BACKGROUND: The efficacy and tolerability of antidepressants (ADs) to treat or avoid episodes of depression in bipolar disorder (BPD) patients as well as reasons for using them remain unresolved. METHODS: We analyzed patient-characteristics and outcomes of episodes of acute major depression among 290 adult, DSM-IV BPD patients (71% type-I, 52% women) at the Hospital Clinic of Barcelona; 80% were given an AD and 20% were not; 80% of both groups also received mood-stabilizers. We evaluated factors associated with AD-treatment using bivariate analyses and multiple logistic-regression modeling. RESULTS: Factors associated with AD-use by multivariate modeling ranked:[a] more years ill,[b] depressive first-lifetime episode,[c] more depressions/year,[d] melancholic index episode, and [e] less affective illness in first-degree relatives. Within 8weeks, depression improved by ≥50%, less often among BPD patients given an AD (64.4%; 38.6% without switching into hypo/mania) than not (82.1%; 78.6% without switching). CONCLUSIONS: Use of ADs to treat acute BP-depression was very common and associated with a more severe clinical history. Mood-switching was prevalent with AD-treatment even with mood-stabilizers present.

Specification of the earliest institution devoted primarily to the treatment of the mentally ill in the Western World remains elusive. Uncertainty arises from limited documentation and gradual evolution of most candidate sites from hospices for the poor, foreign, or homeless, or as clinical centers for the care of a range of persons with general medical and psychiatric disorders. Plausible candidates identified in the late fourteenth and early fifteenth centuries include Bethlem Asylum in London. Much less often considered are two centers in medieval Spain: the Moorish Maristan at Granada (1365) and the Christian Hospital of Our Lady Mary for Lunatics, the Insane and Innocents at Valencia (1409). Since the early Spanish sites are not well known, we have summarized available information concerning their foundation, facilities, theories and practices, as arising from the cultural and political background of the times and regions.

Early onset in bipolar disorder (BPD) has been associated with greater familial risk and unfavorable clinical outcomes. We pooled data from seven international centers to analyze the relationships of family history and symptomatic as well as functional measures of adult morbidity to onset age, or onset in childhood (age <12), adolescence (12-18), or adulthood (19-55 years). In 1,665 adult, DSM-IV BPD-I patients, onset was 5% in childhood, 28% in adolescence, and 53% at peak ages 15-25. Adolescent and adult onset did not differ by symptomatic morbidity (episodes/year, percentage of months ill, co-morbidity, hospitalization, suicide attempts) or family history. Indications of favorable adult functional outcomes (employment, living independently, marriage and children, and a composite measure including education) ranked, by onset: adult > adolescent > child. Onset in childhood versus adolescence had more episodes/year and more psychiatric co-morbidity. Family history was most prevalent with childhood onset, similar over onset ages 12-40 years, and fell sharply thereafter. Multivariate modeling sustained the impression that family history and poor functional, but not symptomatic, outcomes were associated with younger, especially childhood onset. Early onset was more related to poor functional outcomes than greater symptomatic morbidity, with least favorable outcomes and greater family history with childhood onset.

BACKGROUND: Suicidal risks may be similar in bipolar I and II disorders, but predictive risk factors are not well established for each disorder type or across cultures. METHOD: Accordingly, we compared selected demographic and clinical factors for long-term association with nonlethal suicidal acts or ideation in 290 DSM-IV bipolar I (n = 204) and II (n = 86) disorder patients followed for a mean of 9.3 years at the University of Barcelona, using preliminary bivariate comparisons followed by multivariate logistic regression modeling. RESULTS: Rates of suicidal ideation (41.5%) and acts (19.7%) were similarly prevalent with bipolar I and II disorders and somewhat more common among women. Factors significantly and independently associated with suicidal acts were determined by multivariate modeling and ranked in order of their strength of association: suicidal ideation, more mixed episodes, Axis II comorbidity, female sex, more antidepressant trials, rapid cycling, predominant lifetime depression, having been hospitalized, older onset, and longer delay of diagnosis. Suicidal ideation was associated with suicidal acts, more antidepressant trials, predominant depressions, more mixed-episodes/year, depressive first-lifetime episodes, electroconvulsive therapy use, delay of bipolar disorder diagnosis, unemployment, melancholic features, Axis II disorders, rapid cycling, and more depressions per year. Risk factors selectively associated with suicidal risk, overall, included more mixed-states per year and melancholic features, whereas hospitalization, unemployment, and predominantly depressive recurrences were more characteristic of diagnostic subtypes. CONCLUSIONS: Suicidal risk-factors found to be independent of bipolar disorder diagnostic subtype included mixed-states, melancholic depressive features, and more antidepressant trials.

OBJECTIVE: Because bipolar disorder can be difficult to diagnose, we compared characteristics of women with confirmed versus presumably misdiagnosed bipolar disorder. METHOD: This cohort study was conducted from July 2005 to January 2010 in the outpatient clinic of the Emory Women's Mental Health Program, Atlanta, Georgia. Young adult women (mean age = 32 years) who were either pregnant or planning to conceive and who reported having previous clinical diagnoses of bipolar disorder completed 2 independent diagnostic assessments: the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) and an evaluation by a perinatal mood-disorder expert who was masked to the SCID findings. We compared clinical characteristics of women with confirmed versus presumably misdiagnosed bipolar disorder by bivariate testing followed by multivariate logistic regression modeling. RESULTS: Of 199 participants, 141 (70.9%) had confirmed DSM-IV bipolar disorder on the basis of concordant assessments, 23 (11.6%) were considered misdiagnosed, and 35 (17.6%) who had discordant diagnostic assessments were excluded from further analysis. Multivariate modeling indicated that confirmed bipolar disorder was associated with a history of antidepressant-associated mania/hypomania (OR = 13.30; 95% CI, 3.32-53.20; P =.0003), psychotic symptoms (OR = 12.40; 95% CI, 2.14-71.10; P =.005), and sustained euthymia during mood-stabilizer treatment (OR = 4.53; 95% CI, 1.32-15.60; P =.02); presumably misdiagnosed bipolar disorder was associated with childhood physical abuse (OR = 8.73; 95% CI, 2.33-32.70; P =.001) and comorbid obsessive-compulsive disorder (OR = 7.26; 95% CI, 1.86-28.30; P =.004). CONCLUSIONS: Several clinical factors found to distinguish women with confirmed versus presumably misdiagnosed bipolar disorder may help to refine clinical diagnosis.

Baldessarini RJ, Undurraga J, Vázquez GH, Tondo L, Salvatore P, Ha K, Khalsa H-MK, Lepri B, Ha TH, Chang JS, Tohen M, Vieta E. Predominant recurrence polarity among 928 adult international bipolar I disorder patients. Objective:  To test the hypothesis that patients with bipolar disorder (BPD) differ demographically and clinically within subgroups based on the predominant-polarity of major recurrences. Method:  We tested factors for association with predominantly (≥2 : 1) depressive vs. mania-like episodes with 928 DSM-IV type-I BPD subjects from five international sites. Results:  Factors preliminarily associated with predominant-depression included: electroconvulsive treatment, longer latency-to-BPD diagnosis, first episode depressive or mixed, more suicide attempts, more Axis-II comorbidity, ever having mixed-states, ever married, and female sex. Predominant-mania was associated with: initial manic or psychotic episodes, more drug abuse, more education, and more family psychiatric history. Of the 47.3% of subjects without polarity-predominance, risks for all factors considered were intermediate. Expanding the definition of polarity-predominance to ≥51% added little, but shifting mixed-states to 'predominant-depression' increased risk of suicidal acts from 2.4- to 4.5-fold excess over predominant-mania-hypomania, and suicidal risk was associated continuously with increasing proportions of depressive or mixed episodes. Conclusion:  Subtyping by predominant-polarity yielded predictive associations, including the polarity of first episodes and risk of suicide attempts. Such subtyping may contribute to improve planning of clinical care and to biological studies of BPD.

Antidepressant-placebo response-differences (RDs) in controlled trials have been declining, potentially confounding comparisons among older and newer drugs. For clinically employed antidepressants, we carried out a meta-analytic review of placebo-controlled trials in acute, unipolar, major depressive episodes reported over the past three decades to compare efficacy (drug-placebo RDs) of individual antidepressants and classes, and to consider factors associated with year-of-reporting by bivariate and multivariate regression modeling. Observed drug-placebo differences were moderate and generally similar among specific drugs, but larger among older antidepressants, notably tricyclics, than most newer agents. This outcome parallels selective increases in placebo-associated responses as trial-size has increased in recent years. Study findings generally support moderate efficacy of clinically employed antidepressants for acute major depression, but underscore limitations of meta-analyses of controlled trials for ranking drugs by efficacy. We suggest that efficiency and drug-placebo differences may be improved with fewer sites and subjects, and better quality-control of diagnostic and clinical assessments.Neuropsychopharmacology advance online publication, 14 December 2011; doi:10.1038/npp.2011.306.

The preferential dopamine D(3)-agonist pramipexole (4.25±0.38mg/day) or placebo were added for up to 12weeks to ongoing antipsychotic treatment for 24 adult patients with DSM-IV schizophrenia or schizoaffective disorder. Pramipexole was generally well-tolerated (82% trial-completion), and yielded greater decreases in PANSS-total scores (drug/placebo=2.1; p=0.04), with similar decreases in PANSS positive and negative scores and 6.7-fold greater reduction of serum prolactin concentrations compared to placebo. There were no differences in ratings of mood, cognition or extrapyramidal symptoms, all of which were low at intake.

BACKGROUND Since the current epidemiology of depression is not well documented in Latin America, we conducted a community-based survey study in Argentina. METHODS The Beck Depression Inventory (BDI) and a general health questionnaire were completed by 1335 adult participants, representing most of the neighborhoods of Buenos Aires. RESULTS Prevalence of high total BDI scores (≥13) indicating probable current clinically significant depression was 20.0%(women: 20.6%; men: 19.6%). Probable depression was associated with being unmarried and older, less educated, reporting recent stressors and significant medical illness. LIMITATIONS Sampling was cross-sectional and by convenience; probable depression was not verified by clinical assessment. CONCLUSIONS Within methodological limits, probable current clinically significant depression was highly prevalent in an urban community sample in Argentina, at rates and with risk factors similar to those found in other world regions.

BACKGROUND: Preliminary review of a century of studies of the course of manic-depressive syndromes produced 40 reports, of which approximately one-third report evidence of shortening wellness intervals or cycle-lengths with more recurrences, and two-thirds did not. METHODS: We evaluated inter-episode intervals (cycle-length) in 128 clinically-treated, DSM-IV bipolar-I disorder patients followed prospectively and systematically over 5.7years, with 6.5 episodes/person. RESULTS: As expected, cycle-length varied inversely with total cycle-count/person; however, multivariate linear regression found only longer initial hospitalization and fewer total cycles to be associated with cycle-length, whereas cycle-number (1, 2, 3, etc.), sex, intake-age, and first-episode polarity were not. Regression of within-subject cycle-length versus cycle-number yielded individual slope-functions with pseudo-random distribution (28% fell within ±1month/cycle of the null [zero-slope]). Mean duration of early and late euthymic intervals (cycles 2 vs. 5) in patients with matched recurrence-counts was nearly identical. CONCLUSIONS: The course of bipolar-I disorder from onset was largely random or chaotic over nearly 6years from onset. Only a minority of patients showed either cycle-acceleration or slowing, without changes in wellness intervals. The findings may be influenced by treatment-effects, but seem to indicate that most current bipolar-I disorder patients are unlikely to show progressive shortening of recurrence-cycles.