Chief, Bipolar Disorders Clinic, Stanford University School of Medicine (2017 - Present)
Education & Certifications
Residency:Stanford University School of Medicine (2009) CA
Medical Education:Columbia University College of Physicians and Surgeons (2005) NY
Board Certification: Psychiatry, American Board of Psychiatry and Neurology (2010)
Lifetime eating disorder comorbidity associated with delayed depressive recovery in bipolar disorder.
International journal of bipolar disorders
2017; 5 (1): 25-?
Although eating disorders (EDs) are common in bipolar disorder (BD), little is known regarding their longitudinal consequences. We assessed prevalence, clinical correlates, and longitudinal depressive severity in BD patients with vs. without EDs.Outpatients referred to Stanford University BD Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) affective disorders evaluation, and while receiving naturalistic treatment for up to 2 years, were monitored with the STEP-BD clinical monitoring form. Patients with vs. without lifetime EDs were compared with respect to prevalence, demographic and unfavorable illness characteristics/current mood symptoms and psychotropic use, and longitudinal depressive severity.Among 503 BD outpatients, 76 (15.1%) had lifetime EDs, which were associated with female gender, and higher rates of lifetime comorbid anxiety, alcohol/substance use, and personality disorders, childhood BD onset, episode accumulation (≥10 prior mood episodes), prior suicide attempt, current syndromal/subsyndromal depression, sadness, anxiety, and antidepressant use, and earlier BD onset age, and greater current overall BD severity. Among currently depressed patients, 29 with compared to 124 without lifetime EDs had significantly delayed depressive recovery. In contrast, among currently recovered (euthymic ≥8 weeks) patients, 10 with compared to 95 without lifetime EDs had only non-significantly hastened depressive recurrence.Primarily Caucasian, insured, suburban, American specialty clinic-referred sample limits generalizability. Small number of recovered patients with EDs limited statistical power to detect relationships between EDs and depressive recurrence.Further studies are warranted to explore the degree to which EDs impact longitudinal depressive illness burden in BD.
View details for DOI 10.1186/s40345-017-0094-4
View details for PubMedID 28480483
American tertiary clinic-referred bipolar II disorder versus bipolar I disorder associated with hastened depressive recurrence.
International journal of bipolar disorders
2017; 5 (1): 2-?
Bipolar disorder (BD) is a chronic, frequently comorbid condition characterized by high rates of mood episode recurrence and suicidality. Little is known about prospective longitudinal characterization of BD type II (BD II) versus type I (BD I) in relation to time to depressive recurrence and recovery from major depressive episode. We therefore assessed times to depressive recurrence/recovery in tertiary clinic-referred BD II versus I patients.Outpatients referred to Stanford BD Clinic during 2000-2011 were assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and with Clinical Monitoring Form during up to 2 years of naturalistic treatment. Prevalence and clinical correlates of bipolar subtype in recovered (euthymic ≥8 weeks) and depressed patients were assessed. Kaplan-Meier analyses assessed the relationships between bipolar subtype and longitudinal depressive severity, and Cox proportional hazard analyses assessed the potential mediators.BD II versus BD I was less common among 105 recovered (39.0 vs. 61.0%, p = 0.03) and more common among 153 depressed (61.4 vs. 38.6%, p = 0.006) patients. Among recovered patients, BD II was associated with 6/25 (24.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics and hastened depressive recurrence (p = 0.015). Among depressed patients, BD II was associated with 8/25 (33.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics, but only non-significantly associated with delayed depressive recovery.BD II versus BD I was significantly associated with current depression and hastened depressive recurrence, but only non-significantly associated with delayed depressive recovery. Research on bipolar subtype relationships with depressive recurrence/recovery is warranted to enhance clinical management of BD patients.
View details for DOI 10.1186/s40345-017-0072-x
View details for PubMedID 28124233
View details for PubMedCentralID PMC5267582
Abnormal sleep duration associated with hastened depressive recurrence in bipolar disorder.
Journal of affective disorders
2017; 218: 374-379
Abnormal sleep duration (ASD, <6 or ≥9h) is common in bipolar disorder (BD), and often persists beyond acute mood episodes. Few longitudinal studies have examined the ASD's impact upon BD illness course. The current study examined the longitudinal impact of ASD upon bipolar depressive recurrence/recovery.Outpatients referred to the Stanford BD Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation at baseline, and with the Clinical Monitoring Form at monthly follow-ups for up to two years of naturalistic treatment. Prevalence and clinical correlates of ASD in 93 recovered (euthymic ≥8 weeks) and 153 depressed BD patients were assessed. Kaplan-Meier analyses (Log-Rank tests) assessed relationships between baseline ASD and longitudinal depressive severity, with Cox Proportional Hazard analyses assessing potential mediators.ASD was only half as common among recovered versus depressed BD outpatients, but was significantly associated with hastened depressive recurrence (Log-Rank p=0.007), mediated by lifetime anxiety disorder and attenuated by lifetime history of psychosis, and had only a non-significant tendency towards association with delayed depressive recovery (Log-Rank p=0.07). In both recovered and depressed BD outpatients, baseline ASD did not have significant association with any baseline BD illness characteristic.Self-reported sleep duration. Limited generalizability beyond our predominately white, female, educated, insured American BD specialty clinic sample.Baseline ASD among recovered BD patients may be a risk marker for hastened depressive recurrence, suggesting it could be an important therapeutic target between mood episodes.
View details for DOI 10.1016/j.jad.2017.05.015
View details for PubMedID 28500982
Lifetime anxiety disorder and current anxiety symptoms associated with hastened depressive recurrence in bipolar disorder.
Journal of affective disorders
2017; 219: 165-171
To assess differential relationships between lifetime anxiety disorder/current anxiety symptoms and longitudinal depressive severity in bipolar disorder (BD).Stanford BD Clinic outpatients enrolled during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and followed with the STEP-BD Clinical Monitoring Form while receiving naturalistic treatment for up to two years. Baseline unfavorable illness characteristics/current mood symptoms and times to depressive recurrence/recovery were compared in patients with versus without lifetime anxiety disorder/current anxiety symptoms.Among 105 currently recovered patients, lifetime anxiety disorder was significantly associated with 10/27 (37.0%) demographic/other unfavorable illness characteristics/current mood symptoms/current psychotropics, hastened depressive recurrence (driven by earlier onset age), and a significantly (> two-fold) higher Kaplan-Meier estimated depressive recurrence rate, whereas current anxiety symptoms were significantly associated with 10/27 (37.0%) demographic/other unfavorable illness characteristics/current mood symptoms/current psychotropics and hastened depressive recurrence (driven by lifetime anxiety disorder), but only a numerically higher Kaplan-Meier estimated depressive recurrence rate. In contrast, among 153 currently depressed patients, lifetime anxiety disorder/current anxiety symptoms were not significantly associated with time to depressive recovery or depressive recovery rate.American tertiary BD clinic referral sample, open naturalistic treatment.Research is needed regarding differential relationships between lifetime anxiety disorder and current anxiety symptoms and hastened/delayed depressive recurrence/recovery - specifically whether lifetime anxiety disorder versus current anxiety symptoms has marginally more robust association with hastened depressive recurrence, and whether both have marginally more robust associations with hastened depressive recurrence versus delayed depressive recovery, and related clinical implications.
View details for DOI 10.1016/j.jad.2017.05.007
View details for PubMedID 28558363
Current irritability associated with hastened depressive recurrence and delayed depressive recovery in bipolar disorder.
International journal of bipolar disorders
2016; 4 (1): 15-?
Current irritability is associated with greater retrospective and current bipolar disorder (BD) illness severity; less is known about prospective longitudinal implications of current irritability. We examined relationships between current irritability and depressive recurrence and recovery in BD.Outpatients referred to the Stanford BD Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation at baseline, and with the Clinical Monitoring Form during follow-up during up to 2 years of naturalistic treatment. Prevalence and clinical correlates of any current irritability in depressed and recovered (euthymic ≥8 weeks) BD patients were assessed. Kaplan-Meier analyses (Log-Rank tests) assessed relationships between current irritability and longitudinal depressive severity, with Cox Proportional Hazard analyses assessing potential mediators.Recovered BD outpatients with vs. without current irritability had significantly higher rates of 13/19 (68.4 %) other baseline unfavorable illness characteristics/current mood symptoms and hastened depressive recurrence (Log-Rank p = 0.020), driven by lifetime history of anxiety disorder and prior year rapid cycling, and attenuated by history of psychosis. Depressed BD outpatients with vs. without current irritability had significantly higher rates of 7/19 (36.8 %) other unfavorable illness characteristics/current mood symptoms and delayed depressive recovery (Log-Rank p = 0.034), NOT mediated by any assessed parameter.Limited generalizability beyond our predominately white, female, educated, insured American BD specialty clinic sample.Current irritability was associated with hastened depressive recurrence and delayed depressive recovery in BD. Treatment studies targeting irritability may yield strategies to mitigate increased longitudinal depressive burden.
View details for DOI 10.1186/s40345-016-0056-2
View details for PubMedID 27473754
View details for PubMedCentralID PMC4967068
Age at onset in patients with bipolar I and II disorder: a comparison of large sample studies
JOURNAL OF AFFECTIVE DISORDERS
2016; 201: 57-63
Bipolar Disorder (BD) is a leading cause of disability worldwide and factors contributing to its burden include chronic relapsing course, comorbidity, suicide risk, and early age at onset (AAO). In particular, recent investigation has shown that BD onset may occur earlier than previously believed, even though whether BDI and II are different in such regard is still debated. Reduced samples may, moreover, limit the confidence in the published studies, with geographic issues, in turn, representing potentially conditioning factors. The present review was aimed to select and analyze large sample studies comparing AAO in BDI vs II patients.A PubMed literature search was performed, considering English-written articles published up to December 2015, comparing AAO in BDI vs II patients with sample size≥100 subjects per group.Seventeen studies were considered suitable for revision, with 8 studies reporting statistically significant differences and 9 not. Among studies reporting statistically significant differences, mostly conducted in Europe, 6 showed an earlier AAO in BDI, while 2 in BDII subjects.Only studies with large samples included, considering AAO as a continuous variable, and providing a comparison between the bipolar subtypes.Our findings suggest that AAO per se does not seem to reliably differentiate BDI from BDII patients and that such variable should likely be investigated in the context of other clinical characteristics, in order to assess its overall influence over BD course. Geographic factors may, in turn, play a potential role with future investigation warranted to further explore this specific issue.
View details for DOI 10.1016/j.jad.2016.04.009
View details for Web of Science ID 000377392900009
View details for PubMedID 27177297
Current irritability robustly related to current and prior anxiety in bipolar disorder
JOURNAL OF PSYCHIATRIC RESEARCH
2016; 79: 101-107
Although current irritability and current/prior anxiety have been associated in unipolar depression, these relationships are less well understood in bipolar disorder (BD). We investigated relationships between current irritability and current/prior anxiety as well as other current emotions and BD illness characteristics.Outpatients referred to the Stanford Bipolar Disorders Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Prevalence and clinical correlates of current irritability and current/prior anxiety and other illness characteristics were examined.Among 497 BD outpatients (239 Type I, 258 Type II; 58.1% female; mean ± SD age 35.6 ± 13.1 years), 301 (60.6%) had baseline current irritability. Patients with versus without current irritability had significantly higher rates of current anxiety (77.1% versus 42.9%, p < 0.0001) and history of anxiety disorder (73.1% versus 52.6%, p < 0.0001). Current irritability was more robustly related to current anxiety than to current anhedonia, sadness, or euphoria (all p < 0.001), and current irritability-current anxiety associations persisted across current predominant mood states. Current irritability was more robustly related to past anxiety than to all other assessed illness characteristics, including 1° family history of mood disorder, history of alcohol/substance use disorder, bipolar subtype, and current syndromal/subsyndromal depression (all p < 0.05).Limited generalizability beyond our predominately white, female, educated, insured American BD specialty clinic sample.In BD, current irritability was robustly related to current/prior anxiety. Further studies are warranted to assess longitudinal clinical implications of relationships between irritability and anxiety in BD.
View details for DOI 10.1016/j.jpsychires.2016.05.006
View details for Web of Science ID 000378179000015
View details for PubMedID 27218815
Gender by onset age interaction may characterize distinct phenotypic subgroups in bipolar patients
JOURNAL OF PSYCHIATRIC RESEARCH
2016; 76: 128-135
Although bipolar disorder (BD) is a common recurrent condition with highly heterogeneous illness course, data are limited regarding clinical implications of interactions between gender and onset age. We assessed relationships between onset age and demographic/illness characteristics among BD patients stratified by gender.Demographic and unfavorable illness characteristics, descriptive traits, and clinical correlates were compared in 502 patients from Stanford University BD Clinic patients enrolled in the Systematic Treatment Enhancement Program for BD between 2000 and 2011, stratified by gender, across pre-, peri-, and post-pubertal (<12, 13-16, and >17 years, respectively) onset-age subgroups.Among 502 BD patients, 58.2% were female, of whom 21.9% had pre-pubertal, 30.7% peri-pubertal, and 47.4% post-pubertal onset. Between genders, although demographics, descriptive characteristics, and most clinical correlates were statistically similar, there were distinctive onset-age related patterns of unfavorable illness characteristics. Among females, rates of 6/8 primary unfavorable illness characteristics were significantly higher in pre-pubertal and peri-pubertal compared to post-pubertal onset patients. However, among males, rates of only 3/8 unfavorable illness characteristics were significantly higher in only pre-pubertal versus post-pubertal onset patients, and none between peri-pubertal versus post-pubertal onset patients.Caucasian, insured, suburban, American specialty clinic-referred sample limits generalizability, onset age based on retrospective recall.We describe different phenotypic presentations across age at illness onset groups according to gender. Among females and males, peri-pubertal and post-pubertal onset age groups were more different and more similar, respectively. Further investigation is warranted to assess implications of gender-by-onset-age interactions to more accurately delineate distinctive BD phenotypes.
View details for DOI 10.1016/j.jpsychires.2016.02.009
View details for Web of Science ID 000373412400016
View details for PubMedID 26926801
Differential prevalence and demographic and clinical correlates of second-generation antipsychotic use in bipolar I versus bipolar II disorder
JOURNAL OF PSYCHIATRIC RESEARCH
2016; 76: 52-58
To assess second-generation antipsychotic (SGA) use, demographics, and clinical correlates in patients with bipolar I disorder (BDI) versus bipolar II disorder (BDII).Stanford Bipolar Disorder (BD) Clinic outpatients enrolled during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Current SGA use, demographics, and clinical correlates were assessed for BDI versus BDII.Among 503 BD outpatients, in BDI versus BDII, SGA use was more than twice as common (44.0% versus 21.2%), and doses were approximately twice as high. BDI patients taking (N = 107) versus not taking (N = 136) SGAs less often had current full time employment and college degree; and more often had lifetime psychiatric hospitalization, current depression, and current complex pharmacotherapy, and had a higher mean current Clinical Global Impression for Bipolar Version Overall Severity score, and these persisted significantly after covarying for employment and education. Prior psychiatric hospitalization was the most robust correlate of SGA use in BDI patients. In contrast, these demographic and clinical correlates of SGA use were not statistically significant among patients with BDII, although BDII (but not BDI) patients taking (N = 55) versus not taking (N = 205) SGAs were more likely to have current mood stabilizer use (67.3% versus 51.7%).American tertiary bipolar disorder clinic referral sample, cross-sectional design.Current SGA use was robustly associated with prior psychiatric hospitalization in BDI and to a more limited extent with current mood stabilizer use in BDII. SGA use associations with other unfavorable illness characteristics in BDI were less robust.
View details for DOI 10.1016/j.jpsychires.2016.01.016
View details for Web of Science ID 000373412400007
View details for PubMedID 26874463
Different characteristics associated with suicide attempts among bipolar I versus bipolar II disorder patients
JOURNAL OF PSYCHIATRIC RESEARCH
2016; 76: 94-100
Suicide attempts are common in patients with bipolar disorder (BD), and consistently associated with female gender and certain unfavorable BD illness characteristics. Findings vary, however, regarding effects of BD illness subtype and yet other illness characteristics upon prior suicide attempt rates. We explored the effects of demographics and BD illness characteristics upon prior suicide attempt rates in patients stratified by BD illness subtype (i.e., with bipolar I disorder (BDI) versus bipolar II disorder (BDII)).Outpatients referred to the Stanford BD Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Rates of prior suicide attempt were compared in patients with and without diverse demographic and BD illness characteristics stratified by BD subtype.Among 494 BD outpatients (mean ± SD age 35.6 ± 13.1 years; 58.3% female; 48.6% BDI, 51.4% BDII), overall prior suicide attempt rates in were similar in BDI versus BDII patients, but approximately twice as high in BDI (but not BDII) patients with compared to without lifetime eating disorder, and in BDII (but not BDI) patients with compared to without childhood BD onset. In contrast, current threshold-level suicidal ideation and lifetime alcohol use disorder robustly but less asymmetrically increased prior suicide attempt risk across BD subtypes.American tertiary bipolar disorder clinic referral sample, cross-sectional design.Further studies are needed to assess the extent to which varying clinical characteristics of samples of patients with BDI and BDII could yield varying prior suicide attempt rates in patients with BDI versus BDII.
View details for DOI 10.1016/j.jpsychires.2016.02.006
View details for Web of Science ID 000373412400012
View details for PubMedID 26921874
The Prevalence and Diagnostic Validity of Short-Duration Hypomanic Episodes and Major Depressive Episodes.
Current psychiatry reports
2016; 18 (3): 27-?
Current diagnostic criteria for a hypomanic episode, as outlined in both the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV and DSM-5), require a minimum duration of four consecutive days of symptoms of mood elevation. The 4-day criterion for duration of hypomania has been challenged as arbitrary and lacking empirical support, with many arguing that shorter-duration hypomanic episodes are highly prevalent and that those experiencing these episodes are clinically more similar to patients with bipolar disorder than to those with unipolar major depressive disorder. We review the current evidence regarding the prevalence, diagnostic validity, and longitudinal illness correlates of shorter-duration hypomanic episodes and summarize the arguments for and against broadening the diagnostic criteria for hypomania to include shorter-duration variants. Accumulating findings suggest that patients with major depressive episodes and shorter-duration hypomanic episodes represent a complex clinical phenotype, perhaps best conceptualized as being on the continuum between those with unipolar depressive episodes alone and those with DSM-5-defined bipolar II disorder. Further investigation is warranted, ideally involving large prospective, controlled studies, to elucidate the diagnostic and treatment implications of depression with shorter-duration hypomanic episodes.
View details for DOI 10.1007/s11920-016-0669-2
View details for PubMedID 26830885
Italian Bipolar II vs I patients have better individual functioning, in spite of overall similar illness severity.
Introduction Bipolar disorders (BDs) comprise different variants of chronic, comorbid, and disabling conditions, with relevant suicide and suicide attempt rates. The hypothesis that BD types I (BDI) and II (BDII) represent more and less severe forms of illness, respectively, has been increasingly questioned over recent years, justifying additional investigation to better characterize related sociodemographic and clinical profiles.A sample of 217 outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)-described BD (141 BDI, 76 BDII), without a current syndromal mood episode, was recruited, and sociodemographic and clinical characteristics of BDI and II patients were compared.BDII patients had significantly more favorable sociodemographics, in relation to occupational stability, cohabitation, and marital status. However, BDII compared with BDI patients had significantly longer duration of untreated illness, more frequent lifetime anxiety disorders comorbidity, longer most recent episode duration, higher rate of depressive first/most recent episode, and more current antidepressant use. In contrast, BDI compared with BDII patients had significantly more severe illness in terms of earlier age at onset; higher rate of elevated first/most recent episode, lifetime hospitalizations, and involuntary commitments; lower Global Assessment of Functioning score; and more current antipsychotic use. BDI and II patients had similar duration of illness, psychiatric family history, lifetime number of suicide attempts, current subthreshold symptoms, history of stressful life events, and overall psychiatric/medical comorbidity.BDII compared with BDI patients had more favorable sociodemographic features, but a mixture of specific unfavorable illness characteristics, confirming that BDII is not just a milder form of BD and requires further investigation in the field.
View details for PubMedID 26905615
- Treatment of bipolar disorder: Review of evidence regarding quetiapine and lithium JOURNAL OF AFFECTIVE DISORDERS 2016; 191: 256-273
American tertiary clinic-referred bipolar II disorder compared to bipolar I disorder: More severe in multiple ways, but less severe in a few other ways
JOURNAL OF AFFECTIVE DISORDERS
2015; 188: 257-262
Prevalence and relative severity of bipolar II disorder (BDII) vs. bipolar I disorder (BDI) are controversial.Prevalence, demographics, and illness characteristics were compared among 260 BDII and 243 BDI outpatients referred to the Stanford University BD Clinic and assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation.BDII vs. BDI outpatients had statistically similar prevalence (51.7% vs. 48.3%), and in multiple ways had more severe illness, having significantly more often: lifetime comorbid anxiety (70.8% vs. 58.4%) and personality (15.4% vs. 7.4%) disorders, first-degree relative with mood disorder (62.3% vs. 52.3%), at least 10 prior mood episodes (80.0% vs. 50.9%), current syndromal/subsyndromal depression (52.3% vs. 38.4%), current antidepressant use (47.3% vs. 31.3%), prior year rapid cycling (33.6% vs. 13.4%), childhood onset (26.2% vs. 16.0%), as well as earlier onset age (17.0±8.6 vs. 18.9±8.1 years), longer illness duration (19.0±13.0 vs. 16.1±13.0), and higher current Clinical Global Impression for Bipolar Disorder-Overall Severity (4.1±1.4 vs. 3.7±1.5). However, BDII vs. BDI patients significantly less often had prior psychosis (14.2% vs. 64.2%), psychiatric hospitalization (10.0% vs. 67.9%), and current prescription psychotropic use, (81.5% vs. 93.0%), and had a statistically similar rate of prior suicide attempt (29.5% vs. 32.1%).American tertiary bipolar disorder clinic referral sample, cross-sectional design.Further studies are warranted to determine the extent to which BDII, compared to BDI, can be more severe in multiple ways but less severe in a few other ways, and contributors to occurrence of more severe forms of BDII.
View details for DOI 10.1016/j.jad.2015.09.001
View details for Web of Science ID 000364168100036
View details for PubMedID 26378735
COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL
DEPRESSION AND ANXIETY
2015; 32 (8): 594-604
Childhood maltreatment (CM) history has been associated with poor treatment response in major depressive disorder (MDD), but the mechanisms underlying this relationship remain opaque. Dysfunction in the neural circuits for executive cognition is a putative neurobiological consequence of CM that may contribute importantly to adverse clinical outcomes. We used behavioral and neuroimaging measures of executive functioning to assess their contribution to the relationship between CM and antidepressant response in MDD patients.Ninety eight medication-free MDD outpatients participating in the International Study to Predict Optimized Treatment in Depression were assessed at baseline on behavioral neurocognitive measures and functional magnetic resonance imaging during tasks probing working memory (continuous performance task, CPT) and inhibition (Go/No-go). Seventy seven patients completed 8 weeks of antidepressant treatment. Baseline behavioral and neuroimaging measures were assessed in relation to CM (history of childhood physical, sexual, and/or emotional abuse) and posttreatment depression outcomes.Patients with maltreatment exhibited decreased modulation of right dorsolateral prefrontal cortex (DLPFC) activity during working memory updating on the CPT, and a corresponding impairment in CPT behavioral performance outside the scanner. No between-group differences were found for imaging or behavior on the Go/No-go test of inhibition. Greater DLPFC activity during CPT significantly predicted posttreatment symptom improvement in patients without maltreatment, whereas the relationship between DLPFC activity and symptom change was nonsignificant, and in the opposite direction, in patients with maltreatment.The effect of CM on prefrontal circuitry involved in executive function is a potential predictor of antidepressant outcomes.
View details for DOI 10.1002/da.22368
View details for Web of Science ID 000358621900006
Childhood-compared to adolescent-onset bipolar disorder has more statistically significant clinical correlates
JOURNAL OF AFFECTIVE DISORDERS
2015; 179: 114-120
The strengths and limitations of considering childhood-and adolescent-onset bipolar disorder (BD) separately versus together remain to be established. We assessed this issue.BD patients referred to the Stanford Bipolar Disorder Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Patients with childhood- and adolescent-onset were compared to those with adult-onset for 7 unfavorable bipolar illness characteristics with replicated associations with early-onset patients.Among 502 BD outpatients, those with childhood- (<13 years, N=110) and adolescent- (13-18 years, N=218) onset had significantly higher rates for 4/7 unfavorable illness characteristics, including lifetime comorbid anxiety disorder, at least ten lifetime mood episodes, lifetime alcohol use disorder, and prior suicide attempt, than those with adult-onset (>18 years, N=174). Childhood- but not adolescent-onset BD patients also had significantly higher rates of first-degree relative with mood disorder, lifetime substance use disorder, and rapid cycling in the prior year. Patients with pooled childhood/adolescent - compared to adult-onset had significantly higher rates for 5/7 of these unfavorable illness characteristics, while patients with childhood- compared to adolescent-onset had significantly higher rates for 4/7 of these unfavorable illness characteristics.Caucasian, insured, suburban, low substance abuse, American specialty clinic-referred sample limits generalizability. Onset age is based on retrospective recall.Childhood- compared to adolescent-onset BD was more robustly related to unfavorable bipolar illness characteristics, so pooling these groups attenuated such relationships. Further study is warranted to determine the extent to which adolescent-onset BD represents an intermediate phenotype between childhood- and adult-onset BD.
View details for DOI 10.1016/j.jad.2015.03.019
View details for Web of Science ID 000354606500015
View details for PubMedID 25863906
Bipolar therapeutics update 2014: A tale of 3 treatments.
journal of clinical psychiatry
2015; 76 (1): 69-70
In the 2010s, advances in the treatment of bipolar disorder slowed, with only 1 agent approved by the US Food and Drug Administration (FDA) for acute bipolar I depression (in 2013), compared to the robust progress in the 2000s, during which 7 agents were approved for acute mania, 2 for acute bipolar depression, and 6 for bipolar disorder preventive treatment. This slowing of progress may have been in part due to decreased pharmaceutical company enthusiasm for developing compounds for psychiatric indications, as well as the tendency for periods of consolidation (development of derivative and better-tolerated treatments) to follow periods of rapid advances (development of efficacious novel treatments) in pharmacotherapy advancement.
View details for DOI 10.4088/JCP.14ac09649
View details for PubMedID 25650673
The prevalence and burden of bipolar depression.
Journal of affective disorders
2014; 169: S3-11
Bipolar disorder is characterized by debilitating episodes of depression and mood elevation (mania or hypomania). For most patients, depressive symptoms are more pervasive than mood elevation or mixed symptoms, and thus have been reported in individual studies to impose a greater burden on affected individuals, caregivers, and society. This article reviews and compiles the literature on the prevalence and burden of syndromal as well as subsyndromal presentations of depression in bipolar disorder patients.The PubMed database was searched for English-language articles using the search terms "bipolar disorder," "bipolar depression," "burden," "caregiver burden," "cost," "costs," "economic," "epidemiology," "prevalence," "quality of life," and "suicide." Search results were manually reviewed, and relevant studies were selected for inclusion as appropriate. Additional references were obtained manually from reviewing the reference lists of selected articles found by computerized search.In aggregate, the findings support the predominance of depressive symptoms compared with mood elevation/mixed symptoms in the course of bipolar illness, and thus an overall greater burden in terms of economic costs, functioning, caregiver burden, and suicide.This review, although comprehensive, provides a study-wise aggregate (rather than a patient-wise meta-analytic) summary of the relevant literature on this topic.In light of its pervasiveness and prevalence, more effective and aggressive treatments for bipolar depression are warranted to mitigate its profound impact upon individuals and society. Such studies could benefit by including metrics not only for mood outcomes, but also for illness burden.
View details for DOI 10.1016/S0165-0327(14)70003-5
View details for PubMedID 25533912
- Balancing benefits and harms of treatments for acute bipolar depression. Journal of affective disorders 2014; 169: S24-33
- The prevalence and burden of bipolar depression. Journal of affective disorders 2014; 169: S3-11
Trends in pharmacotherapy in patients referred to a bipolar specialty clinic, 2000-2011
JOURNAL OF AFFECTIVE DISORDERS
2014; 155: 283-287
To assess mood stabilizer (MS) and second-generation antipsychotic (SGA) prescribing trends in bipolar disorder (BD) outpatients referred to a bipolar disorder specialty clinic over the past 12 years.BD outpatients referred to the Stanford University Bipolar Disorder Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Prescription rates for MSs and SGAs were compared during the first (2000-2005) and second (2006-2011) six years.Among 597 BD patients (mean±SD age 35.4±8.6 years; 58.1% female; 40.7% Type I, 43.6% Type II, and 15.7% Type Not Otherwise Specified; taking 2.6±1.7 prescription psychotropic medications), lamotrigine, quetiapine, and aripiprazole usage more than doubled, from 14.7% to 37.2% (p<0.0001), 7.2% to 19.7% (p<0.0001), and 3.1% to 10.9% (p=0.0003), respectively, while olanzapine and risperidone use decreased by more than half from 15.0% to 6.6% (p=0.0043), and from 8.7% to 3.8% (p=0.039), respectively. SGA use increased from 34.1% to 44.8% (p=0.013), although MS use continued to be more common (in 65.2% for 2006-2011). Use of other individual MSs and SGAs and MSs as a class did not change significantly.Over 12 years, in patients referred to a BD specialty clinic, lamotrigine, quetiapine, and aripiprazole use more than doubled, and olanzapine and risperidone use decreased by more than half. Tolerability (for lamotrigine, aripiprazole, olanzapine, and risperidone) more than efficacy (for quetiapine) differences may have driven these findings. Additional studies are needed to explore the relative influences of enhanced tolerability versus efficacy upon prescribing practices in BD patients.
View details for DOI 10.1016/j.jad.2013.10.054
View details for Web of Science ID 000329574500041
View details for PubMedID 24314912
Superior chronic tolerability of adjunctive modafinil compared to pramipexole in treatment-resistant bipolar disorder
JOURNAL OF AFFECTIVE DISORDERS
2013; 150 (1): 130-135
Suboptimal outcomes are common in bipolar disorder (BD) pharmacotherapy, and may be mitigated with novel adjunctive agents such as modafinil (a low-affinity dopamine transport inhibitor) and pramipexole (a dopamine D2/D3 receptor agonist). While uncontrolled long-term effectiveness data have been reported for these treatments, reports specifically assessing their comparative acute versus chronic tolerability in BD are lacking. Such information, particularly in relation to discontinuation causes, has substantial relevance, providing initial indications to clinicians which treatment may be better tolerated, and to researchers which agent ought to be assessed in longer-term controlled trials.BD outpatients assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Affective Disorders Evaluation, and followed with the STEP-BD Clinical Monitoring Form, were naturalistically prescribed adjunctive modafinil or pramipexole, and somatic/psychiatric intolerability discontinuation rates were compared.Among 63 BD outpatients (mean±SD age 43.5±14.3 years, 60.3% female, 42.9% type I, 44.4% type II, 12.7% type not otherwise specified), taking 3.5±1.5 (median 3) concurrent prescription psychotropics, adjunctive modafinil (n=24) for 626.9±863.9 (286) days versus pramipexole (n=39) for 473.7±613.4 (214; p=0.51) days yielded a 26.0% lower somatic/psychiatric intolerability discontinuation rate (12.5% vs. 38.5%; p<0.05), with most of the difference accounted for by more pramipexole somatic intolerability discontinuations, due to nausea and sedation, after the first 12 weeks of treatment.No placebo comparison group. Small sample of predominantly female Caucasian insured outpatients, taking complex concurrent medication regimens.Further studies are warranted to assess our preliminary observation that modafinil, compared to pramipexole, may be better tolerated for longer-term BD treatment.
View details for DOI 10.1016/j.jad.2012.11.030
View details for Web of Science ID 000322762600019
View details for PubMedID 23261131
- Long-term aripiprazole effectiveness in bipolar disorder patients decreases with pharmacotherapeutic complexity and degree of baseline mood disturbance ASIAN BIOMEDICINE 2013; 7 (4): 537-544
- Bipolar disorder and attention-deficit/hyperactivity disorder comorbidity in children and adolescents: evidence-based approach to diagnosis and treatment. journal of clinical psychiatry 2013; 74 (6): 628-629
Brain-derived neurotrophic factor val66met genotype and early life stress effects upon bipolar course
JOURNAL OF PSYCHIATRIC RESEARCH
2013; 47 (2): 252-258
Gene-environment interactions may contribute to bipolar disorder (BD) clinical course variability. We examined effects of brain-derived neurotrophic factor (BDNF) val66met genotype and early life stress (ELS) upon illness severity and chronicity in adult BD patients.80 patients (43 BD I, 33 BD II, 4 BD not otherwise specified, mean ± SD age 46.4 ± 14.0 years, 63.7% female) receiving open evidence-based and measurement-based care in the Stanford Bipolar Disorders Clinic for at least 12 months underwent BDNF val66met genotyping and completed the Childhood Trauma Questionnaire. BDNF met allele carrier genotype and history of childhood sexual and physical abuse were evaluated in relation to mean prior-year Clinical Global Impressions-Bipolar Version-Overall Severity of Illness (MPY-CGI-BP-OS) score and clinical and demographic characteristics.BDNF met allele carriers (but not non-met allele carriers) with compared to without childhood sexual abuse had 21% higher MPY-CGI-BP-OS scores (3.5 ± 0.7 versus 2.9 ± 0.7, respectively, t = -2.4, df = 28, p = 0.025) and 35% earlier BD onset age (14.6 ± 5.7 versus 22.8 ± 7.9 years, respectively, t = 3.0, df = 27, p = 0.006). Regression analysis, however, was non-significant for a BDNF-childhood sexual abuse interaction.small sample of predominantly female Caucasian insured outpatients taking complex medication regimens; only one gene polymorphism considered.Between group comparisons suggested BDNF met allele carrier genotype might amplify negative effects of ELS upon BD illness severity/chronicity, although with regression analysis, there was not a significant gene-environment interaction. Further studies with larger samples are warranted to assess whether BDNF met allele carriers with ELS are at risk for more severe/chronic BD illness course.
View details for DOI 10.1016/j.jpsychires.2012.10.015
View details for Web of Science ID 000314330100016
View details for PubMedID 23182421
Enhanced Ziprasidone Combination Therapy Effectiveness in Obese Compared to Nonobese Patients With Bipolar Disorder
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
2012; 32 (6): 814-819
To assess longer-term ziprasidone effectiveness in obese and non-obese patients with bipolar disorder (BD).Outpatients assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation and monitored with the Systematic Treatment Enhancement Program for BD Clinical Monitoring Form received open ziprasidone.Eighty-two patients (39 patients with BD I, 39 patients with BD II, and 4 patients with BD not otherwise specified; mean age, 41.1 years; females, 78.0%; obese, 48.8%) received ziprasidone combined with an average of 3.6 (in 74.4% at least 3) other prescription psychotropics and 1.2 prescription nonpsychotropics. Mean (median) ziprasidone final dose and duration were 134.3 (150) mg/d and 489 (199.5) days, respectively. Ziprasidone yielded in obese compared to nonobese patients less discontinuation (42.5% vs 71.4%, P = 0.01), albeit with a higher rate of addition of subsequent psychotropic medication (62.5% vs 35.7%, P = 0.03). Moreover, obese compared to nonobese patients had a higher rate of shift to final-visit euthymia (27.5% vs 0.0%, P = 0.0002), and more weight loss (-20.7 lbs vs -0.6 lbs, P = 0.001), and obese (but not nonobese) patients had significant improvements in mean Clinical Global Impression-Severity of Illness (decreased 0.6 points; P = 0.03) and Global Assessment of Functioning (increased 3.3 points, P = 0.01) scores. Weight change correlated significantly with Global Assessment of Functioning change (P = 0.047) but not with Clinical Global Impression-Severity of Illness change. Limitations are small sample size and open-label, uncontrolled, observational design.Controlled and additional observational studies seem warranted to confirm our preliminary findings suggesting ziprasidone may be more effective in obese compared to nonobese patients with BD already receiving combination pharmacotherapy.
View details for DOI 10.1097/JCP.0b013e318270dea9
View details for Web of Science ID 000310923500014
View details for PubMedID 23131875
Pilot study of the efficacy of double-blind, placebo-controlled one-week olanzapine stabilization therapy in heterogeneous symptomatic bipolar disorder patients
JOURNAL OF PSYCHIATRIC RESEARCH
2012; 46 (7): 920-926
Olanzapine has demonstrated efficacy in acute mania and bipolar I disorder (BDI) maintenance, but efficacy in brief therapy in more diverse populations, including patients with bipolar II disorder (BDII)/bipolar disorder not otherwise specified (BDNOS) with syndromal/subsyndromal depressive/mood elevation symptoms and taking/not taking concurrent medications remains to be established.Fifty adult outpatients (24 BD1, 22 BDII, 4 BDNOS, mean ± SD age 40.8 ± 11.5 years, 28.1% female, already taking 1.1 ± 1.2 [median 1] prescription psychotropics) with 17-item Hamilton Depression Rating Scale (HDRS) ≥10 and/or Young Mania Rating Scale (YMRS) ≥10 and ≤24, were randomized to double-blind olanzapine (2.5-20 mg/day) versus placebo for one week.Among 45 patients with post-baseline ratings, olanzapine (9.0 ± 5.8 mg/day, n = 23) compared to placebo (n = 22) tended to yield greater Clinical Global Impressions-Bipolar Version-Overall Severity of Illness (-1.4 ± 0.9 versus -0.8 ± 1.1, p = 0.08) and Hamilton Anxiety Scale (-7.9 ± 6.3 versus -3.8 ± 6.1, p = 0.07) improvements, and YMRS/HDRS remission rate (47.8% versus 22.7%, p = 0.08), but significantly increased median weight (+2 versus -1 lbs, p = 0.001), and rates of excessive appetite (54.2% versus 22.7%, p = 0.04) and tremor (50.0% versus 9.1% p = 0.004). Number Needed to Treat and 95% Confidence Interval for YMRS/HDRS remission were 4 (1-∞). Numbers Needed to Harm for excessive appetite and tremor were 4 (1-21) and 3 (1-6), respectively.Olanzapine tended to yield affective improvement and significantly increased weight, appetite, and tremor. Larger controlled studies appear feasible and warranted to assess brief olanzapine therapy in heterogeneous symptomatic bipolar disorder patients.
View details for DOI 10.1016/j.jpsychires.2012.04.004
View details for Web of Science ID 000306536100012
View details for PubMedID 22579071
Effectiveness of quetiapine plus lamotrigine maintenance therapy in challenging bipolar disorder patients
JOURNAL OF AFFECTIVE DISORDERS
2012; 137 (1-3): 139-145
Assess quetiapine plus lamotrigine (QTP+LTG) combination maintenance therapy effectiveness in challenging bipolar disorder (BD).Outpatients assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Affective Disorders Evaluation and followed with the STEP-BD Clinical Monitoring Form were naturalistically prescribed QTP+LTG.Fifty-four outpatients with challenging BD, taking in addition to QTP+LTG, a mean±SD of 2.1±1.6 (in 63.0% at least 2) other psychotropic and 2.3±1.9 non-psychotropic prescription medications, had QTP+LTG maintenance trials. Median(mean±SD) QTP+LTG duration was 401(730±756) days. Final QTP and LTG doses were 87.5(188±211) and 300(287±108) mg/day, respectively. Half (27/54) of patients discontinued QTP (in 19), LTG (in 6), or QTP+LTG (in 2), after 294(415±414) days - due to side-effects in 10, inefficacy in seven, non-adherence in five, and other reasons in five. 42.6%(23/54) had additional pharmacotherapy intervention for emergent mood symptoms, after 175(261±237) days, with at least one psychotropic added (in 16/54) or substantively (by ≥50%) increased (in 7/54). 55.6%(30/54) had recurrent mood episodes, after 126(187±158) days, most often depressive (in 35.2%), although 64.8%(35/54) were euthymic at final visit taking QTP+LTG. Sedation increased significantly during treatment among those with side-effect discontinuations, and 19.2%(10/52, all having QTP added to LTG) had clinically significant (≥7%) weight gain.No placebo comparison group. Small sample of predominantly female Caucasian insured outpatients taking complex concurrent medication regimens.Additional studies are warranted to confirm our preliminary observation that QTP+LTG maintenance may be effective in patients with challenging BD.
View details for DOI 10.1016/j.jad.2011.12.024
View details for Web of Science ID 000301759900018
View details for PubMedID 22240084
Clinical Relevance of Treatments for Acute Bipolar Disorder: Balancing Therapeutic and Adverse Effects
2011; 33 (12): B40-B48
The US Food and Drug Administration (FDA) has approved 10 treatments for acute mania, but only 2 for acute bipolar depression. These agents differ from one another with respect to their efficacy and tolerability profiles, such that certain medications may be optimal for some patients but not others.Our aim was to compare the therapeutic and adverse effects of treatments for acute mania and acute bipolar depression to inform clinical decision making.Using data from large, randomized, double-blind, placebo-controlled acute mania and acute bipolar depression trials, we assessed number needed to treat (NNT) for response, number needed to harm (NNH) for sedation/weight gain, and likelihood to help or harm (LHH = NNH ÷ NNT) compared with placebo.For acute mania, lithium compared with other FDA-approved agents yielded substantively less sedation (NNH, 27 vs 5-17) yet broadly similar efficacy (NNT, 4 vs 4-8), and thus a more favorable efficacy:sedation likelihood (LHH, 6.8 vs 0.7-3.4). For acute bipolar depression, lamotrigine compared with FDA-approved treatments yielded substantively less sedation (NNH, 42 vs 6-12), weight gain (NNH, -34 vs 6-19), and efficacy (NNT, 12 vs 4-6), but still more favorable efficacy:sedation likelihood (LHH, 3.5) than quetiapine (LHH, 1.0) and efficacy:weight gain likelihood (LHH, -2.8) than the olanzapine plus fluoxetine combination (LHH, 1.5).For acute mania, lithium compared with other FDA-approved agents yielded less sedation yet similar efficacy, indicating utility for patients sensitive to sedation. For acute bipolar depression, lamotrigine compared with FDA-approved treatments yielded better tolerability but poorer efficacy, suggesting utility in patients sensitive to sedation/weight gain with milder episodes, whereas the FDA-approved treatments might have utility in patients with more severe episodes.
View details for DOI 10.1016/j.clinthera.2011.11.020
View details for Web of Science ID 000298831400034
View details for PubMedID 22177379
Treatments for bipolar disorder: can number needed to treat/harm help inform clinical decisions?
ACTA PSYCHIATRICA SCANDINAVICA
2011; 123 (3): 175-189
To compare bipolar treatment interventions, using number needed to treat (NNT) and number needed to harm (NNH).Results of randomized controlled clinical trials were used to assess efficacy (NNT for response and relapse/recurrence prevention vs. placebo) and tolerability (e.g. NNH for weight gain and sedation vs. placebo).United States Food and Drug Administration-approved bipolar disorder pharmacotherapies all have single-digit NNTs (i.e. > 10% advantage over placebo), but NNHs for adverse effects that vary widely. Some highly efficacious agents are as likely to yield adverse effects as therapeutic benefit, but may be interventions of choice in more acute severe illness. In contrast, some less efficacious agents with better tolerability may be interventions of choice in more chronic mild-moderate illness.Clinical trials can help inform clinical decision making by quantifying the likelihood of benefit vs. harm. Integrating such data with individual patient circumstances, values, and preferences can help optimize treatment choices.
View details for DOI 10.1111/j.1600-0447.2010.01645.x
View details for Web of Science ID 000286890300002
View details for PubMedID 21133854
The Link Between Bipolar Disorders and Creativity: Evidence from Personality and Temperament Studies
CURRENT PSYCHIATRY REPORTS
2010; 12 (6): 522-530
Although extensive literature supports connections between bipolar disorder and creativity, possible mechanisms underlying such relationships are only beginning to emerge. Herein we review evidence supporting one such possible mechanism, namely that personality/temperament contribute to enhanced creativity in individuals with bipolar disorder, a theory supported by studies showing that certain personality/temperamental traits are not only common to bipolar disorder patients and creative individuals but also correlate with measures of creativity. Thus, we suggest based on studies using three important personality/temperament measures-the Neuroticism, Extraversion, and Openness Personality Inventory (NEO); the Myers-Briggs Type Indicator (MBTI); and the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A)-that changeable (increased TEMPS-A-cyclothymia) and at times negative (increased NEO-neuroticism) affect and open-minded (increased NEO-openness) and intuitive (increased MBTI-intuition) cognition may contribute importantly to enhanced creativity in individuals with bipolar disorder.
View details for DOI 10.1007/s11920-010-0159-x
View details for Web of Science ID 000289733500006
View details for PubMedID 20936438
Toward interaction of affective and cognitive contributors to creativity in bipolar disorders: A controlled study
JOURNAL OF AFFECTIVE DISORDERS
2010; 125 (1-3): 27-34
Enhanced creativity in bipolar disorder patients may be related to affective and cognitive phenomena.32 bipolar disorder patients (BP), 21 unipolar major depressive disorder patients (MDD), 22 creative controls (CC), and 42 healthy controls (HC) (all euthymic) completed the Revised Neuroticism Extraversion Openness Personality Inventory (NEO), the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), the Myers-Briggs Type Inventory (MBTI); the Barron-Welsh Art Scale (BWAS), the Adjective Check List Creative Personality Scale, and the Figural and Verbal Torrance Tests of Creative Thinking. Mean scores were compared across groups, and relationships between temperament/personality and creativity were assessed with bivariate correlation and hierarchical multiple linear regression.BP and CC (but not MDD) compared to HC had higher BWAS-Total (46% and 42% higher, respectively, p<0.05) and BWAS-Dislike (83% and 93% higher, p<0.02) scores, and higher MBTI-Intuition preference type rates (78% vs. 50% and 96% vs. 50%, p<0.05). BP, MDD, and CC, compared to HC, had increased TEMPS-A-Cyclothymia scores (666%, 451% and 434% higher, respectively, p<0.0001), and NEO-Neuroticism scores (60%, 57% and 51% higher, p<0.0001). NEO-Neuroticism and TEMPS-A Cyclothymia correlated with BWAS-Dislike (and BWAS-Total), while MBTI-Intuition continuous scores and NEO-Openness correlated with BWAS-Like (and BWAS-Total).Relatively small sample size.We replicate the role of cyclothymic and related temperaments in creativity, as well as that of intuitive processes. Further studies are needed to clarify relationships between creativity and affective and cognitive processes in bipolar disorder patients.
View details for DOI 10.1016/j.jad.2009.12.018
View details for Web of Science ID 000281377100004
View details for PubMedID 20085848