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Background: Lithium is an old proven medication, but it is infrequently used in current practice. This review examines evidence for its benefits and risks and provides clinical guidance to its use. Method: Narrative review. Results: Besides its benefit in bipolar illness, lithium has important underappreciated proven benefits in prevention of unipolar depression and suicide. Emerging data support neurobiological benefits for cognition and possible dementia prevention. Likely benefits also exist in low doses for mood temperaments (cyclothymia and hyperthymia). High doses (over 1.0 mmol/L) should be avoided since they increase side effects, complications associated with long‐term use, and risk of toxicity. Conversely, low dosing can be legitimate, especially for suicide and dementia prevention. Nuisance side effects of lithium may affect adherence, and medically serious side‐effects can occur. Managing strategies are available for side effects. Conclusion: Lithium is the most effective medication in psychiatry, because it has disease‐modifying, not just symptomatic, effects. It is effective not only for bipolar illness but also for prevention of suicide, episodes of unipolar depression, mood temperaments, and possibly dementia. Its many benefits need better appreciation, while lowered dosing can reduce risks. [ABSTRACT FROM AUTHOR]

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The author reflects on the criticism of the public health perspective on the widespread use of antidepressants. The author states that medical profession thought that depression in the community will be resolved through diagnosis of major depressive disorder (MDD) in persons with depressive symptoms and consequent prescription of the antidepressant medication. He said the antidepressant medications have shown to improve acute severe symptoms associated with the biological disease of depression.

Objective: To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD). Methods: 73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d) or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE), while also meeting 2 or 3 (but not more nor less) DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery- Åsberg Depression Rating Scale (MADRS) scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo. Results: The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038). Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036). Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms. Conclusions: There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state. [ABSTRACT FROM AUTHOR]

Several letters to the editor are presented in response to articles in previous issues including "Venlafaxine ER for the Treatment of Pediatric Subjects With Depression: Results of Two Placebo-Controlled Trials," "Is Bipolar Disorder Overdiagnosed?" and "Atypical Antipsychotics in the Treatment of Children and Adolescents: Clinical Applications."

Abstract: In contemporary psychiatry, depression and mania are conceived as different entities. They may occur together, as in bipolar disorder, or they may occur separately, as in unipolar depression. This view is partly based on a narrow definition of mania and a rather broad definition of depression. Generally, depression is seen as more prominent, common, and problematic; while mania appears uncommon and treatment-responsive. We suggest a reversal: mania viewed broadly, not as simply episodic euphoria plus hyperactivity, but a wide range of excitatory behaviors; and depression seen more narrowly. Further, using pharmacological and clinical evidence, and in contrast to previous theories of mania interpreted as a flight from depression, we propose the primacy of mania hypothesis (PM): depression is a consequence of the excitatory processes of mania. If correct, current treatment of depressive illness needs revision. Rather than directly lifting mood with antidepressants, the aim would be to suppress manic-like excitation, with depression being secondarily prevented. Potential objections to, and empirical tests of, the PM hypothesis are discussed. [Copyright &y& Elsevier]

The widely held clinical view of ‘antidepressants’ as highly effective and specific for the treatment of all types of depressive disorders is exaggerated. This sobering conclusion is supported by recent findings from the NIMH-sponsored STEP-BD and STAR*D projects. Antidepressants have limited short-term efficacy in unipolar depressive disorders and less in acute bipolar depression; their long-term prophylactic effectiveness in recurrent unipolar major depression remains uncertain, and is doubtful in recurrent bipolar depression. These limitations may, in part, reflect the excessively broad concept of major depression as well as unrealistic expectations of universal efficacy of drugs considered ‘antidepressants.’ Treatment-refractory depression may reflect failure to distinguish depressive conditions, particularly bipolar disorder, that are inherently less responsive to antidepressants. Antidepressants probably should be avoided in bipolar depression, mixed manic-depressive states, and in neurotic depression. Expectations of antidepressants for specific types of patients with symptoms of depression or anxiety require critical re-evaluation. A revival of the concept of neurotic depression would make it possible to identify patients with mild-to-moderate, chronic or episodic dysthymia and anxiety who are unlikely to benefit greatly from antidepressants. Diagnostic criteria for a revival of the concept of neurotic depression are proposed. [ABSTRACT FROM AUTHOR]

Abstract: Background: It has been proposed that antidepressants can induce a chronic, dysphoric, irritable state in bipolar patients (called ACID for antidepressant-associated chronic irritable dysphoria). This phenomenon has only been described in case series format, and has not been prospectively validated. Methods: Prospective data from the first 1500 patients (62.7% with bipolar I, 30.1% with bipolar II, and 7.2% with NOS) treated in the STEP-BD database were examined and those who were euthymic for at least one month at study entry, subsequently developed a depressive episode, and were then followed for one year were identified. Outcome of those who received an antidepressant for this depressive episode (n =27) was compared to those who did not (n =56), with particular attention given to the presence of the proposed symptom triad of ACID, namely dysphoria, irritability, and middle insomnia. Results: Patients treated with antidepressants were ten times more likely to develop ACID than those who were not (Hazard ratio=9.95, CI=1.103–89.717, P =0.04). However, the hazard ratio dropped to 1.05 (P =0.99) when corrected for significant covariates, notably past antidepressant-related manic switch and sex. Discussion: This study does not support the existence of ACID as an independent phenomenon. Rather, ACID appears to be part of a broader spectrum of antidepressant treatment-emergent affective switches. [Copyright &y& Elsevier]

Objective: Long-term antidepressant (AD) treatment for depression in bipolar disorder (BPD) patients is highly prevalent, but its benefits and risks remain uncertain, encouraging this meta-analysis of available research. Method: We reviewed randomized controlled trials for BPD involving ≥6 months of treatment with AD ± mood stabilizer (MS) vs. placebo ± MS, using meta-analyses to compare reported risks of new depression vs. mania. Results: In seven trials (350 BPD patients) involving 12 contrasts, long-term treatments that included ADs yielded 27% lower risk of new depression vs. MS-only or no treatment [pooled relative risk, RR = 0.73; 95% CI 0.55–0.97; number-needed-to-treat (NNT) = 11], but 72% greater risk for new mania [RR = 1.72; 95% CI 1.23–2.41; number-needed-to-harm (NNH) = 7]. Compared with giving an MS-alone, adding an AD yielded neither major protection from depression (RR = 0.84; 95% CI 0.56–1.27; NNT = 16) nor substantial increase in risk of mania (RR = 1.37; 95% CI 0.81–2.33; NNH = 16). Conclusion: Long-term adjunctive AD treatment was not superior to MS-alone in BPD, further encouraging reliance on MSs as the cornerstone of prophylaxis. [ABSTRACT FROM AUTHOR]

The authors reflect on the challenges related to the diagnosis of bipolar disorders. They claim that several researchers and clinicians air their doubts over the efficiency of the International Classification of Diseases (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria in diagnosing unipolar depression and bipolar disorder. They emphasize that this shortcoming results in the recurrent depression of patients.

The Diagnostic Guidelines Task Force of the International Society for Bipolar Disorders (ISBD) presents in this document and this special issue a summary of the current nosological status of bipolar illness, a discussion of possible revisions to current DSM-IV and ICD-10 definitions, an examination of the relevant literature, explication of areas of consensus and dissensus, and proposed definitions that might guide clinicians in the most valid approach to diagnosis of these conditions given the current state of our knowledge. [ABSTRACT FROM AUTHOR]

The article talks about the practice of hippocratic psychopharmacology in women, children and the elderly. The author asserts that the treatment of bipolar disorder (BD) in such populations can be enhanced by considering a basic Hippocratic approach to medicine. He notes that the key Hippocratic concept is that nature cures and the doctor only assists. He also claims that most psychiatrists practice non-Hippocratically.

The article reflects the authors' view on the significance of defining the boundaries of childhood bipolar disorder. According to the author, pediatric bipolar disorder is notoriously controversial, with the point of the debate being whether the condition can be diagnosed in prepubertal children at all. Significant information, views and analyses of the author relative to the matter are presented.

Objective: To determine if galantamine is effective in the treatment of chronic cognitive impairment in bipolar disorder. Methods: All charts of patients meeting DSM-IV criteria for bipolar disorder treated with galantamine in an academic bipolar disorder specialty clinic psychiatric practice were reviewed and clinical response was assessed retrospectively using the Clinical Global Impression scale for Improvement. Results: Galantamine was effective in two of four patients, both of whom took at least 24 mg/day. It was ineffective in two patients who only took 8 mg/day. Sedation limited higher dosing in one patient, and a second patient experienced sedation and tremor. Improvement in cognition was not associated with improvement in mood. Galantamine appeared neutral in its effect on mood. Conclusions: This pilot case series suggests that galantamine may have some utility in improving chronic cognitive impairment in bipolar disorder. Larger studies are required to clarify these initial pilot data. [ABSTRACT FROM AUTHOR]

The major clinical morbidity of bipolar disorder is chronic depression. Yet this depression, which is resistant to our best pharmacological treatments, may represent something else. We suggest it may involve existential despair, as a consequence of the losses incurred by this illness, as well as the result of our treatment approaches. Such chronic depressive symptoms may be seen as existential, rather than biological, consequences of the failed hopes of mania. Contrary to traditional psychoanalytic views, we suggest that psychotherapeutic work can be done with manic patients through existential and interpersonal methods to develop a strong therapeutic alliance with the manic patient. We draw on the existential work of Karl Jaspers and the counter-projective methods of Harry Stack Sullivan to lay out these approaches. An existentially oriented therapeutic alliance can be seen as a mood-stabilizing treatment in patients with bipolar disorder, which augments the benefits of mood stabilizing medications. [ABSTRACT FROM AUTHOR]

The diagnosis and treatment of bipolar disorder (BD) has been inconsistent and frequently misunderstood in recent years. To identify the causes of this problem and suggest possible solutions, we undertook a critical review of studies concerning the nosology of BD and the effects of antidepressant agents. Both the underdiagnosis of BD and its frequent misdiagnosis as unipolar major depressive disorder (MDD) appear to be problems in patients with BD. Underdiagnosis results from clinicians' inadequate understanding of manic symptoms, from patients' impaired insight into mania, and especially from failure to involve family members or third parties in the diagnostic process. Some, but by no means all, of the underdiagnosis problem may also result from lack of agreement about the breadth of the bipolar spectrum, beyond classic type I manic-depressive illness (what Ketter has termed "Cade's Disease"). To alleviate confusion about the less classic varieties of bipolar illness, we propose a heuristic definition, "bipolar spectrum disorder." This diagnosis would give greater weight to family history and antidepressant-induced manic symptoms and would apply to non-type I or II bipolar illness, in which depressive symptom, course, and treatment response characteristics are more typical of bipolar than unipolar illness. The role of antidepressants is also controversial. Our review of the evidence leads us to conclude that there should be less emphasis on using antidepressants to treat persons with this illness. [ABSTRACT FROM AUTHOR]

Defines the concept of mood stabilizer. Treatment of phases of affective illness, mania, prophylaxis and depression; Efficacy of mood stabilizer for acute mood episodes without causing affective switch; Distinction between typical neuroleptic and standard antidepressant agents from lithium.

The DSM system has never acknowledged a central position for mixed states; thus, mixed depressions have been almost completely neglected for decades. Now, DSM-5 is proposing diagnostic criteria for depression with mixed features that will lead to more misdiagnosis and inadequate treatment of this syndrome. Different criteria, based on empirically stronger evidence than exists for the DSM-5 criteria, should be adopted. [ABSTRACT FROM AUTHOR]

El artículo ofrece unos pensamientos del autor que acercan el tratamiento del trastorno bipolar con ciclos rápidos. El autor habla de la posibilidad de que los antidepresivos podrían aumentar el riesgo de los síntomas del paciente. También se discute los resultados del estudio "STEP-BD" sobre los antidepresivos.

This article presents a study regarding the treatment of rapid-cycling bipolar disorder. It discusses that the term rapid-cycling bipolar disorder was first coined in the 1970s to identify lithium nonresponders in randomized clinical trials and became the subject of decades of further research. Rapid-cycling patients are less likely to respond to treatment and do worse in follow-up than patients without rapid cycling. The largest randomized clinical trial of rapid cycling shows an association between antidepressant use and rapid cycling.

Soldani F, Ghaemi SN, Baldessarini RJ. Research reports on treatments for bipolar disorder: preliminary assessment of methodological quality. Acta Psychiatr Scand 2005: 112: 72–74.© 2005 Blackwell Munksgaard. To assess frequencies of types of publications about bipolar disorder (BD) and evaluate methodological quality of treatment studies. We classified 100 randomly selected articles (1998–2002) from five psychiatric journals with highest impact ratings, by topic areas, and assessed methods employed in treatment studies. Topics ranked: treatment (41%; 37% on pharmacotherapy) > biology (31%) > psychopathology (14%) = miscellaneous (14%). Of treatment studies, only 19% of original articles were randomized, 15% were relatively large ( n ≥ 50) but non-randomized, 65% were small non-randomized, case-series or -reports, and 53% relied on baseline-to-endpoint contrasts without a control group. Patient dropout rates were≥40% in 43% of prospective studies. Only two reports provided confidence intervals; one included a power analysis, and 53% included no references on study design or statistical methods. Even in highly respected journals, the typical methodological quality of recent reports on therapeutics for BD was unexpectedly limited, and psychopathology and psychotherapies were little studied. [ABSTRACT FROM AUTHOR]

Baldassano CF, Ghaemi SN, Chang A, Lyman A, Lipari M. Acute treatment of bipolar depression with adjunctive zonisamide: a retrospective chart review.Bipolar Disord 2004: 6: 432–434.© Blackwell Munksgaard, 2004This retrospective chart review evaluated the use of zonisamide as adjunctive treatment in patients with bipolar depression.The charts of outpatients with bipolar I or II disorder treated with adjunctive zonisamide were reviewed. The efficacy of zonisamide was assessed via comparison of physician-rated Global Assessment of Functioning (GAF) and Clinical Global Impression of Severity (CGI-S) Scale scores at baseline and after 6 weeks of therapy using pairedt-tests. Patients who scored≤2 on the CGI-S after 6 weeks of zonisamide therapy were considered good responders to zonisamide.Charts for 12 patients (four men and eight women) with a mean (±SD) age of 39.6 (±7.6) years were evaluated. Patients received a mean (±SD) zonisamide dosage of 236 (±68) mg/day. Mean GAF scores significantly improved from 44.0 at baseline to 59.3 at week 6 (P = 0.05). Mean CGI-S scores improved from 4.54 at baseline to 3.42 at week 6, but the change was not statistically significant. Six patients (50.0%) were considered responders to zonisamide. Four patients discontinued zonisamide therapy, two for an adverse event (sedation) and two for lack of efficacy.Zonisamide may be a useful adjunctive treatment for some patients with bipolar depression. Conclusions from this study are limited due to its retrospective design. Further investigation of zonisamide in the treatment of bipolar depression is warranted. [ABSTRACT FROM AUTHOR]

Objective: Antidepressant responses were compared in DSM-IV bipolar and unipolar depression. Method: The authors analyzed clinical records for outcomes of antidepressant trials for 41 patients with bipolar depression and 37 with unipolar depression, similar in age and sex distribution. Results: Short-term nonresponse was more frequent in bipolar (51.3%) than unipolar (31.6%) depression. Manic switching occurred only in bipolar depression but happened less in patients taking mood stabilizers (31.6% versus 84.2%). Cycle acceleration occurred only in bipolar depression (25.6%), with new rapid cycling in 32.1%. Late response loss (tolerance) was 3.4 times as frequent, and withdrawal relapse into depression was 4.7 times less frequent, in bipolar as in unipolar depression. Mood stabilizers did not prevent cycle acceleration, rapid cycling, or response loss. Modern antidepressants, in general, did not have lower rates of negative outcomes than tricyclic antidepressants. Conclusions: The findings suggest an unfavorable cost/benefit ratio for antidepressant treatment of bipolar depression. [ABSTRACT FROM AUTHOR]

Focuses on manic-depressive illness. Criteria for diagnostic validity in psychiatric disorders; Genetic research on manic-depressive illness; Patterns of mood-stabilizing treatment.

The article examines the effect of obsessive-compulsive disorder (OCD) in the vulnerability to patients with bipolar disorder (BD). An overview on the investigations and observations in the co-occurrence of anxiety and bipolar disorders, is provided. Also emphasized is the essential of neurobiological substrates to illuminate pathogenetic mechanisms associated with comorbid BD-OCD.

The article examines the confusion of a person with bipolar disorder (BP) on the understanding of what a self is. It discusses a postmodernist perspective on the absence of a real or constructed self. It explains the value of accepting that BP is a psychiatric disease that does not affect the personality of an individual, in addition to the misconception of non-clinicians that a person who has BP also has depression or mania.

The author reflects on the International Society for Bipolar Disorders (ISBD) diagnostic guidelines task force report which focuses on the absence of diagnostic guidelines for mixed states. In relation, he comments that everyone wants research data to answer several questions, but only few studies were conducted. To address the issue, he suggests that mobility should be given an emphasis.

The article provides information on the case of a young bipolar disorder (BD) patient who was treated with antidepressants for a long period of time who presented depressed mood, feelings of inadequacy, anhedonia, and decreased appetite after a year. Topics discussed include a study on the clinical debate regarding the use of antidepressants in BD and antidepressants used and discontinued after his suicide attempt.

The article discusses the case of a female patient with severe recurrent depression, having a positive family history for bipolar disease. Topics discussed include symptoms of the patient, suicide attempt by taking high doses of antidepressants and benzodiazepine, and non-effectiveness of standard antidepressants on the patient. Also highlighted is the patient's clinical remission following lithium monotherapy.

Abstract: Background: Numerous reviews and meta-analyses of the antidepressant literature in major depressive disorders (MDD), both acute and maintenance, have been published, some claiming that antidepressants are mostly ineffective and others that they are mostly effective, in either acute or maintenance treatment. Objective: The aims of this study were to review and critique the latest and most notable antidepressant MDD studies and to conduct our own reanalysis of the US Food and Drug Administration database studies specifically analyzed by Kirsch et al. Methods: We gathered effect estimates of each MDD study. In our reanalysis of the acute depression studies, we corrected analyses for a statistical floor effect so that relative (instead of absolute) effect size differences were calculated. We also critiqued a recent meta-analysis of the maintenance treatment literature. Results: Our reanalysis showed that antidepressant benefit is seen not only in severe depression but also in moderate depression and confirmed a lack of benefit for antidepressants over placebo in mild depression. Relative antidepressant versus placebo benefit increased linearly from 5% in mild depression to 12% in moderate depression to 16% in severe depression. The claim that antidepressants are completely ineffective, or even harmful, in maintenance treatment studies involves unawareness of the enriched design effect, which, in that analysis, was used to analyze placebo efficacy. The same problem exists for the standard interpretation of those studies, although they do not prove antidepressant efficacy either, since they are biased in favor of antidepressants. Conclusions: In sum, we conclude that antidepressants are effective in acute depressive episodes that are moderate to severe but are not effective in mild depression. Except for the mildest depressive episodes, correction for the statistical floor effect proves that antidepressants are effective acutely. These considerations only apply to acute depression, however. For maintenance, the long-term efficacy of antidepressants is unproven, but the data do not support the conclusion that they are harmful. [Copyright &y& Elsevier]

The author discusses the debate about the heterogeinity of depression. He mentions the two topics of the debate related to this issue such as endogenous versus exogenous depression which are both affects the mood of the person with depression. Also, the author discussed about psychopathology, reactive depression, and major depressive disorder (MDD).

This study investigates treatment with lamotrigine after an acute response to the drug in recently depressed subjects with bipolar disorder. This issue is clinically important, given the depressive burden of bipolar disorder. The design is that of a randomized double blind placebo controlled clinical trial comparing five groups: three doses regimens of lamotrigine, lithium and placebo. Randomisation took place after 463 patients were stabilised on lamotrigine during an open label phase of treatment for acute major depression. Data analyses show lamotrigine and lithium being superior to placebo in preventing additional treatment interventions, because of the occurrence of a mood episode.

Background: Depression is a leading cause of disability. International guidelines recommend screening for depression and the Patient Health Questionnaire 9 (PHQ-9) has been identified as the most reliable screening tool. We reviewed the evidence for using it within the primary care setting.Methods: We retrieved studies from MEDLINE, Embase, PsycINFO, CINAHL and the Cochrane Library that carried out primary care-based depression screening using PHQ-9 in populations older than 12, from 1995 to 2018.Results: Forty-two studies were included in the systematic review. Most of the studies were cross-sectional (N=40, 95%), conducted in high-income countries (N=27, 71%) and recruited adult populations (N=38, 90%). The accuracy of the PHQ-9 was evaluated in 31 (74%) studies with a two-stage screening system, with structured interview most often carried out by primary care and mental health professionals. Most of the studies employed a cut-off score of 10 (N=24, 57%, total range 5 - 15). The overall sensitivity of PHQ-9 ranged from 0.37 to 0.98, specificity from 0.42 to 0.99, positive predictive value from 0.09 to 0.92, and negative predictive value from 0.8 to 1.Limitations: Lack of longitudinal studies, small sample size, and the heterogeneity of primary-care settings limited the generalizability of our results.Conclusions: PHQ-9 has been widely validated and is recommended in a two-stage screening process. Longitudinal studies are necessary to provide evidence of long-term screening effectiveness. [ABSTRACT FROM AUTHOR]

Background: It has been proposed that the broad major depressive disorder (MDD) construct is heterogenous. Koukopoulos has provided diagnostic criteria for an important subtype within that construct, "mixed depression" (MxD), which encompasses clinical pictures characterized by marked psychomotor or inner excitation and rage/anger, along with severe depression. This study provides psychometric validation for the first rating scale specifically designed to assess MxD symptoms cross-sectionally, the Koukopoulos Mixed Depression Rating Scale (KMDRS).Methods: 350 patients from the international mood network (IMN) completed three rating scales: the KMDRS, Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). KMDRS' psychometric properties assessed included Cronbach's alpha, inter-rater reliability, factor analysis, predictive validity, and Receiver Operator Curve analysis.Results: Internal consistency (Cronbach's alpha = 0.76; 95% CI 0.57, 0.94) and interrater reliability (kappa = 0.73) were adequate. Confirmatory factor analysis identified 2 components: anger and psychomotor excitation (80% of total variance). Good predictive validity was seen (C-statistic = 0.82 95% CI 0.68, 0.93). Severity cut-off scores identified were as follows: none (0-4), possible (5-9), mild (10-15), moderate (16-20) and severe (> 21) MxD.Limitations: Non DSM-based diagnosis of MxD may pose some difficulties in the initial use and interpretation of the scoring of the scale. Moreover, the cross-sectional nature of the evaluation does not verify the long-term stability of the scale.Conclusions: KMDRS was a reliable and valid instrument to assess MxD symptoms. [ABSTRACT FROM AUTHOR]

Abstract: 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 (+) diagnosis were: higher current CGI (OR=1.23, 95% CI 1.23, 2.84), lower rates of previous bipolar type I diagnosis (OR=0.54, 95% CI −3.28, −0.13), mixed symptoms on the index episode (OR=10.02, 95% CI 2.32, 24.12), rapid cycling course (OR=2.6 95% CI 1.45, 3.56), past substance abuse (OR=3.02, 95% CI 2.01, 5.67) and lower education status (OR=0.44, 95% CI −3.23, −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. [Copyright &y& Elsevier]

Abstract: Some see current views of mental illness, such as depression, as merely contemporary social constructions, with madness seen as a modernist break from medieval and ancient concepts. In contrast to these assumptions, here we describe one of the earliest texts on melancholia and mania, by Ibn Imran, an Arab physician of the 10th century. [Copyright &y& Elsevier]

Abstract: Objective: To examine the efficacy and tolerability of aripiprazole treatment for acute bipolar depression. Methods: A six-week prospective, nonrandomized, open label study was conducted in depressed bipolar outpatients (types I, II, and NOS), as diagnosed by DSM-IV criteria. Previous treatments were continued unchanged, and new treatments not permitted, except lorazepam up to 2 mg daily. Aripiprazole was dosed flexibly up to a maximum of 30 mg daily, based on tolerability and efficacy. Montgomery–Asberg Depression Rating Scale (MADRS) and Mania Rating Scale (MRS) scores were used to assess changes in mood symptoms. Side effect outcomes were measured. Data was analyzed using last observation carried forward methodology and Analysis of Variance. Results: Twenty patients (15 men, 5 women) with bipolar disorder (10 type I, 7 type II, 3 type NOS) enrolled in the study. Mean endpoint dose was 13.6 mg/d±10.0 mg/d. Thirteen (65%) patients completed 6 weeks of treatment. MADRS and MRS scores significantly improved during treatment. 44% of patients who completed at least one week of treatment were considered responders, based on ≥50% decrease in MADRS scores from baseline. Side effect measures were mostly unchanged during treatment. Conclusion: Depressive symptoms improved in bipolar patients treated with open-label aripiprazole. [Copyright &y& Elsevier]

Background: This study aims to replicate the sensitivity and specificity of the Mood Disorder Questionnaire (MDQ) for bipolar disorder and assess the impact of insight on the MDQ’s sensitivity. Unlike prior telephone-based validation, this is the first clinical study to assess the validity of the MDQ. Methods: 37 consecutive patients with bipolar spectrum illness received the MDQ, as well as 36 consecutive patients with unipolar depression. MDQ diagnoses were compared to DSM-IV-based SCID diagnoses. A total of 16 bipolar patients also received the Scale to Assess Unawareness of Mental Disorder (SUMD) to measure insight. Results: Overall sensitivity for the MDQ was 0.58, higher in bipolar I disorder (0.69) than in bipolar II/NOS (0.30, P=0.06). The sample was highly insightful, but the two patients with lowest insight both had false negative screens. Patients’ low ratings of severity of mania (question 3 of the MDQ) explained almost half of all false negative results. Specificity was 0.67. Conclusions: The MDQ demonstrates good sensitivity in insightful patients with bipolar I disorder, but may be less useful in patients with impaired insight or milder bipolar spectrum conditions. [Copyright &y& Elsevier]

Abstract: 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 appearto influence treatment response. [Copyright &y& Elsevier]