Epidemiologic studies report a lifetime prevalence of BPD ranging from 1% to 10% of the U.S population.
The prevalence of BPD is the same in males and females, although male patients have more manic episodes and female patients have more depressive episodes. In addition to the adverse psychosocial, vocational, and societal impacts of BPD, the lifetime suicide rate associated with BPD (15.6%) is higher than corresponding rates in any other psychiatric disorder. The diagnostic criteria for a major depressive episode can be found in the chapter on depression.
A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting throughout at least 1 week (or any duration if hospitalization is necessary). The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others or to necessitate hospitalization to prevent harm to self or others, or the mood disturbance has psychotic features. A distinct period of persistently elevated, expansive, or irritable mood, lasting throughout at least 4 days, that is clearly different from the usual nondepressed mood.
The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic. The episode is not severe enough to cause marked impairment in social or occupational functioning, or to necessitate hospitalization, and there are no psychotic features.
The criteria are met both for a manic episode (Box 1) and for a major depressive episode (see Box 3 in the chapter on depression) (except for duration) nearly every day for at least 1 week. BPD is subdivided into types I and II to reflect the type of manic episodes the patient reports. Criteria, except for duration, are currently (or most recently) met for a manic, a hypomanic, a mixed, or a major depressive episode. The mood symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. The mood symptoms in the first two criteria are not better accounted for as schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Figures 4 through 6 graphically illustrate common courses of mood episodes in patients with different subtypes of BPD. Figure 3 depicts four separate symptom domains that can be seen in various combinations with BPD. If an active mood episode is identified, rule out mood disorder due to a general medical condition or one that is substance-related. If psychosis accompanies a mood episode, rule out schizophrenia, schizoaffective disorder, delusional disorder, or psychosis due to a general medical condition. BPD is an important consideration in the differential diagnosis of a major depressive episode. Patients who are agitated or irrational or who present a danger to themselves or others require urgent (next day) or emergent (same day) evaluation by a psychiatrist, unless the primary physician is comfortable with acute stabilization. Mania is generally more easily managed than depression, although it requires hospitalization more often. Mixed depressive and manic episodes present a difficult treatment challenge best met by first stabilizing manic behavior and then addressing depression. OFC is the only FDA-approved treatment for acute bipolar depression and delivers both antidepressant and antipsychotic medications simultaneously in one preparation. Other atypical antipsychotics continue to receive attention as potential antidepressant agents in BPD.
Neither is currently FDA approved for this indication, and the strength of the data supporting their use for bipolar depression is modest at best. Electroconvulsive therapy can effectively be used to treat either manic or depressive episodes, although it is generally reserved for medication-refractory cases. Screening tools are available, although they should not be viewed as an alternative to thorough diagnostic evaluation.


The literature regarding medication treatment for children and adolescents with BPD is limited, and many of the current recommendations are based on studies of adults.
Mania can be seen early in the course of human immunodeficiency virus (HIV) infection but is more common as the illness progresses.
Maintaining a strong working alliance with the bipolar patient typically requires additional time, effort, and skill. Treatment strategies must be individualized and adjusted at different phases of the mood disorder.
Olanzapine-fluoxetine combination (OFC) and mood stabilizers are first-line treatments for bipolar depression. Ryan MM, Lockstone HE, Huffaker SJ, et al: Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes. Valtonen HM, Suominen K, Mantere O, et al: Suicidal behaviour during different phases of bipolar disorder. Calabrese JR, Keck PE Jr, Macfadden W, et al: A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Ghaemi SN, Miller CJ, Berv DA, et al: Sensitivity and specificity of a new bipolar spectrum diagnostic scale.
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The disturbance of mood in BPD is episodic and recurrent, cycling at varying intervals from one mood state to another. This broad range is due at least in part to inconsistent inclusion of BPD subtypes from one study to the next.
The first lifetime manifestation of BPD is typically a major depressive episode (MDE), with onset during late adolescence or early adulthood.
A higher rate of mood and anxiety disorders exists in the first-degree relatives of persons with BPD than in the general population. Neuroimaging studies point to involvement of cortical, limbic, basal ganglia, and cerebellar structures in BPD. In addition to episodes of either full-blown mania or major depression, patients can have episodes of subsyndromal depression, hypomania, or mixed states characterized by simultaneous occurrence of both depressive and manic features. A diagnosis of bipolar I disorder is given if there has been at least one lifetime episode of mania or a true mixed episode; a diagnosis of bipolar II disorder depends on at least one lifetime episode of hypomania, with none of the episodes achieving criteria for mania.
When available, obtain collateral information from family or other associates as well as medical records that document previous treatment trials. For less-pressing cases of suspected BPD, appropriate treatment may be started while awaiting completion of the referral process to a psychiatrist.
United States Food and Drug Administration (FDA)-approved agents for treating BPD are listed in Table 1. An atypical antipsychotic or a mood stabilizer is typically administered to stabilize the manic behavior, and depression is addressed with standard antidepressant treatment. Antidepressants, when prescribed alone, are not effective for bipolar depression and are not formally indicated for such use by the FDA. Investigation of quetiapine (Seroquel) as monotherapy for bipolar depression has produced promising results and might receive FDA approval in the near future.
Their off-label use is nevertheless recommended, given the paucity of effective treatments for bipolar depression. Once this mood disorder has declared itself, the patient should be counseled regarding the chronic risk for relapse and recurrence; lifetime treatment is recommended. The Bipolar Spectrum Diagnostic Scale (BSDS) involves an easy-to-read, one-page story that depicts typical mood swing experiences. In contrast, the postpartum period is associated with increased risk for bipolar relapse and illness onset.
Review of the literature on major mental disorders in adult patients with mitochondrial diseases.


Downregulation in components of the mitochondrial electron transport chain in the postmortem frontal cortex of subjects with bipolar disorder. The histology is characteristic of lichen planus and distinguishes it from other linear dermatoses. Ecchordosis Physaliphora vs chordomas with low radiological agressivity: a diagnostic challenge. The first episode of mania or hypomania might not occur until several years later, and until that time a diagnosis of BPD cannot be made. Traditionally, classic BPD has been depicted as mood episodes alternating from mania to depression and back, but the variable course depicted in Figure 3 is more common. This may have led to an overdiagnosis of BPD, which until recently was underdetected or misdiagnosed as recurrent major depressive disorder (MDD). Occasionally, the primary care physician who is familiar with the assessment and treatment of BPD may accept full responsibility for the BPD patient's management, although this typically happens after consultation with a psychiatrist. Olanzapine, used either alone or as OFC has been associated with weight gain and hyperglycemia, and there are published case reports of diabetic ketoacidosis. Periodic medical monitoring for complications is crucial in preventing unwanted outcomes, such as the metabolic syndrome. Treatment of acute mood episodes during pregnancy requires a careful consideration of the potential teratogenic effects of medications versus the harmful effects of an ill mother on the unborn child. It is uncommon for the first manic episode to occur after age 30 years, although onset after age 60 years has been reported. The natural course of bipolar disorder is for episode frequency to gradually increase and for an ever-increasing percentage of episodes to be characterized by depression. In addition to mood elevation, the symptoms of mania include inflated self-esteem, decreased need for sleep, pressured and often loud speech, flight of ideas, distractibility, and increased goal-directed behavior often focused on pleasurable activities that have a high potential for becoming reckless and self destructive. This is an error that is easily committed even by experienced clinicians, because MDEs and dysthymia constitute the predominant mood disturbance in BPD, especially BPD type II. Clinical experience suggests, however, that agents approved for mania are generally effective for hypomania, sometimes at lower doses. These include simultaneously administering an antidepressant and an antipsychotic, administering mood-stabilizing medication, or administering the combination formulation of olanzapine and fluoxetine (OFC, Symbyax). Because these potential adverse outcomes are not unique to olanzapine and are regarded as an effect of the atypical antipsychotic class, OFC should be considered as a first-line treatment for bipolar depression. Treatment of mania secondary to HIV-related illness should be directed toward symptoms and underlying causes. In general, late-onset mania suggests drug toxicity or an underlying medical disorder until proved otherwise. Inquiry about a personal or family history of manic or hypomanic episodes is therefore crucial when evaluating a patient who presents with an MDE. Mild mania and hypomania often respond to one antimanic drug, whereas acute manic crises often require two or more agents to stabilize the mood.
Titration of both agents should be monitored closely to avoid lithium toxicity (tremor, nausea, diarrhea) or lamotrigine-induced rash that, if unchecked, can progress to toxic epidermal necrolysis or Stevens-Johnson syndrome.
Many strategies have been advanced, therefore, to reduce the risk potential of pharmacologic treatment of BPD in the pregnant woman. Pharmacologic management of mania in HIV-infected persons often includes a combination of an anticonvulsant mood stabilizer plus an antipsychotic.
These have included monotherapy with the lowest effective dose of a drug for the shortest period, preconception coadministration of multivitamins with folate, and avoidance of antimanic agents during the first trimester.
Patients with primary BPD who are also HIV seropositive should receive recommended treatment for acute mood episodes, although careful attention must be paid to an increased risk for drug interactions in this population.



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