 2: epidemiology, biology, and treatment.

This article reviews the rapidly accumulating literature on the relationship between mood disorders and diabetes mellitus. Recent studies have demonstrated that depression and its associated symptoms constitute a major risk factor in the development of type 2 diabetes and may accelerate the onset of diabetes complications. Since the mid-1980s, multiple longitudinal and cross-sectional studies have scrutinized the association of diabetes with depressive symptoms and major depression. Utilizing the search terms depressive disorders, psychiatry, diabetes, and pathophysiology in MEDLINE searches (1966-2003), this article reviews studies investigating pathophysiological alterations related to glucose intolerance and diabetes in depressed patients. The few randomized, controlled studies of treatment of depression in patients with diabetes are also described. Short-term treatment of depression in patients with diabetes improves their dysphoria and other signs and symptoms of depression. Future research will confirm whether response to psychotherapy and/or psychopharmacologic treatment improves glucose control, encourages compliance with diabetes treatment, and perhaps even increases longevity.

Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment.

BACKGROUND: Tryptophan (TRP) degradation into kynurenine (KYN) by the enzyme, indoleamine-2,3-dioxygenase, during immune activation may contribute to development of depressive symptoms during interferon (IFN)-alpha therapy. METHODS: Twenty-six patients with malignant melanoma were randomly assigned in double-blind fashion to receive either placebo or paroxetine, beginning 2 weeks before IFN-alpha treatment and continuing for the first 12 weeks of IFN-alpha therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-alpha treatment, measurements of TRP, KYN, and neopterin (a marker of immune activation), were obtained, along with structured assessments of depression, anxiety, and neurotoxicity. RESULTS: Regardless of antidepressant treatment status, all patients exhibited significant increases in KYN, neopterin, and the KYN/TRP ratio during IFN-alpha therapy. Among antidepressant-free patients, patients who developed major depression exhibited significantly greater increases in KYN and neopterin concentrations and more prolonged decreases in TRP concentrations than did nondepressed, antidepressant-free patients. Moreover, in antidepressant-free patients, decreases in TRP correlated with depressive, anxious, and cognitive symptoms, but not neurovegetative or somatic symptoms. No correlations were found between clinical and biological variables in antidepressant-treated patients. CONCLUSIONS: The results suggest that reduced TRP availability plays a role in IFN-alpha-induced depressive symptoms, and paroxetine, although not altering the KYN or neopterin response to IFN-alpha, attenuates the behavioral consequences of IFN-alpha-mediated TRP depletion.

Association of exaggerated HPA axis response to the initial injection of interferon-alpha with development of depression during interferon-alpha therapy.

OBJECTIVE: The authors assessed the relationship between the hypothalamic-pituitary-adrenal (HPA) axis response to interferon-alpha (IFN-alpha) and the development of major depression during IFN-alpha treatment. METHOD: Adrenocorticotropic hormone (ACTH), cortisol, and interleukin-6 (IL-6) plasma concentrations were measured in 14 patients with malignant melanoma at regular intervals during the first 12 weeks of IFN-alpha therapy, both immediately before and 1, 2, and 3 hours after IFN-alpha administration. Symptom criteria for major depression were also evaluated at each visit. RESULTS: ACTH and cortisol responses but not IL-6 responses to the initial administration of IFN-alpha were significantly higher in the seven patients who subsequently developed symptom criteria for major depression than in those who did not. No differences in hormonal or cytokine responses were found between these two groups during chronic IFN-alpha administration. CONCLUSIONS: The HPA axis response to the acute administration of IFN-alpha reveals a vulnerability to IFN-alpha-induced depression, possibly due to sensitization of corticotropin-releasing factor pathways.

Plasma homocysteine and immune activation in patients with malignant melanoma undergoing treatment with IFN-alpha.

Immune activation and cell proliferation may contribute to the development of increased homocysteine concentrations in patients with malignant diseases. In this study, we investigated the effect of interferon-alpha (IFN-alpha) on plasma homocysteine concentrations in patients being treated for malignant melanoma. In parallel, neopterin formation and tryptophan degradation were monitored to assess the capacity of IFN-alpha to activate macrophages. Plasma concentrations of homocysteine, folate, and vitamin B(12) were determined in 15 patients with malignant melanoma during 12 weeks of high-dose IFN-alpha therapy. Concurrently, concentrations of neopterin, tryptophan, and kynurenine were measured, and the kynurenine/tryptophan ratio (kyn/trp) was calculated. Homocysteine and folate concentrations during treatment with IFN-alpha did not differ from baseline. In contrast, significant increases in neopterin formation and tryptophan degradation were apparent during IFN-alpha therapy. Plasma concentrations of vitamin B(12) and cysteine also increased. These results indicate that IFN-alpha directly activates macrophages to release neopterin and to degrade tryptophan, but obviously treatment with INF-alpha did not affect homocysteine metabolism.

Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions.

We have previously shown that the risk of major depression in patients with malignant melanoma undergoing interferon-alpha (IFN-alpha) therapy can be reduced by pretreatment with the antidepressant, paroxetine. Using dimensional analyses, the present study assessed the expression and treatment responsiveness of specific clusters of neuropsychiatric symptoms over the first three months of IFN-alpha therapy. Forty patients with malignant melanoma eligible for IFN-alpha treatment were randomly assigned to receive either paroxetine or placebo in a double-blind design. Neuropsychiatric assessments were conducted at regular intervals during the first twelve weeks of IFN-alpha therapy and included the 21-item Hamilton Depression Rating Scale, the 14-item Hamilton Anxiety Rating Scale and the Neurotoxicity Rating Scale. Neurovegetative and somatic symptoms including anorexia, fatigue and pain appeared within two weeks of IFN-alpha therapy in a large proportion of patients. In contrast, symptoms of depressed mood, anxiety and cognitive dysfunction appeared later during IFN-alpha treatment and more specifically in patients who met DSM-IV criteria for major depression. Symptoms of depression, anxiety, cognitive dysfunction and pain were more responsive, whereas symptoms of fatigue and anorexia were less responsive, to paroxetine treatment. These data demonstrate distinct phenomenology and treatment responsiveness of symptom dimensions induced by IFN-alpha, and suggest that different mechanisms mediate the various behavioral manifestations of cytokine-induced "sickness behavior."

Depression, deficits in functional capacity, and impaired glycemic control in urban African Americans with type 2 diabetes.

BACKGROUND: Effective depression treatment does not reliably reduce glycosylated hemoglobin (HbA1c) in depressed patients with type 2 diabetes, possibly in part due to deficits in functional capacity, i.e. performance of certain everyday living skills, essential for effective diabetes self-management. We sought to determine: a) the magnitude of deficits in functional capacity among urban, African American (AA) patients with type 2 diabetes, and b) whether these deficits were associated with poorer glycemic control. METHODS: At their initial visit to an inner-city diabetes clinic, 172 AA patients with type 2 diabetes were assessed with a variety of instruments, including the Mini International Neuropsychiatric Interview (MINI) and the UCSD Performance Skills Assessment-Brief (UPSA-B). They then entered a comprehensive diabetes management intervention, whose success was indexed by HbA1c levels at up to four reassessments over a one-year period. A mixed-effects model repeated-measures method was used to predict HbA1c. RESULTS: The prevalence of depression was 19%; the mean UPSA-B score was 81 ± 17. After multivariate adjustment, increased HbA1c levels over time were predicted by the presence of major depression (B = .911, p = .002) and decreasing (worse) scores on the UPSA-B (B = -.016, p = .027), respectively. Further adjustment for increasing the dosage of oral or insulin during the treatment eliminated the association between the UPSA score and HbA1c level (B = -.010, p = .115). CONCLUSIONS: Depression, as well as deficits in functional capacity, predicted reduced effectiveness of a diabetes self-management intervention. Future studies will determine whether interventions targeted at both improve glycemic control.

Diagnosis and treatment of depression in patients with congestive heart failure: a review of the literature.

CONTEXT: Major depressive disorder (MDD) can be challenging to diagnose in patients with congestive heart failure, who often suffer from fatigue, insomnia, weight changes, and other neurovegetative symptoms that overlap with those of depression. Pathophysiologic mechanisms (eg, inflammation, autonomic nervous system dysfunction, cardiac arrhythmias, and altered platelet function) connect depression and congestive heart failure. OBJECTIVE: We sought to review the prevalence, diagnosis, neurobiology, and treatment of depression associated with congestive heart failure. DATA SOURCES: A search of all English-language articles between January 2003 and January 2013 was conducted using the search terms congestive heart failure and depression. STUDY SELECTION: We found 1,498 article abstracts and 19 articles (meta-analyses, systematic reviews, and original research articles) that were selected for inclusion, as they contained information about our focus on diagnosis, treatment, and pathophysiology of depression associated with congestive heart failure. The search was augmented with manual review of reference lists of articles from the initial search. Articles selected for review were determined by author consensus. DATA EXTRACTION: The prevalence, diagnosis, neurobiology, and treatment of depression associated with congestive heart failure were reviewed. Particular attention was paid to the safety, efficacy, and tolerability of antidepressant medications commonly used to treat depression and how their side-effect profiles impact the pathophysiology of congestive heart failure. Drug-drug interactions between antidepressant medications and medications used to treat congestive heart failure were examined. RESULTS: MDD is highly prevalent in patients with congestive heart failure. Moreover, the prevalence and severity of depression correlate with the degree of cardiac dysfunction and development of congestive heart failure. Depression increases the risk of congestive heart failure, particularly in those patients with coronary artery disease , and is associated with a poorer quality of life, increased use of health care resources, more frequent adverse clinical events and hospitalizations, and twice the risk of mortality. CONCLUSIONS: At present, limited empirical data exist with regard to treatment of depression in the increasingly large population of patients with congestive heart failure. Evidence reveals that both psychotherapeutic treatment (eg, cognitive-behavioral therapy) and pharmacologic treatment (eg, use of the selective serotonin reuptake inhibitor sertraline) are safe and effective in reducing depression severity in patients with cardiovascular disease. Collaborative care programs featuring interventions that work to improve adherence to medical and psychiatric treatments improve both cardiovascular disease and depression outcomes. Depression rating scales such as the 9-item Patient Health Questionnaire should be used to monitor therapeutic efficacy.

Dry eye syndrome, posttraumatic stress disorder, and depression in an older male veteran population.

PURPOSE: To evaluate whether veterans with posttraumatic stress disorder (PTSD) or depression have differences in dry eye symptoms and signs compared to a population without these conditions. METHODS: Male patients aged ≥50 years with normal eyelid, conjunctival, and corneal anatomy were recruited from the Miami Veterans Affairs Eye Clinic (N = 248). We compared dry eye symptoms (determined by the Dry Eye Questionnaire 5 [DEQ5] score) to tear film indicators obtained by clinical examination (i.e., tear osmolarity, corneal staining, tear breakup time, Schirmer's, meibomian gland quality, orifice plugging, lid vascularity) between patients with PTSD or depression and those without these conditions. Student's t-tests, χ(2) analyses, and linear and logistic regressions were used to assess differences between the groups. RESULTS: DEQ5 scores were higher in the PTSD (mean = 13.4; standard error [SE] = 1.1; n = 22) and depression (mean = 12.0; SE = 0.8; n = 40) groups compared to the group without these conditions (mean = 9.8; SE = 0.4; n = 186; P < 0.01 and P = 0.02, respectively). More patients in the PTSD and depression groups had severe dry eye symptoms, defined as a DEQ5 score ≥ 12 (77% and 63% vs. 41%; P < 0.01 and P = 0.02, respectively). No significant differences in tear film indicators were found among the three groups. Multivariable logistic regression indicated that a PTSD diagnosis (odds ratio [OR] = 4.08; 95% confidence interval [CI] = 1.10-15.14) and use of selective serotonin reuptake inhibitors (OR = 2.66; 95% CI = 1.01-7.00) were significantly associated with severe symptoms. CONCLUSIONS: Patients with PTSD have ocular surface symptoms that are not solely explained by tear indicators. Identifying underlying conditions associated with ocular discomfort is essential to better understand the mechanisms behind ocular pain in dry eye syndrome.

Neurobehavioral effects of interferon-α in patients with hepatitis-C: symptom dimensions and responsiveness to paroxetine.

In patients at high risk for recurrence of malignant melanoma, interferon-α (IFN-α), a stimulator of innate immunity, appears to induce distinct neurobehavioral symptom dimensions: a mood and anxiety syndrome, and a neurovegetative syndrome, of which the former is responsive to prophylactic administration of paroxetine. We sought to determine whether symptom dimensions (and treatment responsiveness) arise in patients with hepatitis C administered IFN-α and ribavirin. In a randomized, double-blind, 6-month study, 61 patients with hepatitis C eligible for therapy with IFN-α and ribavirin received the antidepressant paroxetine (n=28) or a placebo (n=33). Study medication began 2 weeks before IFN-α/ribavirin therapy. Neuropsychiatric assessments included the 10-item Montgomery-Asberg Depression Rating Scale (MADRS). The items of the MADRS were grouped into depression, anxiety, cognitive dysfunction, and neurovegetative symptom dimensions, and analyzed using a mixed model. By 2 weeks of IFN-α/ribavirin therapy, all four dimensions increased, with the symptom dimensions of anxiety and cognitive dysfunction fluctuating and worsening, respectively, in both groups over time. The depression symptom dimension was significantly lower in the paroxetine treatment group (p=0.04); severity of the neurovegetative symptom dimension was similar in both groups. Similar to patients with malignant melanoma receiving high-dose IFN-α, the depression symptom dimension is more responsive to paroxetine treatment in individuals undergoing concomitant IFN-α/ribavirin therapy. However, the anxiety, cognitive dysfunction, and neurovegetative symptom dimensions appear less responsive to prophylactic paroxetine administration. Different neurobiologic pathways may contribute to the responsiveness of IFN-α-induced symptom dimensions to antidepressant treatment, requiring relevant psychopharmacologic strategies.