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Sidney H Kennedy

Publications and source records attributed to Sidney H Kennedy.

At least 19 recordsLinked to original sources
PubMed2026

Exploring sex differences in endocannabinoid system biomarkers and their relationship with antidepressant treatment outcomes in major depressive disorder: a CAN-BIND 1 secondary analysis.

BACKGROUND: Sex differences in major depressive disorder (MDD) are well documented, but it remains unclear whether sex-related variation in peripheral endocannabinoid system (ECS)-related biomarkers is detectable in MDD. OBJECTIVES: To examine baseline sex differences in ECS-related mRNA expression, DNA methylation, and single nucleotide polymorphisms (SNPs) in MDD, and associations between baseline ECS markers and antidepressant outcomes in sex-stratified analyses. METHODS: Among 178 participants with MDD from CAN-BIND-1, all received escitalopram for 8 weeks; non-responders then received adjunctive aripiprazole from Weeks 8-16.Response was defined as ≥ 50% reduction in MADRS score, and remission as MADRS ≤ 10. ANCOVAs examined baseline sex differences and sex-stratified biomarker associations with percent MADRS reduction at Weeks 8 and 16, as well as categorical response and remission outcomes. Covariates included site, baseline MADRS, age, and ethnicity. False discovery rate correction was applied. RESULTS: Baseline sex differences in methylation were observed for CACNA1H, GABRB2, MAGL, and GABRR2, though none survived correction. No baseline sex differences in mRNA expression or SNPs were detected after correction. Lower baseline DAGLA mRNA in males was associated with greater Week 8 symptom improvement (FDR corrected). This association was not observed in females. No associations with response or remission at Weeks 8 or 16 survived correction. IMPLICATIONS: Baseline sex differences in peripheral ECS-related markers were not detected in this sample. Larger studies are needed to verify whether ECS-related biomarkers, particularly DAGLA, contribute to antidepressant outcomes in a sex-specific manner.

Humans↗
PubMed2006

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↗
PubMed2006

Deep brain stimulation for treatment-resistant depression: a psychiatric perspective.

Traditionally, the therapeutic approach to treatment-resistant depression (TRD) has relied on pharmacotherapy in various sequences and combinations, in addition to evidence-based psychotherapy or electroconvulsive therapy. Despite refinements to the existing therapeutic modalities, there remains a significant subpopulation of severely ill patients with refractory mood disorders who fail to achieve a clinical response despite aggressive psychosocial and biological treatments. Interest in the use of deep brain stimulation (DBS) for treatment-resistant psychiatric illness has emerged in recent years for a number of reasons: 1) as part of a general re-evaluation of both noninvasive and invasive brain stimulation techniques, 2) because of the demonstrated clinical efficacy of DBS for movement disorders, and 3) as a logical consequence of studies defining the functional neurocircuitry of several psychiatric disorders. This review will examine the progress of DBS in the treatment of Parkinson's disease and the potential implications for its use in TRD, as well as the role of the psychiatrist in selection and ongoing management of patients who receive this procedure.

Brain Mapping↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2006

Sexual function during bupropion or paroxetine treatment of major depressive disorder.

OBJECTIVE: The primary objective was to evaluate sexual function (SF) separately in men and women with major depressive disorder (MDD) before and during treatment with bupropion sustained release (SR) or paroxetine. The secondary objectives involved a comparative evaluation of the Sex Effects Scale (Sex FX) and the Investigator-Rated Sexual Desire and Functioning Scale (IRSD-F), as well as a comparison of antidepressant outcomes and an examination of the relation between level of depression and SF over time. METHOD: There were 141 patients (68 women and 73 men) who met DSM-IV criteria for a current major depressive episode. They were randomly assigned to receive bupropion SR (150 to 300 mg daily) or paroxetine (20 to 40 mg daily) under double-blind trial conditions. Patients were assessed at baseline and at 2, 4, 6, and 8 weeks with the 17-item Hamilton Depression Rating Scale (HDRS17), Sex FX, and IRSD-F. RESULTS: Prior to treatment, women reported significantly lower SF on both the Sex FX and IRSD-F scales, compared with men. During treatment, there were no significant drug differences on measures of SF over time for women; however, men who were treated with paroxetine reported a worsening of SF, whereas bupropion SR did not significantly alter SF. Both bupropion SR and paroxetine produced clinically and statistically significant reductions in HDRS17 scores as well as comparable rates of response and remission. There was a statistically significant correlation between the 2 measures of SF at all visits. There was also a significant inverse relation between depression and SF in women, but not in men, irrespective of drug. CONCLUSION: According to the Sex FX scale, a significant difference in antidepressant-related sexual dysfunction was detected in men, but not women, during treatment with bupropion SR or paroxetine.

Adolescent↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2006

Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis.

OBJECTIVE: Escitalopram is the most selective of the selective serotonin reuptake inhibitor (SSRI) antidepressants. Previous studies have suggested that escitalopram is superior to citalopram in efficacy. We conducted a meta-analysis of studies in which escitalopram was compared with other antidepressants to assess the relative efficacy of these agents. METHODS: Data from all randomized, double-blind studies in major depression in which escitalopram was compared with active controls (citalopram, fluoxetine, paroxetine, sertraline and venlafaxine XR [extended release]) were pooled. The 10 studies were conducted in both specialist settings and general practice. Patients met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), for major depressive disorder and were at least 18 years old. In all but 2 studies, patients were required to have a score of 22 or more on the Montgomery-Asberg Depression Rating Scale (MADRS). The primary outcome measure was the estimated difference in treatment effect in MADRS total score at the end of the study. Secondary outcome measures were the response to treatment (defined as a > or = 50% reduction in baseline MADRS total score) and remission rate (defined as MADRS total score < or = 12 at end of study). RESULTS: A total of 2687 patients were included in the analyses (escitalopram n = 1345, conventional SSRIs n = 1102, venlafaxine XR n = 240). Escitalopram was superior to all comparators in overall treatment effect, with an estimated difference in treatment effect of 1.07 points (95% confidence interval [CI] 0.42-1.73, p < 0.01), and in response (odds ratio [OR] 1.29, 95% CI 1.07-1.56, p < 0.01) and remission (OR 1.21, 95% CI 1.01-1.46, p < 0.05) rates. In analysis by medication class, escitalopram was significantly superior to the SSRIs and comparable to venlafaxine, although the overall results do not necessarily reflect a significant difference between escitalopram and individual SSRIs. These results were similar in the severely depressed population (patients with baseline MADRS > or = 30). The withdrawal rate due to adverse events was 6.7% for escitalopram compared with 9.1% for the comparators (p < 0.05). CONCLUSIONS: In this meta-analysis, escitalopram showed significant superiority in efficacy compared with the active controls.

Antidepressive Agents, Second-Generation↗
PubMed2005

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↗
PubMed2005

Validation of an IVRS version of the MADRS.

Interest in self-reported measures of depression in clinical trials has grown in recent years. This study compared the reliability and validity of the clinician-administered Montgomery-Asberg Depression Rating Scale (MADRS) to a computer-administered version administered over the telephone using Interactive Voice Response (IVR) technology. Sixty subjects were administered both the clinician- and computer-administered versions of the MADRS in a counter-balanced order. A subsample of 20 patients was reassessed 24h later by both methods. Mean score differences between IVR and clinician were not statistically significant (<1 point) and a high correlation was found between forms (r=.815, p<.001). Reliability measures (Cronbach's Alpha and 24-h test-retest) were comparable. Clinicians rated the severity of subjects' sadness and pessimistic thoughts lower than subjects self-report. The data obtained in this pilot study provide support for the equivalence between the clinician and IVR versions of the MADRS.

Adult↗