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Published: August 2010

Bipolar Disorder

Sami Khalife

Vivek Singh

David J. Muzina

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Definition and etiology

Bipolar affective disorder (BPD), classified as a mood disorder,1 is a chronic, recurrent illness associated with high rates of morbidity, disability, and premature death from suicide. The disturbance of mood in BPD is episodic and recurrent, cycling at varying intervals from one mood state to another. Current classification schemes are based on the predominant pattern of mood (i.e., depression, mania, hypomania, or mixed states), the intensity of mood, and the rate of cycling from one mood to another (Figure 1). Disturbed mood in BPD is typically accompanied by reckless and impulsive behavior, psychotic symptoms (e.g., delusions, hallucinations, and disorganized thinking), and cognitive disturbances.

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Prevalence and risk factors

Epidemiologic studies report a lifetime prevalence of BPD ranging from 1% to 10% of the U.S population. This broad range is due at least in part to inconsistent inclusion of BPD subtypes from one study to the next. Although much debate exists regarding the true prevalence of BPD, most experts agree that it is higher than the traditionally accepted rate of 0.5% to 1.5%.

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. The first lifetime manifestation of BPD is typically a major depressive episode (MDE), with onset during late adolescence or early adulthood. 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. It is uncommon for the first manic episode to occur after age 30 years, although onset after age 60 years has been reported. In general, late-onset mania suggests drug toxicity or an underlying medical disorder until proved otherwise.

BPD is a familial disorder with genetic underpinnings. A higher rate of mood and anxiety disorders exists in the first-degree relatives of persons with BPD than in the general population. The primary risk factor for the development of BPD is a family history of BPD. A family history of BPD in a patient who presents with an MDE should alert the clinician to the possibility of an underlying bipolar diathesis and the corresponding treatment guidelines this entails.2

Factors that increase the risk of relapse or recurrence following a period of euthymic mood include not taking maintenance medication, abrupt discontinuation or rapid tapering of mood-stabilizing medication, the postpartum period, season, abnormal levels of psychosocial stress, serious medical illness (e.g., depression following myocardial infarction), and endogenous hormone fluctuations (e.g., thyroid dysfunction, menstrual cycle, menopause).

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Pathophysiology and natural history

The pathophysiology of BPD is under active investigation. Neuroimaging studies point to involvement of cortical, limbic, basal ganglia, and cerebellar structures in BPD. Genetic research has identified various loci that might contribute to the genesis of BPD. Lines of evidence point consistently to one or more defects in mitochondrial energy production as a basis for BPD.3 DNA microarray technology used to analyze gene expression in postmortem brain has disclosed abnormalities related to the electron transport chain and G-protein coupled receptor signaling.4,5 Lithium treatment, continued until the time of death, has been associated with evidence in postmortem brain of enhanced neuroprotection.5 These and other findings underscore the biologic basis of BPD and suggest directions for future targeted drug development.

The natural history of BPD is depicted in Figure 2. 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. 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. 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 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 risk of suicide by persons with BPD is highest during depressed or mixed states. Hopelessness can help to predict suicidal behavior during depression. Younger age and patients’ subjective rating of depression severity can predict an elevated risk of suicide in mixed episodes.6,7

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Signs, symptoms, and diagnosis

The hallmark and distinguishing feature of BPD is episodic abnormally elevated mood. Classic mood elevation in BPD is characterized by euphoria and excitement. In practice, the predominant mood is often irritability rather than euphoria. 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. Hypomania is a lesser form of mania, that is, mania minus the grossly impaired judgment that results in damaging, irresponsible behavior (e.g., excessive and indiscriminate sexual activity, spending, or traveling without heed to their consequences). Boxes 1 through 3 feature the diagnostic criteria for mania, hypomania, and mixed states as described in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM IV-TR).1 The diagnostic criteria for a major depressive episode can be found in the chapter on depression.

Box 1: DSM IV-TR Criteria for a Manic Episode
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).
During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
  • Inflated self-esteem or grandiosity
  • Decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
  • More talkative than usual or pressure to keep talking
  • Flight of ideas or subjective experience that thoughts are racing
  • Distractibility (attention too easily drawn to unimportant or irrelevant external stimuli)
  • Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
  • Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., unrestrained buying sprees, sexual indiscretions, or foolish business investments)
The symptoms do not meet criteria for a mixed episode (see Box 3).
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.
The symptoms are not due to the direct physiologic effects of a substance (e.g., a drug of abuse, medication, or other treatment) or a general medical condition (e.g., hyperthyroidism)

Note: Features in italics distinguish a manic from a hypomanic episode. Features of hypomanic episodes are listed in Box 2.
DSM IV-TR, Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM IV-TR).
Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.


Box 2: DSM IV-TR Criteria for a Hypomanic Episode
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.
During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
  • Inflated self-esteem or grandiosity
  • Decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
  • More talkative than usual or pressure to keep talking
  • Flight of ideas or subjective experience that thoughts are racing
  • Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)
  • Increase in goal-directed activity (socially, at work or school, or sexually) or psychomotor agitation
  • Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., unrestrained buying sprees, sexual indiscretions, or foolish business investments)
The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic.
The disturbance in mood and the change in functioning are observable by others.
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 symptoms are not due to the direct physiologic effects of a substance (e.g., a drug of abuse, medication, or other treatment) or a general medical condition (e.g., hyperthyroidism)

Note: Features in italics distinguish a manic from a hypomanic episode. Features of manic episodes are listed in Box 1.
DSM IV-TR, Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM IV-TR).
Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.


Box 3: DSM IV-TR Criteria for a Mixed Episode
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.
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.
The symptoms are not due to the direct physiologic effects of a substance (e.g., a drug of abuse, medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

DSM IV-TR, Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM IV-TR).
Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.


Diagnostic criteria for BPD require a history of at least one manic or hypomanic episode.1 BPD is subdivided into types I and II to reflect the type of manic episodes the patient reports. 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. The significance of this distinction continues to be debated. Recurrent MDEs typify both BPD types I and II. The complete diagnostic criteria for BPD types I and II are listed in Boxes 4 and 5.

Box 4: DSM IV-TR Criteria for Bipolar Type I Disorder Not Otherwise Specified
Criteria, except for duration, are currently (or most recently) met for a manic, a hypomanic, a mixed, or a major depressive episode.
There has previously been at least one manic episode or mixed 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.
The mood symptoms in the first two criteria are not due to the direct physiologic effects of a substance (e.g., a drug of abuse, medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.


Box 5: DSM IV-TR Criteria for Bipolar Type II Disorder
Presence (or history) of one or more major depressive episodes.
Presence (or history of at least one hypomanic episode.
There has never been a manic episode or a mixed episode.
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.
The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.


Figures 4 through 6 graphically illustrate common courses of mood episodes in patients with different subtypes of BPD. Current thinking questions the adherence to strict diagnostic criteria for BPD episodes. This may have led to an overdiagnosis of BPD, which until recently was underdetected or misdiagnosed as recurrent major depressive disorder (MDD). 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. Inquiry about a personal or family history of manic or hypomanic episodes is therefore crucial when evaluating a patient who presents with an MDE. Other features of BPD that distinguish it from MDD include earlier age at onset; more frequent mood episodes, rapid onset of symptoms; shorter symptom-free intervals; chaotic interpersonal, social, and vocational adjustments; and response to antidepressant treatment characterized by unusual sensitivity to standard antidepressant doses or rapid loss of initial therapeutic response.

Figure 3 depicts four separate symptom domains that can be seen in various combinations with BPD.

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Summary

  • 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.
  • Definitive diagnosis is not always possible after a first visit. When available, obtain collateral information from family or other associates as well as medical records that document previous treatment trials.

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Treatment

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. For less-pressing cases of suspected BPD, appropriate treatment may be started while awaiting completion of the referral process to a psychiatrist. 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.

The basic principles of managing the bipolar patient are listed in Box 6. United States Food and Drug Administration (FDA)-approved agents for treating BPD are listed in Table 1.

Box 6: Basic Principles of Managing the Bipolar Patient
Create and foster a therapeutic alliance
  • Take extra time to listen and communicate with patients and their families
  • Encourage peer-to-peer support
Offer education about the diagnosis and treatment
  • Educate patient and family about the seriousness of the illness and benefits of appropriate therapy
  • Provide the patient with patient-education materials
Enhance adherence with treatment
  • Educate the patient and family about medication treatment options, therapeutic effects, possible adverse effects, and the likely need for long-term medication
  • Encourage the patient and family to express their treatment preferences
Monitor and manage symptoms and risk
  • Encourage the patient to permit ongoing involvement of one or more trusted family members or friends in the patient's treatment
  • Solicit information from family and other third parties when assessing risk, especially suicide risk, substance use, and social isolation
  • Encourage open discussion about the need to recognize and manage risky behavior (e.g., limit access to dangerous machinery, credit cards)
  • During times the patient is well, engage the patient and family (or partner) to develop interventions that target reckless or dangerous behavior during future illness episodes
  • Encourage self monitoring of mood and medication use and of sleep patterns
  • Encourage regularity of sleep, daily activities, and medication use

Table 1: FDA-Approved Drugs for Bipolar Type I Disorder
Drug Mania Depression Maintenance
Aripiprazole x x x
Carbamazepine ER x
Chlorpromazine x
Lamotrigine x
Lithium x x
Olanzapine x x
Olanzapine-fluoxetine combination x
Quetiapine x
Risperidone x
Valproate, Divalproex ER x
Ziprasidone x

FDA, United States Food and Drug Administration.

Mania is generally more easily managed than depression, although it requires hospitalization more often. Many more FDA-approved options exist for mania than for bipolar depression. There are no FDA-approved treatments for hypomania. Clinical experience suggests, however, that agents approved for mania are generally effective for hypomania, sometimes at lower doses. Mild mania and hypomania often respond to one antimanic drug, whereas acute manic crises often require two or more agents to stabilize the mood.

Mixed depressive and manic episodes present a difficult treatment challenge best met by first stabilizing manic behavior and then addressing depression. An atypical antipsychotic or a mood stabilizer is typically administered to stabilize the manic behavior, and depression is addressed with standard antidepressant treatment. An alternative is to initiate treatment with a combined pharmacologic approach. These include simultaneously administering an antidepressant and an antipsychotic, administering mood-stabilizing medication, or administering the combination formulation of olanzapine and fluoxetine (OFC, Symbyax).

OFC is the only FDA-approved treatment for acute bipolar depression and delivers both antidepressant and antipsychotic medications simultaneously in one preparation. Antidepressants, when prescribed alone, are not effective for bipolar depression and are not formally indicated for such use by the FDA. Olanzapine, used either alone or as OFC has been associated with weight gain and hyperglycemia, and there are published case reports of diabetic ketoacidosis. 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. OFC is for oral use only. Dosing can be started with OFC 6/25 (olanzapine 6 mg and fluoxetine 25 mg) daily and adjusted as necessary to OFC 12/50 (olanzapine 12 mg and fluoxetine 50 mg) daily.

Other atypical antipsychotics continue to receive attention as potential antidepressant agents in BPD. Investigation of quetiapine (Seroquel) as monotherapy for bipolar depression has produced promising results and might receive FDA approval in the near future. A dosage range of 300 to 600 mg daily is recommended for treating depression associated with acute BPD type I or II.8

Recent evidence-based practice guidelines also recommend the mood stabilizers lithium or lamotrigine (Lamictal), or both, as first-line agents for acute bipolar depression.7 Neither is currently FDA approved for this indication, and the strength of the data supporting their use for bipolar depression is modest at best. Their off-label use is nevertheless recommended, given the paucity of effective treatments for bipolar depression. Lithium is most effective at doses that achieve serum blood levels of 0.8 to 1.5 mEq/L. Lamotrigine should be started at 25 mg daily and increased every 1 to 2 weeks to a therapeutic dose, typically in the range of 50 to 200 mg daily. 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.

Table 2 outlines the initial steps recommended for treating acutely depressed versus manic states in patients with bipolar disorder.9

Table 2: Initial Treatment Guidelines for Bipolar Disorder
Step 1 Step 2 Step 3 and Beyond



Drug Starting Dose Target Drug Starting Dose Options
Depression
Lithium 300-450 mg bid Serum level > 0.8 mEq/L OFC* 6 mg/25 mg hs Combinations of lithium, lamotrigine, OFC, quetiapine
Lamotrigine 25 mg qd Dose 50-200 mg/day Quetiapine 100 mg hs; increase to 300 mg hs by day 3 Add traditional antidepressant to one or more of these
Initial and target doses may be affected by concomitant meds (see prescribing information) ECT
Mania §
Lithium 300-450 mg tid Serum level generally 1.0-1.5 mEq/L Choose 2 of the following in combination: Other 2-drug combinations (choose from lithium, VPA, AAPs, carbamazepine, oxcarbamazepine, topiramate)
Valproic acid 500 mg tid ECT
Divalproex 750 mg hs Lithium Clozapine
Atypical antipsychotic Initial dosing varies, refer to prescribing information VPA or divalproex Triple drug therapy
AAP

*FDA approved for BPD type I depression.
Pending FDA approval for BPD types I and II depression
Selective serotonin reuptake inhibitor, serotonin and norepinephrine uptake inhibitor, buproprion, venlafaxine, mirtazapine.
§For moderate to severe manic episodes, two-drug combination therapy is recommended as first step.
Excluding clozapine and aripiprazole.
Excluding olanzapine and clozapine. These are less than ideal initial choices because of tolerability issues, primarily metabolic and/or hematologic.
AAP, atypical antipsychotic; BPD, bipolar disorder; ECT, electroconvulsive therapy; FDA, United States Food and Drug Administration; meds, medications; OFC, olanzapine-fluoxetine combination; VPA, valproic acid.
Based on Suppes T, Dennehy EB, Hirschfeld RM, et al: The Texas implementation of medication algorithms: Update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry 2005;66:870-886.

Electroconvulsive therapy can effectively be used to treat either manic or depressive episodes, although it is generally reserved for medication-refractory cases.

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Summary

  • 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.
  • Consider hospitalization for acute mania.
  • Numerous approved and effective treatments are available for mania. They are also effective, but not FDA approved, for hypomania and mixed states.
  • Olanzapine-fluoxetine combination (OFC) and mood stabilizers are first-line treatments for bipolar depression. Monotherapy with a traditional antidepressant is discouraged.

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Prevention and screening

BPD cannot be prevented. Once this mood disorder has declared itself, the patient should be counseled regarding the chronic risk for relapse and recurrence; lifetime treatment is recommended. Periodic medical monitoring for complications is crucial in preventing unwanted outcomes, such as the metabolic syndrome.

Screening tools are available, although they should not be viewed as an alternative to thorough diagnostic evaluation. The Mood Disorder Questionnaire (MDQ) is a validated screening instrument for BPD.10 It can be found online (search “MDQ download”) in both English and Spanish versions. The Bipolar Spectrum Diagnostic Scale (BSDS) involves an easy-to-read, one-page story that depicts typical mood swing experiences. The patient places a check mark at the end of each sentence that conforms with the patient's own experience.11 The BSDS is also available online (search “bipolar diagnostic spectrum scale”).12

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Special populations

Children and Adolescents

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.

Pregnant Women

Pregnancy does not affect the risk of bipolar relapse. In contrast, the postpartum period is associated with increased risk for bipolar relapse and illness onset. 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. Many women require maintenance treatment during pregnancy. Many strategies have been advanced, therefore, to reduce the risk potential of pharmacologic treatment of BPD in the pregnant woman. 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.

Human Immunodeficiency Virus–Seropositive Patients

Mania can be seen early in the course of human immunodeficiency virus (HIV) infection but is more common as the illness progresses. Irritability is more common than euphoria. Manic episodes appear to be more common in the setting of opportunistic infections (e.g., cryptococcal meningitis) associated with acquired immunodeficiency syndrome (AIDS) and also in association with drugs used to treat patients with HIV and AIDS (e.g., zidovudine, efavirenz, steroids). Treatment of mania secondary to HIV-related illness should be directed toward symptoms and underlying causes. Pharmacologic management of mania in HIV-infected persons often includes a combination of an anticonvulsant mood stabilizer plus an antipsychotic. 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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References

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association, 2000.
  2. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Bipolar Disorder. 2nd ed. Washington, DC: American Psychiatric Association, 2002, pp 525-612.
  3. Fattal O, Budur K, Vaughan AJ, Franco K. Review of the literature on major mental disorders in adult patients with mitochondrial diseases. Psychosomatics. 2006, 47: 1-7.
  4. 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. Mol Psychiatry. 2006, 11: 965-978.
  5. Sun X, Wang JF, Tseng M, Young LT. Downregulation in components of the mitochondrial electron transport chain in the postmortem frontal cortex of subjects with bipolar disorder. J Psychiatry Neurosci. 2006, 31: (3): 189-196.
  6. Baldessarini RJ, Pompili M, Tondo L. Suicide in bipolar disorder: Risks and management. CNS Spectrums. 2006, 11: 465-471.
  7. Valtonen HM, Suominen K, Mantere O, et al: Suicidal behaviour during different phases of bipolar disorder. J Affect Disord. 2007, 97: 101-107.
  8. Muzina DJ, Calabrese JR. Guidelines for the treatment of bipolar disorder. In: Stein DJ, Schatzberg A, Kupfer DJ (eds): Textbook of Mood Disorders. Washington, DC: American Psychiatric Association, 2005, pp 463-483.
  9. Suppes T, Dennehy EB, Hirschfeld RM, et al: The Texas implementation of medication algorithms: Update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry. 2005, 66: 870-886.
  10. Hirschfeld RM, Williams JB, Spitzer RL, et al: Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000, 157: 1873-1875.
  11. 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. Am J Psychiatry. 2005, 162: 1351-1360.
  12. Ghaemi SN, Miller CJ, Berv DA, et al: Sensitivity and specificity of a new bipolar spectrum diagnostic scale. J Affect Disord. 2005, 84: 273-277.

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Suggested Readings

  • American Psychiatric Association. Practice Guideline for the Treatment of Patients with Bipolar Disorder. 2nd ed. Washington, DC: American Psychiatric Association, 2002, pp 525-612.
  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association, 2000.
  • Baldessarini RJ, Pompili M, Tondo L. Suicide in bipolar disorder: Risks and management. CNS Spectrums. 2006, 11: 465-471.
  • 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. Am J Psychiatry. 2005, 162: 1351-1360.
  • Fattal O, Budur K, Vaughan AJ, Franco K. Review of the literature on major mental disorders in adult patients with mitochondrial diseases. Psychosomatics. 2006, 47: 1-7.
  • Ghaemi SN, Miller CJ, Berv DA, et al: Sensitivity and specificity of a new bipolar spectrum diagnostic scale. J Affect Disord. 2005, 84: 273-277.
  • Hirschfeld RM, Williams JB, Spitzer RL, et al: Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000, 157: 1873-1875.
  • Muzina DJ, Calabrese JR. Guidelines for the treatment of bipolar disorder. In: Stein DJ, Schatzberg A, Kupfer DJ (eds): Textbook of Mood Disorders. Washington, DC: American Psychiatric Association, 2005, pp 463-483.
  • 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. Mol Psychiatry. 2006, 11: 965-978.
  • Suppes T, Dennehy EB, Hirschfeld RM, et al: The Texas implementation of medication algorithms: Update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry. 2005, 66: 870-886.
  • Sun X, Wang JF, Tseng M, Young LT. Downregulation in components of the mitochondrial electron transport chain in the postmortem frontal cortex of subjects with bipolar disorder. J Psychiatry Neurosci. 2006, 31: (3): 189-196.
  • Valtonen HM, Suominen K, Mantere O, et al: Suicidal behaviour during different phases of bipolar disorder. J Affect Disord. 2007, 97: 101-107.

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