Leonardo Tondo

Suicidal behaviour in bipolar disorder: risk and prevention.

Bipolar (manic-depressive) disorder is a common and severe illness. It is also potentially fatal as a result of accidents and increased mortality associated with comorbid substance use and medical illnesses, but its highest lethality results from suicide. Suicide rates, averaging 0.4% per year in men and women diagnosed with bipolar disorder, are >20-fold higher than in the general population. Suicidal acts often occur early in the illness course and in association with severe depressive and dysphoric-agitated mixed phases of illness, especially following repeated, severe depressions.Systematic consideration of risk and protective factors enhances assessment of potentially suicidal patients. Short-term interventions employed empirically to manage acute suicidality include close clinical supervision, rapid hospitalisation and use of electroconvulsive treatment. Several plausible therapeutic interventions have limited evidence of long-term effectiveness against mortality risks associated with any psychiatric disorder, including antidepressant, antimanic, antipsychotic and electroconvulsive, as well as psychosocial, treatments. However, in bipolar disorder and other major affective disorders, lithium maintenance treatment is a notable exception, with strong and consistent evidence that it reduces suicidal risk.The growing range of drugs being introduced to treat acute and long-term phases of bipolar disorder, including antiepileptic drugs, atypical antipsychotics and relatively safe, modern antidepressants, require research assessment for their ability to limit premature mortality from suicide and other causes. For now, however, more can be done to improve treatment in major affective illnesses by application of current knowledge in a systematic fashion, with close and sustained clinical follow-up of patients at risk, hopefully with a resulting reduction of mortality rates.

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

OBJECTIVE The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. METHOD An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. RESULTS There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. CONCLUSIONS Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Lower suicide risk with long‐term lithium treatment in major affective illness: a meta‐analysis

Objective: To compare suicide rates with vs. without long‐term lithium treatment in major affective disorders.

Mania associated with antidepressant treatment: comprehensive meta-analytic review

Tondo L, Vázquez G, Baldessarini RJ. Mania associated with antidepressant treatment: comprehensive meta‐analytic review.

Pediatric-Onset Bipolar Disorder: A Neglected Clinical and Public Health Problem Gianni

&NA; Bipolar disorder (BPD), probably the most prevalent psychotic disorder in adults, has been relatively neglected or controversial in children and adolescents over the past century. We reviewed the literature on early‐onset BPD.* Estimates of prevalence, particularly before puberty, are limited by historical biases against pediatric mood disorders and by formidable diagnostic complexity and comorbidity. Although clinical features of pediatric and adult BPD have similarities, pediatric cases probably cannot be defined solely by features characteristic of adult cases. Onset was before age 20 years in at least 25% of reported BPD cases, with some increase in this incidence over the past century. Pediatric BPD is familial more often than is adult‐onset BPD, may be associated with a premorbid cyclothymic or hyperthymic temperament, and can be precipitated by antidepressant treatment. Pediatric BPD episodes frequently include irritability, dysphoria, or psychotic symptoms; they are commonly chronic and carry high risks of substance abuse and suicide. BPD is often recognized in adolescents, but the syndrome or its antecedents are almost certainly underrecognized and undertreated in children. Controlled studies of short‐and long‐term treatment, course, and outcome in this disorder remain strikingly limited, and the syndrome urgently requires increased clinical and scientific interest.

Suicide in Bipolar Disorder: Risks and Management

Bipolar disorders are prevalent, often severe, and disabling illnesses with elevated lethality largely due to suicide. Suicide rates average approximately 1% annually, or perhaps 60 times higher than the international population rate of 0.015% annually. Suicidal acts typically occur early in bipolar disorders and in association with severe depressive or mixed states. The high lethality of suicidal acts in bipolar disorders is suggested by a much lower ratio of attempts:suicide (approximately 3:1) than in the general population (approximately 30:1). Risk factors can help to identify patients at increased suicidal risk, but ongoing clinical assessment is essential to limit risk. Empirical short-term interventions to manage acute suicidal risk include close clinical supervision, rapid hospitalization, and electroconvulsive therapy. Remarkably, however, evidence of the long-term effectiveness of most treatments against suicidal behavior is rare. A notable exception is lithium prophylaxis, which is associated with consistent evidence of major (approximately 80%), sustained relative reductions of risk of suicides and attempts, and lower lethality (increased attempts:suicide ratio). Such benefits are unproved for other treatments commonly used to treat bipolar disorder patients, including anticonvulsants, antipsychotics, antidepressants, and psychosocial interventions. Applying available knowledge systematically, with close and sustained clinical supervision, can enhance management of suicidal risk in bipolar disorders patients.

Suicidal risks among 2826 Sardinian major affective disorder patients

Objective:  We estimated risks of suicidal behaviors in 2826 mood‐disorder patients evaluated and followed in a Sardinian mood disorders research center over the past 30 years.

Episodes of Mood Disorders in 2,252 Pregnancies and Postpartum Periods

OBJECTIVE The risks of major affective episodes during pregnancy and during the postpartum period have rarely been compared in large samples across diagnoses. The authors hypothesized that perinatal episodes would mainly be depressive, would occur more in the postpartum than the prenatal period, and would be more prevalent with bipolar than unipolar depressive disorders. METHOD The authors pooled clinical information on 2,252 pregnancies of 1,162 women with clinically treated DSM-IV bipolar I disorder (479 pregnancies/283 women), bipolar II disorder (641/338), or recurrent major depressive disorder (1,132/541) to compare rates of affective episode types by diagnosis during pregnancy and the postpartum period and to identify risk factors. RESULTS Among women with bipolar disorder, 23% had illness episodes during pregnancy and 52% during the postpartum period. Among women with unipolar depression, 4.6% had illness episodes during pregnancy and 30% during the postpartum period. Based on exposure-adjusted risk per pregnancy, episodes were 3.5 times more prevalent during the postpartum period than during pregnancy, and the risk was consistently higher with bipolar disorder. Depression was the most frequent morbidity during and following pregnancy. In multivariate modeling, factors associated with affective episodes in pregnancy, in descending order, were younger age at onset, previous postpartum episodes, fewer years of illness, bipolar disorder, fewer children, and not being married. Postpartum episodes were associated with younger age at onset, illness during pregnancy, bipolar disorder, fewer children, and more education. Moreover, pregnancy was less likely and perinatal episodes more likely if diagnosis preceded a first pregnancy. First lifetime episodes occurred in the perinatal period in 7.6% of cases. CONCLUSIONS Among women with major affective disorders, illness risk was much greater during the postpartum period than during pregnancy. Illness mainly involved depression and was strongly associated with younger age at illness onset, bipolar disorder, and high lifetime occurrence rates. The relative risk during pregnancy compared with nonpregnant periods remains uncertain.

Effect of lithium maintenance on suicidal behavior in major mood disorders

Abstract We reviewed evidence of a possible antisuicide action of lithium maintenance treatment in mood disorders. Of 28 published studies involving over 17,000 patients with major affective illnesses, most yielded supportive evidence: risk of suicides and attempts averaged 3.2 versus 0.37 per 100 patient‐years without versus with lithium (8.6‐fold difference). In a new study of 284 bipolar I‐ and II‐disordered patients, corresponding rates (2.2 vs. 0.39/100 patient‐years) differed by 5.6‐fold (p< 0.001); moreover, after disocontinuing lithium rates of suicidal acts rose by 7‐fold (16‐fold within the first year), and fatalities increased by nearly 9‐fold. Lithium maintenance treatment in recurring major mood disorders has strong evidence of antisuicide effects not demonstrated with any other mood stabilizer. Close association of suicide and depression in bipolar disorder emphasizes the need for improved identification and treatment of bipolar depression.

Effects of rapid cycling on response to lithium maintenance treatment in 360 bipolar I and II disorder patients

INTRODUCTION Rapid cycling (RC) in bipolar disorders is widely believed to predict future morbidity and poor treatment response, although empirical testing of its predictive utility remains limited. METHODS In 360 DSM-IV bipolar I (N=218) and II (N=142) disorder subjects (64% women) followed over an average of 13.3 years, we evaluated factors associated with RC status with bivariate and multivariate techniques, and response to lithium maintenance treatment (recurrence rates, time ill, survival analysis of time to recurrence on lithium). RESULTS RC risk (15.6% of cases) was 5. 1-times greater in bipolar II vs. I subjects (30.3%/6.0%), in minor excess in women vs. men (17.9%/11.5%), and associated with premorbid cyclothymia, depressive first episodes, older onset age, and being employed or married. Before lithium, RC vs. non-RC cases had more mean total (3.9/1.2), manic, and depressive episodes/year, and greater percent time ill (60%/38%). During treatment, prior RC status was unrelated to time to first recurrence and other measures of morbidity and improvement including percent time ill, although depressive episodes were 2.7-times more frequent, and there was 13.7% less chance of full protection from all recurrences in RC cases. LIMITATIONS The study is naturalistic, without random assignment or blind assessment. CONCLUSIONS The RC bipolar subtype was strongly associated with type II diagnosis, higher average prelithium episode frequency and percent time ill, and weakly with female sex, but not with greater overall morbidity during treatment.