The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

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Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

Mortality of patients with mood disorders: follow-up over 34–38 years

The emerging epidemiology of hypomania and bipolar II disorder.

Background: Given the therapeutic and prognostic importance of the unipolar-bipolar dichotomy, predicting which patients will become bipolar subsequent to index diagnosis of major depressive disorder (MDD) is of paramount clinical significance. We sought to characterize the profile of patients with MDD who would convert to the more subtle bipolar subtype (known as BPII) on the basis of clinical and personality variables obtained during MDD episodes. Methods: A total of 559 patients, comprehensively evaluated with the Schedule of Affective Disorders and Schizophrenia and "unipolar" MDD at entry, were administered 17 self-report personality measures. Hypomanic and manic episodes were systematically recorded over a prospective observation period of up to 11 years. We compared 48 converters to BPII (8.6%) with 22 converters to bipolar I (BPI) (3.9%) and the remaining larger group of unipolar patients. Results: Except for greater acuteness, severity, and psychotic symptomatology, BPI converters were essentially similar to MDD nonconverters. By contrast, BPII converters were robustly distinguished from those with MDD who remained unipolar on the basis of self-report measures along the newly derived factors of Mood Lability, Energy-Activity, and Daydreaming. This profile was associated with early age at onset of MDD and pleomorphic psychopathology beyond the usual affective realm, high rates of substance abuse, as well as educational, marital, and occupational disruption and minor antisocial acts prior to discrete hypomanic episodes. Overall, BPII switchers had a more protracted and tempestuous course with shorter well intervals. "Habitual self" descriptions of temperamental instability during MDD episodes provided useful clinical information for predicting which depressed patients will switch to BPII, attaining a sensitivity of 91% for all three factors combined (23 items); Mood Lability alone (nine items) was the most specific predictor (86%), though of lower sensitivity (42%). Conclusions: The BPII subtype is best understood by such lability intruding into, and possibly its accentuation during, depressive episodes, thereby creating an intimate interweaving of trait and state. Clinicians must note that the foregoing temperamental profile appears more fundamental in defining the affective dysregulation of the BPII subtype than hypomanic episodes emphasized inDSM-IV.

Switching from 'unipolar' to bipolar II. An 11-year prospective study of clinical and temperamental predictors in 559 patients.

Family, twin, and adoption studies have been essential in defining the genetic epidemiology of bipolar disorder over the past several decades. Family studies have documented that first-degree relatives of affected individuals have an excess risk of the disorder, while twin studies (and to a lesser extent, adoption studies) suggest that genes are largely responsible for this familial aggregation. We review these studies, including the magnitude of familial risk and heritability estimates, efforts to identify familial subtypes of bipolar disorder, and the implications of family/genetic data for validating nosologic boundaries. Taken together, these studies indicate that bipolar disorder is phenotypically and genetically complex.

Family, twin, and adoption studies of bipolar disorder.

The Course of Development of Mania in Patients with Recurrent

The authors attempted to assess the extent to which bipolar patients are misdiagnosed as unipolar by evaluating the development of mania in patients who had recognized bipolar illness and by means of follow-up data on patients who had recurrent depressions. Mania occurred early in the course of bipolar illness: almost 80% of the bipolar patients were initially hospitalized for mania. Follow-up data and theoretically based calculations suggest that the chance of a patient with recurrent depressions becoming bipolar is about 5%. Based on these findings, the authors make suggestions for the classification of unipolar patients.

The course of development of mania in patients with recurrent depression.

The effect of lithium treatment on thyroid function in patients with primary affective disorder.

Lithium treatment in older patients.

Of the 241 lithium clinic patients at the New York State Psychiatric Institute with bipolar I affective disorder, 38 (15.7%) had never been hospitalized or somatically treated for depression. These "unipolar manic" patients had a significantly lower incidence of rapid cycling and suicide attempts than other bipolar I patients. No differences were found, however, in risk of illness in first-degree relatives. Lithium was an effective prophylactic agent in these patients. Some patients originally classified as "unipolar manic" were found to have depressive episodes with additional information and clinical observation. "Unipolar mania" appears to be a subgroup of bipolar I illness, but there are no data to support the hypothesis that it is a separate entity.

Ronald R. Fieve

Papers

The Course of Development of Mania in Patients with Recurrent

The course of development of mania in patients with recurrent depression.

The effect of lithium treatment on thyroid function in patients with primary affective disorder.

Lithium treatment in older patients.

Unipolar mania: a distinct clinical entity?