Bipolar Disorder

Bipolar Disorder

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Bipolar disorder is a mood disorder characterized by episodes of depression, mania, or hypomania.1 It has an associated prevalence of around 1%, which is much lower than the lifetime risk associated with unipolar depression.2 The incidence of bipolar disorder follows a bimodal distribution, with two peaks in the age of onset at around 15-24 years and 45-54 years. There is a roughly equal distribution of prevalence between men and women.3,4 Bipolar disorder is commonly seen in conjunction with other mental health illnesses (e.g. anxiety disorders) and increases a person's risk of physical health issues, including cardiovascular disease.1

We have also produced a video demonstration of how a patient with bipolar disorder may present.

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The aetiology of bipolar disorder is complex and involves genetic, environmental, and neurobiological components. Though bipolar disorder is heritable within families, having an affected first-degree relative does not guarantee a person will be affected with the disorder, and therefore genetics alone does not explain the entire aetiology.1

Genetic factors

First-degree relatives of a person affected with bipolar disorder are at increased risk of developing bipolar and unipolar mood disorders and schizoaffective disorder. Heritability is around 60% in monozygotic twins and around 20% in dizygotic twins.1 The genetic risk associated with bipolar disorder is a type of polygenic inheritance (the sum effect of many low-penetrance mutations). Some polymorphisms in genes that code for monoamine transporters and brain-derived neurotrophic factor (BDNF) are associated with an increased risk of bipolar disorder.

Evidence suggests there is an overlap in the genetic risk between bipolar disorder and schizophrenia.3 Genetic contributions may also be associated with copy number variants and gene-gene interactions.1

Environmental factors

The majority of environmental factors which contribute to the aetiology of bipolar disorder are not specific to this condition. Instead, they are associated with the risk of psychiatric disorders in general.1 Negative life events can precipitate depressive or manic episodes in people with bipolar disorder. The literature suggests that this may be mediated by circadian rhythm disruptions in genetically predisposed individuals.

Neurobiological Factors

Research has suggested that the development of mania may be connected to higher levels of dopamine in the brain. Mania is characterized by elevated mood, less need for sleep, and lack of social inhibitions, and many drugs that affect dopamine levels in the central nervous system also have similar effects. It is thought that these changes may be region-specific and involve changes in secondary messenger systems, in addition to an exaggerated response to dopamine receptor activation. Additionally, similar to unipolar depression, the hypothalamic-pituitary-adrenal axis can be disrupted, causing higher levels of cortisol secretion, and mania has also been known to manifest after the administration of exogenous corticosteroids.

Risk Factors

It is unclear what one single cause of bipolar disorder is, though various risk factors have been associated with an increased likelihood of developing the disorder, including genetic factors, prenatal exposure to Toxoplasma gondii, premature birth, childhood maltreatment, the postpartum period, and cannabis use.

Clinical Features

Bipolar disorder can take different forms, and two of the main forms are bipolar I and bipolar II. In bipolar I, the person has experienced at least one episode of mania, while in bipolar II, the person has experienced at least one episode of hypomania but never an episode of mania, and must have also experienced at least one episode of major depression. Cyclothymia is another disorder related to bipolar disorder, and is characterized by a persistent instability of mood, involving numerous periods of depression and mild elation, neither of which is severe or long-lasting enough to be considered bipolar disorder or recurrent depressive disorder.

Bipolar Disorder

Bipolar disorder is a mental health condition marked by oscillating states of depression and mania, or hypomania.


The clinical features of mania include an elevated mood, increased activity level and grandiose ideas of self-importance. According to the ICD-10, mania is characterized by:

  • Elevated mood that is out of keeping with the patient's circumstances
  • Elation accompanied by increased energy, resulting in overactivity, pressure of speech, and a decreased need for sleep
  • Inability to maintain attention, often with marked distractibility
  • Self-esteem that is often inflated with grandiosity and increased confidence
  • Loss of normal social inhibitions

For a diagnosis, the manic episode should last for at least seven days and have a significant negative effect on work and social activities. An increase in energy and several of the other mentioned symptoms should also be present.

In addition to these features, mania can also manifest with psychotic symptoms such as delusions and hallucinations, which are often auditory. These psychotic symptoms tend to be mood-congruent and grandiose in nature, and flight of ideas and thought disorder may also occur.


Hypomania is less severe than mania and is marked by an elevation of mood to a lesser degree. According to the ICD-10, an episode of hypomania should include:

  • Persistent, mild elevation of mood
  • Increased energy and activity, usually with marked feelings of wellbeing
  • Increased sociability, talkativeness, over-familiarity, increased sexual energy and a decreased need for sleep (but not to a degree that causes a significant negative effect on functioning regarding work or social activities)
  • Irritability may be present
  • Absence of psychotic features (delusions or hallucinations)

For a diagnosis, more than one of these features should be present for at least several days. Functional impairment tends to be less severe than that seen in mania and is not significant enough to cause a negative effect on occupational or social activities.

Differential Diagnoses

Several differential diagnoses should be considered in the context of suspected bipolar disorder.


Delusions and hallucinations can occur in both bipolar disorder and schizophrenia. In bipolar disorder, these are mood congruent and so tend to be grandiose, whilst in schizophrenia, they tend to be more bizarre and difficult to understand. Where features of schizophrenia and bipolar disorder are present in a roughly equal proportion, schizoaffective disorder should be considered.

Organic Brain Disorder

Frontal lobe pathologies can result in a loss of social inhibitions, that can also occur in mania or hypomania. Neurological investigation and imaging through CT or MRI can differentiate an organic cause from bipolar disorder.

Drug Use

The effects of some psychotropic drugs can cause a similar clinical presentation to mania, but this generally resolves as the drug wears off. Some prescribed medications (e.g. steroids) can cause elation.

Recurrent Depression

This should be distinguished from bipolar II by exploring any possible episodes of hypomania with thorough history taking.

Emotionally Unstable Personality Disorder (EUPD)/Borderline Personality Disorder

This condition is characterized by affective instability which can appear similarly to rapid cycling bipolar disorder. However, mood changes tend to occur more quickly in EUPD.

Other features of mania like grandiose ideas and a rise in energy are typically not seen in EUPD.


This is a condition connected to bipolar disorder presenting with chronic mood disturbance, with both depressive and hypomanic periods. This is different from bipolar II since, in cyclothymia, periods of depressed mood are less extreme and do not fulfill the criteria for a depressive episode.


Investigations can be done to rule out organic causes of a patient's clinical presentation and are mainly dependent on the situation. Relevant investigations might include:

  • Baseline blood tests: FBC, U&Es, LFTs, TFTs, CRP, B12, folate, vitamin D, ferritin
  • HIV testing
  • Toxicology screen
  • Physical examination including neurological examination
  • CT head


Bipolar disorder needs to be thought of when there is evidence of:

  • Mania: symptoms must have lasted for at least seven days
  • Hypomania: symptoms must have lasted for at least four days
  • Depression (characterized by low mood, loss of interest or pleasure, and low energy) with a history of manic or hypomanic episodes

A mixture of both manic and depressive features is sometimes termed a mixed affective state.

To affirm a diagnosis of bipolar disorder, a referral should be made to a specialist mental health service. This varies depending on the area but might take the form of a bipolar disorder service, a psychosis service, or a specialist integrated community-based service.

When a child or young individual under the age of 18 is thought to have bipolar disorder, they should be referred to Child and Adolescent Mental Health Services (CAMHS).


Bipolar disorder is managed through the acute treatment of manic and depressive episodes and longer-term mood stabilization.

Acute management of mania

During an acute episode of mania, people with a new diagnosis of bipolar disorder should be managed in secondary care with a trial of oral antipsychotics:

  • Haloperidol
  • Olanzapine
  • Quetiapine
  • Risperidone

The choice of drug depends on the clinical context and individual patient factors.

If the chosen drug is poorly tolerated or shows low clinical efficacy after increasing the dose as needed, a second antipsychotic from the list above should normally be given.

If the patient is on antidepressant medication, this should be reduced and ended. Benzodiazepines can be used as an adjunct to manage symptoms of increased activity and allow for better sleep.

Acute management of depression in bipolar disorder

Managing depression in the context of bipolar disorder is difficult since standard antidepressant management options can have lower efficacy in bipolar depression compared to unipolar depression. They can also be connected with a risk of inducing mania or rapid cycling.

Pharmacological and Psychological Management of Bipolar Disorder

Pharmacological options for managing depressive episodes in bipolar disorder include fluoxetine combined with olanzapine, quetiapine alone, olanzapine alone, and lamotrigine alone.11 In addition, psychological interventions such as cognitive behaviour therapy may be useful.11

Long-term Management of Bipolar Disorder

After the acute episode has resolved, long-term management usually involves a mood stabilising medication like lithium.11 If lithium is not effective, sodium valproate may be added.11 Sodium valproate should not be used in pregnant women due to its teratogenic effects and is not recommended in women of childbearing age, unless the illness is very severe and there is no effective alternative. In this case, the patient should have a pregnancy prevention plan.12

Lithium is associated with a significant reduction in the risk of relapse with a manic episode, though evidence for its effectiveness in preventing depressive relapse is less clear. It is also associated with a significant reduction in death by suicide.13 Around half of patients will show a good response to lithium, although those with rapid-cycling bipolar disorder, mixed affective states, or mood-incongruent features of psychosis may have a lower response rate.1

In addition to pharmacological management, structured psychotherapies have an important role in long-term management, such as cognitive behavioural therapy, interpersonal therapy, or family-focused therapies.


Complications of bipolar disorder include:

  • Increased risk of death by suicide
  • Increased risk of death by general medical conditions such as cardiovascular disease
  • Side effects of antipsychotic drugs: these can include metabolic effects, weight gain and extrapyramidal symptoms
  • Socioeconomic effects: major mental illness is associated with a negative drift down the socioeconomic ladder

Key points

  • Bipolar disorder is a long-term mental illness characterised by episodes of depression and mania or hypomania with a prevalence of around 1% in the population
  • The aetiology of bipolar disorder is complex and involves a genetic risk conferred by many gene polymorphisms, each with a small effect, and the interaction of this genetic risk with environmental and neurobiological factors
  • Bipolar I is the more severe form of the disorder and is characterised by at least one episode of mania
  • Bipolar II is characterised by at least one depressive episode with at least one hypomanic episode, but no episodes of mania
  • Diagnosis is made by specialist services within secondary care using clinical criteria and the exclusion of relevant differential diagnoses
  • In the acute setting, mania is managed with antipsychotic medications and discontinuation of antidepressants
  • Depressive episodes are managed using antidepressants and antipsychotic medications
  • In the long term, bipolar disorder is managed with mood stabilisers such as lithium and structured psychotherapies


  1. Harrison P. Shorter Oxford Textbook of Psychiatry. 2017.
  2. Fajutrao L, Locklear J, Priaulx J, Heyes A. A systematic review of the evidence of the burden of bipolar disorder in Europe. 2009. Available from: LINK
  3. Rowland TA, Marwaha S. Epidemiology and risk factors for bipolar disorder. 2018. Available from: LINK
  4. Tsuchiya KJ, Byrne M, Mortensen PB. Risk factors in relation to an emergence of bipolar disorder: a systematic review. 2003. Available from: LINK
  5. Alloy LB, Nusslock R, Boland EM. The development and course of bipolar spectrum disorders: an integrated reward and circadian rhythm dysregulation model. 2015. Available from: LINK
  6. Cousins DA, Butts K, Young AH. The role of dopamine in bipolar disorder. 2009. Available from: LINK
  7. Jones I, Chandra PS, Dazzan P, Howard LM. Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. 2014. Available from: LINK
  8. World Health Organization.


  • ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. 1992.
  • National Institute for Health and Care Excellence. Bipolar disorder: What else might it be? 2021.
  • National Institute for Health and Care Excellence. Bipolar disorder: When should I suspect bipolar disorder? 2021.
  • National Institue for Health and Care Excellence. Bipolar disorder: Scenario: Primary care management. 2021.

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