Predictors of nonresponse to cognitive behavioural therapy or venlafaxine using glucose metabolism in major depressive disorder.

BACKGROUND: Longitudinal neuroimaging investigations of antidepressant treatment offer the opportunity to identify potential baseline biomarkers associated with poor outcome. METHODS: To explore the neural correlates of nonresponse to cognitive behavioural therapy (CBT) or venlafaxine (VEN), we compared pretreatment (18)F-fluoro-2-deoxy-d-glucose positron emission tomography scans of participants with major depressive disorder responding to either 16 weeks of CBT (n = 7) or VEN treatment (n = 9) with treatment nonresponders (n = 8). RESULTS: Nonresponders to CBT or VEN, in contrast to responders, exhibited pretreatment hypermetabolism at the interface of the pregenual and subgenual cingulate cortices. LIMITATIONS: Limitations of our study include the small sample sizes and the absence of both arterial sampling to determine absolute glucose metabolism and high-resolution structural magnetic resonance imaging coregistration for region-of-interest analyses. CONCLUSION: Our current findings are consistent with those reported in previous studies of relative hyperactivity in the ventral anterior cingulate cortex in treatment-resistant populations.

Insulin, insulin-like growth factors and incretins: neural homeostatic regulators and treatment opportunities.

Mood disorders may be conceptualized as progressive neurodegenerative disorders associated with cognitive decline. Novel treatments capable of preserving and/or enhancing cognitive function represent an area of priority for research in the future. Insulin, insulin-like growth factor (IGF)-1 and incretins may play a critical role in both physiological and pathophysiological processes of the CNS. An emerging paradigm regarding the pathophysiology of mood disorders posits that alterations in biological networks that mediate stress compromise optimal neuronal and glial function. A growing body of evidence indicates that central administration of insulin may enhance cognitive function in both healthy and cognitively impaired individuals. The neuroactive peptides, insulin, IGF-1 and incretins, or agents that facilitate their central effects (e.g. insulin-sensitizing agents), may constitute novel and possibly disease-modifying neurocognitive treatments.

Bipolar disorder and suicide: research synthesis and clinical translation.

Attempted suicide and suicide are prevalent in individuals with bipolar disorder (BD). Extant evidence indicates that history of suicide attempts, percentage of time spent in a depressed state, and hostility are factors associated with suicide attempts and completed suicide. Childhood adversity (eg, sexual and physical abuse) is emerging as a risk factor for suicide attempts in adults with BD. The pertinacity of medical comorbidity (eg, obesity, metabolic syndrome) in the bipolar population is further underscored by its preliminary association with suicidality. Biomarkers such as cerebrospinal fluid monoamine metabolite levels may be predictive of suicide attempts and lethality in BD. Compelling evidence supports an antisuicide effect of long-term lithium prophylaxis; lithium's salutary effect is mediated primarily by reduced lethality of suicidal acts. Conventional unimodal antidepressants may engender or exacerbate suicidality in susceptible individuals with BD. A nascent database suggests that adjunctive psychosocial interventions may further reduce suicide risk in bipolar individuals.

The hepatic safety profile of duloxetine: a review.

BACKGROUND: Hepatotoxicity related to the use of duloxetine resulted in rewording of the US product insert. OBJECTIVE: To characterize the hepatic safety profile of duloxetine. METHODS: We conducted a PubMed search of all English-language articles published between January 1990 and December 2007 and contacted the manufacturer (Eli Lilly, Inc.). RESULTS: Elevations of alanine aminotransferase to three times the upper limit of normal occurs in 0.9-1.7% of duloxetine-treated patients versus 0.0-0.3% of placebo-treated patients. Hepatocellular, cholestatic and mixed hepatocellular-cholestatic forms of hepatic injury have been described. CONCLUSION: Duloxetine does not appear to pose a greater hazard for hepatic toxicity when compared to other conventional antidepressants. Systematic monitoring of liver aminotransferases does not appear to be warranted with routine duloxetine use.

Medical and substance-related comorbidity in bipolar disorder: translational research and treatment opportunities.

It is well established that individuals with bipolar disorder are differentially affected by substance-related as well as medical disorders (ie, cardiometabolic disorders, respiratory disorders, neurological disorders, and infectious diseases). Emerging evidence indicates that some comorbid conditions (eg, diabetes mellitus) in bipolar individuals may be subserved by overlapping neurobiological networks. Disturbances in glucocorticoid/insulin signaling and immunoinflammatory effector systems are points of pathophysiological commonality between bipolar disorder and "stress-sensitive" medical disorders. Subphenotyping bipolar disorder as a function of comorbidity and temporality of onset may provide an opportunity for refining disease pathophysiological models and developing innovative disease-modifying therapies.

The relationship between childhood abuse and suicidality in adult bipolar disorder.

This study evaluates the effect of childhood sexual and physical abuse on suicidality in adults with bipolar disorder. We conducted a retrospective chart review of adult outpatients (N= 381) with DSM-IV-TR-defined bipolar disorder seeking evaluation and treatment at an academic specialty research program (i.e., Mood Disorders Pharmacology Unit, University Health Network, University of Toronto) between October 2002 and November 2005. Eighteen percent (n = 68) of adult patients with bipolar disorder had a recorded history of childhood abuse (p = 0.009). Sixty-three percent (n = 43) of bipolar patients with a history of childhood abuse reported lifetime suicidality (chi2 = 6.885, df= 1, p = 0.009). Logistic regression analysis indicated that Childhood abuse was a significant predictor of lifetime suicidality in adult bipolar patients (OR = 2.05, CI = 1.19-3.510). Childhood abuse is associated with suicidal ideation and suicide attempts in adults with bipolar disorder. Anamnestic inquiry regarding childhood maltreatment is salient to risk assessment, illness management planning, preventative strategies, and treatment interventions in bipolar disorder.

Differences in brain glucose metabolism between responders to CBT and venlafaxine in a 16-week randomized controlled trial.

OBJECTIVE: Neuroimaging investigations reveal changes in glucose metabolism (fluorine-18-fluorodeoxyglucose positron emission tomography [PET]) associated with response to disparate antidepressant treatment modalities, including cognitive behavior therapy (CBT), antidepressant pharmacotherapies, and deep brain stimulation. Using a nonrandomized design, the authors previously compared changes following CBT or paroxetine in depressed patients. In this study, the authors report changes in fluorine-18-fluorodeoxyglucose PET in responders to CBT or venlafaxine during a randomized controlled trial. METHODS: Subjects meeting DSM-IV-TR criteria for a major depressive episode and a diagnosis of a major depressive disorder received a fluorine-18-fluorodeoxyglucose PET scan before randomization and after 16 weeks of antidepressant treatment with either CBT (N=12) or venlafaxine (N=12). Modality-specific and modality-independent regional brain metabolic changes associated with response status were analyzed. RESULTS: Response rates were comparable between the CBT (7/12) and venlafaxine (9/12) groups. Response to either treatment modality was associated with decreased glucose metabolism bilaterally in the orbitofrontal cortex and left medial prefrontal cortex, along with increased metabolism in the right occipital-temporal cortex. Changes in metabolism in the anterior and posterior parts of the subgenual cingulate cortex and the caudate differentiated CBT and venlafaxine responders. CONCLUSIONS: Responders to either treatment modality demonstrated reduced metabolism in several prefrontal regions. Consistent with earlier reports, response to CBT was associated with a reciprocal modulation of cortical-limbic connectivity, while venlafaxine engaged additional cortical and striatal regions previously unreported in neuroimaging investigations.

Quetiapine in the treatment of acute bipolar mania: efficacy across a broad range of symptoms.

OBJECTIVE: An ideal antimanic therapy is well tolerated and offers full multidimensional symptom relief. The efficacy of quetiapine in the treatment of acute bipolar mania has previously been established. This post-hoc analysis aims to extend our understanding of quetiapine's antimanic efficacy by evaluating its therapeutic effect across the full spectrum of manic symptoms. METHODS: Patient-level data from four similar, randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of quetiapine in bipolar disorder patients with DSM-IV acute mania were combined. Two trials investigated quetiapine as monotherapy (twice daily) and two trials assessed the combination of quetiapine with either lithium (Li) or divalproex (DVP). Changes in scores on the total Young Mania Rating Scale (YMRS), and on each of the 11 items comprising the YMRS, were the primary measures of interest in this analysis. Changes in the Supplemental Aggression and Agitation subscales of the Positive and Negative Syndrome Scale (PANSS) were secondary measures analyzed. RESULTS: Quetiapine as monotherapy, or in combination with Li or DVP, was a highly effective treatment for acute mania, as shown by overall change scores in the total YMRS. Patients treated with quetiapine monotherapy exhibited a significantly greater reduction (versus placebo) in YMRS total scores at Day 4 (-3.5 versus -2.2; p=0.021), with an increasing between-group difference reported throughout the duration of the trials at Day 21 (-13.6 versus -7.8; p<0.001) and at study endpoint on Day 84 (-19.0 versus -9.6; p<0.001). Quetiapine was also superior in efficacy to placebo on all categorical (i.e., response and remission rates) and secondary outcome parameters. On each of the 11 YMRS items, including the double-weighted core manic items, quetiapine was significantly superior to placebo (p<0.05). Effect sizes at Day 84 ranged from 0.37 to 0.61. Quetiapine in combination with Li/DVP offered a significant benefit over Li/DVP monotherapy, starting at Day 7 (p<0.05) and continuing to the primary study endpoint on Day 21 (p=0.01). Four of 11 YMRS items improved significantly more on quetiapine combination therapy than on Li/DVP monotherapy. The efficacy of quetiapine in these trials appeared independent of baseline disease severity, the presence of psychosis, and treatment-emergent sedation/somnolence. Quetiapine monotherapy produced significantly greater improvement than placebo on the PANSS Activation and the PANSS Supplemental Aggression Risk subscale scores. Similar findings were obtained with quetiapine combined with Li or DVP. CONCLUSIONS: Patients with bipolar disorder may report severe and complex manic symptoms. The results herein indicate that quetiapine is efficacious across the multiple dimensions of mania, including medically serious symptoms commonly encountered in practice.

Problem gambling in bipolar disorder: results from the Canadian Community Health Survey.

OBJECTIVE: This investigation was undertaken to explore the prevalence and associated features of problem gambling amongst individuals with bipolar I disorder. METHODS: The data for this analysis were procured from the Canadian Community Health Survey: Mental Health and Well-being (CCHS 1.2) conducted by Statistics Canada. Individuals screening positive for a lifetime (World Mental Health- Composite International Diagnostic Interview) WMH-CIDI-defined manic episode (i.e. bipolar I disorder) or depressive episode (i.e. major depressive disorder) and current (i.e. past 12-month) problem gambling were compared to the general population without these disorders. Past year problem gambling was operationalized with the Canadian Problem Gambling Index (CPGI). RESULTS: The sample consisted of 36,984 individuals (> or = 15 years old); the weighted prevalence of problem gambling was significantly higher (6.3%) amongst the population with bipolar disorder as compared to the general population (2.0%, p<0.001) and those with major depressive disorder (2.5%, p<0.01). Compared to those without bipolar disorder, the odds of problem gambling for bipolar individuals were over twice as high (OR=2.3; 95% CI 1.4-3.7), even when controlling for potential confounders. Males also had higher odds of problem gambling (OR=1.8; 95% CI 1.4-2.3), as did individuals without post-secondary education (OR=1.4; 95% CI 1.1-1.8). Persons who were married/cohabiting had lowered odds of problem gambling, compared with those who were unmarried (OR=0.6; 95% CI 0.5-0.8). Comorbid alcohol dependence (OR=3.4; 95% CI 2.3-5.0) and illicit drug dependence (OR=2.6; 95% CI 1.1-6.2) each conferred an increased risk for problem gambling. Physical activity level (moderate to active) was associated with a decreased risk for problem gambling (OR=0.8; 95% CI 0.6-0.9). CONCLUSIONS: Individuals with bipolar I disorder are differentially affected by problem gambling. Opportunistic screening for problem gambling is warranted, particularly in persons with comorbid alcohol or substance dependence.

Neuroimaging approaches in mood disorders: technique and clinical implications.

BACKGROUND: Clinical research in mood disorders increasingly involves advanced neuroimaging techniques. The encompassing aim of this review is to provide the mental health care practitioner with a pragmatic understanding of neuroimaging approaches and their possible clinical application. METHODS: We conducted a literature search of English-language articles using the search terms, major depressive disorder and bipolar disorder, cross-referenced with available neuroimaging technologies and analytical approaches, The search was supplemented with a manual review of relevant references. We organize the review by reviewing frequently asked questions on the topic of neuroimaging by mental health-care providers. RESULTS: Magnetic resonance (MR) approaches provide information on white and gray matter pathology (segmentation), cellular metabolism (MRS), oxygen consumption (BOLD), and neurocircuitry (DTI). Radionuclide-based neuroimaging methodologies provide quantitative estimates of brain glucose metabolism, regional blood flow, and ligand-receptor/transporter binding. Clinical implications of neuroimaging methodologies are reviewed. CONCLUSIONS: Advances in neuroimaging technology have refined models of disease pathophysiology in mood disorders and the mechanistic basis of antidepressant action. Multivariate analysis of functional and structural neuroimaging data, longitudinal analysis in the depressed and remitted states, and inclusion of representative patients with medical and psychiatric comorbidities will enhance the clinical translation of future research findings.

Comparing features of bipolar disorder to major depressive disorder in a tertiary mood disorders clinic.

BACKGROUND: We sought to describe features that distinguish individuals with bipolar disorder from major depressive disorder. METHODS: A retrospective chart review of adult outpatients (N = 1000) seeking evaluation and treatment was conducted at the Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto between October 2002 and November 2005 was conducted. Sociodemographic parameters, illness-characteristics and therapeutic interventions were evaluated and compared. RESULTS: The MDPU referring diagnosis were major depressive disorder (52%), bipolar disorder (29%), and unspecified (19%). Of all individuals with a non-bipolar entry diagnosis (n = 699), 23% (n = 159) were subsequently diagnosed with bipolar disorder (p < 0.001); the majority of whom (n = 117, 74%) received a non-bipolar I disorder diagnosis [e.g. bipolar II disorder (n = 71); bipolar NOS disorder (n = 46) (p < 0.001)]. Higher rates of unemployment/disability, previous depressive episodes, psychiatric hospitalization, comorbid hypertension, and lifetime substance use disorders, as well as an earlier age of illness-onset were more frequently endorsed by individuals with a diagnosis of bipolar disorder. Fifteen percent of individuals who were newly-diagnosed with bipolar disorder reported a history of antidepressant-associated mania. CONCLUSIONS: The majority of individuals with a newly-diagnosed bipolar disorder at this tertiary center have a non-bipolar I disorder (i.e., bipolar spectrum). Several indices of illness severity differentiate individuals with bipolar disorder from major depressive disorder.

Should Depressive Syndromes Be Reclassified as "Metabolic Syndrome Type II"?

BACKGROUND: A nascent explanatory theory regarding the pathophysiology of major depressive disorder posits that alterations in metabolic networks (e.g., insulin and glucocorticoid signaling) mediate allostasis. METHOD: We conducted a PubMed search of all English-language articles published between January 1966 and September 2006. The search terms were: neurobiology, cognition, neuroprotection, inflammation, oxidative stress, glucocorticoids, metabolic syndrome, diabetes mellitus, insulin, and antidiabetic agents, cross-referenced with the individual names of DSM-III-R/IV/-TR-defined mood disorders. The search was augmented with a manual review of article reference lists; articles selected for review were determined by author consensus. RESULTS: Disturbances in metabolic networks: e.g., insulin-glucose homeostasis, immuno-inflammatory processes, adipokine synthesis and secretion, intra-cellular signaling cascades, and mitochondrial respiration are implicated in the pathophysiology, brain volumetric changes, symptomatic expression (e.g., neurocognitive decline), and medical comorbidity in depressive disorders. The central nervous system, like the pancreas, is a critical modulator of the metabolic milieu and is endangered by chronic abnormalities in metabolic processes. We propose the notion of "metabolic syndrome type II" as a neuropsychiatric syndrome in which alterations in metabolic networks are a defining pathophysiological component. CONCLUSION: A comprehensive management approach for depressive disorders should routinely include opportunistic screening and primary prevention strategies targeting metabolically mediated comorbidity (e.g., cardiovascular disease). Innovative treatments for mood disorders, which primarily target aberrant metabolic networks, may constitute potentially novel, and disease-modifying, treatment avenues.

Relationship between regional brain metabolism, illness severity and age in depressed subjects.

We sought to examine the effects of age, depression chronicity, and treatment responsiveness on glucose metabolism in a large well-characterized sample of depressed men and a psychiatrically unaffected control group. The subjects were unmedicated, symptomatic, right-handed males (n=66) who met DSM-IV criteria for a major depressive episode in the context of a major depressive disorder (MDD, n=66) and never depressed, right-handed, healthy control subjects (HC, n=24). Subjects in the MDD group were subsequently classified as responders, or non-responders to a six-week trial of paroxetine monotherapy (20-60 mg). Statistical parametric mapping (SPM) was used to analyze the relationship between age and cerebral glucose metabolism (18-fluorodeoxyglucose positron emission tomography) and the modulation by treatment responsivity and a history of prior depressive episodes. Metabolic activity in the rostral and dorsal anterior cingulate cortex showed a significant negative correlation with age in MDD, but not in HC. Non-response to treatment and previous depressive episodes were associated with a higher degree of age-dependent hypometabolism in the rostral and anterior cingulate cortex. The age-dependent changes documented herein may influence the distinct clinical presentation and treatment response described in older-age depression.

Thiazolidinediones: from antioxidant to neurotherapeutic?

A prevailing paradigm regarding the pathophysiology of mood disorders posits that these syndromes are possibly neurodegenerative. Alterations in interacting biological networks which subserve metabolism, inflammation, immune function, and stress response are hypothesized to mediate the neurotoxicity and allostasis associated with mood disorders. Preclinical evidence indicates that thiazolidinediones (TZDs) exert neurotherapeutic (e.g., neurotrophic) effects. Preliminary clinical evidence also suggests that TZDs may be salutary for mental disorders in which neurocognitive deficits are a central feature. We propose that TZDs constitute a potentially novel disease-modifying treatment avenue for mood disorders.

Residual anxiety symptoms in depressed primary care patients.

BACKGROUND: The goal of this study was to characterize the burden of anxiety among residual depressive symptoms in naturalistic primary care settings. METHODS: A post-hoc analysis of a database comprised of naturalistically treated depressed patients across Canada was done. This bilingual (English and French), multi-center, randomized validation study was conducted in 47 primary care settings in four provinces of Canada. Patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text-Revision (DSM-IV-TR) criteria for a major depressive episode, in the context of a major depressive disorder (N=454) were enrolled. Eligible patients received open-label, flexible-dose antidepressant treatment. The analysis reported here was limited to patients whose depression severity was evaluated using the Hamilton Depression Rating Scale (HAMD-17) (n=205). Patients completing 8 weeks of open-label antidepressant treatment (n=157) were considered evaluable. As a proxy for anxiety symptoms, scores on 6 items from the HAMD-17 (psychological anxiety, somatic anxiety, gastrointestinal distress, fatigue, hypochondriasis, and insight into illness) were summed to arrive at a composite anxiety score, which was then used to calculate an anxiety ratio (with the composite anxiety score as the numerator and the total HAMD-17 score as the denominator). RESULTS: The composite anxiety ratio at baseline did not correlate with the probability of remitting at endpoint (p=0.534). After 8 weeks of antidepressant therapy, remitting patients evinced a statistically significant decrease in anxiety ratio (p=0.041). Moreover, an inverse correlation was noted between severity of anxious symptoms at endpoint and probability of remission (p=0.026). The burden of anxiety, presented as the anxiety ratio, was higher in non-remitting patients at endpoint (p=0.828). CONCLUSION: Residual depressive symptoms represent ongoing illness activity in depression. Sharpening the focus of therapeutic interventions in the clinical environment calls for tracking and managing residual anxiety symptoms.

Medical comorbidity in bipolar disorder: re-prioritizing unmet needs.

PURPOSE OF REVIEW: The aim of this review is to synthesize results from extant investigations which report on the co-occurrence of bipolar disorder and medical comorbidity. RECENT FINDINGS: We conducted a MEDLINE search of all English-language articles published between January 2004 and November 2006. Most studies report on medical comorbidity in bipolar samples; relatively fewer studies report the reciprocal association. Individuals with bipolar disorder are differentially affected by several 'stress-sensitive' medical disorders notably circulatory disorders, obesity and diabetes mellitus. Neurological disorders (e.g. migraine), respiratory disorders and infectious diseases are also prevalent. Although relatively few studies have scrutinized the co-occurrence of bipolar disorder in medical settings, individuals with epilepsy, multiple sclerosis, migraine and circulatory disorders may have a higher prevalence of bipolar disorder. A clustering of traditional and emerging (e.g. immuno-inflammatory activation) risk factors presage somatic health issues in the bipolar disorder population. Iatrogenic factors and insufficient access to primary, preventive and integrated healthcare systems are also contributory. SUMMARY: Somatic health issues in individuals with bipolar disorder are ubiquitous, under-recognized and suboptimally treated. Facile screening for risk factors and laboratory abnormalities along with behavioral modification for reducing medical comorbidity are warranted.

Calculated bioavailable testosterone levels and depression in middle-aged men.

BACKGROUND: The association between circulating total testosterone (TT) levels and depressive symptoms remains unclear. We sought to determine the relationship between physiologically active bioavailable testosterone (BT) and depressive symptoms in middle-aged men with and without major depressive disorder (MDD). METHODS: We assessed and compared calculated BT levels in two groups of middle-aged men (40-65 years): untreated subjects meeting DSM-IV-TR-defined criteria for a major depressive episode as part of major depressive disorder (N=44) and a matched non-depressed control group (N=50). RESULTS: Depressed men had lower mean BT levels (3.51+/-1.69 vs. 4.69+/-2.04 nmol/L; p=0.008) and TT levels (11.94+/-4.63 vs. 17.64+/-1.02 nmol/L; p<0.001) when compared to the control group. Biochemical hypogonadism (i.e., BT level< or =2.4 nmol/L or TT level< or =12.14 nmol/L) was also more prevalent in depressed men vs. non-depressed controls (34% vs. 6%, p<0.001; 61% vs. 14%, p<0.001, respectively). CONCLUSIONS: Changes in physiologically active BT concentration may be a vulnerability factor for depressive symptoms in middle-aged depressed men.

Measurable outcomes in psychiatric disorders: remission as a marker of wellness.

BACKGROUND: Mental disorders are highly prevalent, heterogeneous, and of multifactorial etiology. Collectively, they are associated with significant morbidity, mortality, and economic cost. Wellness is the optimal outcome in the management of chronic medical and psychiatric disorders. OBJECTIVES: This review provides a synopsis of definitions and operational criteria for remission in major depressive disorder, bipolar disorder, schizophrenia, anxiety disorders, and attention-deficit/hyperactivity disorder (ADHD). The overall goals were to propose a treatment framework that gives primacy to therapeutic outcomes and to provide a rationale for psychiatry to quantify and measure patient outcome. METHODS: Articles proposing definitions for remission were identified using a MEDLINE search (1966-April 2005) of the English-language literature (key terms: remission, anxiety disorders, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder, and schizophrenia). RESULTS: Operationalizing and quantifying critical end points in psychiatric disorders may help sharpen the focus of therapeutic activity and benefit patient outcome. In the absence of a validated biomarker of psychiatric illness activity, symptomatic remission and functional restoration are the only available markers of wellness in psychiatry. There is an emerging consensus regarding a definition for remission in major depressive disorder; several working definitions for bipolar disorder, schizophrenia, and anxiety disorders have been proposed. Developments in adult mood disorders-albeit incomplete-have been informative; managing psychiatric disorders that first appear in childhood (eg, ADHD) may also benefit by objectifying patient outcome. CONCLUSIONS: Research is needed to determine the impact of applying a remission-focused model of illness management--emphasizing quantifiable, objective, and measurable end points--on overall patient outcomes.

Improving outcomes in depression: a focus on somatic symptoms.

BACKGROUND: It is hypothesized that somatic symptom alleviation is a significant predictor of overall outcome in depressed primary care patients. METHODS: Depressed primary care patients (N=205) meeting DSM-IV-TR criteria received open-label antidepressant therapy. The primary symptom measurement tool used was the 17-item Hamilton Depression Rating Scale (HAMD-17), with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression Improvement/Severity (CGI-I/S) used as secondary measures. As proxies for somatic symptoms, 8 items from the HAMD-17 (HAMD-S) and 3 items from the MADRS (MADRS-S) that measure somatic symptoms were identified and extracted. RESULTS: There was a significant correlation between improvement on the HAMD-S score and overall reduction on the MADRS total score (r=.766, P<.001), response (r=.594, P<.001), and remission (r=.552, P<.001). Improvement on the MADRS-S also correlated with overall HAMD-17 improvement (r=.782, P<.001), along with response (r=.649, P<.001) and remission (r=.539, P<.001) rates. Both the HAMD-S and the MADRS-S correlated with global improvement as measured by the CGI-I/S (P<.001). CONCLUSIONS: A reciprocal interaction between somatic symptoms and other depressive-symptom domains is implied by this analysis. Clinicians are encouraged to identify, track, and target the somatic symptoms of depressive illnesses.

Medical comorbidity in bipolar disorder: implications for functional outcomes and health service utilization.

OBJECTIVE: This is the first cross-national population-based investigation exploring the prevalence and functional implications of comorbid general medical disorders in bipolar disorder. METHODS: Data were extracted from the Canadian Community Health Survey (N = 36,984). Analyses were conducted to ascertain the prevalence and prognostic implications of predetermined comorbid general medical disorders among persons who screened positive for a lifetime manic episode (indicative of a diagnosis of bipolar disorder). Within the subpopulation of people who screened positive for a manic episode, the effect of medical comorbidity on employment, functional role, psychiatric care, and medication use was examined. RESULTS: When the data were weighted to be representative of the household population of the ten provinces in 2002, an estimated 2.4 percent of respondents screened positive for a lifetime manic episode. Rates of chronic fatigue syndrome, migraine, asthma, chronic bronchitis, multiple chemical sensitivities, hypertension, and gastric ulcer were significantly higher in the bipolar disorder group (all p < .05). Chronic medical disorders were associated with a more severe course of bipolar disorder, increased household and work maladjustment, receipt of disability payments, reduced employment, and more frequent medical service utilization. CONCLUSIONS: Comorbid medical disorders in bipolar disorder are associated with several indices of harmful dysfunction, decrements in functional outcomes, and increased utilization of medical services.