Bipolar disorder is a potentially lifelong, debilitating disorder characterized by episodes of either mania or hypomania, and episodes of depressed mood. Patients with bipolar disorder encounter difficulties with education, jobs, interpersonal struggle, psychosocial dysfunction, marital problems, and multiple suicide attempts and completions.

Bipolar Disorder: A Quick Diagnostic Review

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) currently lists five types of bipolar and related disorders: bipolar 1, bipolar 2, cyclothymic disorder, other specified bipolar and related disorders, and unspecified bipolar and related disorders.

Bipolar 1 and 2 are the most common subtypes, with bipolar 1 disorder being more severe as to manic episodes.Both bipolar 1 and 2 disorder share many similarities, with the key differences being that bipolar 1 requires at least one manic episode, while bipolar 2 requires at least one hypomanic episode and at least one episode of major depressive disorder. Although major depressive episodes are common in patients with bipolar 1 disorder, it is not necessary for a type I diagnosis. See the full bipolar disorder DSM-5 diagnostic criteria.

The mean age of onset for bipolar 1 disorder is 18 years,1 and there is often a significant delay between the onset of symptoms and contact with mental health services. The lifetime prevalence of bipolar 1 disorder is estimated at 1% to 2.4% of the adult population, with occurrence rates similar between males and females. More on lifetime prevalence by sex and associated genetic and environmental risks for bipolar disorder.

Herein, we focus on current treatment recommendations for bipolar 1 disorder as derived from the American Psychiatric Association’s most current practice guidelines,2,3 the DSM-5,1 and the literature.4-10

Diagnostic Coding for Bipolar 1 Disorder

The diagnostic code for bipolar 1 disorder is based on:

  • type of current or most recent episode (current or most recent episode manic, hypomanic, or depressed)
  • severity (mild, moderate, or severe) of episode
  • presence of psychotic features
  • remission status

Bipolar 1 Assessment and Evaluation

Assessing patients suspected of having have bipolar 1 should include ruling out other psychiatric disorders or causes of symptoms and3,8

Comprehensive assessment of the patient, patient’s family history, substance use history, home environment, and current caregivers or legal guardians, if applicable

  1. Complete history in regard to the type of the first episode, predominant polarity of illness, duration of episodes, severity of episodes, inter-episodic duration, suicidal behavior, history of violence or agitation, and presence of rapid cycling features
  2. Differential assessment to rule out alternative explanations such as major depressive disorder, generalized anxiety disorder, posttraumatic stress disorder, substance/medication-induced bipolar disorder, attention deficit hyperactivity disorder (ADHD), or personality disorders such as borderline personality disorder
  3. Mental status examination, paying specific attention to appearance, affect/mood, thought content, thought process, perception, speech, cognition, and judgment/insight
  4. Physical examination
  5. Treatment history

Standardized scales for assessing bipolar disorder may assist the clinician in retrieving focused information necessary for an assessment. Available scales include but are not limited to:

  • Patient Health Questionnaire-9 (PHQ-9), which positively screens for Major Depressive Disorder and Bipolar Disorder, depressive episode, also referred to as bipolar depression
  • Young Mania Rating Scale, recommended by the Department of Veteran Affairs and Department of Defense (VA/DOD) to assess the severity of a manic episode11

Treatment for Bipolar 1

Treatment Settings

Consider inpatient hospitalization for cases of suicidality, severe agitation, violence, malnutrition, catatonia, psychotic symptoms, delirium, or a patient that is unable to care for themselves, requiring supervision and additional support.

Bipolar 1 Disorder Pharmacological Options

First-line treatment options for bipolar 1 disorder are broadly classified as mood stabilizers, which include the following:

  • antimanic medications
  • anticonvulsants
  • antipsychotics
  • antidepressants (see also, a recent perspective that reviews the use of antidepressants in people with bipolar disorder)

Electroconvulsive therapy (ECT) is considered for patients with bipolar 1 disorder, experiencing severe or treatment-resistant manic or depressive episodes.

Bipolar 1 Disorder Nonpharmacologic and Psychosocial Treatments

Psychoeducation and management as an adjunct to pharmacotherapy may be helpful during the acute phase of bipolar depression and maintenance therapy. Such interventions may help reduce the risk of relapse and increase the likelihood of treatment adherence.

Successful examples include CBT, social rhythm theory, family interventions, group therapy, social skills training, and vocational rehabilitation.12 Certain mental health apps for bipolar disorder may be helpful as well to help patients track their moods.

Medications for Manic, Hypomanic, or Mixed Episodes

Per the American Psychiatric Association’s practice guidelines,2 in cases of severe mania or mixed episodes (mania or hypomania concurrent with symptoms of major depressive disorder), the initiation of either lithium plus an antipsychotic or valproate plus an antipsychotic is recommended as first line. For less ill patients, monotherapy with lithium, valproate, or an antipsychotic may be utilized. Use of depot antipsychotics may be used if the patient is not willing to take oral medications.

Several large multicentric double-blind, placebo-controlled and comparative randomized studies have supported the use of antipsychotics, including the following, in the management of acute mania:3

  • olanzapine
  • quetiapine
  • aripiprazole
  • risperidone
  • paliperidone
  • ziprasidone

For patients with breakthrough episodes of mania or hypomania (that is, despite receiving maintenance medication therapy, experience a manic/hypomanic or mixed episode), the first step in management involves optimization of the ongoing agent. Optimization may be achieved by monitoring serum levels of agents such as lithium or valproate. If necessary, the addition of antipsychotics and benzodiazepines may be used, depending on the severity of episode.

If the first-line agent, at optimal doses, fails to produce significant clinical benefit, alternative strategies may include switching lithium to valproate or vice versa, or adding carbamazepine or oxcarbazepine in lieu of additional first-line medication, or adding antipsychotics if not already used.

Clozapine may be particularly effective in the treatment of refractory illness.

Medications for Bipolar Depression

The main goal of treatment of bipolar depression – that is, an individual diagnosed with bipolar 1 disorder or with a history of mania, currently experiencing a major depressive episode – is remission of the major depressive episode in addition to avoiding precipitation of a manic or hypomanic episode.

The American Psychiatric Association’s practice guidelines recommend the initiation of either lithium or lamotrigine as first-line treatment for bipolar depression. Antidepressant monotherapy is not recommended. However, in cases with severely ill patients, lithium may be augmented with an antidepressant.2

Recent studies have shown support for the use of quetiapine monotherapy, olanzapine in combination with fluoxetine for management of bipolar depression.6,7 Studies also provide evidence for use of the antipsychotic lurasidone in the management of acute episodes of bipolar depression.

For patients who experience breakthrough depressive episodes (that is, despite receiving maintenance medication therapy, experience a major depressive episode), first-line intervention should be to optimize the dose of the medication.

When an acute depressive episode of bipolar disorder does not respond to first-line agents at optimal doses, the next steps may include adding lamotrigine, bupropion, or paroxetine.

See also, a clinical update on bipolar depression treatments including urgent and first-line therapies.

Medications for Rapid Cycling in Bipolar Disorder

Patients with bipolar 1 disorder may also experience rapid cycling. The DSM-5 defines rapid cycling as the presence of at least 4 mood episodes in the previous 12 months that meet the criteria for manic, hypomanic, or major depressive episodes.

Initial management of rapid cycling should involve evaluating the patient for underlying medical conditions which may contribute to cycling, such as hypothyroidism or a substance-induced disorder. Medications, particularly antidepressants, may also contribute to cycling and should be discontinued if possible.

Data suggests that lithium, valproate, or lamotrigine may be used as first-line agents to treat rapid cycling.6 If monotherapy fails, then a combination of mood stabilizers or mood stabilizers in combination with antipsychotics may be considered. Of note, rapid cycling appears to present more often in women.

Bipolar 1 Maintenance Treatment

Following remission of an acute episode, patients may remain at high risk for relapse for up to 6 months. This period of time is considered to be part of the maintenance phase.1 Maintenance treatment for bipolar 1 should be focused on preventing the relapse of manic or depressive episodes, reducing residual symptoms, reducing suicide risk, and improving the overall quality of life for the patient. Per the American Psychiatric Association guidelines, lithium, valproate, and lamotrigine exhibit significant utility in the maintenance of bipolar disorder.2,3

Of note, for patients treated with an antipsychotic medication during a preceding acute episode, the need for ongoing antipsychotic medication should be reassessed. Antipsychotics should be discontinued upon entering maintenance therapy unless they are required for control of persistent psychosis.2,3

As a clinical resource, the American Psychiatric Association has published a quick reference guide on treating bipolar disorders.

Last Updated: Jul 20, 2021