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ABSTRACT: This study aimed to determine the distributions of the age at onset (AAO) in patients with major depressive disorder (MDD) using admixture analysis and to determine the clinical differences between subgroups with different AAO.
Participants were administered the Mini-International Neuropsychiatric Interview to obtain clinical data. Admixture analysis was performed using the STATA module DENORMIX to identify subgroups characterized by differences in AAO.
The best fit model was the three-component model with the following means, standard deviations and proportions: 14.60 (3.75) years (49.1%), 29.15 (6.75) years (34.1%) and 46.96 (6.06) years (16.8%) (χ(2)=3.64, 2 df, P=.162). The three subgroups were divided by AAO of 22 and 40. After controlling for duration of illness, there were no significant differences between the three AAO subgroups in terms of gender and psychiatric family history. However, the early-onset subgroup was significantly more likely to report being single compared to the intermediate- and late-onset groups. The proportion of individuals meeting criteria for lifetime comorbid panic disorders and obsessive-compulsive disorder did not differ significantly between the AAO groups. However, the early-onset group reported a higher incidence of attention-deficit/hyperactivity disorder (5.1% vs. 1.7% and 1.2%, P=.086), although this was not statistically significant.
Our study identified three characteristically different AAO subgroups in individuals suffering from MDD. The subgroups may reflect different underlying neurobiological mechanisms involved.
General hospital psychiatry 08/2012; 34(6):686-91. · 2.67 Impact Factor
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Roger S McIntyre,
Joanna K Soczynska,
Samantha S Liauw,
Hanna O Woldeyohannes,
Elisa Brietzke,
Jay Nathanson,
Mohammed Alsuwaidan, David J Muzina,
Valerie H Taylor,
Danielle S Cha,
Sidney H Kennedy
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ABSTRACT: We sought to determine whether a reported history of childhood adversity is associated with components of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP-III)-defined metabolic syndrome in adults with mood disorders.
This was a cross-sectional analysis of adult outpatients (N = 373; n = 230 female, n = 143 male; mean age [SD] = 42.86 [14.43]) from the International Mood Disorders Collaborative Project (University of Toronto and Cleveland Clinic) with DSM-IV-defined major depressive disorder and bipolar I/II disorder. Childhood adversity was measured with the Klein Trauma & Abuse-Neglect self-report scale. The groups with and without childhood adversity were compared to determine possible differences in the rates of metabolic syndrome and its components. Logistic and linear regressions adjusted for age, sex, education, employment status, and smoking were used to evaluate the association between childhood adversity and components of metabolic syndrome.
For the full sample, 83 subjects (22.25%) met criteria for metabolic syndrome. Individuals reporting a history of any childhood adversity had higher systolic and diastolic blood pressure (systolic: p = 0.040; diastolic: p = 0.038). Among subjects with a history of sexual abuse, a significant proportion met criteria for obesity (45.28% vs. 32.88%; p = 0.010); a trend toward overweight was found for subjects with a history of physical abuse (76.32% vs. 63.33%; p = 0.074), although this relationship did not remain significant after adjusting for potential confounders. There was no statistically significant difference in the overall rate of dyslipidemia and/or metabolic syndrome between subjects with and without childhood adversity.
The results herein provide preliminary evidence suggesting that childhood adversity is associated with metabolic syndrome components in individuals with mood disorders.
The International Journal of Psychiatry in Medicine 01/2012; 43(2):165-77. · 1.03 Impact Factor
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ABSTRACT: To examine the safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania.
Subjects (n = 18) who were acutely manic, did not respond to lithium, anticonvulsants, and neuroleptics, and/or had intolerable side effects to them in previous manic episodes were openly treated with olanzapine monotherapy (5-40 mg/d) for 12 weeks. The primary and secondary outcomes included the change from baseline to endpoint in Young Mania Rating Scale (YMRS) total score, Clinical Global Impression for Bipolar Disorder-Severity Scale (CGI-S), 17-item Hamilton Depression Rating Scale (HAM-D) and Positive and Negative Syndrome Scale (PANSS), and response and remission rate.
The mean change in YMRS total score from baseline to endpoint was -23.3 ± 8.4 (p < 0.001). Fifteen (88.5%) patients achieved response (≥50% reduction in YMRS total score) and 14 (77.8%) achieved remission (YMRS total score ≤9 at endpoint). Mean changes from baseline to endpoint in CGI-S for mania and PANSS total score were significant, but not the changes in HAM-D total score or CGI-S for depression. The most common adverse events were sedation, self-reported weight gain, ≥7% increase in body weight, dizziness, and akathisia.
These preliminary results suggest that olanzapine monotherapy is effective and relatively safe in patients with treatment-resistant bipolar mania. Randomized, double-blind, placebo-controlled study is warranted.
Human Psychopharmacology Clinical and Experimental 11/2011; 26(8):588-95. · 2.48 Impact Factor
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ABSTRACT: To conduct an exploratory evaluation of the acute efficacy of extended-release divalproex sodium compared to placebo in patients with bipolar I or II depression.
Outpatients aged 18-70 years with mood stabilizer-naive bipolar I or II disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 6 weeks of divalproex sodium monotherapy or placebo. The primary outcome measure was mean change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcomes included rates of response and remission, changes in the Clinical Global Impressions-Bipolar (CGI-BP) Severity of Illness scores, and changes in anxiety symptoms as measured by the Hamilton Anxiety Rating Scale. The study was conducted between 2003 and 2007.
Fifty-four subjects with bipolar I (n = 20) or bipolar II (n = 34) disorder were randomly assigned to divalproex or placebo; 67% (36 of 54) met DSM-IV criteria for rapid cycling. Divalproex treatment produced statistically significant improvement in MADRS scores compared with placebo from week 3 onward. The proportions of patients meeting response criteria were 38.5% (10 of 26) in the divalproex group versus 10.7% (3 of 28) for the placebo group (P = .017). The proportions of patients meeting remission criteria were 23.1% (6 of 26) for divalproex versus 10.7% (3 of 28) for placebo (P = .208). Subgroup analysis revealed no separation between divalproex and placebo for those with bipolar II diagnoses. Nausea, increased appetite, diarrhea, dry mouth, and cramps were the most common side effects.
These data suggest that divalproex sodium is efficacious and reasonably well tolerated in the acute treatment of mood stabilizer-naive patients with bipolar depression, particularly for those with rapid-cycling type I presentations, and that confirmatory large-scale studies are indicated.
The Journal of Clinical Psychiatry 06/2011; 72(6):813-9. · 5.80 Impact Factor
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04/2011: pages 45 - 60; , ISBN: 9780470975114
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ABSTRACT: Non-adherence to antidepressant medications is a contributing factor to disease relapse and may result in needless increases in antidepressant dosing.
We analyzed de-identified patient claims data from Medco Health Solutions, Inc.'s information database and measured adherence as the medication possession ratio (MPR), with adequate adherence as MPR ≥80%. Adherence was calculated for patients in whom antidepressants were dose escalated and who were on the same antidepressant medication for at least 180 days before the upward dosage titration. Statistical analysis was performed on subgroups comparing adherence with mail vs. retail channels, differences in age and gender, generic prescription vs. brand only, and prescription by psychiatrist vs. non-psychiatrist.
29.7% of patients were non-adherent to their antidepressant medication during the 6 months prior to a prescribed increase in dosage. Non-adherence was significantly lower among patients using the Medco Therapeutic Resource Centers® mail order vs. retail channel. Younger age correlated with poorer adherence. Rates of non-adherence were also significantly greater among women, those receiving generic medications, and among patients with overall lower disease comorbidity. Adherence was not significantly impacted by prescription from a psychiatrist or a non-psychiatrist.
Retrospective design and use of an administrative patient claims database.
Suboptimal medication adherence commonly precedes an upward dosage titration of antidepressant medications. Utilization of a mail order channel may improve adherence. Clinicians prescribing antidepressants should explore adherence issues carefully prior to recommending an increase in dosage.
Journal of affective disorders 10/2010; 130(1-2):46-52. · 3.76 Impact Factor
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ABSTRACT: To screen patients with fibromyalgia for bipolar disorder and to determine if there were any clinical clues, other than the Mood Disorders Questionnaire (MDQ), which might suggest a diagnosis of comorbid bipolar disorder.
A total of 128 consecutive new fibromyalgia patients referred to a tertiary care center rheumatology practice were enrolled and assessed using a standard clinical protocol that included the completion of four screening questionnaires: (i) MDQ for bipolar disorder, (ii) Beck Depression Inventory (BDI) for depression, (iii) Epworth Sleepiness Scale (ESS) for daytime sleepiness, and (iv) Fibromyalgia Impact Questionnaire Disability Index (FIQ-DI) to assess for functional capacity.
A quarter of the fibromyalgia subjects, 25.19%, had a positive screen for bipolar disorder (MDQ >or= 7); 78.12% were clinically depressed (BDI >or= 10); and 52.13% reported daytime sleepiness (ESS >or= 10). Fibromyalgia subjects who screened positive for bipolar disorder had more severe depression than those with a negative screen [median BDI: 26.0 (19.0, 32.0) versus 15.0 (9.0, 24.0), p < 0.001].
We report a high prevalence of positive testing for bipolar disorder in this fibromyalgia cohort. Clinical data and questionnaire instruments other than nonspecific high depression severity failed to identify these patients. Since the norepinephrine serotonin reuptake inhibitors duloxetine and milnacipran have been recently approved by the U.S. Food and Drug Administration for the treatment of fibromyalgia, and because patients with bipolar disorder may experience destabilization of mood when treated with such agents, patients with fibromyalgia should be systematically screened for bipolar disorder prior to treatment.
Bipolar Disorders 08/2010; 12(5):514-20. · 5.29 Impact Factor
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Roger S McIntyre,
Sidney H Kennedy,
Joanna K Soczynska,
Ha T T Nguyen,
Timothy S Bilkey,
Hanna O Woldeyohannes,
Jay A Nathanson,
Shikha Joshi,
Jenny S H Cheng,
Kathleen M Benson, David J Muzina
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ABSTRACT: Relatively few studies have evaluated the clinical implications of lifetime attention-deficit/hyperactivity disorder (ADHD) in adults with bipolar disorder or major depressive disorder (MDD). Herein, we sought to determine the prevalence as well as the demographic and clinical correlates of lifetime ADHD in persons with a mood disorder.
The first 399 patients enrolled in the International Mood Disorders Collaborative Project (IMDCP) were evaluated for lifetime ADHD using the Mini-International Neuropsychiatric Interview-Plus (MINI-Plus) as the primary instrument to derive current and lifetime DSM-IV diagnoses. All analyses of variables of interest were conducted utilizing the MINI-Plus, the Adult ADHD Self-Report Scale-v1.1, and the Wender Utah Rating Scale-Short Form. The effect of ADHD on clinical presentation, course of illness variables, comorbidity, anamnesis, treatment, and outcome are reported. The IMDCP is a joint initiative of the Mood Disorders Psychopharmacology Unit at the University Health Network, University of Toronto, Toronto, Ontario, Canada, and the Cleveland Clinic Center for Mood Disorders Treatment and Research at Lutheran Hospital, Cleveland, Ohio. All data for this study were procured between January 2008 and January 2009.
The percentages of subjects with MDD or bipolar disorder meeting the DSM-IV criteria for lifetime adult ADHD were 5.4% and 17.6% (P < .001), respectively. Lifetime comorbid ADHD in both mood disorder populations was associated with earlier age at illness onset (MDD, P = .049; bipolar disorder, P = .005), a higher number of psychiatric comorbidities (eg, MDD and current panic disorder with agoraphobia [P = .002]; bipolar disorder and social phobia [P = .012]), and decreased quality of life (MDD, P = .018).
The overarching findings herein are that the adult ADHD phenotype is commonly reported by individuals with MDD or bipolar disorder and is associated with a greater illness burden and complexity.
The Primary Care Companion to The Journal of Clinical Psychiatry 01/2010; 12(3).
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ABSTRACT: Results from pivotal registration trials in major depressive disorder cohere with outcomes from effectiveness studies indicating that the majority of individuals receiving single-agent pharmacotherapy fail to achieve and sustain symptomatic remission. Several factors provided the impetus for this review: suboptimal efficacy with existing pharmacotherapy for major depressive disorder, quetiapine XR efficacy in the acute and maintenance treatment of bipolar depression, emerging pharmacodynamic evidence that quetiapine XR (and/or its metabolites) uniquely engages monoaminergic systems salient to symptom relief in depressive syndromes, the increasing use of second-generation antipsychotics in the treatment of major depressive disorder and the recent FDA review of quetiapine XR in major depressive disorder. Studies reviewed herein are pivotal registration trials that evaluated the acute and maintenance efficacy and tolerability of quetiapine XR (as monotherapy and as adjunctive treatment) in major depressive disorder. In addition, we also review recent investigations characterizing the pharmacodynamic effect of quetiapine's principal active metabolite, norquetiapine. All studies were obtained from AstraZeneca (Wilmington, DE, USA) and have been presented at national/international scientific meetings. Taken together, extant studies demonstrated that quetiapine XR (50 - 300 mg) provides rapid and sustained symptomatic improvement in the acute and maintenance treatment of major depressive disorder. Quetiapine XR may also offer advantages relative to duloxetine in time to onset of antidepressant action. The major limitations of quetiapine XR use in major depressive disorder relate to weight gain and disrupted glucose/lipid homeostasis as well as sedation/somnolence. Quetiapine XR has tolerability advantages compared with duloxetine on measures of sexual dysfunction. The data from the studies reviewed herein also indicate that quetiapine XR poses a low risk for extrapyramidal side effects in middle-aged and elderly individuals with major depressive disorder.
Expert Opinion on Pharmacotherapy 12/2009; 10(18):3061-75. · 3.20 Impact Factor
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David J Muzina
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ABSTRACT: Lithium has long been considered as less than ideal in the management of rapid cycling and mixed states in bipolar disorder. However, these forms of bipolarity represent a generally more difficult phase of the illness to treat with any medication. Increasing knowledge about lithium's other beneficial effects, including protection against suicide and neuromodulatory effects which may protect the brain, make it a first-line treatment for any form of bipolar disorder. As newer therapies become available or receive further exploration, we should look to the past and re-embrace lithium as a core therapeutic modality for bipolarity as we move forward in the field, particularly for forms of the disorder such as rapid cycling and mixed states, historically thought to be more treatment resistant.
Bipolar Disorders 07/2009; 11 Suppl 2:84-91. · 5.29 Impact Factor
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David J Muzina
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ABSTRACT: Aripiprazole is a second-generation antipsychotic with a unique pharmacologic receptor profile that has efficacy in the treatment and prevention of mania in bipolar I disorder. This article reviews the evidence supporting treatment of adults with bipolar I disorder using aripiprazole as monotherapy or adjunctively during acute mania and its utility as an intramuscular agent for agitation in manic patients. Results from one of the longest bipolar maintenance trials which support aripiprazole as a prophylactic mood stabilizer, specifically against manic relapses, will be discussed as well as a post-hoc analysis that suggests efficacy for rapid cycling bipolar disorder. Safety and tolerability issues, patient-focused perspectives and aripiprazole's place in therapy for bipolar mania will be covered.
Neuropsychiatric Disease and Treatment 02/2009; 5:279-88. · 1.81 Impact Factor
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ABSTRACT: To study treatment-emergent mania/hypomania (TEM) associated with second-generation antidepressant monotherapy in patients with rapid cycling bipolar disorder (RCBD).
Data of patients with RCBD (n = 180) enrolled into two clinical trials were used to study the risk for TEM during second-generation antidepressant monotherapy. History of TEM was retrospectively determined at the initial assessment by asking patients whether they were exposed to second-generation antidepressants and if a hypomania/mania episode emerged during the first four weeks of treatment. Data were analyzed using t-test, chi-square, and logistic regression.
Of the 180 patients (bipolar I disorder, n = 128; bipolar II disorder, n = 52) with RCBD, 85% (n = 153) had at least one antidepressant treatment. Among these patients, 94.1% (144/153) had at least one antidepressant monotherapy treatment. Overall, 49.3% of patients had at least one TEM and 29.1% (116/399) of treatment trials were associated with TEM. In regression analysis, an inverse association between the number of mood episodes in the last 12 months and TEM was observed with an odds ratio of 0.9. However, gender, bipolar subtype, a lifetime history of comorbid anxiety disorder, substance use disorder, or psychosis, and age of mood disorder onset were not associated with TEM. For individual antidepressants, the rates of TEM varied from 42.1% for fluoxetine to 0% for fluvoxamine and mirtazapine. As a group, there was no difference between selective serotonin reuptake inhibitors and venlafaxine or bupropion in the incidence of TEM.
Use of second-generation antidepressants as monotherapy in RCBD is accompanied by clinically relevant rates of TEM. Even in patients with RCBD, differential vulnerabilities to antidepressant TEM may exist.
Bipolar Disorders 01/2009; 10(8):907-15. · 5.29 Impact Factor
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ABSTRACT: Subjective experience of illness affects outcomes among populations with bipolar disorder (BD). This cross-sectional study combined qualitative and quantitative approaches to evaluate perceived treatment effects, concerns and expectations among 90 individuals with BD.
Adults with Type I BD, mean age 36.6 years, 51% women, completed a semi-structured interview that was audio taped, transcribed, coded and analyzed along emergent themes. Quantitative scales measured depressive symptoms (Hamilton Depression Scale/HAM-D), psychopathology (Clinical Global Impression/CGI), and insight and treatment attitudes (Insight and Treatment Attitudes Questionnaire/ITAQ).
Individuals had moderate depression and psychopathology with good insight into need for treatment. Drug treatment was perceived as beneficial, by "stabilizing" or "balancing" mood (42%, N=38), decreasing anxiety/depressive symptoms (19%, N=17) and improving sleep (10%, N=9). While 39%, (N=35) of individuals denied medication concerns, nearly 29%, (N=26) feared possible long-term effects, particularly diabetes or liver/kidney damage. Media stories and advertisements contributed to medication fears. Hopes and expectations for treatment ranged from those that were symptom or functional status-based, such as desiring mood stabilization and elimination of specific symptoms (23%, N=21), to more global hopes such as "being normal" (20%, N=18) or "cured" (18%, N=16).
Limitations include relatively small sample, lack of a comparator, inclusion of only depressed individuals and those willing to discuss their illness experience.
While individuals with BD appreciate the effects of medications, concerns regarding adverse effects and discrepancy between actual and hoped-for outcomes can be substantial. Subjective experience with medications using qualitative and quantitative methods should be explored in order to optimize treatment collaboration and outcomes.
Journal of affective disorders 12/2008; 115(3):360-6. · 3.76 Impact Factor
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Bipolar Disorders 10/2008; 10(6):750-751. · 5.29 Impact Factor
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ABSTRACT: Pharmacological treatment of bipolar disorder has centered on the use of medications called ‘mood stabilizers.’ However, this term is not well understood or defined. This chapter discusses the debate about mood stabilizers in the context of a review of evidence for various medications used to treat bipolar mania, bipolar depression, and in the maintenance treatment of this chronic and recurrent affective illness. Based on existing evidence it appears that there are no ideal or fully effective mood stabilizers currently available, including lithium. Lithium, antiepileptic drugs (AEDs) such as lamotrigine, carbamazepine, and divalproex, and atypical antipsychotic medications all appear to have some partial role in the overall management of bipolar disorder with particular phase-specific strengths and weaknesses. Reconceptualization of mood stabilizers is suggested, noting that currently available medications are all partial mood stabilizers. These partial mood stabilizers possess efficacies that may be described as unidirectional, bidirectional, intermediate, or mixed. It is hoped with future research and understanding of the underlying pathophysiology of bipolar disorder that more complete; ideal mood stabilizers may be developed. Until such time, clinicians must utilize the best available evidence for the partial mood stabilizers to formulate individualized mood stabilizing treatment plans for each unique patient with bipolar disorder.
08/2008: pages 2202 - 2222; , ISBN: 9780470515167
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ABSTRACT: 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.
Current Psychiatry Reports 03/2008; 10(1):66-72. · 2.71 Impact Factor
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ABSTRACT: This review focused on the treatment-emergent mania/hypomania (TEM) associated with repetitive transcranial magnetic stimulation (rTMS) treatment of depression. English-language literature published from 1966-2006 and indexed in Medline was searched. Ten of 53 randomized controlled trials on rTMS treatment of depression specifically addressed TEM. The pooled TEM rate is 0.84% for the active treatment group and 0.73% for the sham group. The difference is not statistically significant. Along with case reports, a total of 13 cases of TEM associated with rTMS treatment of depression have been published. Most of these patients were diagnosed with bipolar disorder and the majority of patients experiencing TEM took medication concurrent with rTMS. The parameters of rTMS used in these cases were scattered over the spectrum of major parameters explored in previous studies. Most train durations and intervals were within the published safety guidelines of the field. Reducing the frequency of sessions from two per day to one per day might be associated with a lower likelihood of TEM recurrence. The severity of manic symptoms varied significantly, but all cases responded to treatment that included a decrease or discontinuation of antidepressant and/or rTMS treatment and/or use of anti-manic medication. Current data suggests that rTMS treatment carries a slight risk of TEM that is not statistically higher than that associated with sham treatment. More systematic studies are needed to better understand TEM associated with rTMS. Special precautions and measures should be adopted to prevent, monitor, and manage TEM in research and practice.
The International Journal of Neuropsychopharmacology 03/2008; 11(1):119-30. · 4.58 Impact Factor
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ABSTRACT: This study compared the sensitivity and tolerability of antipsychotics in patients with bipolar disorder or schizophrenia.
English-language literature from January 1966 to December 2006 cited in MEDLINE was searched for the terms antipsychotics, typical antipsychotics, atypical antipsychotic, generic and brand names of antipsychotics, safety, tolerability, discontinuation due to adverse events, somnolence, and bipolar mania, bipolar depression, bipolar disorder, manic-depressive illness, or schizophrenia, randomized, double blind, and controlled clinical trial.
Randomized, double-blind, placebo-controlled, monotherapy studies of anti-psychotics in both bipolar disorder and schizophrenia were prioritized.
Absolute risk increase (ARI) or reduction (ARR) and the numbers needed to treat to harm (NNTH) or benefit (NNTB) for the discontinuation due to adverse events and somnolence relative to placebo were estimated.
Ten acute trials in mania, 3 in bipolar depression, and 8 in schizophrenia were identified, along with 2 maintenance studies in bipolar disorder and 2 in schizophrenia. In schizophrenia, ziprasidone caused significantly more discontinuations due to adverse events than placebo, with an NNTH of 19, while aripiprazole caused significantly fewer discontinuations due to adverse events than placebo, with an NNTB of 12. In mania, there was no statistically significant difference in discontinuation due to adverse events between antipsychotics and placebo. However, in bipolar depression, both quetiapine and olanzapine caused more discontinuations due to adverse events than placebo, with NNTHs of 7 and 24, respectively. All atypical antipsychotics caused a significantly greater incidence of somnolence than placebo in mania and depression, with NNTHs from 5 to 8 for mania and 2 to 6 for depression. In schizophrenia, only olanzapine, ziprasidone, and aripiprazole (NNTHs from 5 to 14) caused a significantly higher incidence of somnolence. There was no significant difference between schizophrenia and mania in the discontinuation due to adverse events or somnolence of all studied antipsychotics. However, there was a significantly higher incidence of discontinuation due to adverse events and somnolence caused by quetiapine in bipolar depression than that in schizophrenia or mania.
Patients with bipolar disorder appear more sensitive to antipsychotics, and depressed patients are less tolerant to somnolence than those with either mania or schizophrenia.
The Journal of Clinical Psychiatry 03/2008; 69(2):302-9. · 5.80 Impact Factor
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ABSTRACT: For the majority of patients with bipolar disorder, major depressive episodes represent the most debilitating and difficult-to-treat illness dimension. Patients spend significantly more time depressed than manic or hypomanic, and attempt suicide more frequently during this illness phase, yet the availability of treatments remains limited. The discovery of more effective therapeutics for managing depressive episodes is arguably the greatest unmet need in bipolar disorder. This article provides an evidence-based summary of pharmacological treatments for the acute and longitudinal management of bipolar depression. Clinical trial results are reviewed for a diverse array of compounds, inclusive of traditional mood stabilizers (eg, lithium and divalproex), atypical antipsychotics, unimodal antidepressants, and modafinil. Where applicable, differences in efficacy across compounds are examined through discussion of number needed to treat and effect size determinations. A pragmatic clinical approach is presented for management of the depressed phase of bipolar disorder.
Dialogues in clinical neuroscience 02/2008; 10(2):181-92.
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ABSTRACT: The essential features of bipolar affective disorder involve the cyclical occurrence of high (manic or hypomanic episodes) and low mood states. Depressive episodes in both bipolar I and II disorder are more numerous and last for longer duration than either manic or hypomanic episodes. In addition depressive episodes are associated with higher morbidity and mortality. While multiple agents, including all 5 atypical antipsychotics, have demonstrated efficacy and earned US FDA indication for manic phase of bipolar illness, the acute treatment of bipolar depression is less well-studied. The first treatment approved by the US FDA for acute bipolar depression was the combination of the atypical antipsychotic olanzapine and the antidepressant fluoxetine. Recently, quetiapine monotherapy has demonstrated efficacy in the treatment of depressive episodes associated with both bipolar I and II disorder and has earned US FDA indication for the same.
Neuropsychiatric Disease and Treatment 01/2008; 3(6):847-53. · 1.81 Impact Factor
