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1.  The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders 
The American journal of psychiatry  2013;170(11):1249-1262.
The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders.
An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder.
There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder.
Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.
PMCID: PMC4091043  PMID: 24030475
2.  Screening for Bipolar Disorder in a County Jail at the Time of Criminal Arrest 
Journal of psychiatric research  2007;42(9):778-786.
This study assessed the operating characteristics of the Mood Disorder Questionnaire (MDQ) among offenders arrested and detained at a county jail.
The MDQ, a brief self-report instrument designed to screen for all subtypes of bipolar disorder (BP I, II and NOS) was voluntarily administered to adult detainees at the Ottawa County Jail in Port Clinton, Ohio. A confirmatory diagnostic evaluation was also performed using the Mini-International Neuropsychiatric Interview (MINI). The MDQ was scored using a standard algorithm requiring endorsement of 7/13 mood items as well as two items that assess whether manic or hypomanic symptoms co-occur and cause moderate to severe functional impairment. In addition to the standard algorithm for scoring the MDQ, modifications were also tested in an attempt to improve overall sensitivity.
Among 526 jail detainees who completed the MDQ, 37 (7%) screened positive for bipolar disorder. Of 164 detainees who agreed to a research diagnostic evaluation, 32 (19.5%) screened positive on the MDQ, while 55 (33.5%) met criteria for bipolar disorder according to the MINI. When administered to the sample of 164 adult jail detainees, the sensitivity of the MDQ was 0.47 and the specificity was 0.94. The MDQ was significantly better at detecting BP I (0.59) than BP II/NOS (0.19; p = 0.008). Modification of scoring the MDQ improved the sensitivity for detection of BP II from 0.23 to 0.54 with minimal decrease in specificity (0.84). The optimum sensitivity and specificity of the MDQ was achieved by decreasing the item threshold to 3/13 and eliminating the symptom co-occurrence and functional impairment items.
The MDQ was found to have limited utility as a screening tool for bipolar disorder in a correctional setting, particularly for the BP II subtype.
PMCID: PMC2475656  PMID: 17935734
Bipolar Disorder; Mood Disorder Questionnaire; Jail; Screening; Bipolar II; Psychometrics
3.  Bipolar Disorder with frequent mood episodes in the National Comorbidity Survey Replication (NCS-R) 
Molecular psychiatry  2009;15(11):1075-1087.
Virtually nothing is known about the epidemiology of rapid cycling bipolar disorder (BPD) in community samples. Nationally representative data are reported here for the prevalence and correlates of a surrogate measure of DSM-IV rapid cycling BPD from the National Comorbidity survey Replication (NCS-R), a national survey of the US household population. DSM-IV disorders were assessed in the NCS-R with the WHO Composite International Diagnostic Interview (CIDI). Although the CIDI did not assess rapid cycling, it did assess the broader category of 12-month BPD with frequent mood episodes (FME), having at least four episodes of mania/hypomania or major depression in the 12 months before interview. Roughly one-third of NCS-R respondents with lifetime DSM-IV BPD and half with 12-month BPD met criteria for FME. FME was associated with younger age-of-onset (of BP-I, but not BP-II) and higher annual persistence (73% of the years since first onset of illness with an episode) than non-FME BPD. No substantial associations of FME vs. non-FME BPD were found with socio-demographics, childhood risk factors (parental mental disorders, other childhood adversities), or comorbid DSM-IV disorders. However, FME manic episodes had greater clinical severity than non-FME episodes (assessed with a fully-structured version of the Young Mania Rating Scale) and FME hypomanic episodes had greater role impairment than non-FME episodes (assessed with the Sheehan Disability Scales). Whether these indicators of severity merely reflect attenuated effects of rapid cycling or independent effects of sub-threshold rapid cycling warrants further study given the high proportion of lifetime cases that met criteria for FME.
PMCID: PMC2891194  PMID: 19564874
Bipolar Disorder; Rapid-cycling bipolar disorder; Mania; Hypomania; National Comorbidity Survey Replication (NCS-R); Comorbidity; Treatment
4.  The prevalence and effects of mood disorders on work performance in a nationally representative sample of US workers 
The American journal of psychiatry  2006;163(9):1561-1568.
Research on the workplace costs of mood disorders has focused largely on major depressive episodes (MDE). Bipolar disorder (BPD) has been overlooked both by failing to distinguish MDE due to major depressive disorder (MDD) versus BPD and by failing to evaluate the workplace costs of mania and hypomania.
The National Comorbidity Survey Replication (NCS-R) assessed DSM-IV MDD and BPD with the WHO Composite International Diagnostic Interview (CIDI) and assessed work impairment with the WHO Health and Work Performance Questionnaire (HPQ). Regression analysis of MDD and BPD predicting HPQ among workers (n = 3378) was used to estimate the workplace costs of mood disorders.
1.1% of workers met CIDI criteria for 12-month BPD (bipolar I or bipolar II) and 6.4% for 12-month MDD. BPD was associated with 65.5 and MDD with 27.2 annual lost workdays per ill worker. Subgroup analysis showed that the higher work loss associated with BPD than MDD is due to more severe and persistent MDE in BPD than MDD rather than to stronger effects of mania-hypomania than depression. Annual human capital loss per ill worker was estimated at $9619 for BPD and $4426 for MDD. Annual projections to the US labor force were $14.1 billion for BPD and $36.6 billion for MDD.
Employer interest in the workplace costs of mood disorders should be broadened beyond MDD to include BPD. Effectiveness trials are needed to study the return on employer investment of coordinated programs for workplace screening and treatment of BPD and MDD.
PMCID: PMC1924724  PMID: 16946181
5.  Lifetime and 12-Month Prevalence of Bipolar Spectrum Disorder in the National Comorbidity Survey Replication 
Archives of general psychiatry  2007;64(5):543-552.
There is growing recognition that bipolar disorder (BPD) has a spectrum of expression substantially more common than the 1% BP-I prevalence traditionally found in population surveys.
To estimate the prevalence and correlates of bipolar spectrum disorder in the US population.
Interviews with a nationally representative sample of English-speaking adult (ages 18+) household residents in the continental US
9,282 respondents.
Main Outcome Measures
Version 3.0 of the WHO Composite International Diagnostic Interview, a fully structured lay-administered diagnostic interview, was used to assess DSM-IV lifetime and 12 month Axis I disorders. Sub-threshold BPD was defined as recurrent hypomania without a major depressive episode or with fewer symptoms than required for threshold hypomania. Severity was assessed with the Young Mania Rating Scale for mania/hypomania and the Quick Inventory of Depressive Symptoms Self-Report for depression. Role impairment among 12-month cases was assessed with the Sheehan Disability Scales.
Lifetime (and 12-month) prevalence estimates are 1.0% (0.6%) for BP-I, 1.1% (0.8%) for B P-II, and 2.4% (1.4%) for sub-threshold BPD. Comorbidity with other lifetime Axis I disorders is the norm both for threshold and sub-threshold cases. While the vast majority of people with BPD receive lifetime professional treatment for emotional problems, use of antimanic medication is much less common than use of inappropriate medications, especially in general medical settings. Clinical severity and role impairment are greater for mania than hypomania, but higher for BP-II than BP-I episodes of MDE. Although clinical severity and role impairment are greater for threshold than sub-threshold BPD, sub-threshold cases consistently have moderate-to-severe clinical severity and role impairment.
Inappropriate treatment of BPD is a serious problem in the U.S. population. Sub-threshold BPD is commonly occurring, clinically significant, and under-detected in treatment settings. Explicit criteria are needed to define sub-threshold BPD for future clinical and research purposes.
PMCID: PMC1931566  PMID: 17485606
Bipolar Disorder; Bipolar Spectrum; Mania; Hypomania; National Comorbidity Survey Replication (NCS-R); Comorbidity; Treatment
6.  Validity of the Assessment of Bipolar Spectrum Disorders in the WHO CIDI 3.0 
Journal of affective disorders  2006;96(3):259-269.
Although growing interest exists in the bipolar spectrum, fully structured diagnostic interviews might not accurately assess bipolar spectrum disorders. A validity study was carried out for diagnoses of threshold and sub-threshold bipolar disorders (BPD) based on the WHO Composite International Diagnostic Interview (CIDI) in the National Comorbidity Survey Replication (NCS-R). CIDI BPD screening scales were also evaluated.
The NCS-R is a nationally representative US household population survey (n = 9282 using CIDI to assess DSM-IV disorders. CIDI diagnoses were evaluated in blinded clinical reappraisal interviews using the non-patient version of the Structured Clinical Interview for DSM-IV (SCID).
Excellent CIDI-SCID concordance was found for lifetime BP-I (AUC = .99 κ = .88, PPV = .79, NPV = 1.0), either BP-II or sub-threshold BPD (AUC = .96, κ = .88, PPV = .85, NPV = .99), and overall bipolar spectrum disorders (i.e., BP-I/II or sub-threshold BPD; AUC = .99, κ = .94, PPV = .88, NPV = 1.0). Concordance was lower for BP-II (AUC = .83, κ = .50, PPV = .41, NPV = .99) and sub-threshold BPD (AUC = .73, κ = .51, PPV = .58, NPV = .99). The CIDI was unbiased compared to the SCID, yielding a lifetime bipolar spectrum disorders prevalence estimate of 4.4%. Brief CIDI-based screening scales detected 67–96% of true cases with positive predictive value of 31–52%.
CIDI prevalence estimates are still probably conservative, though, but might be improved with future CIDI revisions based on new methodological studies with a clinical assessment more sensitive than the SCID to sub-threshold BPD.
Bipolar spectrum disorders are much more prevalent that previously realized. The CIDI is capable of generating conservative diagnoses of both threshold and sub-threshold BPD. Short CIDI-based scales are useful screens for BPD.
PMCID: PMC1821426  PMID: 16997383
Bipolar Disorders; Bipolar Spectrum; Mania; Hypomania; Composite International Diagnostic Interview (CIDI); Validity; National Comorbidity Survey Replication (NCS-R)

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