Pediatric multi-drug-resistant tuberculosis in Germany - diagnostic and therapeutic challenges of an "orphan disease".

Delay in diagnosing multidrug-resistant tuberculosis (MDR-pTB) in children prolongs time to effective treatment. Data on risk factors for pediatric MDR from low-incidence countries are scarce. Retrospective nationwide case-control study to analyze MDR-pTB cases in Germany between 2010 and 2020 in comparison to a drug-susceptible (DS)-pTB group. We included 52 MDR cases (24 tuberculosis (TB), 28 TB infection (TBI); mean age 7.3 years) and 56 DS cases (31 TB, 26 TBI; mean age 7.9 years). Groups were similar for sex, household size, and migration background. Compared to the DS group, more children with MDR were born in the Commonwealth of Independent States (CIS) (22% MDR-pTB vs. 13% DS-pTB, n.s.) and had more MDR index cases (94% MDR-pTB, 5% DS-pTB, p < 0.001). The interval between first healthcare contact and initiation of effective therapy was significantly longer in MDR-pTB (47 days) than in DS-pTB (11 days, p < 0.001), correlating with disease progression. Treatment for MDR-pTB was successful in 74%, but 22% experienced long-term adverse effects (e.g., hepatopathy, hearing loss). CONCLUSIONS: Close contact to MDR cases or birth in MDR-TB-high-incidence countries are risk factors for MDR-pTB. Early identification of potential MDR index cases by contact investigation, and susceptibility testing in children from high-burden MDR-TB countries are essential for timely diagnosis and treatment, reducing the severity of disease and treatment side effects. TRIAL REGISTRATION: Deutsches Register Klinischer Studien ( https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023817 ), DRKS00023817, 2020-09-08. WHAT IS KNOWN: •Management of children with MDR-TB remains challenging due to difficulties in diagnosing MDR-TB (lack of information on MDR index case, lack of microbiological confirmation in paucibacillary disease). •Choice of treatment regimen and monitoring of side effects. WHAT IS NEW: •Children with an MDR-TB index or born in a MDR-TB-high-incidence country are at higher risk of developing MDR-TB in a low incidence country. •The time lag to initiate treatment in MDR-TB is longer than in DS-TB and MDR-TB treatment involves a higher risk of adverse effects in longer treatment regimens especially with injectables.

The contribution of early adverse stress to complex and severe depression in depressed outpatients.

BACKGROUND: To assess whether linear effects or threshold effects best describe the association between early adverse stress (EAS) and complex and severe depression (i.e., depression with treatment resistance, psychotic symptoms, and/or suicidal ideation), and to examine the attributable risk of complex and severe depression associated with EAS. METHODS: A cross-sectional study was conducted using deidentified clinical data (on demographics, presence of complex and severe depression, and exposure to seven types of EAS) from 1,013 adults who were seen in an outpatient mental health clinic in Santiago, Chile, for a major depressive episode. Multivariate logistic regressions were fitted to estimate odds ratios (ORs), using a bootstrap approach to compute 95% bias-corrected confidence intervals (95% BC CIs). A detailed examination of the cumulative risk score and calculations of the attributable risk was conducted. RESULTS: Exposure to at least five EASs was reported by 3.6% of the sample. In the multivariate logistic regression models, there was a marked increase in the odds of having complex and severe depression associated with exposure to at least five EASs (OR = 4.24; 95% BC CI: 1.25 to 9.09), according to a threshold effect. The attributable risk of complex and severe depression associated with exposure to at least one EAS was 36.8% (95% BC CI: 17.7 to 55.9). CONCLUSIONS: High levels of EAS distinctively contribute to complex clinical presentations of depression in adulthood. Patients with complex clinical presentations of depression and history of EAS should need a differentiated treatment approach, particularly those having high levels of EAS.

A collaborative, computer-assisted, psycho-educational intervention for depressed patients with chronic disease at primary care: protocol for a cluster randomized controlled trial.

BACKGROUND: Depression and chronic diseases are frequently comorbid public health problems. However, clinical guidelines often fail to consider comorbidities. This study protocol describes a cluster randomized trial (CRT) aimed to compare the effectiveness of a collaborative, computer-assisted, psycho-educational intervention versus enhanced usual care (EUC) in the treatment of depressed patients with hypertension and/or diabetes in primary care clinics (PCC) in Santiago, Chile. METHODS: Two-arm, single-blind, CRT carried out at two municipalities in Santiago, Chile. Eight PCC will be randomly assigned (1:1 ratio within each municipality, 4 PCC in each municipality) to the INTERVENTION or EUC. A total of 360 depressed patients, aged at least 18 years, with Patient Health Questionnaire-9 Item [PHQ-9] scores ≥15, and enrolled in the Cardiovascular Health Program at the participating PCC. Patients with alcohol/substance abuse; current treatment for depression, bipolar disorder, or psychosis; illiteracy; severe impairment; and resident in long-term care facilities, will be excluded. Patients in both arms will be invited to use the Web page of the project, which includes basic health education information. Patients in the INTERVENTION will receive eight sessions of a computer-assisted, psycho-educational intervention delivered by trained therapists, a structured telephone calls to monitor progress, and usual medical care for chronic diseases. Therapists will receive biweekly and monthly supervision by psychologist and psychiatrist, respectively. A monthly meeting will be held between the PCC team and a member of the research team to ensure continuity of care. Patients in EUC will receive depression treatment according to clinical guidelines and usual medical care for chronic diseases. Outcome assessments will be conducted at 3, 6, and 12 months after enrollment. The primary outcome will be depression improvement at 6 months, defined as ≥50% reduction in baseline PHQ-9 scores. Intention-to-treat analyses will be performed. DISCUSSION: This study will be one of the first to provide evidence for the effectiveness of a collaborative, computer-assisted, psycho-educational intervention for depressed patients with chronic disease at primary care in a Latin American country. TRIAL REGISTRATION: retrospectively registered in ClinicalTrials.gov , first posted: November 3, 2020, under identifier: NCT04613076 .

[Systematic review of treatment alternatives for depressed adults with early adverse stress]. / Tratamiento de la depresión en adultos con estrés adverso temprano: revisión sistemática de su efecto en síntomas relacionados a trauma, ansiedad, desajuste social y calidad de vida.

BACKGROUND: Early adverse stress is a risk factor for the appearance of mental health ailments during adulthood. AIM: To systematically review treatment outcomes on mental health symptoms and functional domains, and of interventions aimed at treating adults with depressive disorders and early adverse stress (EAS). MATERIAL AND METHODS: Systematic review and meta-analysis including experimental and quasi-experimental published studies indexed in the CINAHL, EMBASE, PubMed, and Web of Science databases, which explored the effectiveness of treatment interventions for depressive disorders in adults exposed to EAS. Data on outcomes was extracted from the included studies. A narrative, qualitative approach or a quality-effects model for meta-analysis were used for synthesizing these data. RESULTS: Thirteen studies were included. Psychological or combined treatment interventions for depression in adults exposed to EAS may be effective in reducing trauma-related symptoms and social dysfunction in the short-and mid-term, with small effect size and without substantive heterogeneity. The assessment of anxiety symptoms and health-related quality of life yielded mixed results. CONCLUSIONS: Despite the ubiquity of EAS and its adverse and long-lasting consequences for well-being and health, treatment alternatives are scant. This review suggests that there are treatment interventions for depression in adults exposed to EAS that may achieve integral mental health benefits, alleviating its impact on various symptoms and functional domains, when EAS is explicitly considered in the treatment intervention.

Lurasidone Efficacy in Mixed Depressive States: A Comparison of Standard Rating Scales to the Koukopoulos Mixed Depression Rating Scale.

INTRODUCTION: A new mood rating scale for mixed states of depression along with manic-like excitatory symptoms, the Koukopoulos Mixed Depression Rating Scale (KMDRS), was assessed in a post hoc analysis of a randomized clinical trial of lurasidone versus placebo in major depressive disorder (MDD) with mixed features. METHODS: The KMDRS was compared with the Montgomery Asberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS). Item weighting was performed and compared with an original KMDRS validation data set. Weighting was used to provide imputed KMDRS scores in the lurasidone study, based on observed MADRS and YMRS scores. RESULTS: Standardized effect sizes were larger for MADRS (0.61) and YMRS (0.79) than for KMDRS (0.44, Cohen d). CONCLUSIONS: This analysis did not find that the KMDRS produced a larger effect size than the MADRS in Diagnostic and Statistical Manual for Mental Disorder-5 (DSM-5) defined MDD with mixed features. The lower utility of KMDRS may be due to the imputed nature of this analysis, or also to the DSM-5 defined patient population, which may reflect mixed hypomania rather than mixed depression.

Development and validation of a three-item version of the Edinburgh Postnatal Depression Scale.

OBJECTIVE: To develop and validate a brief screening instrument for postpartum depression in resource-constrained primary care settings. METHOD: Secondary data analysis of a cohort of 305 mothers (Mdnage = 26) attending well-child check-ups in six primary care centers in Santiago, Chile, answered the Edinburgh Postnatal Depression Scale (EPDS), the 36-Item Short Form Health Survey, and the Mini International Neuropsychiatric Interview depression module. A predictive model for postpartum depression was built using logistic and least absolute shrinkage and selection operator regressions, with bootstrap validation. RESULTS: A three-item version of the EPDS exhibited excellent discriminative capacity (c statistic = 0.95) and showed no significant differences versus the full version of the EPDS (χ2 (1) = 1.75, p = .187). The best trade-off between sensitivity (92.86%) and specificity (86.70%) was achieved at a cut-off score of 8/9. CONCLUSIONS: The three-item version of the EPDS can save clinicians valuable time, which might potentially improve communication of results to patients.

[Validation of the Childhood Trauma Questionnaire-Short Form in Chile]. / Validación de la versión en español del Childhood Trauma Questionnaire-Short Form en Chile, en una muestra de pacientes con depresión clínica.

BACKGROUND: Childhood Trauma Questionnaire-Short Form (CTQ-SF) is an instrument to assess child abuse and neglect Aim: to adapt and confirm the psychometric properties of the Spanish version of the CTQ-SF in Chile. MATERIAL AND METHODS: The CTQ-SF was applied to 89 clinically depressed subjects (77.5% women) who consulted at an outpatient mental health clinic. Confirmatory factor analysis (CFA), reliability (Cronbach's α) tests, and convergent validity analyses with clinical markers of complex depression were carried out. RESULTS: The Chilean version of the CTQ-SF demonstrated an acceptable fit to a five-factor model, with adequate psychometric properties. The CFA revealed that a better fit to a five-factor model would be achieved after elimination of two items from the physical neglect scale, the less reliable scale of the questionnaire. The physical abuse scale discriminated between patients with a complex depression versus non-complex depression, and all the CTQ-SF's scales discriminated between patients with high suicide risk and/or history of psychiatric admissions versus those patients without this background. CONCLUSIONS: the Chilean version of the CTQ-SF shows evidence of structural and discriminant validity, and reliability, in a clinical sample. Better alternatives to specifically assess the physical neglect construct should be developed.

[Screening depressive episodes in adolescents. Validation of the Patient Health Questionnaire-9 (PHQ-9)]. / Tamizaje de episodio depresivo en adolescentes. Validación del instrumento PHQ-9.

BACKGROUND: There is a paucity of validated instruments for screening depression in adolescent populations in Chile. AIM: To determine the diagnostic accuracy of the adolescent version of Patient Health Questionnaire-9 (PHQ-9). MATERIAL AND METHODS: The PHQ-9 was transculturally adapted and administered to adolescents aged 15 to 19 years residing in Santiago de Chile, who were then evaluated with a semi structured interview (Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version or K-SADS-PL) and the Beck Depression Inventory. Internal validity, concurrent validity, and discriminatory power of the PHQ-9 were analyzed. RESULTS: We evaluated 245 adolescents aged 16.2 ± 1 years (71% females). Two hundred and ten presented with a depressive episode and 35 were healthy. The sensitivity and specificity of the scale were 86.2 and 82.9% for 11 points, with a positive likelihood ratio of 5.02. CONCLUSIONS: The PHQ-9 is sensitive and specific enough to be used as a screening tool in adolescents with suspected depression. At a 11-point cut-off score as proposed, the likelihood to find a positive result in a subject with depression is five times higher.

Marital Functioning in Couples Practicing Periodic Abstinence for Family Planning.

OBJECTIVE: To compare dyadic (marital) functioning between users of natural family planning (NFP) and users of artificial methods of contraception (AMC). METHOD: A cross-sectional study was conducted in healthy, over eighteen-year-old couples living in stable relationships recruited from primary and secondary health centers in Santiago, Chile. Participants were assessed using a structured interview on sociodemographic and sexual aspects. Primary outcome, marital functioning, was studied using the Dyadic Adjustment Scale (DAS). RESULTS: One hundred and thirty-eight couples were studied, sixty-nine in each user group. Both groups had a similar average time living together (124.3 vs. 126.9 months). DAS results were consistent with functional couples in both groups, but on average, the NFP group had a significantly higher DAS score than AMC. After controlling for age, socioeconomic status, time in the relationship, and religious commitment in multivariable analysis, the NFP group had a 47 percent (odds ratio = 1.47) greater possibility of having a functional marital score above the cutoff (DAS > 114) when compared with the AMC group. The AMC group reported more frequency of sexual intercourse but similar sexual satisfaction. Most (>60 percent) of the NFP couples mentioned that their methods improved their relationship. CONCLUSION: There are sociodemographic differences between both groups, explained partly by unequal access to NFP centers. Both groups have DAS scores within functional range, but NFP users have a higher probability of being in that functional range. This study of mentally and emotionally healthy couples highlights the importance of family planning methods on intimate relationships. Summary Marital functioning is affected by family planning methods. A structured interview and a specific inventory to address conjugal functioning were applied to a group of healthy couples who live in stable relationships and are users of natural family planning (NFP) or artificial methods of contraception (AMC). The results were consistent with functional couples in both groups, but on average, the NFP group had a significantly higher score than the AMC group. The use of NFP explained this difference. This study of mentally and emotionally healthy couples highlights the importance of family planning methods on intimate relationships.

[Comorbidity in people with depression seeking help at primary health care centers in Santiago, Chile]. / Comorbilidad en personas con depresión que consultan en centros de la atención primaria de salud en Santiago, Chile.

BACKGROUND: International evidence has shown the complex interaction between depression and chronic physical diseases. Depression in scenarios involving multiple comorbidities has not received enough attention in Chile. AIM: To characterize the depressed people who consult at Primary Health Care Centers (PHCCs), taking into account the presence of chronic physical or psychiatric comorbidity. MATERIALS AND METHODS: A secondary analysis of databases used in a clinical trial. Two hundred fifty six adults seeking professional help were recruited in four PHCCs located in the Metropolitan Region. These people had a major depressive episode, identified with a structured psychiatric interview (MINI), and gave their informed consent to participate. Socio-demographic information was collected, depressive symptomatology was measured with the patient health questionnaire 9 (PHQ-9), psychiatric morbidity was assessed using the Mini International Neuropsychiatric Interview (MINI), and chronic physical diseases were self-reported by the patients. Descriptive analyses of all the variables were conducted. RESULTS: Seventy percent of patients had a history of depression, with a median of two prior depressive episodes. Depressive symptoms were mostly considered as moderate to severe and severe and 31% of the patients had high suicide risk. Seventy eight percent displayed a physical or psychiatric comorbidity. Of these patients, 29% only had a chronic physical comorbidity, while 46% suffered from an additional psychiatric disorder. CONCLUSIONS: Depressed individuals who seek help at PHCCs constitute an especially complex population that must be treated taking into account multiple comorbidities.

Statin Use and Adrenal Aldosterone Production in Hypertensive and Diabetic Subjects.

BACKGROUND: Statins substantially reduce cardiovascular mortality and appear to have beneficial effects independent of their lipid-lowering properties. We evaluated the hypothesis that statin use may modulate the secretion of aldosterone, a well-known contributor to cardiovascular disease. METHODS AND RESULTS: We measured adrenal hormones in 2 intervention studies. In study 1 in hypertensive subjects, aldosterone was analyzed at baseline and after angiotensin II stimulation on both high- and low-sodium diets (1122 observations, 15% on statins for >3 months). Statin users had 33% lower aldosterone levels in adjusted models (P<0.001). Cortisol was not modified by statins. In secondary analyses, the lowest aldosterone levels were seen with lipophilic statins and with higher doses. Statin users had lower blood pressure and reduced salt sensitivity of blood pressure (both P<0.001). In study 2, aldosterone was measured in diabetic patients on a high-sodium diet, before and after angiotensin II stimulation (143 observations, 79% statin users). Again, statin users had 26% lower aldosterone levels (P=0.006), particularly those using lipophilic statins. Ex vivo studies in rat adrenal glomerulosa cells confirmed that lipophilic statins acutely inhibited aldosterone, but not corticosterone, in response to different secretagogues. CONCLUSIONS: Statin use among hypertensive and diabetic subjects was associated with lower aldosterone secretion in response to angiotensin II and a low-sodium diet in 2 human intervention studies. This effect appeared to be most pronounced with lipophilic statins and higher doses. Future studies to evaluate whether aldosterone inhibition may partially explain the robust cardioprotective effects of statins are warranted.

A 13-week, randomized double-blind, placebo-controlled, cross-over trial of ziprasidone in bipolar spectrum disorder.

OBJECTIVE: Features of bipolarity in a major depressive disorder sample were used to define a "bipolar spectrum disorder" population for treatment with a neuroleptic agent, ziprasidone. METHODS: Forty-nine acutely depressed patients were randomized to ziprasidone-washout-placebo or placebo-washout-ziprasidone in this double-blind, prospective, 13-week crossover trial. All patients met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for a major depressive episode and were positive for at least 3 predictors of bipolarity: family history of bipolar disorder, antidepressant-induced mania, highly recurrent depressive episodes (>5), atypical depression, early onset of depression (

Antidepressants in Type II Versus Type I Bipolar Depression: A Randomized Discontinuation Trial.

BACKGROUND: We sought to test the hypothesis that antidepressants (ADs) may show preferential efficacy and safety among patients with type II bipolar disorder (BD, BD-II) more than patients with type I BD (BD-I). METHODS: Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, BD-I (n = 21) and BD-II (n = 49) in acute major depressive episodes were treated with ADs plus mood stabilizers to euthymia sustained for 2 months and then randomized openly to continue or discontinue ADs for up to 3 years. Outcomes were episode recurrences and changes in standardized symptom ratings. RESULTS: In follow-up averaging 1.64 years, both subgroups showed improvement in depressive episode frequency with AD continuation, but contrary to the hypothesis, more improvement was seen in BD-I than in BD-II (for type II, mean [standard deviation] decrease in depressive episodes per year, 0.21 [0.26]; for type I, mean (SD) decrease, 0.35 [0.15]). Subjects with BD-II who continued on ADs had slightly more depressive, but fewer manic/hypomanic, episodes than subjects with BD-I. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission. CONCLUSIONS: The findings do not confirm the hypothesis that long-term AD treatment in patients with BP-II has better outcomes than in patients with BD-I, except somewhat lower risk of manic/hypomanic episodes.

[Mental health financing in Chile: a pending debt]. / Financiamiento de la salud mental en Chile: una deuda pendiente.

In spite of the high prevalence of mental health disorders in Chile, there is a significant financing deficit in this area when compared to the world's average. The financing for mental health has not increased in accordance with the objectives proposed in the 2000 Chilean National Mental Health and Psychiatry Plan, and only three of the six mental health priorities proposed by this plan have secure financial coverage. The National Health Strategy for the Fulfilment of Health Objectives for the decade 2011-2020 acknowledges that mental disorders worsen the quality of life, increase the risk of physical illness, and have a substantial economic cost for the country. Thus, this article focuses on the importance of investing in mental health, the cost of not doing so, and the need for local mental health research. The article discusses how the United States is trying to eliminate the financial discrimination suffered by patients with mental health disorders, and concludes with public policy recommendations for Chile.

Mixed depression: clinical features and predictors of its onset associated with antidepressant use.

BACKGROUND: Mixed depression (MxD) is narrowly defined in the DSM-IV and somewhat broader in the DSM-5, although both exclude psychomotor agitation as a diagnostic criterion. This article proposes a clinical description for defining MxD, which emphasizes psychomotor excitation. METHODS: Two hundred and nineteen consecutive outpatients were diagnosed with an MxD episode using criteria proposed by Koukopoulos et al. [Acta Psychiatr Scand 2007;115(suppl 433):50-57]; we here report their clinical features and antidepressant-related effects. RESULTS: The most frequent MxD symptoms were: psychic agitation or inner tension (97%), absence of retardation (82%), dramatic description of suffering or weeping spells (53%), talkativeness (49%), and racing or crowded thoughts (48%). MxD was associated with antidepressants in 50.7% of patients, with similar frequency for tricyclic antidepressants (45%) versus selective serotonin reuptake inhibitors (38.5%). Positive predictors of antidepressant-associated MxD were bipolar disorder type II diagnosis, higher index depression severity, and higher age at index episode. Antipsychotic or no treatment was protective against antidepressant-associated MxD. CONCLUSIONS: MxD, defined as depression with excitatory symptoms, can be clinically identified, is common, occurs in both unipolar depression and bipolar disorder, and is frequently associated with antidepressant use. If replicated, this view of MxD could be considered a valid alternative to the DSM-5 criteria for depression with mixed features.

Effectiveness of short-term olanzapine in patients with bipolar I disorder, with or without comorbidity with substance use disorder.

OBJECTIVES: Prognosis of comorbid bipolar disorder (BD) and drug abuse is poor. We assessed the efficacy of olanzapine in manic or mixed BD patients, with (SUD) or without (N-SUD) comorbidity with substance use disorder (SUD) and its effect on drug abuse, days of abuse, and craving. METHODS: Eighty patients with BD-I (40 SUD) were hospitalized for a manic or mixed episode and received add-on olanzapine. Assessments were conducted at admission, discharge, and 4 and 8 weeks after discharge. Primary outcome was the proportion of responders and remitters in each group. We used a logistic regression model to adjust for possible confounders. We assessed craving and drug-abuse days with a visual analog scale and the Timeline Follow-Back. RESULTS: SUD and N-SUD were similar on response and remission, adjusted for sex, age, years ill, age at first episode, first episode depressive, number of hospitalizations, and duration of hospitalization (odds ratio, 1.09; 95% confidence interval, 1.02-2.29). Mood rating scores dropped significantly from baseline to end point in both groups. Timeline follow-back decreased in SUD from 22.5 to 7.3 at 8 weeks postdischarge, whereas craving dropped from 8.3 to 5.1 (P < 0.03). CONCLUSIONS: The effectiveness of short-term olanzapine in BD-I mania or mixed mania did not differ according to SUD comorbidity. Treatment was followed by less substance use/abuse and craving in comorbid bipolar-SUD patients.

[Suicidal ideation, self-directed violence and depression among Chilean school adolescents]. / Ideas autolíticas, violencia autoinfligida, y síntomas depresivos en escolares chilenos.

BACKGROUND: Suicidal behaviors and depression are prevalent phenomena among adolescents, and are considered a public health problem. AIM: To determine the prevalence of depressive symptoms and suicidal behaviors and the relationship between both phenomena, in a representative sample of students from ninth grade in Santiago, Chile. MATERIAL AND METHODS: We recruited a probability sample of 2,597 adolescents who answered a questionnaire with questions about suicidal behavior and the Beck Depression Inventory (BDI-II). RESULTS: The lifetime prevalence of suicidal ideation and planning was 21 and 14%, respectively. The prevalence for the past two weeks was 6.7 and 4.4% for suicidal ideation and planning, respectively. Autolytic behaviors, once in lifetime and in the past week were referred by 26 and 4% of respondents, respectively. In one third of these, self-harm coincided with recent suicide ideation or planning. All levels of suicidal behavior were more frequently reported by women. Clinically significant depressive symptoms were present in 23.5% of adolescents. Females doubled male rates. Severe depressive symptoms were present in 9.4% of the sample. A higher level of suicidal behavior correlated with more severe forms of depression. Sixty percent of adolescents who reported recent self-harm, had clinically relevant depressive symptoms. Two thirds of them had severe symptoms. CONCLUSIONS: Suicidal behavior in Chilean adolescents is prevalent, and there is an association between this behavior and the level of depression. The school is a good place to identify and develop preventive measures for teenagers.

Clinical research diagnostic criteria for bipolar illness (CRDC-BP): rationale and validity.

BACKGROUND: In the 1970 s, scientific research on psychiatric nosology was summarized in Research Diagnostic Criteria (RDC), based solely on empirical data, an important source for the third revision of the official nomenclature of the American Psychiatric Association in 1980, the Diagnostic and Statistical Manual, Third Edition (DSM-III). The intervening years, especially with the fourth edition in 1994, saw a shift to a more overtly "pragmatic" approach to diagnostic definitions, which were constructed for many purposes, with research evidence being only one consideration. The latest editions have been criticized as failing to be useful for research. Biological and clinical research rests on the validity of diagnostic definitions that are supported by firm empirical foundations, but critics note that DSM criteria have failed to prioritize research data in favor of "pragmatic" considerations. RESULTS: Based on prior work of the International Society for Bipolar Diagnostic Guidelines Task Force, we propose here Clinical Research Diagnostic Criteria for Bipolar Illness (CRDC-BP) for use in research studies, with the hope that these criteria may lead to further refinement of diagnostic definitions for other major mental illnesses in the future. New proposals are provided for mixed states, mood temperaments, and duration of episodes. CONCLUSIONS: A new CRDC could provide guidance toward an empirically-based, scientific psychiatric nosology, and provide an alternative clinical diagnostic approach to the DSM system.

Safety and Efficacy of Adjunctive Second-Generation Antidepressant Therapy With A Mood Stabiliser or an Atypical Antipsychotic in Acute Bipolar Depression: Randomised Systematic Review and Meta-Analysis of A Placebo-Controlled Trials.

(Reprinted with permission from Lancet Psychiatry 2016; 3: 1138-46).