Bipolar disorder in adults

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Last reviewed: 30 Aug 2024

Last updated: 27 Sep 2024

27 Sep 2024

FDA approves iloperidone for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults

Iloperidone has received Food and Drug Administration (FDA) approval for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. Iloperidone is a mixed dopamine D2/serotonin 5-HT2A receptor antagonist and belongs to the class of atypical antipsychotics.

The FDA approval was based on results of a phase 3 randomized, double-blind, placebo-controlled trial showing that patients with bipolar mania treated with iloperidone had significant improvements in their Young Mania Rating Scale scores, compared with patients those who received placebo, with symptom improvement as early as 14 days after the initial dose.[252]

Iloperidone is not currently available in Europe.

See Management: emerging

Original source of update

Bipolar disorder is a recurrent and often chronic mental illness marked by episodes of hypomania or mania and depression, associated with a change or impairment in functioning. It is associated with a reduction in life expectancy of around 10-20 years (primarily attributable to cardiovascular disease and suicide).

The long-term course of illness is characterized by a predominance of depression, although a history of at least one manic, hypomanic, or mixed episode is required to make the diagnosis of bipolar disorder.

Diagnosis is based on a comprehensive clinical assessment, encompassing the mental status exam at the time of the evaluation and the longitudinal history from the patient and family, using diagnostic criteria for bipolar disorder.

Misdiagnosis and delayed diagnosis of bipolar disorder are common, with depressive disorders, including unipolar major depressive disorder, accounting for the most frequent diagnostic errors.

The management of acute mania, as well as maintenance treatment, requires mood stabilizers or antipsychotics, as monotherapy or in combination. There are fewer approved treatment options for acute bipolar depression; traditional antidepressants alone are not indicated.

Bipolar disorder requires an individualized long-term management plan that includes maintenance medication(s), adjunctive psychosocial therapies, careful monitoring for any treatment-emergent complications, and promotion of a healthy lifestyle including sleep hygiene, exercise, and stress management.

Definition

Bipolar disorder, previously termed manic depression, is an episodic mood disorder characterized by manic, or hypomanic, and depressive episodes. Two subtypes are recognized: bipolar I disorder and bipolar II disorder.

Bipolar I disorder is characterized by manic episodes, which are distinct periods of abnormally and persistently elevated, expansive, or irritable mood, with abnormally and persistently increased energy or activity, lasting for at least 1 week. Although the lifetime occurrence of a major depressive episode is not a requirement for diagnosis, most people with bipolar I disorder experience a major depressive episode at some point during their lives.[1]

Bipolar II disorder is characterized by a current or past hypomanic episode and a current or past major depressive episode. Hypomanic episodes present with similar symptoms as mania but cause less impairment and are of shorter duration, lasting for at least 4 consecutive days.[1]

History and exam

Key diagnostic factors

major depressive episode(s)
episode(s) of mania
episode(s) of hypomania
inflated self-esteem or grandiosity
decreased need for sleep
more talkative than usual, or feels pressure to keep talking
flight of ideas, or subjective experience that thoughts are racing
distractibility
increase in goal-directed activity or psychomotor agitation
excessive involvement in pleasurable activities that have a high potential for adverse consequences
functional impairment
no substance misuse
no underlying medical cause
not due to somatic antidepressant treatment or other prescribed medication

Full details

Risk factors

family history of bipolar disorder or schizophrenia
onset of mood disorder prior to age 20 years
adverse life events
childhood trauma and/or adversity
previous history of depression
lifetime history of a substance use disorder
presence of an anxiety disorder
obesity
cardiovascular disease

Full details

Diagnostic tests

1st tests to order

Primary Care Evaluation of Mental Disorders (PRIME-MD)
Patient Health Questionnaire (PHQ-9)
Rapid Mood Screener (RMS)
Mood Disorder Questionnaire (MDQ)
Bipolarity Index
Young Mania Rating Scale (YMRS)
CBC
thyroid function tests
serum vitamin D
toxicology screen

Full details

Tests to consider

fasting lipid profile
fasting glucose
MRI brain
actigraphy

Full details

Treatment algorithm

ACUTE

not rapid cycling and without mixed features (with acute mania or hypomania): nonpregnant

not rapid cycling and without mixed features (with acute bipolar I depression): nonpregnant

not rapid cycling and without mixed features (with acute bipolar II depression): nonpregnant

not rapid cycling and with mixed features (with acute mania or hypomania predominant): nonpregnant

not rapid cycling and with mixed features (with acute depression predominant): nonpregnant

not rapid cycling and with mixed features (with equally prominent concurrent manic and depressive symptoms): nonpregnant

rapid cycling: nonpregnant

pregnant

ONGOING

bipolar I after stabilization of acute episode (including rapid cycling but without mixed features): nonpregnant

bipolar II after stabilization of acute episode (including rapid cycling but without mixed features): nonpregnant

not rapid cycling and with mixed features (with mania or hypomania predominant) after stabilization of acute episode: nonpregnant

not rapid cycling and with mixed features (with depression predominant) after stabilization of acute episode: nonpregnant

not rapid cycling and with mixed features (with equally prominent concurrent manic and depressive symptoms) after stabilization of acute episode: nonpregnant

after stabilization of acute episode: pregnant

Contributors

Authors

Adrian Preda, MD

Professor of Clinical Psychiatry

University of California, Irvine

Irvine

Disclosures

AP has been compensated as an expert consultant by GLG, Atheneum, Guidepoint, and as the Editor-in-Chief of Psychiatric News.

Acknowledgements

Dr Adrian Preda would like to gratefully acknowledge Dr Sudhakar Selvaraj, Dr Prashant Gajwani, and Dr David J. Muzina, previous contributors to this topic.

Disclosures

SS has received speaking honoraria from Global Medical Education and honoraria from the British Medical Journal Publishing Group; owns convertible shares at Flow MedTech, Inc (a medical device start-up company); and has been involved in a treatment-resistant depression clinical trial and received research support from COMPASS pathways (a mental healthcare company). PG has served on the speakers' bureau for Merck and Sunovion. DJM is an author of a number of references cited in this topic; has previously received honoraria for research support from Repligen Co; has previously received honoraria as a speaker and/or advisor from AstraZeneca, Pfizer, BMS, Wyeth, Sepracor, and GSK; and is a full-time employee of Medco.

Peer reviewers

Stuart Watson, MD, MRCPsych, MBBS

Clinical Senior Lecturer

Newcastle University

Newcastle

Disclosures

SW declares that he has no competing interests.

Roger McIntyre, MD

Head

Mood Disorders Psychopharmacology Unit

University Health Network

Associate Professor of Psychiatry and Pharmacology

University of Toronto

Ontario

Canada

Disclosures

RM has received research funds from Stanley Medical Research Institute and National Alliance for Research on Schizophrenia and Depression (NARSAD). RM is on the advisory boards for AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline Janssen-Ortho, Solvay/Wyeth, Eli Lilly, Organon, Lundbeck, Biovail, Pfizer, Shire, and Schering-Plough. RM is on the speakers' bureau for Janssen-Ortho, AstraZeneca, Eli Lilly, Lundbeck, Biovail, and Wyeth. RM has received research grants from Eli Lilly, Janssen-Ortho, and Shire.

Jan Scott, MBBS

Professor of Psychological Medicine

University of Newcastle

Honorary Professor

Psychological Treatments Research

Institute of Psychiatry

London

University Department of Psychiatry

Royal Victoria Infirmary

Newcastle upon Tyne

Disclosures

JS has received remuneration for attending advisory boards for AstraZeneca, BSM-Otsuka, Eli Lilly, GSK, and Sanofi-Aventis.

Differentials
- Mood disorder due to general medical condition
- Substance-induced mood disorder
- Major depressive disorder
More Differentials
Guidelines
- Mental Health Gap Action Programme (mhGAP) guideline for mental, neurological and substance use disorders
- Bipolar disorder: assessment and management
More Guidelines
Patient information
Bipolar disorder: what is it?
Bipolar disorder: what medications work?
More Patient information
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Bipolar disorder in adults

FDA approves iloperidone for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults

Summary

Definition

History and exam

Key diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

not rapid cycling and without mixed features (with acute mania or hypomania): nonpregnant

not rapid cycling and without mixed features (with acute bipolar I depression): nonpregnant

not rapid cycling and without mixed features (with acute bipolar II depression): nonpregnant

not rapid cycling and with mixed features (with acute mania or hypomania predominant): nonpregnant

not rapid cycling and with mixed features (with acute depression predominant): nonpregnant

not rapid cycling and with mixed features (with equally prominent concurrent manic and depressive symptoms): nonpregnant

rapid cycling: nonpregnant

pregnant

bipolar I after stabilization of acute episode (including rapid cycling but without mixed features): nonpregnant

bipolar II after stabilization of acute episode (including rapid cycling but without mixed features): nonpregnant

not rapid cycling and with mixed features (with mania or hypomania predominant) after stabilization of acute episode: nonpregnant

not rapid cycling and with mixed features (with depression predominant) after stabilization of acute episode: nonpregnant

not rapid cycling and with mixed features (with equally prominent concurrent manic and depressive symptoms) after stabilization of acute episode: nonpregnant

after stabilization of acute episode: pregnant

Contributors

Authors

Adrian Preda, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Stuart Watson, MD, MRCPsych, MBBS

Disclosures

Roger McIntyre, MD

Disclosures

Jan Scott, MBBS

Disclosures

Differentials

Guidelines

Patient information

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Log in or subscribe to access all of BMJ Best Practice

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