Real-world evidence from a European cohort study of patients with treatment resistant depression: Treatment patterns and clinical outcomes.

BACKGROUND: Treatment resistant depression (TRD) characterizes a subgroup of 10-30% of patients with major depressive disorder, and is associated with considerable morbidity and mortality. A consensus treatment for TRD does not exist, which often leads to wide variations in treatment strategies. Real-world studies on treatment patterns and outcomes in TRD patients in Europe are lacking and could help elucidate current treatment strategies and their efficacy. METHODS: This non-interventional cohort study of patients with TRD (defined as treatment failure on ≥2 oral antidepressants given at adequate dose and duration) with moderate to severe depression collected real-world data on treatment patterns and outcomes in several European countries. Patients were started on a new treatment for depression according to routine clinical practice. RESULTS: Among 411 patients enrolled, after 6 months, only 16.7% achieved remission and 73.5% showed no response. At Month 12, while 19.2% achieved remission and 69.2% showed no response, 33.3% of those in remission at Month 6 were no longer in remission. Pharmacological treatments employed were heterogenous; 54 different drugs were recorded at baseline, and the top 5 treatment types according to drug classes accounted for 40.0% of patients. Even though remission rates were very low, at Month 12, 60.0% of patients had not changed treatment since enrolment. CONCLUSIONS: The heterogeneity of treatments highlights a lack of consensus. Moreover, despite low response rates, patients often remained on treatments for substantial periods of time. These data further support existence of an unmet treatment need for TRD patients in Europe.

Real-world evidence from a European cohort study of patients with treatment resistant depression: Baseline patient characteristics.

BACKGROUND: Treatment resistant depression (TRD; failure to respond to ≥2 treatments) affects ~20% of patients with major depressive disorder (MDD). Real-world data could help describe patient characteristics and TRD disease burden, to assess the unmet needs of TRD patients in Europe. METHODS: This observational study collected data from adults with moderate to severe TRD initiating a new treatment for depression, according to local standards of care. At baseline, socio-demographic characteristics, medical history, prior and current treatments were recorded. Disease severity, health-related quality of life (HRQoL), functionality and productivity were assessed. RESULTS: Overall, 411 eligible patients were enrolled across seven European countries. Mean (standard deviation [SD]) patient age was 51.0 (10.8) years; 62.3% were female. Long-term sick leave was reported by 19.0% of patients; 30.2% were unemployed. The mean (SD) duration of the current episode was 2.6 (3.9) years. At baseline, mean (SD) HRQoL scores for EuroQoL 5-dimension 5-level (UK tariff) and EQ-Visual Analog Scale were 0.41 (0.25) and 41.1 (18.7), respectively. The Work Productivity and Activity Impairment questionnaire demonstrated mean (SD) absenteeism of 57.0% (44.9%) and presenteeism of 54.7% (29.5%); mean (SD) overall work impairment was 60.5% (29.9%). LIMITATIONS: Key limitations are small cohort size, absence of a control group and generalizability to countries with different healthcare models. CONCLUSIONS: TRD patients had a high disease burden, low HRQoL and reduced function and productivity, with a substantial proportion unable to work. This demonstrates an unmet treatment need in TRD patients that, if addressed, could reduce the heavy personal and societal burden.

The implications of hypersomnia in the context of major depression: Results from a large, international, observational study.

According to the DSM-5, "reduction in the need for sleep" is the only sleep-related criteria for mixed features in depressive episodes. We aimed at studying the prevalence, clinical correlates and the role of hypersomnia in a sample of acutely depressed patients. Secondarily, we factors significantly increasing the odds of hypersomnia were studied. We conducted a post-hoc analysis of the BRIDGE-II-Mix study. Variables were compared between patients with hypersomnia (SLEEP+) and with insomnia (SLEEP-) with standard bivariate tests. A stepwise backward logistic regression model was performed with SLEEP+ as dependent variable. A total of 2514 subjects were dichotomized into SLEEP+ (n = 423, 16.8%) and SLEEP- (n = 2091, 83.2%). SLEEP+ had significant higher rates of obese BMI (p < 0.001), BD diagnosis (p = 0.027), severe BD (p < 0.001), lifetime suicide attempts (p < 0.001), lower age at first depression (p = 0.004) than SLEEP-. Also, SLEEP+ had significantly poorer response to antidepressants (AD) such as (hypo)manic switches, AD resistance, affective lability, or irritability (all 0<0.005). Moreover, SLEEP+ had significantly higher rates of mixed-state specifiers than SLEEP- (all 0 < 0.006). A significant contribution to hypersomnia in our regression model was driven by metabolic-related features, such as "current bulimia" (OR = 4.21) and "overweight/obese BMI (OR = 1.42)". Globally, hypersomnia is associated with poor outcome in acute depression. Hypersomnia is strongly associated with mixed features and bipolarity. Metabolic aspects could influence the expression of hypersomnia, worsening the overall clinical outcome. Along with commonly used screening tools, detection of hypersomnia has potential, costless discriminative validity in the differential diagnosis unipolar and bipolar depression.

The relationship between attention deficit hyperactivity disorder, bipolarity and mixed features in major depressive patients: Evidence from the BRIDGE-II-Mix Study.

OBJECTIVE: This study primarily focused on the relationship between comorbid attention deficit-hyperactivity disorder (ADHD), mixed features and bipolarity in major depressive patients. METHODS: The sample comprised 2777 patients with Major Depressive Episode (MDE) enrolled in a multicentre, multinational study originally designed to assess different definitions of mixed depression. Socio-demographic, familial and clinical characteristics were compared in patients with (ADHD + ) and without (ADHD-) comorbid ADHD. RESULTS: Sixty-one patients (2.2%) met criteria for ADHD. ADHD was associated with a higher number of (hypo)manic symptoms during depression. Mixed depression was more represented in ADHD + patients than in ADHD- using both DSM-5 and experimental criteria. Differences were maintained after removing overlapping symptoms between (hypo)mania and ADHD. ADHD in MDE was also associated with a variety of clinical and course features such as onset before the age of 20, first-degree family history of (hypo)mania, past history of antidepressant-induced (hypo)manic switches, higher number of depressive and affective episodes, atypical depressive features, higher rates of bipolarity specifier, psychiatric comorbidities with eating, anxiety and borderline personality disorders. LIMITATIONS: The study was primarily designed to address mixed features in ADHD, with slightly reduced sensitivity to the diagnosis of ADHD. Other possible diagnostic biases due to heterogeneity of participating clinicians. CONCLUSIONS: In a sample of major depressive patients, the comorbid diagnosis of current ADHD is associated with bipolar diathesis, mixed features, multiple psychiatric comorbidity and a more unstable course. Further prospective studies are necessary to confirm the possible mediating role of temperamental mood instability and emotional dysregulation in such a complex clinical presentation.

The impact of affective temperaments on clinical and functional outcome of Bipolar I patients that initiated or changed pharmacological treatment for mania.

BACKGROUND: Affective temperaments have been shown to impact on the clinical manifestations and the course of bipolar disorder. We investigated their influence on clinical features and functional outcome of manic episode. METHOD: In a naturalistic, multicenter, national study, a sample of 194 BD I patients that initated or changed pharmacological treatment for DSM-IV-TR manic episode underwent a comprehensive evaluation including briefTEMPS-M, CTQ, YMRS, MADRS, FAST, and CGI-BP. Factorial, correlation and comparative analyses were conducted on different temperamental subtypes. RESULTS: Depressive, cyclothymic, irritable and anxious temperaments resulted significantly correlated with each other. On the contrary, hyperthymic temperament scores were not correlated with the other temperamental dimensions. The factorial analysis of the briefTEMPS-M sub-scales total scores allowed the extraction of two factors: the Cyclothymic-Depressive-Anxious (Cyclo-Dep-Anx) and the Hyperthymic. At final evaluation Dominant Cyclo-Dep-Anx patients reported higer scores in MADRS and in CTQ emotional neglect and abuse subscale scores than Dominant Hyperthymic patients. The latter showed a greater functional outcome than Cyclo-Dep-Anx patients. CONCLUSIONS: Affective temperaments seem to influence the course of mania. Childhood emotional abuse and neglect were related to the cyclothymic disposition. Cyclothymic subjects showed more residual depressive symptoms and Hyperthymic temperament is associated with a better short-term functional outcome.

Aggressiveness in depression: a neglected symptom possibly associated with bipolarity and mixed features.

OBJECTIVE: To evaluate aggressiveness during a major depressive episode (MDE) and its relationship with bipolar disorder (BD) in a post hoc analysis of the BRIDGE-II-MIX study. METHOD: A total of 2811 individuals were enrolled in this multicenter cross-sectional study. MDE patients with (MDE-A, n = 399) and without aggressiveness (MDE-N, n = 2412) were compared through chi-square test or Student's t-test. A stepwise backward logistic regression model was performed. RESULTS: MDE-A group was more frequently associated with BD (P < 0.001), while aggressiveness was negatively correlated with unipolar depression (P < 0.001). At the logistic regression, aggressiveness was associated with the age at first depressive episode (P < 0.001); the severity of mania (P = 0.03); the diagnosis of BD (P = 0.001); comorbid borderline personality disorder (BPD) (P < 0.001) but not substance abuse (P = 0.63); no current psychiatric treatment (P < 0.001); psychotic symptoms (P = 0.007); the marked social/occupational impairment (P = 0.002). The variable most significantly associated with aggressiveness was the presence of DSM-5 mixed features (P < 0.001, OR = 3.815). After the exclusion of BPD, the variable of lifetime suicide attempts became significant (P = 0.013, OR = 1.405). CONCLUSION: Aggressiveness seems to be significantly associated with bipolar spectrum disorders, independently from BPD and substance abuse. Aggressiveness should be considered as a diagnostic criterion for the mixed features specifier and a target of tailored treatment strategy.

Relationships between mixed features and borderline personality disorder in 2811 patients with major depressive episode.

OBJECTIVE: The study focused on the relationship between mixed depression and borderline personality disorder (BPD). METHOD: The sample comprised 2811 patients with a major depressive episode (MDE). Clinical characteristics were compared in patients with (BPD+) and without (BPD-) comorbid BPD and in BPD+ with (MXS+) and without (MXS-) mixed features according to DSM-5 criteria. RESULTS: A total of 187 patients (6.7%) met the criteria for BPD. A DSM-IV-TR diagnosis of bipolar disorder (BD) was significantly more frequent in patients with BPD+ than in patients with BPD. Patients with BPD+ were significantly younger and reported lower age at onset than BPD-. Patients with BPD+ also showed more hypomania/mania in first-degree relatives in comparison with patients with BPD-, as well as more psychiatric comorbidity, mixed features, atypical features, suicide attempts, prior mood episodes and antidepressant-induced hypo/manic switches. Mixed features according to DSM-5 criteria were observed in 52 (27.8%) BPD+. In comparison with MXS-, MXS+ were significantly younger at age of onset and at prior mood episode and had experienced more mood episodes and hypo/manic switches with antidepressant treatments. CONCLUSION: Major depressive episode patients with comorbid BPD reported a high prevalence of mixed features and BD. The presence of DSM-5 mixed features in MDE patients with BPD may be associated with complex course and reduced treatment response.

Adult separation anxiety differentiates patients with complicated grief and/or major depression and is related to lifetime mood spectrum symptoms.

BACKGROUND: Increasing literature has been focused on complicated grief (CG) and its distinctiveness from other potentially loss related mental disorders such as major depression (MD). In this regard, symptoms of separation distress seem to play a key role. The aim of this study was to compare the clinical features of CG to those of MD and of CG+MD, with particular attention to separation anxiety. METHODS: Fifty patients with CG (26 with and 24 without MD) and 40 with MD were consecutively recruited. Assessments included: SCID-I/P, Inventory of Complicated Grief (ICG), Adult Separation Anxiety Symptom Questionnaire (ASA-27), Work and Social Adjustment Scale (WSAS), Mood Spectrum-Self Report (MOODS-SR)-lifetime version. RESULTS: Patients with MD reported significantly higher ASA-27 scores than patients with CG either alone or with MD. In all groups, ASA-27 total scores were significantly correlated with the MOODS-SR total scores and with those of its depressive component and rhythmicity domain. No significant differences were reported in the WSAS scores. LIMITATIONS: Major limitations are the small sample size and the use of lifetime instruments. CONCLUSIONS: Our results suggest a correlation between adult separation anxiety symptoms and lifetime mood spectrum symptoms both in patients with CG and MD. Further studies are needed to better understand the role of adult separation anxiety in the development of these disorders and for their nosographic autonomy as well.

Relationship between affective temperaments and aggression in euthymic patients with bipolar mood disorder and major depressive disorder.

BACKGROUND: So far there is a scarce of studies dealing with the relationship between different aspects of aggressive behaviour and affective temperaments among various mood disorders. The aim of the present study was to explore in a group of patients with affective mood disorders the relationship between affective temperaments and aggression. METHODS: 100 consecutive outpatients in euthymic phase of mood disorders (46 with bipolar disorder-type I, 18 with bipolar disorder-type II and 36 with major depressive disorder) were self-assessed with the Aggression Questionnaire and the short version of Slovenian Temperament Evaluation of Memphis, Pisa, Paris and San Diego - Autoquestionnaire (TEMPS-A). RESULTS: The factorial analysis of the TEMPS-A subscales revealed 2 main factors: Factor 1 (prominent cyclothymic profile) consisted of cyclothymic, depressive, irritable, and anxious temperaments and Factor 2 (prominent hyperthymic profile) which was represented by the hyperthymic temperament, and by depressive and anxious temperaments as negative components. Patients with prominent cyclothymic profile got their diagnosis later in their life and had significantly higher mean scores on anger and hostility (non-motor aggressive behaviour) compared with patients with prominent hyperthymic profile. LIMITATIONS: We included patients with different mood disorders, therefore the sample selection may influence temperamental and aggression profiles. We used self-report questionnaires which can elicit sociable desirable answers. CONCLUSION: Anger and hostility could represent stable personality characteristics of prominent cyclothymic profile that endure even in remission. It seems that distinct temperamental profile could serve as a good diagnostic and prognostic value for non-motor aspects of aggressive behaviour.

Evidence-based definitions of bipolar-I and bipolar-II disorders among 5,635 patients with major depressive episodes in the Bridge Study: validity and comorbidity.

The definitions of bipolar-I (BP-I) and bipolar-II (BP-II) disorders are currently under revision by the APA and by the WHO. We provide evidence of a revised set of criteria for bipolar disorders and major depressive disorder (MDD) which could serve to strengthen the construct and predictive validity of both disorders and enable more incisive studies of treatments and courses of both disorders. In the diagnostic Bridge Study of 5,635 patients with major depressive episodes from 18 countries (Europe, North Africa, Near East and Far East) leading psychiatrists in each country assessed a pre-specified group of symptoms, illness course, family history and duration of episodes; these data allowed tests of several definitions of bipolarity. The primary revised specifier diagnosis of BP-I disorder included manic episodes based on an additional category A criterion (increased activity/energy) and did not apply any exclusion criteria. The revised BP-II disorders included hypomanic episodes of 1-3 days. Family history and illness course validators (history of mania/hypomania among first degree relatives, 2 or more lifetime episodes and first symptoms having occurred before age 30) discriminated clearly between patients with bipolar-I or bipolar-II disorders meeting bipolarity specifier criteria and those with MDD. Specifier definitions provided better discrimination between MDD and the two bipolar subgroups. Patterns of concurrent comorbidities also differed significantly between patients meeting criteria for MDD compared with those meeting bipolar specifier criteria. Comorbidity patterns differed between bipolar-I and bipolar-II patients. This study provides evidence for the validity of modified (specifier) BP-I and BP-II definitions that incorporate illness course and family history which reduce ambiguities of major depressive episodes between bipolar-I and bipolar-II disorders and MDD.

The bipolar-borderline personality disorders connection in major depressive patients.

OBJECTIVE: The study focuses on the controversial relationship between borderline personality disorder (BPD) and bipolar disorder (BD), defined according to different criteria set, in a world-wide sample of patients with a current major depressive episode (MDE). METHOD: A total of 5635 patients with an MDE were enrolled in a multinational study, designed to assess varying definition of hypo/mania and familial and clinical variables associated with bipolarity. Patients with (BPD+) and without (BPD-)comorbid BPD were compared on sociodemographic, familial and clinical characteristics. RESULTS: Five hundred and thirty-two patients (9.3%) met criteria for BPD. A diagnosis of BD was more frequent in BPD+ than in BPD- using either DSM-IVTR-modified criteria or the bipolar specifier. BPD+ were younger than BPD- depressives with regard to age and age at onset. They also showed more hypomania/mania in first-degree relatives in comparison to BPD- as well as more psychiatric comorbidity, psychotic symptoms, mixed states, atypical features, seasonality of mood episodes, suicide attempts, prior mood episodes and antidepressants-induced hypo/manic switches. CONCLUSION: In our sample, selected on the basis of the presence of a mood disorder, the BD-BPD connection is confirmed by the high prevalence of bipolarity in depressive patients with BPD and by the significant association with familial and clinical features classically considered as external validators of bipolarity.

Attention deficit/hyperactivity disorder symptoms in Italian bipolar adult patients: a preliminary report.

BACKGROUND: It has been recently suggested that bipolar disorder (BD) with comorbid ADHD represents a distinct clinical phenotype of BD. With the aim to assess the impact of ADHD symptoms, we investigated the prevalence, epidemiological and clinical features associated with such a comorbidity in a sample of adult BD patients. METHODS: A total of 96 outpatients (aged 18-65 years) with BD were included. All patients were screened using the Adult ADHD Self-report Scale (ASRS) and the Diagnostic, Clinical and Therapeutic Checklist (DCTC), a semi-structured interview developed for systematic collection of familial, demographic, anamnestic and clinical informations and exploration of DSM-IV-TR diagnostic criteria for mood, anxiety, eating, impulse control and alcohol and substance use disorders. The DCTC also includes the Clinical Global Impression Bipolar scale (CGI-BP), the Global Assessment of Functioning scale (GAF) and the Sheehan Disability Scale (SDS). RESULTS: In our sample, 19 (19.8%) out of 96 BD patients fulfilled ASRS criteria for current and lifetime (onset before 7 years of age) ADHD symptoms (ADHD+). Compared to BD probands without ADHD symptoms (ADHD-), ADHD+ patients showed higher rates of current mixed episode, and lower rates of mania. ADHD+ resulted in more severe mean scores on the CGI-BP mixed, depressive and global subscales. None of the ADHD+ patients were in remission of BD at the time of the evaluation, versus 24 (31.2%) of the ADHD- group. ADHD+ patients also reported higher rate of lifetime comorbidity with Substance Use Disorder (SUD) and Alcohol Abuse in comparison to ADHD- patients. In particular the different rate in substance abuse was related to cocaine and poly-drug abuse. The two groups did not report significant differences in functioning and social adjustment with the exception of familial adjustment that was more compromised in ADHD+ than in ADHD- patients. LIMITATIONS: Retrospective design and limited sample size. CONCLUSIONS: In ADHD+ patients, BD is associated with higher rate of mixed states, more severe psychopathology and more impaired familial functioning as well as higher rates of comorbid substance, alcohol and poly-drug abuse compared to BD patients without adult ADHD. Our findings suggest that ADHD symptoms in adults may influence clinical presentation, course and prognosis of BD. Further prospective research is needed to confirm our findings and to explore treatment implications for the management of BD.

Are bipolar disorders underdiagnosed in patients with depressive episodes? Results of the multicenter BRIDGE screening study in Germany.

BACKGROUND: Recent reports indicate that the prevalence of bipolar disorder (BD) in patients with an acute major depressive episode might be higher than previously thought. We aimed to study systematically all patients who sought therapy for major depressive episode (MDE) within the BRIDGE study in Germany, reporting on an increased number (increased from 2 in the international BRIDGE report to 5) of different diagnostic algorithms. METHODS: A total of 252 patients with acute MDE (DSM-IV confirmed) were examined for the existence of BD (a) according to DSM-IV criteria, (b) according to modified DSM-IV criteria (without the exclusion criterion of 'mania not induced by substances/antidepressants'), (c) according to a Bipolarity Specifier Algorithm which expands the DSM-IV criteria, (d) according to HCL-32R (Hypomania-Checklist-32R), and (e) according to a criteria-free physician's diagnosis. RESULTS: The five different diagnostic approaches yielded immensely variable prevalences for BD: (a) 11.6; (b) 24.8%; (c) 40.6%; (d) 58.7; e) 18.4% with only partial overlap between diagnoses according to the physician's diagnosis or HCL-32R with diagnoses according to the three DSM-based algorithms. CONCLUSIONS: The diagnosis of BD in patients with MDE depends strongly on the method and criteria employed. The considerable difference between criteria-free physician's diagnosis and the remaining algorithms indicate the usefulness of criteria lists within the everyday clinical setting. LIMITATIONS: Diagnoses based on DSM were only made with checklists. The diagnoses of (hypo-) manic episodes in the patient history were not systematically verifiable by indirect anamnesis.

Episode length and mixed features as predictors of ECT nonresponse in patients with medication-resistant major depression.

OBJECTIVES: This study aimed to ascertain predictors of nonresponse to electroconvulsive therapy (ECT) in a large sample of major depressive patients resistant to pharmacologic treatment. METHODS: A total of 208 depressive patients (31 with major depression [UP], 101 with bipolar disorder II [BP II], and 76 with bipolar disorder I [BP I] according to DSM-IV criteria) were included in the study and treated with bilateral ECT on a twice-a-week schedule. The patients were assessed before (baseline) and a week after the ECT course (final score) using the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Young Mania Rating Scale (YMRS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Improvement (CGI). Responders were defined as those patients with a reduction of at least 50% in HAM-D-17 score and a rating of 2 ("much improved") or 1 ("very much improved") in the CGI-Improvement subscale. RESULTS: At the end of the ECT course, 152 patients (64%) were classified as responders and 56 patients (36%) were classified as nonresponders. On backward stepwise logistic regression, bipolar subtype (odds ratio [OR]=17.85; 95% confidence level [CL]=1.786-178.407), higher mean baseline YMRS scores (OR=1.094; 95% CL=1.025-1.166), lower mean baseline HAM-D-17 scores (OR=0.928; 95% CL=0.860-1.002), and length of current episode (OR=1.047; 95% CL=1.009-1.086) were identified as statistically significant predictors of nonresponse. CONCLUSIONS: ECT was an effective treatment for approximately two-thirds of the patients with medication-resistant depression who were included in this study. ECT nonresponse was associated with bipolar subtype, presence of manic symptoms during depression, slightly less severe depressive symptomatology, and protracted duration of the episode.

The influence of affective temperaments and psychopathological traits on the definition of bipolar disorder subtypes: a study on bipolar I Italian national sample.

UNLABELLED: Affective temperament and psychopathological traits such as separation anxiety (SA) and interpersonal sensitivity (IPS) are supposed to impact on the clinical manifestation and on the course of Bipolar Disorder (BD); in the present study we investigated their influence on the definition of BD subtypes. METHOD: : Among 106 BD-I patients with DSM-IV depressive, manic or mixed episode included in a multi-centric Italian study and treated according to the routine clinical practice, 89 (84.0%) were in remission after a follow-up period ranging from 3 to 6 months (Clinical Global Impression-BP [CGI-BP] <2). Remitting patients underwent a comprehensive evaluation including self-report questionnaires such as the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A) scale, Separation Anxiety Symptom Inventory (SASI), Interpersonal Sensitivity Measure (IPSM) and the Semi-structured interview for Mood Disorder (SIMD-R) administered by experienced clinicians. Correlation and factorial analyses were conducted on temperamental and psychopathological measures. Comparative analyses were conducted on different temperamental subtypes based on the TEMPS-A, SASI and IPSM profile. RESULTS: : Depressive, cyclothymic and irritable TEMPS-A score and SASI and IPSM total scores were positively and statistically correlated with each other. On the contrary, hyperthymic temperament score was negatively correlated with depressive temperament and not significantly correlated with the other temperamental and psychopathological dimensions. The factorial analysis of the TEMPS-A subscales and SASI and IPSM total scores allowed the extraction of 2 factors: the cyclothymic-sensitive (explaining 46% of the variance) that included, as positive components, depressive, cyclothymic, irritable temperaments and SASI and IPSM scores; the hyperthymic (explaining the 19% of the variance) included hyperthymic temperament as the only positive component and depressive temperament and IPSM, as negative components. Dominant cyclothymic-sensitive patients (n=49) were more frequently females and reported higher number of depressive, hypomanic and suicide attempts when compared to the dominant hyperthymic patients (n=40). On the contrary, these latter showed a higher number of manic episodes and hospitalizations than cyclothymic-sensitive patients. The rates of first-degree family history for both mood and anxiety disorders were higher in cyclothymic-sensitive than in hyperthymic patients. Cyclothymic sensitive patients also reported more axis I lifetime co-morbidities with Panic Disorder/Agoraphobia and Social Anxiety Disorder in comparison with hyperthymics. As concerns axis II co-morbidity the cyclothymic-sensitive patients met more frequently DSM-IV criteria 1, 5 and 7 for borderline personality disorder than the hyperthymics. On the contrary, antisocial personality disorder was more represented among hyperthymic than cyclothymic patients, in particular for DSM-IV criteria 1 and 6. LIMITATION: : No blind evaluation and uncertain validity of personality inventory. CONCLUSION: : Our results support the view that affective temperaments influence the clinical features of BD in terms of both clinical and course characteristics, family history and axis I and II co-morbidities. Hypothetical temperamental subtypes as measured by TEMPS-A presented important interrelationships that permit to reliably isolate two fundamental temperamental disposition: the first characterized by rapid fluctuations of mood and emotional instability, and the second by hyperactivity, high level of energy and emotional intensity. Dominant cyclothymic and hyperthymic bipolar I patients reported important differences in terms of gender distribution, number and polarity of previous episodes, hospitalizations, suicidality, rates of co-morbid anxiety and personality traits and disorders. Our data are consistent with the hypothesis that affective temperaments, and in particular cyclothymia, could be utilized as quantitative, intermediate phenotypes in order to identify BD susceptibility genes.

Diagnostic criteria for bipolarity based on an international sample of 5,635 patients with DSM-IV major depressive episodes.

To assess the clinical validity of individual DSM-IV criteria for hypomania. In an international sample of 5,635 patients with major depressive episodes (Bridge Study), DSM-IV criteria for hypomania (stem questions, number and quality of symptoms, duration and exclusion criteria) were systematically assessed and their validity analysed on the basis of clinical data including family history, course, and other clinical characteristics. Three stem questions for hypomania, irritability, elevated mood and the added question of increased activity, showed comparable validity. The results support the current DSM-IV requirement for a higher symptom threshold (4 of 7 hypomanic symptoms) in cases of irritable mood. Longer durations of hypomanic episodes were associated with higher scores on all validators. The results did not support the DSM-IV durational requirements for hypomanic episodes (4 days) and manic episodes (7 days). Brief hypomanic episodes of 1, 2 or 3 days were valid and would meet validity criteria for inclusion. The three exclusion criteria in DSM-IV (hypomania due to the use of antidepressants or of other substances, or to other medical conditions) were found to exclude patients with bipolar depression and should therefore not be retained. These results support several revisions of the DSM-IV concept of hypomanic episodes: specifically, the inclusion of increased activity as a gate question, the inclusion of 1 or 2 to 3-day episodes and the elimination of all exclusion criteria.

The impact of premenstrual dysphoric disorder among 92 bipolar patients.

OBJECTIVES: To evaluate the impact of Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition (DSM-IV)-defined premenstrual dysphoric disorder (PMDD) lifetime co-morbidity among 92 bipolar patients. METHOD: Ninety-two women with a lifetime diagnosis of DSM-IV-defined Bipolar Disorder (BD) either type I or type II were consecutively enrolled to determine co-morbidity rates with PMDD and associated clinical features. Measures included the Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID-I) and the Clinical Global Impression (CGI) rating scale. RESULTS: In our sample, 25 (27.2%) patients reported a lifetime history of PMDD according to DSM-IV criteria (PMDD+). PMDD+ reported higher rates of Cyclothymia and BP-II than PMDD- (respectively 72% vs. 36% and 88% vs. 60%). On the contrary, the carbohydrate-craving feature was more represented among PMDD- than PMDD+ (25% vs. 4%). PMDD was also significantly associated with post-partum depression (36% vs. 15%), Obsessive-Compulsive (24% vs. 7.5%) and Body Dysmorphic Disorders (24% vs. 6%). Finally, PMDD+ reported higher total number of Axis I co-morbid disorders than PMDD-. CONCLUSIONS: In our cohort of BD women, PMDD is a frequent co-morbid condition, in particular among patients with BD-II or Cyclothymia. Multiple co-morbidities also represent a clinical variable associated with PMDD. Further perspective studies are necessary to better define the relationships between PMDD and BD.

Lifetime co-morbidity with different subtypes of eating disorders in 148 females with bipolar disorders.

OBJECTIVES: To evaluate the impact of Eating Disorders (EDs) lifetime co-morbidity among female with Bipolar Disorders (BDs) and to compare clinical and cognitive features among EDs subgroups. METHOD: A hundred and forty eight women with a lifetime history of Diagnostic and Statistical Manual, Fourth Edition (DSM-IV)-defined Bipolar-I, Bipolar-II and/or Cyclothymia, were consecutively enrolled to determinate the prevalence of co-morbid DSM-IV-defined Anorexia Nervosa [AN], Bulimia Nervosa [BN] or Binge Eating Disorder [BED]. Measures included the Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID-I), the Clinical Global Impression (CGI) rating scale, the Eating Disorder Examination Questionnaire (EDE-Q) and BMI record. RESULTS: Forty six patients (31%) reported lifetime history of at least one ED: AN was the most common ED (n=23, 15.5%), followed by BED (n=21, 14.2%), and BN (n=8, 5.4%); 6 patients (4.1%) reported multiple lifetime EDs. As expected, BMI was highest in BED patients and lowest in those with AN. Clinical characteristics were similar in the 3 groups, while rapid cycling and co-morbid drug abuse were more common in BED compared to AN or No-ED group. As expected cognitive eating symptoms assessed by the EDE-Q were all more represented in AN than in No-ED patients. AN and BED only differed in restricting behavior and weight concerns. CONCLUSIONS: Our results prompt for the recognition of co-morbid EDs among bipolar patients, indicating that BED, along with other EDs, may influence in different ways both clinical characteristics and course of the illness. Further perspective studies are necessary to better define the relationships between different EDs and Bipolar Spectrum disorders.

Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis.

BACKGROUND: Our aim was to analyse existing data on the efficacy and tolerability of valproate for the treatment of acute bipolar depression. METHODS: Randomized controlled trials comparing valproate with placebo were identified using searches of electronic databases in October 2008. Outcomes investigated were depression, anxiety, hypomania, attrition, and adverse events. Trial quality was assessed, and data were summarized using meta-analyses. RESULTS: Four randomized, controlled, doubleblind trials of 142 participants were included. Trial quality was good, although individual study sample sizes were small. Study duration was six weeks (2 studies) and eight weeks (2 studies). Meta-analysis showed a significant difference in favour of valproate for reduction in depressive symptoms, both on depression symptom scales (standardized mean difference (SMD) -0.35 (95% confidence interval, -0.69, -0.02)), and participants with at least 50% improvement in symptoms - relative risk (RR) 2.00 (1.13, 3.53). Effects on anxiety symptoms were small, SMD -0.32 (-0.72, 0.08) and inconclusive (p=0.12). No evidence of a difference in mania symptoms, withdrawal for any reason, lack of effectiveness or adverse events was detected. Nausea occurred more frequently with valproate compared with placebo though the difference was not significant, RR 2.01 (0.98, 4.11). Other adverse events occurring more frequently with valproate (somnolence, fatigue/muscle weakness, headache, diarrhoea and dry mouth) did not differ significantly between treatment groups. LIMITATIONS: Sample sizes were small warranting a larger study to confirm or disprove these findings. CONCLUSIONS: Valproate is effective for the reduction of depressive symptoms of acute bipolar depression, and was well tolerated.

Response to ECT in bipolar I, bipolar II and unipolar depression.

OBJECTIVES: A significant body of evidence indicates the efficacy of electroconvulsive therapy (ECT) in unipolar depression but mixed results have been reported in bipolar depression. We explored difference of response to ECT in unipolar (UP), bipolar I (BP I) and bipolar II (BP II) depression, in a sample of patients resistant to pharmacological treatment. METHODS: One hundred and thirty depressive patients (17 with Major Depression (UP), 67 with bipolar disorder II (BP II) and 46 with bipolar disorder I (BP I) according to DSM-IV criteria) were included in the study and treated with bilateral ECT, on a twice-a-week schedule. The patients were assessed before (baseline) and a week after the ECT course (final score), using the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Improvement (CGI). RESULTS: The three groups (UP, BP II, BP I) showed a significant improvement after the ECT course. Global response rate (CGI<2) was 94.1% for UP, 79.1% for BP II and 67.4% for BP I. Concerning depressive symptomatology, the remission rate (HAM-D <8) was respectively 70.5 for UP, 56.7% for BP II and 65.3% for BP I. The best results were achieved by UP patients, while BP I group showed the worst results with a lower remission rate and higher scores in YMRS and BPRS psychotic cluster at the final evaluation. CONCLUSION: ECT turns out to be a viable option for the treatment of both unipolar and bipolar depressive patients resistant to pharmacological treatment. Nevertheless, while the UP group showed the best response and clinical outcomes, the BP I patients tended to exhibit residual manic and psychotic symptomatology.