Background: Mixed depression (MxD) is one subtype of depressive experiences within the depressive... more Background: Mixed depression (MxD) is one subtype of depressive experiences within the depressive spectrum. MxD definition is debated among experts. Koukopoulos' proposed diagnostic criteria focused primarily on psychic agitation, marked irritability, and intense mood lability as markers of a mixed depressive episode. The present study validates Koukopoulos' criteria as diagnostic for MxD. Methods: A sample of 435 patients from the International Mood Network (IMN), multi-center, international network of sites, and the Centro LucioBini of Rome was analyzed. Koukopoulos' criteria were assessed in all patients. Results: The most prevalent MxD criteria were "absence of psychomotor retardation" (84%), "mood lability or marked reactivity" (78%), and "psychic agitation or inner tension" (75%). Multivariable predictors of a MxD ( þ) diagnosis were: higher current CGI (OR ¼1.23, 95% CI 1.23, 2.84), lower rates of previous bipolar type I diagnosis (OR¼ 0.54, 95% CI À 3.28, À0.13), mixed symptoms on the index episode (OR ¼10.02, 95% CI 2.32, 24.12), rapid cycling course (OR ¼2.6 95% CI 1.45, 3.56), past substance abuse (OR¼ 3.02, 95% CI 2.01, 5.67) and lower education status (OR¼ 0.44, 95% CI À 3.23, À 0.98). This model showed a sensitivity of 76.4%, specificity of 86.3%, negative predictive value of 75%, and positive predictive value of 86%. Limitations: An external validation of these criteria in an independent sample is warranted. Conclusion: A broad definition of mixed depression was internally validated with multiple diagnostic validators and was sensitively and specifically predicted. Contrary to DSM-5, Koukopoulos' broad criteria include agitation, irritability and mood lability as core features.
Background: Mixed depression reflects the occurrence of a major depressive episode with subsyndro... more Background: Mixed depression reflects the occurrence of a major depressive episode with subsyndromal manic symptoms. Not recognized in DSM-IV, it is included in the proposed changes for DSM-5. Observational and cross-sectional studies have suggested that mixed depression is present in up to one-half of major depressive episodes, whether in MDD or bipolar disorder. Based on observational studies, antidepressants appear to be less effective, and neuroleptics more effective, in mixed than pure depression (major depressive episodes with no manic symptoms). In this report, we examine the specific manic symptoms that are most present in mixed depression, especially as they correlate with prospectively assessed treatment response. Methods: In 72 patients treated in a randomized clinical trial (ziprasidone versus placebo), we assessed the phenomenology of manic symptom type at study entry and their influence as predictors of treatment response. Results: The most common symptom presentation was a clinical triad of flight of ideas (60%), distractibility (58%), and irritable mood (55%). Irritable mood was the major predictor of treatment response. DSM-based diagnostic distinctions between MDD and bipolar disorder (type II) did not predict treatment response. Conclusion: In this prospective study, mixed depression seems to be most commonly associated with irritable mood, flight of ideas, and distractibility, with irritability being an important predictor of treatment outcome with neuroleptic agents. If these data are correct, in the presence of mixed depression, the DSM-based dichotomy between MDD and bipolar disorder does not appear to influence treatment response.
Despite decades of effort, psychiatry still lacks a reliable biological marker to distinguish the... more Despite decades of effort, psychiatry still lacks a reliable biological marker to distinguish the 2 depressive disorders, major depressive disorder (MDD) and bipolar disorder (BD), whose phenomenology can be extremely similar. There remain 2 commonly held assumptions about these 2 disorders. The first assumption is that MDD and BD are clear-cut and easily separable diagnostic conditions, requiring only careful assessment to distinguish. The second assumption is that there is no true difference in the clinical phenomenology of unipolar depression (UD) versus bipolar depression, and that, at least in the midst of a depressive episode, the 2 disorders cannot be distinguished. Unfortunately , both assumptions likely oversimplify the evidence base and tend to inhibit rigorous investigation by introducing biased assessment. The oft-cited observation
Objective: to develop a predictive model to evaluate the factors that modify the access to treatm... more Objective: to develop a predictive model to evaluate the factors that modify the access to treatment for Postpartum Depression (PPD). Methods: prospective study with mothers who participated in the monitoring of child health in primary care centers. For the initial assessment and during 3 months, it was considered: sociodemographic data, gyneco-obstetric data, data on the services provided, depressive symptoms according to the Edinburgh Postpartum Depression Scale (EPDS) and quality of life according to the Short Form-36 Health Status Questionnaire (SF-36). The diagnosis of depression was made based on MINI. Mothers diagnosed with PPD in the initial evaluation, were followed-up. Results: a statistical model was constructed to determine the factors that prevented access to treatment, which consisted of: item 2 of EPDS (OR 0.43, 95%CI: 0.20-0.93) and item 5 (OR 0.48, 95%CI: 0.21-1.09), and previous history of depression treatment (OR 0.26, 95%CI: 0.61-1.06). Area under the ROC curve for the model=0.79; p-value for the Hosmer-Lemershow=0.73. Conclusion: it was elaborated a simple, well standardized and accurate profile, which advises that nurses should pay attention to those mothers diagnosed with PPD, presenting low/no anhedonia (item 2 of EPDS), scarce/no panic/fear (item 5 of EPDS), and no history of depression, as it is likely that these women do not initiate treatment.
Background: Although evidence from Latin America and the Caribbean suggests that depression can b... more Background: Although evidence from Latin America and the Caribbean suggests that depression can be effectively treated in primary care settings, depression management remains unevenly performed. This systematic review evaluates all the international evidence on healthcare team training programs aimed at improving the outcomes of patients with depression. Methods: Three databases were searched for articles in English or Spanish indexed up to November 20, 2014. Studies were included if they fulfilled the following conditions: clinical trials, meta-analyses, or systematic reviews; and if they evaluated a training or educational program intended to improve the management of depression by primary healthcare teams, and assessed change in depressive symptoms, diagnosis or response rates, referral rates, patients' satisfaction and/or quality of life, and the effectiveness of treatments. Results: Nine studies were included in this systematic review. Five trials tested the effectiveness of multi-component interventions (training included), and the remaining studies evaluated the effectiveness of specific training programs for depression management. All the studies that implemented multi-component interventions were efficacious, and half of the training trials were shown to be effective. Limitations: Contribution of training programs alone to the effectiveness of multi-component interventions is yet to be established. The lack of specificity regarding health providers' characteristics might be a confounding factor. Conclusions: The review conducted suggests that stand-alone training programs are less effective than multi-component interventions. In applying the evidence gathered from developed countries to Latin America and the Caribbean, these training programs must consider and address local conditions of mental health systems, and therefore multi-component interventions may be warranted.
Objectives: Prognosis of comorbid bipolar disorder (BD) and drug abuse is poor. We assessed the e... more 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.
Objective High sodium (HS) diet is associated with hypertension (HT) and insulin resistance (IR).... more Objective High sodium (HS) diet is associated with hypertension (HT) and insulin resistance (IR). We evaluated whether HS diet was associated with a dysregulation of cortisol production and metabolic syndrome (MetS). Patients and measurements We recruited 370 adults (18-85 years, BMI 29Á3 AE 4Á4 kg/m 2 , 70% women, 72% HT, 61% MetS). HS diet (urinary sodium >150 mEq/day) was observed in 70% of subjects. We measured plasma hormones, lipid profile, urinary free cortisol (UFC) and cortisol tetrahydrometabolites (THM). Results Urinary sodium was correlated with UFC (r = +0Á45, P < 0Á001), cortisol THM (r = +0Á41, P < 0Á001) and inversely with adiponectin, HDL and aldosterone, after adjusting by age, gender and BMI. Subjects with high, compared with adequate sodium intake (50-149 mEq/day) had higher UFC (P < 0Á001), THM (P < 0Á001), HOMA-IR (P = 0Á04), HT (81% vs 50%, P < 0Á001), MetS (69% vs 41%, P < 0Á001) and lower adiponectin (P = 0Á003). A multivariate predictive model adjusted by confounders showed a high discriminative capacity for MetS (ROC curve 0Á878) using four clinical variables: HS intake [OR = 5Á6 (CI 2Á3-15Á3)], HOMA-IR [OR 1Á7 (1Á3-2Á2)] cortisol THM [OR 1Á2 (1Á1-1Á4)] and adiponectin [OR = 0Á9 (0Á8-0Á9)], the latter had a protective effect. Conclusions High sodium diet was associated with increased urinary cortisol and its metabolites. Also, HS diet was associated with HT, insulin resistance, dyslipidaemia and hypoadiponectinaemia, even when adjusting by confounding variables. Further, we observed that high salt intake, IR and higher cortisol metabolites, alone or combined in a clinical simple model, accurately predicted MetS status, suggesting an additive mechanism in obesity-related metabolic disorders.
Background: Mixed depression (MxD) is one subtype of depressive experiences within the depressive... more Background: Mixed depression (MxD) is one subtype of depressive experiences within the depressive spectrum. MxD definition is debated among experts. Koukopoulos' proposed diagnostic criteria focused primarily on psychic agitation, marked irritability, and intense mood lability as markers of a mixed depressive episode. The present study validates Koukopoulos' criteria as diagnostic for MxD. Methods: A sample of 435 patients from the International Mood Network (IMN), multi-center, international network of sites, and the Centro LucioBini of Rome was analyzed. Koukopoulos' criteria were assessed in all patients. Results: The most prevalent MxD criteria were "absence of psychomotor retardation" (84%), "mood lability or marked reactivity" (78%), and "psychic agitation or inner tension" (75%). Multivariable predictors of a MxD ( þ) diagnosis were: higher current CGI (OR ¼1.23, 95% CI 1.23, 2.84), lower rates of previous bipolar type I diagnosis (OR¼ 0.54, 95% CI À 3.28, À0.13), mixed symptoms on the index episode (OR ¼10.02, 95% CI 2.32, 24.12), rapid cycling course (OR ¼2.6 95% CI 1.45, 3.56), past substance abuse (OR¼ 3.02, 95% CI 2.01, 5.67) and lower education status (OR¼ 0.44, 95% CI À 3.23, À 0.98). This model showed a sensitivity of 76.4%, specificity of 86.3%, negative predictive value of 75%, and positive predictive value of 86%. Limitations: An external validation of these criteria in an independent sample is warranted. Conclusion: A broad definition of mixed depression was internally validated with multiple diagnostic validators and was sensitively and specifically predicted. Contrary to DSM-5, Koukopoulos' broad criteria include agitation, irritability and mood lability as core features.
Background: Mixed depression reflects the occurrence of a major depressive episode with subsyndro... more Background: Mixed depression reflects the occurrence of a major depressive episode with subsyndromal manic symptoms. Not recognized in DSM-IV, it is included in the proposed changes for DSM-5. Observational and cross-sectional studies have suggested that mixed depression is present in up to one-half of major depressive episodes, whether in MDD or bipolar disorder. Based on observational studies, antidepressants appear to be less effective, and neuroleptics more effective, in mixed than pure depression (major depressive episodes with no manic symptoms). In this report, we examine the specific manic symptoms that are most present in mixed depression, especially as they correlate with prospectively assessed treatment response. Methods: In 72 patients treated in a randomized clinical trial (ziprasidone versus placebo), we assessed the phenomenology of manic symptom type at study entry and their influence as predictors of treatment response. Results: The most common symptom presentation was a clinical triad of flight of ideas (60%), distractibility (58%), and irritable mood (55%). Irritable mood was the major predictor of treatment response. DSM-based diagnostic distinctions between MDD and bipolar disorder (type II) did not predict treatment response. Conclusion: In this prospective study, mixed depression seems to be most commonly associated with irritable mood, flight of ideas, and distractibility, with irritability being an important predictor of treatment outcome with neuroleptic agents. If these data are correct, in the presence of mixed depression, the DSM-based dichotomy between MDD and bipolar disorder does not appear to influence treatment response.
Despite decades of effort, psychiatry still lacks a reliable biological marker to distinguish the... more Despite decades of effort, psychiatry still lacks a reliable biological marker to distinguish the 2 depressive disorders, major depressive disorder (MDD) and bipolar disorder (BD), whose phenomenology can be extremely similar. There remain 2 commonly held assumptions about these 2 disorders. The first assumption is that MDD and BD are clear-cut and easily separable diagnostic conditions, requiring only careful assessment to distinguish. The second assumption is that there is no true difference in the clinical phenomenology of unipolar depression (UD) versus bipolar depression, and that, at least in the midst of a depressive episode, the 2 disorders cannot be distinguished. Unfortunately , both assumptions likely oversimplify the evidence base and tend to inhibit rigorous investigation by introducing biased assessment. The oft-cited observation
Objective: to develop a predictive model to evaluate the factors that modify the access to treatm... more Objective: to develop a predictive model to evaluate the factors that modify the access to treatment for Postpartum Depression (PPD). Methods: prospective study with mothers who participated in the monitoring of child health in primary care centers. For the initial assessment and during 3 months, it was considered: sociodemographic data, gyneco-obstetric data, data on the services provided, depressive symptoms according to the Edinburgh Postpartum Depression Scale (EPDS) and quality of life according to the Short Form-36 Health Status Questionnaire (SF-36). The diagnosis of depression was made based on MINI. Mothers diagnosed with PPD in the initial evaluation, were followed-up. Results: a statistical model was constructed to determine the factors that prevented access to treatment, which consisted of: item 2 of EPDS (OR 0.43, 95%CI: 0.20-0.93) and item 5 (OR 0.48, 95%CI: 0.21-1.09), and previous history of depression treatment (OR 0.26, 95%CI: 0.61-1.06). Area under the ROC curve for the model=0.79; p-value for the Hosmer-Lemershow=0.73. Conclusion: it was elaborated a simple, well standardized and accurate profile, which advises that nurses should pay attention to those mothers diagnosed with PPD, presenting low/no anhedonia (item 2 of EPDS), scarce/no panic/fear (item 5 of EPDS), and no history of depression, as it is likely that these women do not initiate treatment.
Background: Although evidence from Latin America and the Caribbean suggests that depression can b... more Background: Although evidence from Latin America and the Caribbean suggests that depression can be effectively treated in primary care settings, depression management remains unevenly performed. This systematic review evaluates all the international evidence on healthcare team training programs aimed at improving the outcomes of patients with depression. Methods: Three databases were searched for articles in English or Spanish indexed up to November 20, 2014. Studies were included if they fulfilled the following conditions: clinical trials, meta-analyses, or systematic reviews; and if they evaluated a training or educational program intended to improve the management of depression by primary healthcare teams, and assessed change in depressive symptoms, diagnosis or response rates, referral rates, patients' satisfaction and/or quality of life, and the effectiveness of treatments. Results: Nine studies were included in this systematic review. Five trials tested the effectiveness of multi-component interventions (training included), and the remaining studies evaluated the effectiveness of specific training programs for depression management. All the studies that implemented multi-component interventions were efficacious, and half of the training trials were shown to be effective. Limitations: Contribution of training programs alone to the effectiveness of multi-component interventions is yet to be established. The lack of specificity regarding health providers' characteristics might be a confounding factor. Conclusions: The review conducted suggests that stand-alone training programs are less effective than multi-component interventions. In applying the evidence gathered from developed countries to Latin America and the Caribbean, these training programs must consider and address local conditions of mental health systems, and therefore multi-component interventions may be warranted.
Objectives: Prognosis of comorbid bipolar disorder (BD) and drug abuse is poor. We assessed the e... more 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.
Objective High sodium (HS) diet is associated with hypertension (HT) and insulin resistance (IR).... more Objective High sodium (HS) diet is associated with hypertension (HT) and insulin resistance (IR). We evaluated whether HS diet was associated with a dysregulation of cortisol production and metabolic syndrome (MetS). Patients and measurements We recruited 370 adults (18-85 years, BMI 29Á3 AE 4Á4 kg/m 2 , 70% women, 72% HT, 61% MetS). HS diet (urinary sodium >150 mEq/day) was observed in 70% of subjects. We measured plasma hormones, lipid profile, urinary free cortisol (UFC) and cortisol tetrahydrometabolites (THM). Results Urinary sodium was correlated with UFC (r = +0Á45, P < 0Á001), cortisol THM (r = +0Á41, P < 0Á001) and inversely with adiponectin, HDL and aldosterone, after adjusting by age, gender and BMI. Subjects with high, compared with adequate sodium intake (50-149 mEq/day) had higher UFC (P < 0Á001), THM (P < 0Á001), HOMA-IR (P = 0Á04), HT (81% vs 50%, P < 0Á001), MetS (69% vs 41%, P < 0Á001) and lower adiponectin (P = 0Á003). A multivariate predictive model adjusted by confounders showed a high discriminative capacity for MetS (ROC curve 0Á878) using four clinical variables: HS intake [OR = 5Á6 (CI 2Á3-15Á3)], HOMA-IR [OR 1Á7 (1Á3-2Á2)] cortisol THM [OR 1Á2 (1Á1-1Á4)] and adiponectin [OR = 0Á9 (0Á8-0Á9)], the latter had a protective effect. Conclusions High sodium diet was associated with increased urinary cortisol and its metabolites. Also, HS diet was associated with HT, insulin resistance, dyslipidaemia and hypoadiponectinaemia, even when adjusting by confounding variables. Further, we observed that high salt intake, IR and higher cortisol metabolites, alone or combined in a clinical simple model, accurately predicted MetS status, suggesting an additive mechanism in obesity-related metabolic disorders.
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Papers by P. Vöhringer