Bipolar I disorder is a mood disorder characterized by the occurrence of at least one manic episode during the patient's lifetime, regardless of whether major depressive episodes are present. It is the most representative and typical form of bipolar disorder, formerly referred to as “manic-depressive psychosis.”
The manic episode, the core diagnostic criterion, consists of a pathological alteration in mood toward euphoria or irritability, accompanied by psychological and motor hyperactivity that significantly impairs overall functioning. In most cases, the course is episodic and cyclical, with alternation among manic and depressive phases and intervals of well-being of varying duration.
It differs from bipolar II disorder in the severity of mood alteration and, specifically, in the presence of full manic episodes, which are absent in type II.
Etiology and risk factors
The etiology of bipolar I disorder is complex and multifactorial, involving interaction between genetic predisposition and environmental factors. No single cause can be identified, but the following elements are recognized:
Genetic factors: family history is one of the principal determinants. The risk of developing the disorder among first-degree relatives is approximately 10 times higher than in the general population.
Neurochemical correlates: dopaminergic, serotonergic, noradrenergic and glutamatergic systems are implicated by models and group studies, without constituting diagnostic biomarkers.
Neuroendocrine regulation: alterations of the hypothalamic-pituitary-adrenal axis have been observed in subgroups and at different phases of illness.
Neuroplasticity: variations in BDNF and other signaling pathways are research associations, not a demonstrated cause or diagnostic test.
Circadian rhythm disturbances: misalignment of sleep-wake rhythms and daily biological oscillations is common in patients with bipolar disorder and may act both as a predisposing factor and an episodic trigger.
Although they are not direct causes, several factors increase the likelihood of developing bipolar I disorder:
Family history of bipolar disorder or other mood disorders
Use of psychoactive substances, including cocaine, amphetamines and cannabis
Stressful events, especially severe or prolonged emotional trauma during childhood or adolescence
Chronic sleep disturbances
Affective lability or impulsive personality traits
These factors do not determine onset of the disorder, but may help trigger it in predisposed individuals or promote recurrence in those already diagnosed.
Clinical manifestations and diagnosis
Bipolar I disorder presents with well-defined clinical episodes alternating with periods of more or less complete remission. The manic episode is the essential diagnostic feature and is characterized by:
Abnormally elevated, expansive or irritable mood, persisting for at least one week, present for most of the day and observable by others
Increased goal-directed activity (occupational, social or sexual) or psychomotor agitation
Inflated self-esteem or grandiose delusions
Reduced need for sleep such as feeling rested after only a few hours
Increased talkativeness or pressure to keep talking
Flight of ideas or subjective experience that thoughts are racing
Distractibility
Impulsive and risky behaviors, such as excessive spending, reckless driving or inappropriate sexual behavior
When mood is only irritable, at least four of the seven associated symptoms listed after increased activity or energy are required. A manic episode may begin suddenly and rapidly reach its peak within a few days, with duration varying from several weeks to several months.
Many patients also experience major depressive episodes, but their presence is not required for diagnosis. The frequency and burden of depression vary over the individual course.
In the most severe cases, psychotic symptoms may occur, with mood-congruent or mood-incongruent delusions and such intense excitement that urgent hospitalization is required.
Diagnosis is clinical and may be made by qualified healthcare professionals; psychiatric assessment is generally appropriate to confirm the presentation, define risk and establish treatment. At least one manic episode lasting at least one week is required, or of any duration if hospitalization is necessary. Psychotic features indicate mania and severity, but alone do not constitute an exception to the duration criterion unless they result in the need for hospitalization.
The diagnostic criteria are as follows:
Presence of at least one manic episode: full criteria must be met for a manic episode, characterized by abnormally elevated, expansive or irritable mood and an abnormal and persistent increase in activity or energy for at least one week, associated with at least three specific symptoms (four if the mood is only irritable).
Functional impact: the episode must cause marked impairment in occupational, social or relational functioning, require hospitalization or be associated with psychotic symptoms.
Exclusion of other conditions: the episode must not be due to the physiological effects of a substance, such as medication or drugs, or a general medical condition, such as endocrine disease or brain lesions.
Distinction from other categories: in the absence of a manic episode, bipolar II disorder, cyclothymia or specified categories are considered; mixed features do not constitute an independent episode in the DSM-5-TR.
The diagnostic process includes:
In-depth clinical interview with reconstruction of symptom history, temporal course and precipitating factors
Structured psychopathological assessment using scales such as the Young Mania Rating Scale (YMRS)
Exclusion of organic or substance-induced causes through laboratory and toxicological tests and, when appropriate, neuroimaging
Involvement of family members, who are often essential for reconstructing the patient's behavior during manic periods
In patients presenting for the first time, diagnosis may be complex: the depressive episode often precedes the manic episode, leading initially to a diagnosis of unipolar depression. Careful history-taking and dynamic reassessment over time are therefore essential.
Treatment, prognosis and complications
Treatment of bipolar I disorder requires a long-term strategy encompassing both acute-phase management and relapse prevention. It is based on:
Treatment of bipolar I disorder depends on phase and severity. Antipsychotics and/or mood stabilizers are used for acute mania; lamotrigine is not effective for acute mania and is used mainly to prevent depressive episodes. Treatments with evidence specific to bipolar depression are selected for depressive episodes; antidepressants must not be used as monotherapy in bipolar I disorder.
Atypical antipsychotics: olanzapine, quetiapine, aripiprazole and risperidone are frequently used, especially during the acute phase or in cases with psychotic symptoms.
Antidepressants: must not be used as monotherapy in bipolar I disorder. Any adjunctive use must be decided case by case with effective antimanic treatment and monitoring for activation or mixed features.
Psychotherapy: useful for psychoeducation, recognition of prodromes, adherence and stress management. Studied interventions include cognitive behavioral therapy, family-focused therapy and interpersonal and social rhythm therapy.
Lifestyle changes: regularizing sleep, avoiding stimulant or psychoactive substances, and maintaining regular physical activity.
In the most severe cases, hospitalization, sometimes under compulsory treatment, may be necessary. Treatment adherence is one of the principal challenges, especially in patients who experience a subjective sense of well-being during manic phases.
The course is highly variable: some patients have long periods of remission, whereas others experience recurrent episodes with poor recovery to baseline. Early onset, episode frequency and psychotic symptoms are associated with a poorer prognosis.
Treatment response may be good when intervention is timely and individualized, but lifelong treatment is commonly required. Treatment adherence is crucial to prevent recurrence and reduce the functional impact of the disease.
The main complications of bipolar I disorder include:
Suicide: high risk, especially during depressive phases or mood switching
Substance misuse: a frequent comorbidity that worsens the course
Social and occupational impairment: difficulty maintaining stable relationships or continuous employment
Cognitive decline: some patients develop long-term memory impairment and executive dysfunction
Prompt recognition and management of complications are crucial to improving outcomes and quality of life.
References
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). American Psychiatric Association Publishing; 2022. doi:10.1176/appi.books.9780890425787.
World Health Organization. Clinical descriptions and diagnostic requirements for ICD-11 mental, behavioural and neurodevelopmental disorders. World Health Organization; 2024.
Yatham LN, Kennedy SH, Parikh SV, et al. CANMAT and ISBD 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97-170. doi:10.1111/bdi.12609. PMID:29536616.
Keramatian K, Chithra NK, Yatham LN. The CANMAT and ISBD Guidelines for the Treatment of Bipolar Disorder: Summary and a 2023 Update of Evidence. Focus (Am Psychiatr Publ). 2023;21(4):344-353. doi:10.1176/appi.focus.20230009. PMID:38695002.
McIntyre RS, Berk M, Brietzke E, et al. Bipolar disorders. Lancet. 2020;396(10265):1841-1856. doi:10.1016/S0140-6736(20)31544-0. PMID:33278937.
National Institute for Health and Care Excellence. Bipolar disorder: assessment and management. Clinical guideline CG185. Published 2014; last updated 2025.
