scholarly journals Bipolar depression: trial-based insights to guide patient care

2008 ◽  
Vol 10 (2) ◽  
pp. 181-192 ◽  
Keyword(s):  
Bipolar Disorder ◽  
Bipolar Depression ◽  
Unmet Need ◽  
Mood Stabilizers ◽  
Number Needed To Treat ◽  
Clinical Approach ◽  
Clinical Trial Results ◽  
Major Depressive Episodes ◽  
Depressive Episodes ◽  
Illness Phase

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.

Treatment of Bipolar Disorder During the Postpartum Period

CNS Spectrums ◽  
2006 ◽  
Vol 11 (S5) ◽  
pp. 13-14
Author(s):  
Adele C. Viguera
Keyword(s):  
Bipolar Disorder ◽  
Postpartum Period ◽  
Clinical Information ◽  
Mood Stabilizer ◽  
Mood Stabilizers ◽  
Antipsychotic Treatment ◽  
Close Monitoring ◽  
Major Congenital Malformations ◽  
Major Depressive Episodes ◽  
Depressive Episodes

AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.

scholarly journals Age at onset, course of illness and response to psychotherapy in bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

2014 ◽  
Vol 44 (16) ◽  
pp. 3455-3467 ◽  
Author(s):  
A. Peters ◽  
L. G. Sylvia ◽  
P. V. da Silva Magalhães ◽  
D. J. Miklowitz ◽  
E. Frank ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Collaborative Care ◽  
Bipolar Depression ◽  
Age At Onset ◽  
Number Needed To Treat ◽  
Systematic Treatment ◽  
Illness Duration ◽  
Bipolar Patients ◽  
Depressive Episodes ◽  
Intensive Psychotherapy

Background.The course of bipolar disorder progressively worsens in some patients. Although responses to pharmacotherapy appear to diminish with greater chronicity, less is known about whether patients' prior courses of illness are related to responses to psychotherapy.Method.Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy with collaborative care (a three-session psycho-educational intervention). We assessed whether the number of previous mood episodes, age of illness onset, and illness duration predicted or moderated the likelihood of recovery and time until recovery from a depressive episode in patients in the two treatments.Results.Independently of treatment condition, participants with one to nine prior depressive episodes were more likely to recover and had faster time to recovery than those with 20 or more prior depressive episodes. Participants with fewer than 20 prior manic episodes had faster time to recovery than those with 20 or more episodes. Longer illness duration predicted a longer time to recovery. Participants were more likely to recover in intensive psychotherapy than collaborative care if they had 10–20 prior episodes of depression [number needed to treat (NNT) = 2.0], but equally likely to respond to psychotherapy and collaborative care if they had one to nine (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes.Conclusions.Number of previous mood episodes and illness duration are associated with the likelihood and speed of recovery among bipolar patients receiving psychosocial treatments for depression.

Effects of In Utero Exposure to AEDs on Morphology and Neurodevelopment

CNS Spectrums ◽  
2006 ◽  
Vol 11 (S5) ◽  
pp. 9-10
Author(s):  
Martha J. Morrell
Keyword(s):  
Bipolar Disorder ◽  
Clinical Information ◽  
Mood Stabilizer ◽  
Mood Stabilizers ◽  
Antipsychotic Treatment ◽  
Close Monitoring ◽  
History Of ◽  
Major Congenital Malformations ◽  
Major Depressive Episodes ◽  
Depressive Episodes

AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.

Effects of the Female Reproductive System on Bipolar Disorder

CNS Spectrums ◽  
2006 ◽  
Vol 11 (S5) ◽  
pp. 5-6
Author(s):  
Terence A. Ketter
Keyword(s):  
Bipolar Disorder ◽  
Reproductive System ◽  
Clinical Information ◽  
Mood Stabilizer ◽  
Mood Stabilizers ◽  
Antipsychotic Treatment ◽  
Close Monitoring ◽  
Female Reproductive System ◽  
Major Depressive Episodes ◽  
Depressive Episodes

AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.

A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes

2014 ◽  
Vol 45 (4) ◽  
pp. 693-704 ◽  
Author(s):  
A. McGirr ◽  
M. T. Berlim ◽  
D. J. Bond ◽  
M. P. Fleck ◽  
L. N. Yatham ◽  
...  
Keyword(s):  
Clinical Remission ◽  
Bipolar Depression ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Number Needed To Treat ◽  
Major Depressive ◽  
Double Blind ◽  
Major Depressive Episodes ◽  
Depressive Episodes ◽  
Rapid Treatment

BackgroundThere is growing interest in glutamatergic agents in depression, particularly ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. We aimed to assess the efficacy of ketamine in major depressive episodes.MethodWe searched EMBASE, PsycINFO, CENTRAL, and Medline from 1962 to January 2014 to identify double-blind, randomized controlled trials with allocation concealment evaluating ketamine in major depressive episodes. Clinical remission, response and depressive symptoms were extracted by two independent raters. The primary outcome measure was clinical remission at 24 h, 3 days and 7 days post-treatment. Analyses employed a random-effects model.ResultsData were synthesized from seven RCTs employing an intravenous infusion and one RCT employing intranasal ketamine, representing 73 subjects in parallel arms and 110 subjects in cross-over designs [n = 34 with bipolar disorder (BD), n = 149 with major depressive disorder (MDD)]. Ketamine was associated with higher rates of clinical remission relative to comparator (saline or midazolam) at 24 h [OR 7.06, number needed to treat (NNT) = 5], 3 days (OR 3.86, NNT = 6), and 7 days (OR 4.00, NNT = 6), as well as higher rates of clinical response at 24 h (OR 9.10, NNT = 3), 3 days (OR 6.77, NNT = 3), and 7 days (OR 4.87, NNT = 4). A standardized mean difference of 0.90 in favor of ketamine was observed at 24 h based on depression rating scale scores, with group comparisons revealing greater efficacy in unipolar depression compared to bipolar depression (1.07 v. 0.68). Ketamine was associated with transient psychotomimetic effects, but no persistent psychosis or affective switches.ConclusionOur meta-analysis suggests that single administrations ketamine are efficacious in the rapid treatment of unipolar and bipolar depression. Additional research is required to determine optimal dosing schedules, route, treatment schedules, and the potential efficacy of other glutamatergic agents.

Treatment of Bipolar Disorder During Pregnancy

CNS Spectrums ◽  
2006 ◽  
Vol 11 (S5) ◽  
pp. 11-12
Author(s):  
Lee S. Cohen
Keyword(s):  
Bipolar Disorder ◽  
Clinical Information ◽  
Mood Stabilizer ◽  
Mood Stabilizers ◽  
Antipsychotic Treatment ◽  
Close Monitoring ◽  
History Of ◽  
Major Congenital Malformations ◽  
Major Depressive Episodes ◽  
Depressive Episodes

AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.

Treatment of mixed features in bipolar disorder

CNS Spectrums ◽  
2016 ◽  
Vol 22 (2) ◽  
pp. 141-146 ◽  
Author(s):  
Joshua D. Rosenblat ◽  
Roger S. McIntyre
Keyword(s):  
Bipolar Disorder ◽  
Bipolar Depression ◽  
Treatment Resistance ◽  
Course Of Illness ◽  
Stabilizing Agents ◽  
Dsm 5 ◽  
Mixed Features ◽  
Post Hoc ◽  
Major Depressive Episodes ◽  
Depressive Episodes

Mood episodes with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)–defined mixed features are highly prevalent in bipolar disorder (BD), affecting ~40% of patients during the course of illness. Mixed states are associated with poorer clinical outcomes, greater treatment resistance, higher rates of comorbidity, more frequent mood episodes, and increased rates of suicide. The objectives of the current review are to identify, summarize, and synthesize studies assessing the efficacy of treatments specifically for BD I and II mood episodes (ie, including manic, hypomanic, and major depressive episodes) with DSM-5–defined mixed features. Two randomized controlled trials (RCTs) and 6 post-hoc analyses were identified, all of which assessed the efficacy of second-generation antipsychotics (SGAs) for the acute treatment of BD mood episodes with mixed features. Results from these studies provide preliminary support for SGAs as efficacious treatments for both mania with mixed features and bipolar depression with mixed features. However, there are inadequate data to definitively support or refute the clinical use of specific agents. Conventional mood stabilizing agents (eg, lithium and divalproex) have yet to have been adequately studied in DSM-5–defined mixed features. Further study is required to assess the efficacy, safety, and tolerability of treatments specifically for BD mood episodes with mixed features.

Treatment of bipolar depression: making sensible decisions

CNS Spectrums ◽  
2014 ◽  
Vol 19 (S1) ◽  
pp. 1-12 ◽  
Author(s):  
Leslie Citrome
Keyword(s):  
Weight Gain ◽  
Adverse Events ◽  
Bipolar Depression ◽  
Similar Efficacy ◽  
Number Needed To Treat ◽  
Major Depressive ◽  
High Urgency ◽  
Poor Outcomes ◽  
Major Depressive Episodes ◽  
Depressive Episodes

A major challenge in the treatment of major depressive episodes associated with bipolar disorder is differentiating this illness from major depressive episodes associated with major depressive disorder. Mistaking the former for the latter will lead to incorrect treatment and poor outcomes. None of the classic antidepressants, serotonin specific reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors have ever received regulatory approval as monotherapies for the treatment of bipolar depression. At present, there are only 3 approved medication treatments for bipolar depression: olanzapine/fluoxetine combination, quetiapine (immediate or extended release), and lurasidone (monotherapy or adjunctive to lithium or valproate). All 3 have similar efficacy profiles, but they differ in terms of tolerability. Number needed to treat (NNT) and number needed to harm (NNH) can be used to quantify these similarities and differences. The NNTs for response and remission for each of these interventions vs placebo range from 4 to 7, and 5 to 7, respectively, with overlap in terms of their 95% confidence intervals. NNH values less than 10 (vs placebo) were observed for the spontaneously reported adverse events of weight gain and diarrhea for olanzapine/fluoxetine combination (7 and 9, respectively) and somnolence and dry mouth for quetiapine (3 and 4, respectively). There were no NNH values less than 10 (vs placebo) observed with lurasidone treatment. NNH values vs placebo for weight gain of at least 7% from baseline were 6, 16, 58, and 36, for olanzapine/fluoxetine combination, quetiapine, lurasidone monotherapy, and lurasidone combined with lithium or valproate, respectively. Individualizing treatment decisions will require consideration of the different potential adverse events that are more likely to occur with each medication. The metric of the likelihood to be helped or harmed (LHH) is the ratio of NNH to NNT and can illustrate the tradeoffs inherent in selecting medications. A more favorable LHH was noted for treatment with lurasidone. However, OFC and quetiapine monotherapy may still have utility in high urgency situations, particularly in persons who have demonstrated good outcomes with these interventions in the past, and where a pressing clinical need for efficacy mitigates their potential tolerability shortcomings. In terms of maintenance therapy, adjunctive quetiapine is the only agent where the NNT vs lithium or valproate alone is less than 10 for both the prevention of mania and the prevention of depression.

Pharmacological Treatments for Bipolar Disorder

2007 ◽  
pp. 323-350 ◽  
Author(s):  
Paul E. Keck ◽  
Susan L. McElroy
Keyword(s):  
Bipolar Disorder ◽  
Bipolar Depression ◽  
Antidepressant Treatment ◽  
Bipolar Disorders ◽  
Mood Stabilizers ◽  
Pharmacological Management ◽  
Randomized Controlled ◽  
Bipolar Ii ◽  
Depressive Episodes ◽  
Subsyndromal Symptoms

The vast majority of clinical trials in patients with bipolar disorders have been conducted in groups with bipolar I illness, although a few trials have recently emerged specifically in patients with bipolar II disorder. The pharmacological management of bipolar disorder involves the treatment of acute manic, hypomanic, mixed, and depressive episodes, as well as the prevention of further episodes and subsyndromal symptoms. Lithium, divalproex, carbamazepine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole have demonstrated efficacy in the treatment of acute mania in randomized, controlled (Type 1) trials. Although the pharmacological treatment of acute bipolar depression remains understudied, data from randomized, controlled trials indicate that lithium, olanzapine, olanzapine-fluoxetine, quetiapine, lamotrigine, tricyclics, MAOIs, fluoxetine, and pramipexole have efficacy in this phase of the illness. The optimal duration of antidepressant treatment, in combination with mood stabilizers, is still unknown. Lithium, lamotrigine, olanzapine, and aripiprazole have been shown to have efficacy in relapse prevention. Less extensive data suggest that divalproex and carbamazepine are also efficacious as preventative treatments.

Selection of Appropriate Therapy: Valproate and Reproductive Function

CNS Spectrums ◽  
2006 ◽  
Vol 11 (S5) ◽  
pp. 7-9
Author(s):  
Natalie Rasgon
Keyword(s):  
Bipolar Disorder ◽  
Reproductive Function ◽  
Clinical Information ◽  
Mood Stabilizer ◽  
Mood Stabilizers ◽  
Antipsychotic Treatment ◽  
Close Monitoring ◽  
Major Congenital Malformations ◽  
Major Depressive Episodes ◽  
Depressive Episodes

AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.

Sign in / Sign up

Export Citation Format

Share Document