Bipolar Disorder

Bipolar disorder (BD), also known as manic depressive illness, is a psychiatric disease characterized by fluctuation of mood states between major depression and overt mania (BD Type I) or hypomania (BD type II). Affected individuals experience changes in energy, activity, sleep, and behavior, with impairment in function in social or work situations. (1)

Depressive Symptoms

In major depressive episodes people may have: depressed mood, diminished pleasure, weight loss, changes in sleep and activity, fatigue, loss of energy, feelings of worthlessness or guilt, difficulty concentrating, or suicidal thoughts. (1)

Manic Symptoms

Manic episodes involve feelings of inflated self-esteem or grandiosity, decreased need for sleep, talkativeness or pressured speech, flight of ideas or racing thoughts, distractibility, increase in goal-directed activity, or risk-taking. (1) Mania may last for a week or more, and require hospitalization. Hypomania is a milder form that doesn’t include psychotic episodes such as hallucinations or delusions. (2)

Mixed Episodes

Mixed episodes are sometimes seen, which consist of agitation, trouble sleeping, appetite changes, suicidal thinking, and feelings of sadness and hopelessness while energized. (1)

Rapid Cycling

Rapid cycling bipolar disorder consists of four or more episodes of major depression, mania, hypomania, or mixed symptoms within one year. (1)


An association with other psychiatric conditions is common, such as substance abuse, anxiety, post-traumatic stress disorder, social phobia, and attention deficit-hyperactive. (3)

Who is Affected by Bipolar Disorder?

Bipolar disorder affects 1.5-4.0% of the population and is among the six leading causes of disability worldwide. At least half of all cases start before age 25, and because the disease tends to become more severe with time, the lifelong emotional and economic impact can be immense, with a higher rate of suicide attempts than any other mental disorder. (3-6)

The cause of BD is unknown but likely to be multifactorial. There is likely a genetic predisposition, but no definitive causes are known. Since multiple chemical pathways and structures in the brain seem to be associated with BD, it is possible that the disorder is due to disruption of several interconnected networks in the brain. Dysregulation of these circuits may underlie the inappropriate activation of emotional brain areas resulting in mood episodes in bipolar patients. (7-8)

Treatment Options

Medical and Non-surgical Therapies

The first line of treatment for BD includes medications and psychotherapy. Medications include mood-stabilizing medications such as lithium and anticonvulsants (valproate acid, lamotrigine, gabapentin, topiramate, or oxcarbazepine), atypical antipsychotics (olanzapine, aripiprazole, quetiapine, rispiradone), and antidepressant medications (used with mood stabilizers). Various psychotherapy techniques have also been shown to be effective, including cognitive behavioral therapy, family-focused therapy, interpersonal/social rhythm therapy, and psychoeducation. (9-10)

While these techniques are effective for a majority of patients with BD, up to 20% fail to respond to standard treatments. Common second-line strategies include a combination of multiple medications as well as other techniques such as high-dose thyroid augmentation, clozapine, calcium channel blockers, and electroconvulsive therapy. Even with all currently available treatments, outcome is quite poor for a significant number of patients due to high rates of relapse, cognitive or functional impairment, and psychosocial disability. For BD patients who remain symptomatic despite aggressive treatment, new therapeutic strategies are needed. (11)

Surgical Interventions

Investigations are currently underway for the use of neuromodulation, primarily in the form of deep brain stimulation (DBS), for the treatment of BD. Some studies on patients with refractory depression, including those with BD, offer promising results in medically refractory patients. (12)

For more information regarding clinical trials that may be enrolling BD patients, please visit


1. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington DC, American Psychiatric Association, 2000. 2. Bipolar Disorder. National Alliance on Mental Illness. (Accessed Oct. 19, 2016).

2. Nock MK, Hwang I, Sampson NA, Kessler RC. Mental disorders, comorbidity and suicidal behavior: results from the National Comorbidity Survey Replication. Mol Psychiatry. 2010 Aug;15(8):868-76.

3. Narrow WE, Rae DS, Robins LN, Regier DA. Revised prevalence estimates of mental disorders in the United States: using a clinical significance criterion to reconcile 2 surveys' estimates. Arch Gen Psychiatry. 2002 Feb;59(2):115-23.

4. Ferrari AJ, Baxter AJ, Whiteford HA. A systematic review of the global distribution and availability of prevalence data for bipolar disorder. J Affect Disord. 2011 Nov;134(1-3):1-13.

5. Smith DJ, Harrison N, Muir W, Blackwood DH. The high prevalence of bipolar spectrum disorders in young adults with recurrent depression: toward an innovative diagnostic framework. J Affect Disord. 2005 Feb;84(2-3):167-78.

6. Weissman MM, Bland RC, Canino GJ, Faravelli C, Greenwald S, Hwu HG, Joyce PR, Karam EG, Lee CK, Lellouch J, Lépine JP, Newman SC, Rubio-Stipec M, Wells JE, Wickramaratne PJ, Wittchen H, Yeh EK. Cross-national epidemiology of major depression and bipolar disorder. JAMA. 1996 Jul 24-31;276(4):293-9.

7. Strakowski SM, Delbello MP, Adler CM. The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings. Mol Psychiatry. 2005 Jan;10(1):105-16.

8. Calabrese JR, Shelton MD, Rapport DJ, et al. A 20-month, double-blind, maintenance trial of lithium vs. divalproex in rapid-cycling bipolar disorder. Am J Psychiatry 2005 Nov;162:2152-2161.

9. Bowden CL, Brugger AM, Swann AC, et al. Efficacy of divalproex vs. lithium and placebo in the treatment of mania. The Depakote Mania Study Group. JAMA 1994 Mar; 271(12):918-24.

10. Gitlin M. Treatment-resistant bipolar disorder. Mol Psychiatry 2006 Mar;11(3):227-40.

11. Lozano AM, Mayberg HS, Giacobbe P, et al. Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry 2008 Sep 15;64(6):461-7.

Submitted Oct. 3, 2016
Jennifer Sweet, MD
Member, International Neuromodulation Society Patient Education Committee, 2016
Case Western Reserve University School of Medicine
Cleveland, OH, USA