Sex differences in antidepressant response in a Canadian primary-care sample.
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Adult↗
Biomedical subjects
Roger S McIntyre
Publications and source records attributed to Roger S McIntyre.
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.
Adult↗
Association of the putative susceptibility gene, transient receptor potential protein melastatin type 2, with bipolar disorder.
Disturbed intracellular calcium (Ca(2+)) homeostasis has been implicated in bipolar disorder (BD). Reduced mRNA levels of the transient receptor potential Ca(2+) permeable channel melastatin type 2, TRPM2, in B lymphoblast cell lines (BLCL) from bipolar I disorder (BD-I) patients showing elevated basal intracellular Ca(2+) ([Ca(2+)](B)), an index of altered intracellular Ca(2+) homeostasis, along with its location within a putative BD susceptibility locus (21q22.3), implicates the involvement of this gene in the Ca(2+) abnormalities and the genetic diathesis to BD. We tested this hypothesis by examining the association of selected single nucleotide polymorphisms (SNPs) and their haplotypes, spanning the TRPM2 gene, with BD and BLCL [Ca(2+)](B), in a case control design. The 5' TaqMan SNP assay was used to detect selected SNPs. BLCL [Ca(2+)](B) was determined by ratiometric fluorometry. SNP rs1618355 in intron 18 was significantly associated with BD as a whole (P < 7.0 x 10(-5); odds ratio (OR) = 2.60), and when stratified into BD-I (P < 7.0 x 10(-5), OR = 2.48) and BD-II (P = 7.0 x 10(-5), OR = 2.88) subgroups. In addition, the alleles of the individual SNPs forming a seven marker at-risk haplotype were in excess in BD (12.0% in BD vs. 0.9% in controls; P = 2.3 x 10(-12)). A weak relationship was also detected between BLCL [Ca(2+)](B) and TRPM2 SNP rs1612472 in intron 19. These findings suggest genetic variants of the TRPM2 gene increase risk for BD and support the notion that TRPM2 may be involved in the pathophysiology of BD.
Adult↗
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.
Biomarkers↗
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.
Adult↗
Anxiety disorders and bipolar disorder: a review.
CONTEXT: Epidemiological, clinical and familial studies indicate that anxiety disorders (ADs) are highly comorbid in persons with bipolar disorder (BPD). The phenomenological overlap between ADs and BPD is reported more frequently in individuals with female predominant bipolar presentations (e.g., bipolar II disorder). Anxiety comorbidity in the BPD population poses a serious hazard. For example, it is associated with an intensification of symptoms, non-recovery, substance use comorbidity and harmful dysfunction (e.g., suicidality). OBJECTIVE: The evidentiary base informing treatment decisions for the anxious bipolar patient is woefully inadequate. Several expert consensus and evidence-based treatment guidelines for BPD suggest various treatment avenues, although these have been insufficiently studied. The encompassing aim of this paper is to synthesize extant studies reporting on the co-occurrence of AD and BPD. Taken together, a compelling basis emerges for prioritizing the identification and management of anxiety symptomatology in the BPD population.
Anxiety Disorders↗
Comorbidity in bipolar disorder: clinical and research opportunities.
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Alcoholism↗
Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: update 2007.
In 2005, the Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder. This update reviews new evidence since the previous publication and incorporates recommendations based on the most current evidence for treatment of various phases of bipolar disorder. It is designed to be used in conjunction with the 2005 CANMAT Guidelines. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate and several atypical antipsychotics continue to be recommended as first-line treatments for acute mania. For the management of bipolar depression, new data support quetiapine monotherapy as a first-line option. Lithium and lamotrigine monotherapy, olanzapine plus selective serotonin reuptake inhibitors (SSRI), and lithium or divalproex plus SSRI/bupropion continue to remain the other first-line options. First-line options in the maintenance treatment of bipolar disorder continue to be lithium, lamotrigine, valproate and olanzapine. There is recent evidence to support the combination of olanzapine and fluoxetine as a second-line maintenance therapy for bipolar depression. New data also support quetiapine monotherapy as a second-line option for the management of acute bipolar II depression. The importance of comorbid psychiatric and medical conditions cannot be understated, and this update provides an expanded look at the prevalence, impact and management of comorbid conditions in patients with bipolar disorder.
Acute Disease↗
The prevalence and impact of migraine headache in bipolar disorder: results from the Canadian Community Health Survey.
OBJECTIVE: To report on the prevalence of comorbid migraine in bipolar disorder and the implications for bipolar age of onset, psychiatric comorbidity, illness course, functional outcome, and medical service utilization. BACKGROUND: Migraine comorbidity is differentially reported in bipolar versus unipolar depressed clinical samples. The bipolar disorder-migraine association and its consequences have been infrequently reported in epidemiological studies. METHODS: Data for this analysis were derived from respondents (n = 36 984) to the Canadian Community Health Survey - Mental Health and Well-Being (CCHS). Respondents reporting a lifetime WHO-CIDI-defined manic episode and physician-diagnosed migraine (lifetime) were compared to respondents without migraine on sociodemography, course of illness, and medical service utilization indices. RESULTS: An estimated 2.4% of the sample met criteria for bipolar disorder. Persons with bipolar disorder had a relatively higher prevalence of migraine versus the general population (24.8% vs. 10.3%; P < .05). The sex-specific prevalence of comorbid migraine in bipolar disorder was 14.9% for males and 34.7% for females. Bipolar males with comorbid migraine were more likely to live in a low income household (P < .05); receive welfare and social assistance (P < .05); report an earlier age of onset of bipolar disorder (P < .05); and have a higher lifetime prevalence of comorbid anxiety disorders (P < .05). Bipolar males with comorbid migraine were also more likely to utilize primary (P < .05) and mental health care services (P < .05) . Bipolar females with comorbid migraine had more comorbid medical disorders (P < .05) and were more likely to require help with personal or instrumental activities of daily living when compared to bipolar females without migraine. CONCLUSION: Bipolar disorder with comorbid migraine is prevalent and associated with greater dysfunction and medical service utilization, notable in males. Opportunistic screening and surveillance for bipolar and comorbid migraine is warranted.
Adolescent↗
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.
Adolescent↗
Obesity in bipolar disorder and major depressive disorder: results from a national community health survey on mental health and well-being.
OBJECTIVE: We aimed to ascertain the prevalence of obesity in individuals with a mood disorder (MD) (that is, bipolar disorder or major depressive disorder), compared with the general population. We further aimed to examine the likelihood of an association between obesity and MD, while controlling for the influence of sociodemographic variables. METHOD: The analysis was based on data from Statistics Canada's Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2), conducted in 2002. The sample (n = 36 984; > or = aged 15 years) was drawn from the Canadian household-dwelling population. The CCHS used diagnostic criteria outlined in the DSM-IV to screen respondents. RESULTS: Individuals with a lifetime history of MD were more likely to be obese (body mass index [BMI] > 30) than were individuals without lifetime MD (19%, compared with 15%, respectively; P < 0.001). In sex-specific multivariate analysis, lifetime MD was associated with elevated odds of obesity in female respondents (95%CI, 1.03 to 1.46, odds ratio 1.22), but not in male respondents. Antipsychotic pharmacotherapy was also associated with obesity. CONCLUSIONS: This is the first Canadian epidemiologic investigation to specifically evaluate anthropometric indices and associated factors in people with MDs. The results herein supplement substantial clinical evidence documenting the association between MDs and stress-sensitive somatic disorders (for example, obesity). These data also underscore the metabolic consequences of some psychotropic agents.
Adolescent↗
Managing psychiatric disorders with antidiabetic agents: translational research and treatment opportunities.
The objective of this paper is to synthesise extant studies describing the neurotherapeutic effects of antidiabetic agents in neuropsychiatric disorders. The authors conducted a MedLine search of all English-language articles published between 1966 and March 2006. The search terms were the nonproprietary names of established and putative antidiabetic agents (e.g., insulin, insulin secretagogues and sensitisers) cross-referenced with the individual names of Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R/IV/-TR-defined mood, psychotic, anxiety and dementing disorders. The search was augmented with a manual review of article reference lists. Contemporary models of disease pathophysiology in major depressive disorder, bipolar disorder and several dementing disorders (e.g., Alzheimer's disease) emphasise alterations in cellular plasticity and cytoarchitecture, with associated regional abnormalities in neuronal and glial density and morphology. Antidiabetic treatments (e.g., thiazolidinediones) may be capable of attenuating this pathological process via disparate mechanisms (e.g., neuroprotective, neurotrophic, anti-inflammatory). Enhanced insulin signalling with antidiabetic treatments may preserve and/or augment cognitive function in several neuropsychiatric disorders. Antidiabetic treatments, which maintain euglycaemia, hold promise as potent and clinically significant therapeutic interventions for several neuropsychiatric disorders.
Adult↗
The effect of antidepressants on glucose homeostasis and insulin sensitivity: synthesis and mechanisms.
OBJECTIVE: To synthesise results from investigations reporting on the effect of antidepressants on glucose-insulin homeostasis. METHOD: The authors conducted a MedLine search of all English language articles from 1966 to October 2005 using the keywords: bipolar disorder, major depressive disorder, diabetes mellitus, glucose homeostasis, and the name of each antidepressant that has been indicated for major depression in Canada and the US up to October 2005. The search was supplemented with a manual review of relevant references. Both preclinical and clinical investigations were reviewed. RESULTS: Some serotonergic antidepressants (e.g., fluoxetine) reduce hyperglycaemia, normalise glucose homeostasis and increase insulin sensitivity, whereas some noradrenergic antidepressants (e.g., desipramine) exert opposite effects. Dual-mechanism antidepressants (e.g., duloxetine and venlafaxine) do not appear to disrupt glucose homeostatic dynamics, whereas nonselective hydrazine monoamine oxidase inhibitors (e.g., phenelzine) are associated with hypoglycaemia and an increased glucose disposal rate. CONCLUSION: Some antidepressants exert a clinically significant effect on metabolism relevant to both therapeutic outcome and adverse events.
Antidepressive Agents↗
The effect of antidepressants on lipid homeostasis: a cardiac safety concern?
OBJECTIVE: The authors sought to summarise and synthesise results from investigations which report on the effect of antidepressants on serum lipid homeostasis. METHOD: The authors conducted a MedLine search of all English-language articles from 1966 to March 2006 using the search terms: major depressive disorder, bipolar disorder, lipids, triglycerides, cholesterol, low-density lipoprotein, high-density lipoprotein, and the non-proprietary names of conventional antidepressants indicated for the treatment of major depressive disorder in North America as of March 2006. The search was supplemented with a manual review of retrieved articles for any further citations reporting the effects of antidepressants on lipid homeostasis. RESULTS: Despite the paucity of well-characterised investigations, the unfavourable effect of weight gain promoting antidepressants (e.g., tricyclics, mirtazapine) on serum lipid parameters (i.e., triglycerides and low-density lipoprotein cholesterol) is a consistent finding. Weight-neutral antidepressants (e.g., bupropion, venlafaxine, duloxetine), however, are less likely to disrupt the lipid milieu. A weight-independent effect on lipid homeostasis is less consistently reported. CONCLUSION: Some antidepressants unfavourably influence the lipid milieu; mediating factors other than weight gain are not well-established. Pivotal studies evaluating the therapeutic index of antidepressants need to systematically collect and report data on the lipid effects of antidepressants.
Adult↗
Measuring the severity of depression and remission in primary care: validation of the HAMD-7 scale.
BACKGROUND: Symptomatic remission is the optimal outcome in depression. A brief, validated tool for symptom measurement that can indicate when remission has occurred in mental health and primary care settings is unavailable. We evaluated a 7-item abbreviated version (HAMD-7) of the 17-item Hamilton Depression Rating Scale (HAMD-17) in a randomized controlled clinical trial of patients with major depressive disorder being cared for in primary care settings. METHODS: We enrolled 454 patients across 47 primary care settings who met DSM-IV-TR criteria for a major depressive disorder. Of these, 410 patients requiring antidepressant medication were randomized to have their symptoms rated with either HAMD-7 (n = 205) or HAMD-17 (n = 205) as the primary measurement tool. The primary outcome was the proportion of patients who achieved a-priori defined responses to 8 weeks of therapy using each instrument. RESULTS: Of the 205 participants per group, 67% of those evaluated with HAMD-7 were classified as having responded to therapy (defined as a > or = 50% reduction from the pretreatment score), compared with 74% of those evaluated with HAMD-17 (p = 0.43). The difference between the groups' changes in scores from baseline (pretreatment) to endpoint was significant (p < 0.001), without a main effect of group (p = 0.84) or group-by-time (p = 0.83) interaction. The HAMD-7 test was brief to administer (e.g., 3-4 min for 85% of the primary care physicians evaluated), which facilitated the efficient and structured evaluation of salient depressive symptoms. INTERPRETATION: The abbreviated HAMD-7 depression scale is equivalent to the HAMD-17 in assessing remission in patients with a major depressive disorder undergoing drug therapy.
Adult↗
Quetiapine or haloperidol as monotherapy for bipolar mania--a 12-week, double-blind, randomised, parallel-group, placebo-controlled trial.
METHODS: Patients (n=302) with bipolar I disorder (manic episode) were randomised to 12 weeks' double-blind treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or haloperidol (up to 8 mg/day). The primary efficacy outcome variable was change from baseline to Day 21 in Young Mania Rating Scale (YMRS) score. RESULTS: YMRS score improved with quetiapine at Day 21 (-12.29 versus -8.32 for placebo; P<0.01). The difference in favor of quetiapine increased by Day 84 (-17.52 versus -9.48; P<0.001). Haloperidol also showed an advantage over placebo at Days 21 and 84 (P<0.001). There was no significant difference in efficacy measures between quetiapine and haloperidol groups at any assessment except Day 21. The only common adverse event with quetiapine was somnolence (12.7%). Extrapyramidal symptoms (EPS), including akathisia, occurred at 59.6% with haloperidol, 12.7% with quetiapine, 15.8% with placebo. Most quetiapine responders (84%) received a dose of 400-800 mg/day. CONCLUSIONS: Quetiapine was effective and well tolerated. The efficacy and tolerability profile of haloperidol (including its propensity for EPS) supported study validity.
Adult↗
Hormone replacement therapy and antidepressant prescription patterns: a reciprocal relationship.
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Antidepressive Agents↗
Antidepressant augmentation with raloxifene.
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Affect↗