Ross Baldessarini

• Massachusetts General Hospital

Objectives Recurrent [hypo]mania without major depressive episodes (“unipolar mania” [UPM]) is an uncommon form of major affective disorder related to bipolar disorder (BD). We characterized UPM patients and estimated the prevalence of their characteristics based on prolonged times‐at‐risk. Methods Using standard bivariate and multivariate statist...

Background Depression is a therapeutic challenge with bipolar disorder (BD) patients and remains a major contributor to disability, comorbidity, and premature mortality. Efficacy and safety of antidepressants for this indication remain particularly controversial and optimally safe and effective treatment of bipolar depression remains uncertain. Me...

Suicidal behavior is prevalent among individuals with psychiatric illnesses, especially mood, substance abuse, and psychotic disorders. Over the past several decades, lithium treatment in patients with mood disorders has been increasingly used to lower the risk of suicidal behavior. This overview considers that lithium treatment has the most abunda...

Suicidal behavior is more prevalent in bipolar disorders than in other psychiatric illnesses. In the last thirty years evidence has emerged to indicate that long-term treatment of bipolar disorder patients with lithium may reduce risk of suicide and attempts, with possibly similar benefits in recurrent major depressive disorder. We review and updat...

Background Rapid cycling (RC) at ≥4 recurrent episodes per year in bipolar disorder (BD) has been recognized since the 1970s. We now comment on our recent review of the topic and extensive RC analysis in a large clinical cohort, emphasizing therapeutics research. Comments Prevalence of RC-BD averages 36% for any year versus 22% in the preceding ye...

Background As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons. Methods We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 A...

Background: Preventing hospitalization of major affective disorder patients is a fundamental clinical challenge for which lithium is expected to be helpful. Methods: We compared hospitalization rates and morbidity of 260 patients with DSM-5 bipolar or major depressive disorder in the 12 months before starting lithium versus 12 months of its use....

Background: Identifying suicidal risk based on clinical assessment is challenging. Suicidal ideation fluctuates, can be downplayed or denied, and seems stigmatizing if divulged. In contrast, vitality is foundational to subjectivity in being immediately conscious before reflection. Including its assessment may improve detection of suicidal risk com...

Learning objectives after participating in this cme activity, the psychiatrist should be better able to: • Analyze and compare the different bipolar disorder (BD) types.• Identify markers that distinguish BD types and explain how the DSM-IV defines the disorder. Abstract: Since the status of type II bipolar disorder (BD2) as a separate and disti...

Background Rapid-cycling (RC; ≥ 4 episodes/year) in bipolar disorder (BD) has been recognized since the 1970s and associated with inferior treatment response. However, associations of single years of RC with overall cycling rate, long-term morbidity, and diagnostic subtypes are not clear. Results We compared descriptive and clinical characteristic...

Background: Suicidal behavior is strongly associated with major affective disorders, but there is a need to quantify and compare specific risk and protective factors in bipolar disorder (BD) and major depressive disorder (MDD). Methods: In 4307 extensively evaluated major affective-disorder participants with BD (n = 1425) or MDD (n = 2882) diagn...

Rapid-cycling in bipolar disorder (RC-BD) is associated with greater illness morbidity and inferior treatment response but many aspects remain unclear, prompting this systematic review of its definitions, prevalence, and clinical characteristics. We searched multiple literature databases through April 2022 for systematic reviews or meta-analyses on...

Background: Pharmacoepidemiological studies of clozapine use to treat bipolar disorder (BD), especially in Asia, are rare, although they can provide insights into associated clinical characteristics and support international comparisons of indications and drug dosing. Methods: We examined the prevalence and clinical correlates of clozapine treat...

Objective Compare patients diagnosed as DSM-5 type II bipolar disorder (BD2) vs. major depressive disorder (MDD). Methods We compared characteristics of 3246 closely and repeatedly evaluated, consenting, adult patient-subjects (n = 706 BD2, 2540 MDD) at a specialty clinic using bivariate methods and multivariable modeling. Results Factors more as...

Bipolar disorder is heterogeneous in phenomenology, illness trajectory, and response to treatment. Despite evidence for the efficacy of multimodal­ity interventions, the majority of persons affected by this disorder do not achieve and sustain full syndromal recovery. It is eagerly anticipated that combining datasets across various information sourc...

Lithium salts are widely used clinically, mainly for treatment of bipolar disorder, in which it is highly effective. Various preparations have been developed and tested, including older immediate-release (IR) forms of lithium carbonate and other salts and formulations with slow-release (SR) properties, developed in hopes of increasing the tolerabil...

Background: Several second-generation antipsychotic drugs (SGAs) have evidence of benefit for acute major depressive episodes in bipolar disorder (BD) patients. However, their comparative efficacy in types I vs II BD (BD1 vs BD2) remains uncertain. Methods: We carried out a systematic literature search for randomized, double-blinded, controlled...

Background: Research findings on factors associated with onset-age (OA) with bipolar (BD) and major depressive disorders (MDD) have been inconsistent, but often indicate greater morbidity following early OA. Methods: We considered factors associated with OA in 1033 carefully evaluated, systematically followed mood disorder subjects with DSM-5 BD...

Objective To compare characteristics of bipolar disorder patients diagnosed as DSM-5 types I (BD-1) vs. II (BD-2). Methods We compared descriptive, psychopathological, and treatment characteristics in a sample of 1377 consenting, closely and repeatedly evaluated adult BD patient-subjects from a specialty clinic, using bivariate methods and logisti...

Objective To assess rates and lethality of suicidal behavior in studies of children and adolescents diagnosed with major depressive disorder (MDD) or bipolar disorder (BD). Methods This PROSPERO-registered protocol (CRD-42019159676) systematically reviewed reports on suicidal behavior among juveniles (age ≤ 18 years), and pooled data on risk (% of...

Background: Because use and dosing of mood stabilizers (MSs) to treat bipolar disorder (BD) patients in Asia are not well documented, we examined prevalence and clinical correlates of treatment of Asian BD patients with relatively high doses of MSs. Methods: We conducted a pharmacoepidemiological survey across 13 Asian countries and territory in...

Background This study evaluated associations of PE with symptomatic status in mood and anxiety disorder subjects, and considered many other associated factors so as to expand on comparable previous studies. Methods Consenting adults at a mood disorder center were assessed for associations of PE frequency ([never, past only, ≤once/week] vs. regular...

Background: Time to a new episode of bipolar disorder (BD) is shorter after discontinuing lithium rapidly. We now address this and other factors associated with risk of early illness after discontinuing lithium. Methods: We compared factors for association with recurrences of BD within 12 months of discontinuing long-term lithium treatment, usin...

Background: Psychotic disorders produce important morbidity and disability in children and adolescents. There have been few relevant treatment trials, encouraging assessment of research aimed at testing efficacy and safety of antipsychotics for juveniles. We aimed to compare the short- and long-term efficacy and safety of antipsychotics to treat p...

Background Ratings of affective temperament types show promise in helping to differentiate diagnostic groups among major affective disorders as well as to predict associations with important aspects of morbidity including suicidal risk. Methods The Temperament Evaluation of Memphis, Pisa, Paris, and San Diego auto-rating (TEMPS-A) questionnaire wa...

Despite such early encouragement,¹ systematic assessment and application of biomedical treatments to the increasingly urgent challenge of suicide prevention have been remarkably slow in arriving. Few examples of the approach can be cited: (1) use of electroconvulsive therapy usually as a short-term or emergency intervention in severe depression wit...

Objective As it is not clear how body-mass index (BMI) may relate to diagnosis, symptom-severity, illness-course, and treatment-response among psychiatric patients, we related BMI to psychiatric diagnosis and to selected clinical and demographic factors in major affective disorder subjects. Methods We analyzed mean BMI levels vs. diagnosis, and ev...

Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic review and meta-analysis aims to consolidate the evidence from the highest quality randomized controlled trials (RCTs) published up to July 2021, overcoming the limitations of earl...

Background Study aims were to analyze psychopathological details of prodromes leading to first-lifetime psychotic episodes and apply them to improve prediction of final diagnoses. Methods Comprehensive records of subjects with final diagnoses of bipolar I (BD-I; n=216), schizoaffective (SzAffD; n=71), or psychotic major-depressive (MDD; n=42) diso...

Objective: Rural locations have been associated with suicidal risk; low population density may be a relevant factor. Accordingly, we investigated hypothesized associations between suicidal ideation and behavior with selected geographic and population-related measures and other factors. Methods: Consenting adult patients at a mood disorder center...

Background: Clozapine is the only treatment with regulatory-recognition of lowering suicidal risk, at least in schizophrenia patients. It remains uncertain whether such effects extend to other drugs for psychosis. Methods: We searched for reports on rates of suicidal behavior during treatment with clozapine and other modern drugs for psychosis (...

Background: Successful treatment of major depressive disorder (MDD) can be challenging, and failures ("treatment-resistant depression" [TRD]) are frequent. Steps to address TRD include increasing antidepressant dose, combining antidepressants, adding adjunctive agents, or using nonpharmacological treatments. Their relative efficacy and tolerabilit...

Background: Finasteride is one of several inhibitors of the 5α-reductase that converts testosterone to dihydrotestosterone used to treat hair loss and benign prostatic enlargement. Emerging clinical observations indicate that such treatment may be associated with depression, anxiety, and possibly increased suicidal risks, in addition to sexual dys...

Introduction: Severe depression is prevalent in young persons and can lead to disability and elevated suicidal risk. Objectives: To identify clinical and demographic factors associated with the severity of depression in juveniles diagnosed with a major mood disorder, as a contribution to improving clinical treatment and reducing risk of suicide. Me...

Learning objective: After participating in this activity, learners should be better able to:• Evaluate the evidence regarding the effectiveness of long-term treatment of bipolar disorder with valproate. Background: Prophylactic treatment is critical for bipolar disorder (BD) patients. Valproate is commonly used for this purpose but lacks regulat...

Introduction: Poor adherence to pharmacological treatment is prevalent in schizophrenia, affecting more than half of patients at some time, with increased risks of clinical worsening, adverse outcomes, suicide, and increased resource utilization including hospitalization, with higher costs. Areas Covered: This review considers factors associated wi...

Suicidal behavior is strongly associated with depression, especially with dysphoric agitation, a bipolar diagnosis, and recent hospital discharge. That medicinal treatments might aid in suicide prevention is a relatively new concept, but ethical and scientifically sound trials to test for effects of treatments on suicidal behavior are very limited...

Objective Evidence of increased suicidal risk in association with psoriasis is growing, but findings concerning atopic dermatitis are inconsistent. Methods We systematically reviewed reports of suicidal ideation, attempts, or suicides among subjects diagnosed with psoriasis or atopic dermatitis compared to healthy controls or persons with other il...

Background: Excess mortality is a critical hallmark of bipolar disorder (BD) due to co-occurring general medical disorders and especially from suicide. It is timely to review of the status of suicide in BD and to consider the possibility of limiting suicidal risk. Methods: We carried out a semi-systematic review of recent research reports pertai...

Objective To evaluate morbidity during long‐term follow‐up with clinical treatment of affective and schizoaffective disorder subjects followed from hospitalization for first major psychotic episodes. Methods We followed adult subjects systematically at regular intervals from hospitalization for first‐lifetime episodes of major affective and schizo...

Introduction of lithium carbonate to treat manic excitement in 1949 by John Cade in Melbourne opened a new, revolutionary era in psychiatry with the first clinically effective pharmacological treatment for a major psychiatric disorder. By 1960, there followed explosive discovery and development of at least one of every class of psychotropic medicin...

Background: Efforts to develop less heterogeneous, more clinically useful diagnostic categories for depressive disorders include renewed interest in the concept of melancholia (Mel). However, clinical or biological differentiation of Mel from other (nonMel) episodes of depression has been questioned, and it remains unclear whether pharmacological r...

Objective Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), a...

Background Many risk factors for suicidal behavior have been identified. Much less has been done to associate risk factors with recurrence of suicidal behavior. Methods We compared prevalence of 30 potential risk factors among 8496 depressive patient-subjects from the BRIDGE consortium with no (NSA, n=6267), one (1SA, n=1123), or repeated (≥2) sui...

Depressive phases of bipolar disorders (BD) present major challenges for treatment and comprehensive clinical management. They are the main component of psychiatric morbidity in BD, even with treatment, and are associated with excess morbidity and mortality from co-occurring general-medical disorders as well as very high suicide risk. BD patients e...

Introduction Patterns of clinical use of long‐acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established. Methods Within an extensive research consortium, we evaluated prescription rates for first‐ (FGA) and...

Background: The concept of melancholia has been associated with psychiatric nosology for centuries. Nevertheless, its definition, relationship to the contemporary concept of Major Depressive Disorder, and clinical implications remain uncertain. Methods: In a total sample of 3211 closely evaluated patient-subjects diagnosed with DSM-5 Major Depre...

Objective : As modern studies evaluating suicidal behaviors in large samples of major psychiatric disorder patients are rare, we compared suicidal risks associated with a variety of psychiatric diagnoses. Methods : We quantified rates of intake suicidal ideation and lifetime attempts, suicides, and violent acts (attempts + suicides) in 6050 adult...

Many efforts have been made to develop coherent and clinically useful categories of depressive illness, especially to facilitate prediction of morbidity and guide treatment-response. They include proposals to resurrect the ancient concept of melancholia, as a form of severe depression with particular symptomatic and proposed psychobiological charac...

Interruption of ongoing treatment with benzodiazepines, antidepressants, antipsychotics and mood stabilisers including lithium can be followed by clinically significant withdrawal reactions within hours or days, as well as later increases in relapses or recurrences of the illness being treated. Such observations support the view that stopping treat...

Depression in bipolar disorder (BD) patients presents major clinical challenges. As the predominant psychopathology even in treated BD, depression is associated not only with excess morbidity, but also mortality from co-occurring general-medical disorders and high suicide risk. In BD, risks for medical disorders including diabetes or metabolic synd...

Suicide and suicide attempts have become more prevalent in recent years, with notable increases in the US in all age groups and geographic locations. Risk of suicide is particularly high among patients diagnosed with bipolar disorder or severe depression, especially when associated with mixed features or agitation, or with co-occurring substance ab...

Mixed features of the opposite nominal mood-polarity are increasingly recognized in both depressive and [hypo]manic phases of major affective disorders. They are associated with major increases of risk of suicidal behaviors. The authors reviewed the association of suicidal behavior with mixed features in both major depressive and bipolar disorders,...

Background Antipsychotic drugs and mood-stabilizers are used routinely to treat acute mania. However, combinations of such drugs can produce adverse effects or reduced clinical efficacy due to drug-drug interactions, even if administered within the accepted range. Despite widespread clinical use of such drug-combinations, few have been evaluated sy...

Objectives: To clarify the clinical features preceding the onset of Bipolar disorder (BD) has become a public health priority for the prevention of high morbidity and mortality. BD remains frequently under- or misdiagnosed, and under- or mistreated, often for years. Methods: We assessed the predictive value of precursors and prodromes of BD. We...

Background: Lithium has been used clinically for 70 years, mainly to treat bipolar disorder. Competing treatments and exaggerated impressions about complexity and risks of lithium treatment have led to its declining use in some countries, encouraging this update about its safe clinical use. We conducted a nonsystematic review of recent research re...

Background Rates and risk factors for suicidal behaviour require updating and comparisons among mood disorders. Aims To identify factors associated with suicidal risk in major mood disorders. Method We considered risk factors before, during and after intake assessments of 3284 adults with/without suicidal acts, overall and with bipolar disorder (...

Learning objectives: After participating in this activity, learners should be better able to:• Evaluate risk of suicide and suicide attempts following psychiatric hospitalization• Assess the relationship between suicide attempts and completed suicides BACKGROUND: Suicidal risks among psychiatric patients appear to be especially high soon after hos...

Background: Guidelines for maintenance treatment of juvenile bipolar disorder (jBD) rely heavily on evidence from adult studies and relatively brief trials in juveniles, leaving uncertainties about optimal long-term treatment. We aimed to systematically review long-term treatment trials for jBD. Methods: We analyzed data recovered by systematic...

The recent meta‐analytic review of trials involving anti‐inflammatory agents to treat or to supplement treatment of patients with major depressive disorder (MDD) or depressive symptoms by Köhler‐Forsberg and colleagues [1] includes data derived from 36 controlled trials. Treatments included glucocorticoids as well as cytokine inhibitors, minocyclin...

BACKGROUND:: The potential value of lithium treatment in particular aspects of unipolar major depressive disorder remains uncertain. METHODS:: With reports of controlled trials identified by systematic searching of Medline, Cochrane Library, and PsycINFO literature databases, we summarized responses with lithium and controls followed by selective...

Background: Severe mental illnesses are associated with increased risks for metabolic syndrome (MetS) and other medical disorders, often with unfavorable outcomes. MetS may be more likely with schizoaffective disorder (SzAff) than schizophrenia (Sz). MetS is associated with long-term antipsychotic drug treatment, but relative risk with orally admin...

Objective: Eff ective treatment of adolescents with psychopathological disorders is essential to reduce later morbidity and disability. To evaluate the clinical value of a new adolescent Cooperative Assessment scheme (COOPAS) as indicated by establishing therapeutic alliance, improving symptoms, and particularly by reducing dropouts. Method: Consec...

Objective: To carry out a systematic review and meta-analysis of age of onset (AoO) of bipolar disorder (BD).

Aims To identify early clinical factors predictive of later morbidity in major depressive disorder (MDD). Methods We analysed factors associated with long‐term depressive morbidity (%‐time ill) between a first‐lifetime major depressive episode and last follow‐up of 116 adults diagnosed with DSM‐IV major depressive disorder. Bivariate comparisons w...

Background: It has long been recognized that bipolar disorder (BD) and attention deficit-hyperactivity disorder (ADHD) co-occur in an uncertain proportion of patients, recognized commonly in juvenile years. There is growing suspicion that such co-occurrence is associated with several clinically unfavorable characteristics. Accordingly, we compared...

Background: Some previous studies found decreased concentrations of L-tryptophan (TRY) and increased L-kynurenine (KYN), or its metabolites, in the body fluids of subjects with major depressive disorder (MDD), sometimes in association with suicidal behavior. Such changes might indicate a shift of TRY away from serotonin production, possibly via th...

Background: Aggression by patients with bipolar I disorder (BD-I) is not uncommon. Identifying potential risk factors early in the illness-course should inform clinical management and reduce risk. Methods: In a study sample of 216 initially hospitalized, first-psychotic episode subjects diagnosed with DSM-IV-TR BD-I, we identified recent (within...

Background: Aripiprazole is a widely clinically employed antipsychotic drug for a range of indications. It has unusual pharmacodynamics as a dopamine D2 receptor partial-agonist with complex interactions with serotonin receptors and, a relatively unusual long elimination half-life. Although other atypical antipsychotics have been associated with an...

Background: Aripiprazole is a widely clinically employed antipsychotic drug for a range of indications. It has unusual pharmacodynamics as a dopamine D2 receptor partial-agonist with complex interactions with serotonin receptors and, a relatively unusual long elimination half-life. Although other atypical antipsychotics have been associated with an...

Objective To assess differences between subjects with vs. without mixed features in major affective disorders. Methods In 3099 out‐patient subjects with DSM‐5 major depressive disorder (MDD, n = 1921) or bipolar disorders (BD, n = 1178), we compared those with (Mx) vs. without (Non‐Mx) mixed features (agitated‐irritable depression or dysphoric [hy...

To increase access to treatment, Italy made assessment at community mental health centers (CMHCs) independent of medical referral, resulting in increased numbers of patients to be triaged efficiently. To support this process, we evaluated SCL-90-R item-ratings to identify factors that best predicted adverse early outcomes among persons seeking firs...

We summarize evidence supporting contemporary pharmacological treatment of phases of BD, including: mania, depression, and long-term recurrences, emphasizing findings from randomized, controlled trials (RCTs). Effective treatment of acute or dysphoric mania is provided by modern antipsychotics, some anticonvulsants (divalproex and carbamazepine), a...

Introduction Suicidal behavior is strongly associated with depression in major depressive (MDD) and bipolar (BD) disorders, especially with associated behavioral activation, dysphoria, or agitation. A rare intervention with evidence of suicide risk-reducing as well as mood-stabilizing effects in mood disorder patients is lithium. Methods We reviewe...

Background: Ratings of particular temperament-types with the TEMPS-A autoquestionnaire have been associated with suicidal risk, and combinations of such ratings may enhance the association. However, the predictive value of scores for individual temperaments and combinations remains to be quantified. Method: We evaluated associations of TEMPS-A r...

Learning objectives: After participating in this activity, learners should be better able to:• Evaluate factors that have been identified in prospective studies as predicting the onset of bipolar disorder ABSTRACT: The prodromal phase of bipolar disorder (BD) remains incompletely characterized, limiting early detection of BD and delaying intervent...

Background: Among risk factors for suicidal behavior, there is growing interest in associations with stable affective temperament types, particularly based on assessment with the TEMPS-A self-rating scale. Aim: As research on this topic has not been reviewed systematically, we synthesized relevant, reported research findings. Methods: Systemat...

Purpose/background: High risks of neural tube defects and other teratogenic effects are associated with exposure in early pregnancy to some anticonvulsants, including in women with bipolar disorder. Methods/procedures: Based on a semistructured review of recent literature, we summarized findings pertaining to this topic. Findings/results: Valp...

Objective: This study examined the implementation of crisis intervention teams by law enforcement agencies in Colorado. Methods: Rates of Special Weapons and Tactics (SWAT) use, arrests, use of force, and injuries were assessed during 6,353 incidents involving individuals experiencing a mental health crisis. Relationships among original complain...

Introduction: Lurasidone ([3aR,4S,7R,7aS]-2-[(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1yl-methyl] cyclohexylmethyl]-hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride; Latuda® [LRSD]) is a novel benzisothiazole, second-generation antipsychotic drug developed by Dainippon Sumitomo Pharma Corporation in Japan. Similar to other atypical...

Background: The DSM-5 mixed features specifier for mood disorders encourages renewed interest in mixed states and led us to pool research findings regarding prevalence of mixed features in episodes of major depressive (MDD) and bipolar disorders (BD). Methods: We systematically searched to July 2017 for reports on mixed symptoms in depressive ep...

Background: As suicide is related to many factors in addition to psychiatric illness, broad and comprehensive risk-assessment for risk of suicide is required. This study aimed to differentiate nondiagnostic risk factors among suicides versus comparable psychiatric patients without suicidal behavior. Methods: We carried out a pilot, case-control...