Bipolar II disorder: epidemiology, diagnosis and management

Hecker Psychiatry Research Center, a University of California at San Diego (USA) Collaborating Center at Forli, Italy.
CNS Drugs (Impact Factor: 5.11). 02/2007; 21(9):727-40.
Source: PubMed


Bipolar II disorder (BP-II) is defined, by DSM-IV, as recurrent episodes of depression and hypomania. Hypomania, according to DSM-IV, requires elevated (euphoric) and/or irritable mood, plus at least three of the following symptoms (four if mood is only irritable): grandiosity, decreased need for sleep, increased talking, racing thoughts, distractibility, overactivity (an increase in goal-directed activity), psychomotor agitation and excessive involvement in risky activities. This observable change in functioning should not be severe enough to cause marked impairment of social or occupational functioning, or to require hospitalisation. The distinction between BP-II and bipolar I disorder (BP-I) is not clearcut. The symptoms of mania (defining BP-I) and hypomania (defining BP-II) are the same, apart from the presence of psychosis in mania, and the distinction is based on the presence of marked impairment associated with mania, i.e. mania is more severe and may require hospitalisation. This is an unclear boundary that can lead to misclassification; however, the fact that hypomania often increases functioning makes the distinction between mania and hypomania clearer. BP-II depression can be syndromal and subsyndromal, and it is the prominent feature of BP-II. It is often a mixed depression, i.e. it has concurrent, usually subsyndromal, hypomanic symptoms. It is the depression that usually leads the patient to seek treatment.DSM-IV bipolar disorders (BP-I, BP-II, cyclothymic disorder and bipolar disorder not otherwise classified, which includes very rapid cycling and recurrent hypomania) are now considered to be part of the 'bipolar spectrum'. This is not included in DSM-IV, but is thought to also include antidepressant/substance-associated hypomania, cyclothymic temperament (a trait of highly unstable mood, thinking and behaviour), unipolar mixed depression and highly recurrent unipolar depression.BP-II is underdiagnosed in clinical practice, and its pharmacological treatment is understudied. Underdiagnosis is demonstrated by recent epidemiological studies. While, in DSM-IV, BP-II is reported to have a lifetime community prevalence of 0.5%, epidemiological studies have instead found that it has a lifetime community prevalence (including the bipolar spectrum) of around 5%. In depressed outpatients, one in two may have BP-II. The recent increased diagnosing of BP-II in research settings is related to several factors, including the introduction of the use of semi-structured interviews by trained research clinicians, a relaxation of diagnostic criteria such that the minimum duration of hypomania is now less than the 4 days stipulated by DSM-IV, and a probing for a history of hypomania focused more on overactivity (increased goal-directed activity) than on mood change (although this is still required for a diagnosis of hypomania). Guidelines on the treatment of BP-II are mainly consensus based and tend to follow those for the treatment of BP-I, because there have been few controlled studies of the treatment of BP-II. The current, limited evidence supports the following lines of treatment for BP-II. Hypomania is likely to respond to the same agents useful for mania, i.e. mood-stabilising agents such as lithium and valproate, and the second-generation antipsychotics (i.e. olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole). Hypomania should be treated even if associated with overfunctioning, because a depression often soon follows hypomania (the hypomania-depression cycle). For the treatment of acute BP-II depression, two controlled studies of quetiapine have not found clearcut positive effects. Naturalistic studies, although open to several biases, have found antidepressants in acute BP-II depression to be as effective as in unipolar depression; however, one recent large controlled study (mainly in patients with BP-I) has found antidepressants to be no more effective than placebo. Results from naturalistic studies and clinical observations on mixed depression, while in need of replication in controlled studies, indicate that antidepressants may worsen the concurrent intradepression hypomanic symptoms. The only preventive treatment for both depression and hypomania that is supported by several, albeit older, controlled studies is lithium. Lamotrigine has shown some efficacy in delaying depression recurrences, but there have also been several negative unpublished studies of the drug in this indication.

25 Reads
  • Source
    • "Recent advances in psychiatry have increased our understanding of bipolar spectrum disorders and have further characterized the nature of conditions such as bipolar II disorder, the soft form of bipolar disorder, cyclothymic disorder, depressive mixed state, and the so-called bipolar spectrum disorder (BSD).1–5 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Despite a growing body of knowledge on bipolar spectrum disorder (BSD), relatively little is known about the clinical characteristics of BSD in elderly people. We investigated the prevalence of BSD in elderly patients with recurrent depression. Patients and methods A total of 65 elderly outpatients (≥60 years of age) who met the Diagnostic and Statistical Manual of Mental Disorders IV criteria for recurrent major depressive disorder participated in the study. BSD was diagnosed according to the criteria developed by Ghaemi et al and the Mood Disorder Questionnaire (MDQ) was used to assess bipolarity. Results Of 65 subjects, eleven (16.9%) and 54 (83.1%) were diagnosed with BSD and unipolar depression, respectively. A total of 32.3% (n=22) had a positive screen for bipolar disorder, and we found a significant association between the BSD criteria and the criteria for a positive MDQ (P<0.001). Patients with BSD had a longer duration of illness (P=0.040) and more prior depressive episodes (P<0.001) than did those with unipolar depression. The BSD criteria of first-degree relative with bipolar disorder (P=0.030), antidepressant-induced hypomania (P=0.034), hyperthymic personality (P=0.001), and atypical depression (P=0.030) were highly associated with MDQ-positive patients. Conclusion Our results indicate that many depressed elderly patients have bipolar-related illness; moreover, some features of the depression are associated with bipolarity.
    Neuropsychiatric Disease and Treatment 05/2014; 10:791-5. DOI:10.2147/NDT.S63073 · 1.74 Impact Factor
  • Source
    • "Some cases of treatment-resistant presumably unipolar depression may respond remarkably well to lithium (A.G., personal observation). However, it cannot be excluded that such cases in fact have bipolar II for which lithium is the only preventive treatment for both depression and hypomania that is supported by several controlled studies (Benazzi, 2007). Lithium is also in use in the treatment of cluster headache (Steiner et al., 1997; Van Alboom et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: For many years, a deficiency of monoamines including serotonin has been the prevailing hypothesis on depression, yet research has failed to confirm consistent relations between brain serotonin and depression. High degrees of overlapping comorbidities and common drug efficacies suggest that depression is one of a family of related conditions sometimes referred to as the "affective spectrum disorders", and variably including migraine, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among many others. Herein, we present data from many different experimental modalities that strongly suggest components of mitochondrial dysfunction and inflammation in the pathogenesis of depression and other affective spectrum disorders. The three concepts of monoamines, energy metabolism and inflammatory pathways are inter-related in many complex manners. For example, the major categories of drugs used to treat depression have been demonstrated to exert effects on mitochondria and inflammation, as well as on monoamines. Furthermore, commonly-used mitochondrial-targeted treatments exert effects on mitochondria and inflammation, and are increasingly being shown to demonstrate efficacy in the affective spectrum disorders. We propose that interactions among monoamines, mitochondrial dysfunction and inflammation can inspire explanatory, rather than mere descriptive, models of these disorders.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2011; 35(3):730-43. DOI:10.1016/j.pnpbp.2010.07.030 · 3.69 Impact Factor
  • Source
    • "Additionally, in KO mice, hyperactivity in the tail suspension test tended to be attenuated by acute treatment with the clinically effective anti-mania drug valproic acid, suggesting a facet of mania-like behavior. Therefore, the afternoon behavioral and endocrine phenotypes of PKCI/HINT1 KO mice could be analogous to mania symptoms associated with high plasma cortisol [9,14,53-57]. In that regard, enhanced performances in the place navigation task and persistent struggling in the TST could be considered as enhanced goal-directed activity associated with enhanced energy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Protein kinase C interacting protein (PKCI/HINT1) is a small protein belonging to the histidine triad (HIT) family proteins. Its brain immunoreactivity is located in neurons and neuronal processes. PKCI/HINT1 gene knockout (KO) mice display hyper-locomotion in response to D-amphetamine which is considered a positive symptom of schizophrenia in animal models. Postmortem studies identified PKCI/HINT1 as a candidate molecule for schizophrenia and bipolar disorder. We investigated the hypothesis that the PKCI/HINT1 gene may play an important role in regulating mood function in the CNS. We submitted PKCI/HINT1 KO mice and their wild type (WT) littermates to behavioral tests used to study anti-depressant, anxiety like behaviors, and goal-oriented behavior. Additionally, as many mood disorders coincide with modifications of hypothalamic-pituitary-adrenal (HPA) axis function, we assessed the HPA activity through measurement of plasma corticosterone levels. Compared to the WT controls, KO mice exhibited less immobility in the forced swim (FST) and the tail suspension (TST) tests. Activity in the TST tended to be attenuated by acute treatment with valproate at 300 mg/kg in KO mice. The PKCI/HINT1 KO mice presented less thigmotaxis in the Morris water maze and spent progressively more time in the lit compartment in the light/dark test. In a place navigation task, KO mice exhibited enhanced acquisition and retention. Furthermore, the afternoon basal plasma corticosterone level in PKCI/HINT1 KO mice was significantly higher than in the WT. PKCI/HINT1 KO mice displayed a phenotype of behavioral and endocrine features which indicate changes of mood function, including anxiolytic-like and anti-depressant like behaviors, in conjunction with an elevated corticosterone level in plasma. These results suggest that the PKCI/HINT 1 gene could be important for the mood regulation function in the CNS.
    BMC Neuroscience 11/2009; 10(1):132. DOI:10.1186/1471-2202-10-132 · 2.67 Impact Factor
Show more