Biomedical subjects

Franco Benazzi

Publications and source records attributed to Franco Benazzi.

At least 37 records · Page 2Linked to original sources

PubMed2006

A cross-sectional study of the prevalence of cognitive and physical symptoms during long-term antidepressant treatment.

BACKGROUND: Antidepressant therapies have been associated with a variety of side effects of both physical and psychological nature. Until recently, however, the majority of the studies focusing on side effects of antidepressants have not routinely included assessment of cognitive side effects. The purpose of the present work is to examine cross-sectionally the prevalence of cognitive and physical side effects of antidepressants during long-term treatment of depression. METHOD: Patients at least 18 years of age who were deemed responders to antidepressant therapy following at least 3 months of treatment for major depressive disorder (MDD) (diagnosed according to DSM-IV criteria) and whose MDD was considered to be in partial or full remission were eligible for inclusion in this study. Eligible patients were enrolled between January 2003 and December 2004. Study participants were administered the Harvard Department of Psychiatry/National Depression Screening Day (HANDS) scale, the Epworth Sleepiness Scale, the Brief Fatigue Inventory, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), and a study-specific questionnaire inquiring about the emergence of specific side effects such as apathy, fatigue, and inattentiveness. RESULTS: 117 MDD patients (mean +/- SD age: 43.4 +/- 12.6 years; women: N = 78 [66.7%]) met criteria for response according to the HANDS (score < 9). Cognitive symptoms (apathy, inattentiveness, forgetfulness, word-finding difficulty, and mental slowing) were each reported on both the CPFQ and the study-specific questionnaire by more than 30% of the responders on antidepressants. The physical symptoms of fatigue and sleepiness/sedation were reported by over 40% of the responders on both the CPFQ and the study-specific questionnaire. A significant, positive relationship was found between the CPFQ and the severity of residual depressive symptoms as measured by the HANDS total score (F = 15.3, p = .0002). CONCLUSION: Physical and cognitive symptoms are frequently reported by MDD patients who have responded to antidepressants and are treated in the long term with these agents. It is likely that these symptoms are both side effects of the antidepressants as well as residual symptoms of MDD.

Adult↗

PubMed2006

Various forms of depression.

The current subtyping of depression is based on the Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision (DSM-IV-TR) categorical division of bipolar and depressive disorders. Current evidence, however, supports a dimensional approach to depression, as a continuum/spectrum of overlapping disorders, ranging from bipolar I depression to major depressive disorder. Types of depression which have recently been the focus of most research will be reviewed: bipolar II depression, mixed depression, agitated depression, atypical depression, melancholic depression, recurrent brief depression, minor depressive disorder, seasonal depression, and dysthymic disorder. Most research has focused on bipolar II depression, mixed depression (defined by depression and superimposed manic/hypomanic symptoms), and atypical depression. Mixed depression, by its combination of opposite polarity symptoms, has been found to be common by systematic probing for co-occurring manic/hypomanic symptoms. Mixed depression is a treatment challenge for clinicians, because antidepressants alone (ie, not protected by mood-stabilizing agents) may worsen its manic/hypomanic symptoms, such as irritability and psychomotor agitation, which the Food and Drug Administration (FDA) has listed as possible precursors to suicidality.

Affect↗

PubMed2005

Psychometric delineation of the most discriminant symptoms of depressive mixed states.

Recent studies have shown that depressive mixed state (DMX), i.e., a major depressive episode (MDE) plus 3 or more intra-MDE hypomanic symptoms, is prevalent in bipolar-II disorder (BP-II) and not uncommon in major depressive disorder (MDD) outpatients. The main aim of the present analyses was to find the most discriminant intra-MDE hypomanic signs and symptoms predicting depressive mixed state. Consecutive 602 MDE outpatients (348 BP-II, 254 MDD) were interviewed with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen, by a senior psychiatrist in a private practice. Sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of individual intra-MDE hypomanic signs and symptoms for depressive mixed state showed that irritability had a balanced combination of SE, SP, PPV, NPV, and that psychomotor agitation and greater talkativeness had the highest SP and PPV, but lower SE. By virtue of reducing misdiagnoses, SP and PPV are the most important of these tests for clinicians. On the basis of SP and PPV, our results suggest that, though not the most prevalent, irritability (50.3%) and psychomotor agitation (27.7%) represent the most discriminant features of depressive mixed state. Presence of these features should serve as a "red flag" to help clinicians probe more skillfully for the diagnosis of depressive mixed state. Beyond its diagnostic significance, the foregoing signs and symptoms are among the clinical features the FDA lists as presaging "suicidality" on antidepressant monotherapy.

Adult↗

PubMed2005

Impact of temperamental mood lability on depressive mixed state.

BACKGROUND: Cyclothymic temperament (which includes mood lability) is common in bipolar II disorder (BP-II). Depressive mixed state (DMX), a major depressive episode (MDE) mixed with intra-episode hypomanic symptoms (3 or more, according to a recently validated definition), was found to be common in BP-II and not uncommon in major depressive disorder (MDD). The study aim was to find the impact of temperamental mood lability (TML) on DMX. METHODS: Consecutive 148 BP-II and 117 MDD outpatients presenting for MDE treatment were interviewed by the Structured Clinical Interview for DSM-IV as modified by Benazzi and Akiskal to reduce the false negative BP-II. Intra-MDE hypomanic symptoms were systematically assessed. Kraepelin, Angst, and Akiskal's definitions of temperamental mood lability (i.e., frequent up and down fluctuations of mood between major mood episodes since young age) were followed. RESULTS: DMX was present in 61.5%, TML in 52.8%. In the DMX sample, TML was present in 57.6%, and in the non-DMX sample TML was present in 45.0% (OR = 1.6, 95% CI = 1.0-2.7). In the DMX sample, independent predictors of DMX with TML were BP-II and young age at onset. Intra-MDE hypomanic symptoms, and MDE, melancholic and atypical symptoms were not significantly different between DMX patients with TML and DMX patients without TML, apart from more temperamental interpersonal sensitivity in DMX patients with TML (OR = 2.0, 95% CI = 1.0-3.8). DISCUSSION: DMX patients with TML had a younger onset age, suggesting that TML may facilitate the onset of DMX or that it may be a precursor of DMX. The association of BP-II with DMX, TML, and interpersonal sensitivity can make the course of BP-II more unstable and its treatment more complex.

Adult↗

PubMed2005

Mixed states: the most common outpatient presentation of bipolar depressed adolescents?

BACKGROUND: The purpose of this study was to determine the rate of bipolar disorder in adolescent outpatients presenting with DSM-IV major depressive episode (MDE) and, among the bipolar group, to find out what proportion were in a mixed state. METHODS: 247 MDE Hispanic adolescents presenting to a community mental health clinic received structured screens for hypomania/mania by history. One hundred met the criteria for bipolar I or II disorder, depressed. Patients meeting the full DSM-IV criteria for both MDE andhypomania/mania simultaneously for at least 1 continuous week during the index episode were classified as being in a mixed state. RESULTS: One hundred of the 247 adolescents were bipolar (40.5%). Of these bipolars, 58 (58.0%) were boys. The mean age of the bipolar patients was 14.6 (+/-1.5) years. Eighty-two (82.0%) were in a mixed state. Of those in mixed states, 46 (56.1%) were boys, 45 (54.9%)had psychotic features, 40 (48.8%) had family histories of either major depressive disorder or of bipolar disorders, 26 (31.7%) had family histories of bipolar disorder, 55 (67.1%) had suicidal ideation and 42 (51.2%) had a history of a physically self-destructive act such as wrist cutting or overdoses. DISCUSSION: The mixed state was the most common presentation for bipolar adolescents who were in the midst of an MDE at the time of presentation to a mental health clinic. Such presentation dictates different treatments. Although this clinic caters to Hispanic youth with relatively severe affective illness, we submit that our data can be generalized to other settings in light of the fact that the unavailability of psychiatric beds for such destitute patients is driving them to ambulatory clinics. To the best of our knowledge, this is the first report of such a high prevalence of mixed states in adolescent bipolar patients evaluated in the course of routine clinical practice in an outpatient setting.

Adolescent↗

PubMed2005

Psychopathologic correlates of suicidal ideation in major depressive outpatients: is it all due to unrecognized (bipolar) depressive mixed states?

BACKGROUND: Recent transatlantic concern about suicidality in patients receiving antidepressants prompted us to examine the psychopathologic correlates of suicidal ideation occurring in clinically depressed patients. METHODS: The study sample, which consisted of 644 consecutive major depressive outpatients, of which 58.0% had bipolar II disorder (BP-II), was systematically interviewed with the SCID, in order to delineate the diagnostic and psychopathologic correlates of suicidal ideation. RESULTS: Such ideation, which was present in 49.5% [and favoring BP-II vs. major depressive disorder (MDD)] at an odds ratio (OR) of 1.3 (95% confidence interval = 0.98-1.8), was clinically significantly associated with depressive mixed state (racing/crowded thoughts and psychomotor agitation/activation during index depression), mood lability, decreased self-esteem, anorexia, as well as melancholic and psychotic features. Multiple logistic regression of suicidal ideation versus depressive symptoms and intradepressive excitatory symptoms revealed that decreased self-esteem (OR = 3.3), racing/crowded thoughts (OR = 1.5), and psychomotor agitation/activation (OR = 1.4) were independent and clinically significant correlates of suicidal ideation, irrespective of depression severity. DISCUSSION: From a psychopathologic standpoint, suicidality might be conferred by a combination of both the excited (mixed) depressive and agitated (melancholic) clusters. Trait mood lability appears to favor the genesis of these affective clusters. Within the framework of Kraepelinian psychiatry, both clusters represent depressive mixed states. Given that such states are more prevalent in BP-II, our data provide a possible explanation for the greater suicidality in BP-II patients reported in the literature. In light of the higher odds of suicidal ideation in BP-II versus MDD patients, we hypothesize that the higher prevalence of mental and psychomotor activation in BP-II might be one factor among others that favors the greater likelihood of the transition from suicidal ideation to suicidal action in BP-II. Our analyses delineate a mixed depressive substrate at risk for suicidality. To what extent, if any, antidepressant monotherapy might contribute to the genesis of such states and/or suicidality cannot be answered with the methodology of the present study.

Adult↗

PubMed2005

Atypical depressive syndromes in varying definitions.

BACKGROUND: Atypical depression (AD) exhibits distinct patterns of gender,bipolar-II disorder, genetic, and neuro-biological measures. Using prospective data from a community sample, this paper identifies criteria (and correlates) for an AD syndrome that maximizes the association with female sex and bipolar-II. METHODS: The Zurich cohort study is composed of 591 subjects selected from a population-based cohort of young adults in the canton of Zurich in Switzerland, screened in 1978 and followed with six interviews through 1999. Seven definitions of atypical depression were tested, using varying combinations of vegetative symptoms and mood reactivity. RESULTS: The atypical definitions using 2 of 3 (fatigue, overeating, oversleeping) or 2 of 2 (overeating, oversleeping) vegetative symptoms showed the strongest association with gender, bipolarity, and family history of mania. The 2/3 definition was chosen for further analysis due to its high sensitivity for identifying these characteristics. This syndrome had cumulated weighted prevalence of 16.4% (males 9.7%, females 23%); when associated with major depressive episodes, 8.2% (males 3.2%, females 15.1%). AD patients were characterized by high treatment rates, severity, and work impairment, early age of onset and long illness. AD was comorbid with social phobia, binge eating, neurasthenia, migraine headache, and subjective cognitive impairment.

Adult↗

PubMed2005

Borderline personality-bipolar spectrum relationship.

BACKGROUND: The relationship between borderline personality disorder (BPD) and bipolar disorders, especially bipolar-II disorder (BP-II), is unclear. Several reviews on the topic have come to opposite conclusions, i.e., that BPD is a bipolar spectrum disorder or instead that it is unrelated to bipolar disorders. Study aim was to find which items of BPD were related to BP-II, and which instead had no relationship with BP-II. METHODS STUDY SETTING: An outpatient psychiatry private practice, more representative of mood disorders usually seen in clinical practice in Italy. INTERVIEWER: A senior clinical and mood disorder research psychiatrist. PATIENT POPULATION: A consecutive sample of 138 BP-II and 71 major depressive disorder (MDD) remitted outpatients. ASSESSMENT INSTRUMENTS: The Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version (SCID-CV) was used for diagnosing, the SCID-II Personality Questionnaire was used by patients to self-assess borderline personality traits. Interview methods: Patients were interviewed with the SCID-CV to diagnose BP-II and MDD. The questions of the Personality Questionnaire relative to borderline personality were self-assessed by patients. As clinically significant distress or impairment of functioning was not assessed by the questionnaire, a diagnosis of borderline personality disorder could not be made, but borderline personality traits (BPT) could be assessed (i.e., all DSM-IV BPD items but not the impairment criterion). RESULTS: BPT items were significantly more common in BP-II versus MDD. The best combination of sensitivity and specificity for predicting BP-II was found by using a cutoff number of BPT items > or =5: specificity was 71.4%, sensitivity was 45.9%. BPT (defined by > or =5 items) was present in 29.5% of MDD and in 46.3% of BP-II (p=0.019). Logistic regression of BP-II versus BPT items number found a significant association. Principal component factor analysis of BPT items found two orthogonal factors: "affective instability" including unstable mood, unstable interpersonal relationships, unstable self-image, chronic emptiness, and anger, and "impulsivity" including impulsivity, suicidal behavior, avoidance of abandonment, and paranoid ideation. "Affective instability" was associated with BP-II (p=0.010), but "impulsivity" was not associated with BP-II (p=0.193). Interitem correlation was low. There was no significant correlation between the two factors. DISCUSSION: Study findings suggest that DSM-IV BPD may mix two sets of unrelated items: an affective instability dimension related to BP-II, and an impulsivity dimension not related to BP-II, which may explain the opposite conclusions of several reviews. A subtyping of BPD according to these dimensions is supported by the study findings.

Bipolar Disorder↗

PubMed2005

Gender differences in bipolar-II disorder.

UNLABELLED: Gender differences in bipolar-II disorder (BP-II) are understudied. STUDY AIM: was to test if there were gender differences in the clinical and family history features of BP-II. METHODS: Consecutive 374 BP-II private practice outpatients were interviewed by a senior psychiatrist using the Structured Clinical Interview for DSM-IV, modified to improve the detection of BP-II (by Benazzi and Akiskal 2003, J Affect Disord 73:33-38), the Montgomery Asberg Depression Rating Scale (MADRS), the Hypomania Interview Guide, and the Family History Screen. Logistic regression was used to study associations and control for confounding. Alpha level was set at 0.05; P was two-tailed. RESULTS: Females represented 67.3% of the group. The female to male ratio was independent of age. Females were more common in younger onset BP-II. Females, versus males, had significantly lower age at onset, more axis I comorbidity, atypical depressions, intra-depression hypomanic symptoms (i. e., mixed depression), and family history of suicidal behavior. On the MADRS, females had more sadness, loss of energy, loss of interest, and suicidal ideas. The symptom structure of hypomanic episodes was similar between females and males. LIMITATIONS: Single interviewer, outpatient sample, private practice study setting. DISCUSSION: Clinical differences were found between BP-II females and males. Differences were found only on the depressive pole of the disorder. However, the magnitude of the differences had not a strong clinical significance, suggesting that at present, on the basis of the variables and the population studied, there is little ground to support a female BP-II depression.

Adult↗

PubMed2005

Mixed depression: a clinical marker of bipolar-II disorder.

BACKGROUND: Recent studies have found that mixed depression [i.e., a major depressive episode (MDE) plus intra-MDE hypomanic symptoms] is common in bipolar-II disorder (BP-II), and not uncommon in major depressive disorder (MDD) depressed outpatients. Study aim was to test the predictive power for the diagnosis of BP-II of several dimensional definitions of mixed depression, searching for a clinical marker which could reduce the current underdiagnosis of BP-II. METHODS: Consecutive 348 BP-II and 254 MDD depressed outpatients were interviewed by the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen, by a senior psychiatrist in a private practice. Intra-MDE hypomanic symptoms were systematically assessed. Mixed depression was defined as an MDE plus intra-MDE hypomanic symptoms. RESULTS: Dimensional definitions of mixed depression (at least 2, 3, 4, 5 or more intra-MDE hypomanic symptoms) were tested for predicting BP-II. A definition requiring 2 or more hypomanic symptoms had the highest sensitivity, the lowest specificity, and the lowest positive predictive value. A definition requiring 5 or more hypomanic symptoms had the highest specificity, the lowest sensitivity, and the highest positive predictive value. The most balanced combination of sensitivity and specificity was found for a definition requiring 3 or more hypomanic symptoms. This definition had the highest positive predictive value, and the highest ROC area (i.e., the best global performance). This definition had also the most balanced combination of sensitivity and specificity for predicting bipolar family history. In order to validate this definition as a clinical marker of BP-II, as bipolar validators were used BP-II, young onset, many recurrences, atypical depression features, and bipolar family history (the most important one). Univariate logistic regression found that this definition was associated with most bipolar validators, especially bipolar family history. Multiple logistic regression found that bipolar family history was its strongest predictor. CONCLUSIONS: Findings suggest that a definition of mixed depression requiring 3 or more intra-MDE hypomanic symptoms may be a useful clinical marker for predicting the diagnosis of BP-II. Presence of mixed depression should lead to skillful probing for history of hypomania, which would probably reduce the BP-II misdiagnosed as MDD. Findings may also impact treatment of BP-II, as intra-MDE hypomanic symptoms may become more severe by antidepressants alone, and mood stabilising agents may be required before (or concurrently with) antidepressants.

Adult↗

PubMed2005

Suicidal ideation and bipolar-II depression symptoms.

OBJECTIVE: The FDA issued a warning about a possible risk of suicidal behaviour related to 'newer' antidepressants. Suicidal behaviour is common in bipolar-II (BP-II) depression, which is frequent in outpatients, and often mixed (i.e. it has concurrent hypomanic symptoms). The study aim was to find major depressive episode (MDE) and intra-MDE hypomanic symptoms associated with suicidal ideation. METHODS: A total of 374 consecutive BP-II MDE outpatients were interviewed by the structured clinical interview for DSM-IV (SCID), the hypomania interview guide, and the family history screen. RESULTS: Suicidal ideation was present in 52.6%. Suicidal ideation and lower GAF (meaning more severity), more persistent MDE symptoms, more melancholic depressions were significantly associated. Multiple logistic regression of suicidal ideation versus MDE symptoms and intra-MDE hypomanic symptoms found, as significant independent predictors, decreased self-esteem, racing/crowded thoughts, psychomotor agitation. DISCUSSION: As expected, suicidal ideation and depression severity were associated. Racing/crowded thoughts and psychomotor agitation were independent predictors of suicidal ideation. While cross-sectional associations cannot show a causal association, some evidence from prospective studies supports the direction of the association. As BP-II depression is common and often mixed in outpatients, clinicians should assess intra-MDE racing/crowded thoughts and psychomotor agitation, as antidepressants alone may worsen these symptoms, and this may induce or increase suicidal behaviour. Mood stabilizing agents may be needed to control these excitement symptoms before using antidepressants.

Adult↗

PubMed2005

Testing atypical depression definitions.

The evidence supporting the DSM-IV definition of atypical depression (AD) is weak. This study aimed to test different definitions of AD. Major depressive disorder (MDD) patients (N = 254) and bipolar-II (BP-II) outpatients (N = 348) were interviewed consecutively, during major depressive episodes, with the Structured Clinical Interview for DSM-IV. DSM-IV criteria for AD were followed. AD validators were female gender, young onset, BP-II, axis I comorbidity, bipolar family history. Frequency of DSM-IV AD was 43.0%. AD, versus non-AD, was significantly associated with all AD validators, apart from comorbidity when controlling for age and sex. Factor analysis of atypical symptoms found factor 1 including oversleeping, overeating and weight gain (leaden paralysis at trend correlation), and factor 2 including interpersonal sensitivity, mood reactivity, and leaden paralysis. Multiple logistic regression of factor 1 versus AD validators found significant associations with several validators (including bipolar family history), whereas factor 2 had no significant associations. Findings may support a new definition of AD based on the state-dependent features oversleeping and overeating (plus perhaps leaden paralysis) versus the current AD definition based on a combination of state and trait features. Pharmacological studies are required to support any new definition of AD, as the current concept of AD is based on different response to TCA antidepressants versus non-AD.

Adult↗

PubMed2005

The relationship of major depressive disorder to bipolar disorder: continuous or discontinuous?

Recent studies have questioned current diagnostic systems that split mood disorders into the independent categories of bipolar disorders and depressive disorders. The current classification of mood disorders runs against Kraepelin's unitary view of manic-depressive insanity (illness). The main findings of recent studies supporting a continuity between bipolar disorders (mainly bipolar II disorder) and major depressive disorder are presented. The features supporting a continuity between bipolar II disorder and major depressive disorder currently are 1) depressive mixed states (mixed depression) and dysphoric (mixed) hypomania (opposite polarity symptoms in the same episode do not support a splitting of mood disorders); 2) family history (major depressive disorder is the most common mood disorder in relatives of bipolar probands); 3) lack of points of rarity between the depressive syndromes of bipolar II disorder and major depressive disorder; 4) major depressive disorder with bipolar features such as depressive mixed states, young onset age, atypical features, bipolar family history, irritability, racing thoughts, and psychomotor agitation; 5) a high proportion of major depressive disorders shifting to bipolar disorders during long-term follow-up; 6) a high proportion of major depressive disorders with history of manic and hypomanic symptoms; 7) factors of hypomania present in major depressive disorder episodes; 8) recurrent course of major depressive disorder; and 9) depressive symptoms much more common than manic and hypomanic symptoms in the course of bipolar disorders.

Age of Onset↗

PubMed2005

A downscaled practical measure of mood lability as a screening tool for bipolar II.

BACKGROUND: Current data indicate a strong association between Cyclothymic temperament (and its more ultradian counterpart of mood lability) and Bipolar II (BPII). Administration of elaborate measures of temperament are cumbersome in routine practice. Accordingly, the aim of the present analyses was to test if a practical measure of mood lability was unique to BPII, in comparison with major depressive disorder (MDD). METHODS: Using the Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version as modified by us [J. Affect. Disord. 73 (2003) 33; Curr. Opin. Psychiatry 16 (2003) S71], we interviewed 62 consecutive BPII outpatients, as well as their 59 MDD counterparts during a major depressive episode (MDE). Hypomanic symptoms during MDE were systematically assessed: three or more such symptoms defined depressive mixed state (DMX3) on the basis of previous work by us [J. Affect. Disord. 73 (2003) 113]. A downscaled definition of trait mood lability was adapted from Akiskal et al. [Arch. Gen. Psychiatry 52 (1995) 114] and Angst et al. [J. Affect. Disord. 73 (2003) 133], requiring a positive response to one of two queries on whether one is a person with frequent "ups and downs" in mood, and whether such mood swings occur for no reason. The patients selected for inclusion had not received neuroleptics and antidepressants for at least 2 weeks prior to the index episode, they were free of substance and alcohol abuse, and did not meet the DSM-IV criteria for borderline personality disorder (BPD). Associations between mood swings and clinical variables were tested by logistic regression (STATA 7). RESULTS: Mood swings were endorsed by 50.4% of the entire sample: 62.9% of BPII and 37.2% of MDD (p = 0.0047). This practical measure of mood lability was significantly associated with BPII, lower age at onset, high depressive recurrences, atypical features, and DMX3. When controlled for number of major affective episodes, mood swings were still significantly associated with BP-II. Sensitivity and specificity of mood swings for predicting BPII were 62.9% and 62.7%, respectively. LIMITATION: The low specificity of trait mood lability for BPII diagnosis is probably due to the fact that we used a downscaled simplified measure of this trait. CONCLUSIONS: On the other hand, the relatively high sensitivity of our downscaled measure of mood lability for predicting BPII supports its usefulness as a screening tool for this diagnosis. The lack of association between self-reported mood lability and number of major mood episodes indicates that such lability does not reflect the perception of history of frequent episodes, and that it has some validity as a trait indicator. Given that our sample excluded patients meeting the DSM-IV criteria for BPD, contradicts the opinion of the latter manual that such mood lability represents its pathognomonic characteristic that distinguishes it from BPII. The bipolar nature of mood lability is further supported by significant associations with external validating criteria for bipolarity. Overall, these data indicate that in the differential diagnosis between MDD and BPII, trait mood lability favors the latter at a significant statistical level.

Adult↗

PubMed2005

Atypical depression: a variant of bipolar II or a bridge between unipolar and bipolar II?

BACKGROUND: Although increasing data link atypical depression (AD) to the bipolar spectrum, controversies abound about the extent of the overlap. In particular, the Columbia group, which has pioneered in providing data on operational clarity and pharmacological specificity of atypical depressions, has nonetheless consistently avoided studying its discriminatory validity from bipolar II (BP-II). Accordingly, we undertook a full scale validation of such a link in a large clinical sample of BP-II and unipolar (UP) major depressive disorder (MDD). METHODS: Consecutive 348 BP-II and 254 MDD outpatients presenting with major depressive episodes (MDE) were interviewed off psychoactive drugs with a modified Structured Clinical Interview for DSM-IV, the structured Family History Screen and the Hypomania Interview Guide. We used the DSM-IV criteria for "atypical features" specifier. Depressive mixed state was defined as > or =3 concurrent hypomanic signs and symptoms during MDE. Bipolar validators were age at onset, high depressive recurrence, depressive mixed state and bipolar family history (types I and II). Univariate and multivariate logistic regression were used to examine associations and control for confounding variables. RESULTS: Frequency of AD was 43.0% in the combined BP-II and MDD sample. AD, versus non-AD, had significantly higher rates of BP-II. AD was significantly associated with all bipolar validators, among which family history was the most robust. A dose-response relationship was found between number of atypical symptoms during MDE and bipolar family history loading. The association between bipolar family history and number of atypical symptoms remained significant after controlling for the confounding effect of BP-II. Bipolar family history was strongly associated with the atypical symptoms of leaden paralysis and hypersomnia. CONCLUSION: These results confirm a strong link between AD and bipolar validators along psychopathologic and familial grounds. From a practical standpoint, AD is best viewed as a variant of BP-II. Clinicians confronted with MDE patients presenting with atypical features should strongly consider a BP-II diagnosis. In a more hypothetical vein, atypicality-or some associated features thereof-might serve as a nosologic bridge between UP and BP-II.

Adult↗

PubMed2005

Irritable-hostile depression: further validation as a bipolar depressive mixed state.

BACKGROUND: "Hostile depression" has unofficially long been described as a depressive subtype, but since DSM-III, the affect has been made a defining characteristic of borderline personality disorder. The related affect of irritability in DSM-IV-TR subsumes various hostile nuances and is included in the stem question for mood disorders--especially for hypomanic episodes; in children, it is nonetheless a sign of depression. Then, there is the unofficial more general concept of depression with anger attacks, until recently ostensibly a "unipolar" (UP) disorder. A veritable tower of Babel indeed. In the present analyses, our aim was to extend previous research on irritable-hostile depression to more specific parameters of bipolarity and depressive mixed state (DMX). METHODS: Consecutive 348 bipolar-II (BP-II) and 254 unipolar (UP) major depressive disorder (MDD) outpatients (off psychoactive agents, including substances of abuse), were interviewed with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen. Borderline personality, a confounding variable, rare in the FB setting, was excluded. Irritability was defined according to DSM-IV-TR, which includes various features of hostility and anger. Depressive mixed state (DMX) was defined as a major depressive episode (MDE) plus three or more concurrent intradepressive hypomanic symptoms, whether it occurred in BP-II or MDD. RESULTS: MDE with irritability was present in 59.7% (208/348) of BP-II and in 37.4% (95/254) of MDD (p=0.0000). In BP-II, MDE with, versus MDE without, irritability had significantly younger index age, higher rates of axis I comorbidity, atypical depressive features, and DMX. Upon logistic regression, we found a significant independent association between BP-II MDE with irritability and DMX. In UP, MDE with, versus without, irritability had significantly younger age and age at onset, higher rates of atypical depression, DMX, and bipolar family history. Logistic regression revealed a significant independent association between MDE with irritability and DMX. Given that we had excluded patients with borderline personality, the high prevalence of irritable-hostile depressives in this outpatient population means that hostility cannot be considered the signature of that personality. Factor analysis revealed independent "psychomotor activation" and "irritability-mental activation" factors. Odds ratios of irritability for DMX were highest in the "UP" MDD group (=12.2); for predicting DMX, irritability had the best psychometric profile of sensitivity of 66.3% and a specificity of 86.1% for this group as well. LIMITATION: We did not use specific instruments to measure irritable, hostile, and angry affects. CONCLUSIONS: These analyses show that irritable-hostile depression is distinct from agitated depression. Whether arising from a BP-II or MDD baseline, irritable-hostile depression emerges as a valid entity with strong links to external bipolar validators, such as bipolar family history. Irritable-hostile phenomenology in depression appears to be a strong clinical marker for a DMX. Irritable-hostile depression as a variant of DMX deserves the benefit of what seems to work best in practice, i.e., anticonvulsant mood stabilizers and/or atypical antipsychotics. Formal treatment studies are very much needed.

Adult↗

PubMed2005

Agitated "unipolar" depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy.

BACKGROUND: The nosologic status of agitated depression is unresolved. Are they unipolar (UP) or bipolar (BP)? Are they mixed states? Even more controversial is the notion that antidepressants might play some role in the suicidality of such patients (Akiskal and Mallya, 1987) [Akiskal, H.S., Mallya, G., 1987. Criteria for the "soft" bipolar spectrum: treatment implications. Psychopharmacol Bull. 23, 68-73]. METHODS: After excluding all patients with history of hypomanic episodes occurring outside the frame of a major depressive episode (MDE), even those with a shorter duration of hypomanic symptoms than stipulated in DSM-IV, the remaining consecutive 254 unipolar major depressive disorder (MDD) private adult (> 21 years old) outpatients were interviewed (off psychoactive drugs for 2 weeks) with the Structured Clinical Interview for DSM-IV (SCID-CV), the Hypomania Interview Guide (HIGH-C), and the Family History Screen. Intra-MDE hypomanic symptoms were systematically assessed, with > or = 3 such symptoms required for a diagnosis of depressive mixed state (DMX). Agitated depression was defined as an MDE with HIGH-C psychomotor agitation score > or = 2. Logistic regression was used to study associations and control for confounding variables. RESULTS: In this strictly defined unipolar sample, agitated depression was present in 19.7%. Compared with its non-agitated counterpart, it had significantly fewer recurrences, less chronicity, higher rate of family history for bipolar disorder, and DMX; and, among the intra-depressive non-euphoric hypomanic symptoms (in decreasing order of frequency), distractibility, racing/crowded thoughts, irritable mood, talkativeness, and risky behavior. The most striking finding was the robust association between agitated depression and DMX (OR = 36.9). Furthermore, patients with psychomotor agitation had significantly higher rate of weight loss and suicidal ideation. Of DMX symptoms, we found an association between suicidal ideation, psychomotor activation, and racing thoughts. Agitated depression was tested by forward stepwise logistic regression versus all variables significantly different in the pairwise comparisons, yielding DMX, talkativeness, and suicidal ideation as the independent significant positive predictors. LIMITATIONS: No suicidal ideation scale was used. CONCLUSIONS: Agitated depression emerges as a distinct affective syndrome with weight loss, pressure of speech, racing thoughts and suicidal ideation. Psychomotor activation and racing thoughts during MDD independently predicted suicidal ideation. In this "unipolar" MDD sample, agitated depression had a strong clustering of intra-episode non-euphoric hypomanic symptoms (i.e. DMX) which, coupled with its association with bipolar family history, support its link with the bipolar spectrum. Agitated depression is therefore best regarded as "pseudo-unipolar." These findings overall accord with classical German concepts of agitated depression as a mixed state. Given that these patients are typically activated along the lines of risk-taking behavior, Kraepelin's rubric of "excited (mixed) depression" appears to us the preferred terminology over "agitated depression". CLINICAL IMPLICATIONS: The data reported herein, placed in the setting of the literature reviewed in the discussion suggest that the reports of increased risk of suicidal ideation and/or behavior in some depressed patients treated by antidepressant monotherapy or combinations thereof might be attributed to baseline psychomotor activation/agitation as part of an unrecognized bipolar mixed state. Whether antidepressants induce de novo suicidality in MDD cannot be answered without adequately powered prospective double-blind studies, unlikely to be conducted because of ethical constraints. Nonetheless, we submit that agitated, activated, or otherwise excited depressions (which we consider as depressive mixed states) overlap considerably with the so-called antidepressant "activation syndrome." Furthermore, the rare occurrence of suicidality on antidepressants should not obscure the fact that the advent of the new antidepressants is associated with worldwide decline in suicide rates. We finally wish to point out that our formal nosology (i.e. DSM-IV and ICD-10), in its failure to recognize the bipolar nature of depressive mixed states, thereby fails to shield pseudo-unipolar patients from antidepressant monotherapy, which is inappropriate for such patients.

Adult↗

PubMed2005

Gender, suicidality and bipolar mixed states in adolescents.

BACKGROUND: The purpose of this study was to determine the relationship between mixed states and suicidality among adolescent outpatients presenting with a DSM-IV defined major depressive episode (MDE). METHODS: Two-hundred and forty-seven adolescents meeting the criteria for MDE were screened for the presence of concurrent, intra-MDE hypomania/mania (i.e., mixed states). All patients were asked whether they had current suicidal ideation or had recently attempted any self-destructive physical act associated with the thought of dying (i.e., a suicide attempt). The data were subjected to analysis using univariate logistic regression. RESULTS: One hundred of the 247 (40.5%) adolescents were bipolar type I or type II. Of these, 82% were in mixed states. Of the patients with suicidal ideation, 62.8% were girls, and of those with histories of a suicide attempt, 69.4% were girls. Girls had more than twice the risk of having suicidal ideation (OR=2.2, p=0.004) and nearly 3 times the risk of having histories of a suicide attempt than boys (OR=2.87, p<0.0001). Being in a mixed state per se did not predict either suicidal ideation or a suicide attempt among all of the 247 patients. However, mixed states apparently independently contributed to the risk of (non-fatal) suicidal behavior among girls only. Of the mixed states, girls had nearly 4 times the risk of having made a suicide attempt compared with those without mixed states (OR=3.9, p=0.003). Age, presence of psychotic features and family history of mood disorder had little or no bearing on suicidality. LIMITATIONS: Correlational chart review study, no data collection on Axis I and Axis II comorbidity and adverse life-events. CONCLUSIONS: This report of greater suicidality in adolescent girls in a mixed state parallels the well-known adult literature of high frequency of mixed states in women. The findings are of relevance to the controversy of antidepressants and suicidality in juvenile depressives in that they identify a vulnerable group. In line with earlier suggestions by the senior author [Akiskal, H.S., 1995. Developmental pathways to bipolarity: are juvenile-onset depressions pre-bipolar? J. Am. Acad. Child Adolesc. Psych. 34, 754-763], our data highlight the public health importance of the wider recognition of bipolar mixed states in juvenile patients masquerading as unipolar depression. Finally, it appears to us that it is the failure of our formal nosology on mixed states--rather than the antidepressants per se--which is the root problem in this controversy.

Adolescent↗