Bipolar disorder

What is bipolar disorder?

Bipolar disorder is a chronic episodic illness associated with behavioural disturbances. It used to be called manic depression. It is characterised by episodes of mania (or hypomania) and depression. Either one can occur first and one may be more dominant than the other. Whether or not unipolar mania can exist as a separate condition - mania occurring without clinical or subclinical depression - is debated, and people with a single manic episode are currently subsumed under the heading of bipolar type I disorder in both ICD-11 and DSM-5.^{1 2} Most people with episodes of mania go on to have depressive episodes, and 'pure' mania is relatively rare.³

Types of bipolar disorder

In the 1960s manic-depressive psychosis was divided into unipolar depression (patients with mainly depression), unipolar mania (patients with mainly mania) and bipolar disorder (patients with both depression and mania). This has now mainly been superseded by division into bipolar disorder types I and II.⁴

• Bipolar I: this type presents with manic episodes (most commonly interspersed with major depressive episodes). The manic episodes are severe and result in impaired functioning and frequent hospital admissions.

• Bipolar II: patients do not meet the criteria for full mania and are described as hypomanic. Hypomania in comparison to mania has no psychotic symptoms and results in less associated dysfunction. This type is often interspersed with depressive episodes.

Further details of how the two subtypes relate to current diagnostic systems can be found in the Diagnosis section.

It is important to note that the diagnosis of bipolar disorder should not be made if symptoms are thought to result from drug ingestion or drug withdrawal.⁵

How common is bipolar disorder? (Epidemiology)

• There is limited information available but international studies suggest a lifelong prevalence rate of bipolar disorder of 2.4%.⁶

• Data from the UK Adult Psychiatric Morbidity Survey carried out in 2014 indicated that:⁷

  • Overall, 2.0% of the population screened positive for bipolar disorder:

    • Rates were similar in males and females.

    • Bipolar disorder was more common in younger age groups, being observed in:
      

      • 3.4% of those aged 16-24.

      • 0.4% of those aged 65-74.

    • The World Mental Health Survey identified a rate of 2.4% across 11 countries outside the UK.⁶

    • Overall, data collectively suggest that bipolar I disorder may be slightly more common than bipolar II disorder.⁸

• Relatives of people with bipolar disorder are five to ten times more likely to have bipolar disorder themselves.⁹

• Anxiety and substance misuse are common associated conditions.

Symptoms of bipolar disorder (presentation)^{4 9}

Manic phase

Mania is characterised by elevated mood and increase in quantity and speed of physical and mental activity. Self-important views and ideas are greatly exaggerated. Some patients may be excessively happy, whilst others may be irritable and easily angered.

During the manic phase
The following may be present:⁸

• Grandiose ideas.

• Pressure of speech.

• Excessive amounts of energy.

• Racing thoughts and flight of ideas.

• Overactivity.

• Needing little sleep, or an altered sleep pattern.

• Easily distracted - starting many activities and leaving them unfinished.

• Bright clothes or unkempt.

• Increased appetite.

• Sexual disinhibition.

• Recklessness with money.

• Psychotic symptoms: delusions (often grandiose) or hallucinations (usually voices).

Delusions are often of grandeur (eg, a belief that one is a world leader), of reference (eg, that world events have been specifically triggered for them), or persecutory (eg, false beliefs that others are conspiring against them). Lack of insight can lead to substantial risk to self and others from reckless, dangerous, or unwise behaviour. Actions taken whilst manic can cause long-lasting, and sometimes irreparable, damage to personal relationships, finances, and employment.^{10 11}

Mania often requires intensive treatment, including hospitalisation.¹²

Hypomanic phase

Hypomania is a lesser degree of mania with persistent mild elevation of mood and increased activity and energy. The key distinguishing features from mania are that, in hypomania, there is an absence of psychotic symptoms (hallucinations and delusions) and a lack of significant socio-occupational impairment.¹²

Depressive phase

Symptoms in bipolar depression are similar to those of unipolar depression, including:²

• Depressed mood.

• Diminished interest or pleasure in activities.

• Hopelessness.

• Fatigue.

• Difficulty concentrating.

• Feelings of worthlessness, or excessive/inappropriate guilt.

• Recurrent thoughts of death or suicide.

• Reduced sleep, or excessive sleep.

• Appetite changes (reduced or increased).

• Psychomotor agitation or retardation.

• In severe cases, psychotic features - delusions or hallucinations.

Unipolar depression seems to be characterised more by anxiety and agitation, compared to bipolar depression.¹³

There is an elevated risk of suicide in bipolar disorder, particularly during severe depressive or mixed states.¹⁴

Mixed episodes

People with bipolar disorder can also develop mixed episodes, with features of both depression and mania that are present either simultaneously or alternate very rapidly (within a day, or between day to day).

Suicide risk can be particularly high during a mixed episode; for example, if feelings of hopelessness and despair are paired with impulsivity.

Psychosocial functioning

Bipolar disorder can have a major detrimental effect on psychosocial functioning.¹⁵ This can endure even after clinical remission of symptoms.¹¹ It is important to ask specifically about relationship difficulties and work difficulties.

A 2017 paper looked at the association of binge eating disorder with bipolar disorder.¹⁶ The study evaluated 145 people with bipolar disorder for the presence of binge eating (BE) behaviour. The findings showed that 18.6% of the individuals analysed filled the criteria for BE behaviour of whom 74% were female. These people tended to have higher levels of anxiety and emotional reactivity.

Diagnosis of bipolar disorder⁴

For the diagnosis of bipolar type I, ICD-11requires:²

• A history of at least one manic or mixed episode.

For the diagnosis of bipolar type II, ICD-11 requires:²

• A history of at least one hypomanic episode, and;

• A history of at least one depressive episode, and;

• No history of manic or mixed episodes.

ICD-11 defines a manic episode as an extreme mood state, lasting at least one week (unless shortened by treatment), with:²

• Euphoria, irritability, or expansiveness, and increased activity or a subjective experience of increased energy, and;

• Several (the exact number is not defined, and left to clinical judgement) of:

  • Rapid or pressured speech.

  • Flight of ideas.

  • Increased self-esteem or grandiosity.

  • Decreased need for sleep.

  • Distractibility.

  • Impulsive or reckless behaviour.

  • Emotional lability.

ICD-11 defines a hypomanic episode as a persistent mood state lasting at least several days, characterised by a mild of elevation of mood or increased irritability and increased activity or energy, plus other characteristic symptoms, as listed above. It states that hypomanic symptoms must not be severe enough to cause marked impairment in socio-occupational functioning, nor necessitate hospitalisation, and there must be no accompanying delusions or hallucinations.²

Adults presenting in primary care with depression should be asked about previous periods of overactivity or disinhibited behaviour. If the overactivity or disinhibited behaviour lasted for four days or more, referral for specialist mental health assessment should be considered.

Clinical course

• Frequency and duration of episodes are variable.

• The symptoms of mania (or hypomania) and the presence of depressive symptoms may vary from day to day and also within the day.

• Between episodes patients may lead a normal work life and a normal lifestyle.

• 10-20% have rapid cycling - defined as four or more cycles of depression and mania a year, with no intervening asymptomatic episodes.¹⁷

Clinical assessment of a patient with bipolar disorder⁴

Take a detailed history of the episode - symptoms, presence of hallucinations or delusions, collateral history if the patient consents to this:

• Any previous episodes of mania or depression.

• Any suicidal or homicidal thoughts.

• Any self-neglect.

• Family history.

• Substance misuse, smoking and alcohol intake.

• General physical health.

Differential diagnosis¹⁸

• Hyperthyroidism or hypothyroidism.

• Anorexia nervosa.

• Cerebrovascular event.

• Dementia.

• Other psychiatric disorders - eg, schizophrenia, schizoaffective disorder, cyclothymia.

• Medications - eg, steroids, isoniazid, L-dopa, sympathomimetic amines.

• Chronic kidney disease.

• Acute drug withdrawal or illicit drug ingestion.

• Cerebral insults - eg, neoplasm, infarcts.

Management of bipolar disorder⁴

The basis to any successful management plan is development of good rapport and a trusting relationship with the patient and their carers. Patients require educational information regarding the diagnosis and management strategies. Shared care protocols may be available and patients should have access to community mental health teams.

In primary care, the clinician's role is to maintain an ongoing relationship with the person and their family/carers, help them to follow care plans devised in secondary care, institute crisis plans when appropriate to do so and monitor treatment.

All people with suspected bipolar disorder should be referred to a specialist mental health team to confirm the diagnosis and establish treatment.⁸

This referral should be made urgently if:⁴

• The individual presents with mania.

• The individual has severe depression.

• They pose a risk to themself or others.

Consider requesting a Mental Health Act Assessment (MHAA) if the individual does not agree to voluntary treatment, and is unwell enough that they may need involuntary treatment.

Once stabilised in secondary care, some patients are discharged back to primary care. If relapse occurs, they should be re-referred, or specialist advice should be sought.⁸

Other indications to re-refer patients to secondary care (urgently if necessary) include:

• Severe depression.

• Patient deemed a danger to themself or others.

• Poor or partial response to treatment.

• Significant decline in function.

• Depression associated with a period of overactivity or disinhibited behaviour lasting more than four days.

• Poor adherence to treatment.

• Intolerance to medication.

• Comorbid misuse of alcohol or drugs (dual diagnosis).

• Planning to stop medication after a period of stability.

• Bipolar disorder in pregnancy or if a woman is planning pregnancy.

Most of the evidence for the treatment of bipolar disorder is mainly for bipolar I disorder and may not be easily extrapolated to bipolar II disorder.

Non-pharmacological methods

• Education regarding diagnosis, treatment and side-effects.

• Good communication.

• Self-help groups.

• Support groups.

• Self-monitoring of symptoms, side-effects and triggers.

• Coping strategies.

• Psychological therapy.

• Encouragement of engagement in calming activities.

• Telephone support.

Psychological therapies have been shown to be beneficial - eg, cognitive behavioural therapy which helps to identify triggers and how to avoid them. Other therapies which may help include cognitive interpersonal therapy and behavioural couples therapy.

Pharmacological management

Patients who present with an acute episode should be followed up once a week for six weeks and then every four weeks for the first three months.

The following represents a summary of current guidance on the management of bipolar disorder:⁴

Management of manic episodes

• Manic episodes require urgent control and there may be substantial risk from patients to themselves and others. Liaise with psychiatry teams - always consider hospital admission (as insight is usually lost) and record assessment of any suicidal ideas.

• Aims of treatment are to reduce symptoms rapidly and ensure safety of the patient and others. If the patient is violent or poses a danger to self or others then refer urgently for psychiatric assessment and consider use of the Mental Health Act (MHA) if they are unwilling to be admitted voluntarily.

  • Sections 135 and 136 allow the police to take an individual to a 'place of safety' (usually an Emergency Department) for psychiatric assessment.

• Try to convince patients to have oral therapy voluntarily. In an Emergency Department, common law powers allow for emergency interventions to be performed if they are necessary to avert serious harm; however, this power is short-lived, and lasts only until the crisis subsides. Further assessment and treatment of unwilling patients is usually performed under the stipulations of the Mental Health Act.

  • Following psychiatric assessment, Section 2 of the Mental Health Act allows for involuntary admission and mental health treatment for up to 28 days. A further application may be made under Section 3 for longer involuntary admission (up to 6 months, although it can be renewed). t

• Rapid tranquilisation (parenteral administration of tranquilising drugs) may be needed if there is an immediate risk of harm to self or others from violent behaviour, and non-drug approaches such as de-escalation have not worked - remember, if the patient refuses, you may need either to use Common Law (allows treatment in an emergency) or to use the MHA. Ensure circumstances are well documented, including whether the MHA or Common Law was used.

• Consider stopping antidepressants during an episode of mania or hypomania.

• Haloperidol, olanzapine, quetiapine, or risperidone are all appropriate first-line antipsychotic medications.

• If one antipsychotic is ineffective at the maximum licensed dose or poorly tolerated, an alternative antipsychotic from that list can be chosen.

• If this alternative antipsychotic is ineffective, consider adding lithium.

• If lithium is ineffective or unsuitable, consider valproate instead.

  • Note that valproate should be avoided in anyone of childbearing potential - if it is used, it must be done with extreme caution. See the relevant MHRA safety advice.¹⁹

Treatment of an acute depressive episode

• Primary care clinicians should consider referral to the Mental Health Team, as most treatment is best initiated in secondary care.

• A risk assessment of suicidal ideation should be made. If it is considered that compulsory hospital admission would be in the patient's interest, the MHA or Common Law may need to be invoked. See the separate Compulsory Hospitalisation article for further details.

• Antidepressants may be less effective in bipolar disorder, even if depression is the main feature. They should be used carefully, as they may induce mania or hypomania or rapid cycling. If antidepressants are required then they should be prescribed with mood-stabilising or antipsychotic medication.

• Mild depression may not require any specific therapy and patients should be reviewed initially on a 1- to 2-week basis.

If depression develops rapidly in a patient with a previous manic episode who is not on treatment then an anti-manic drug should be started (as above).

• Patients with moderate-to-severe depression, who are not already taking bipolar medications, should be offered fluoxetine combined with olanzapine, or quetiapine on its own.

• If there is no response, lamotrigine on its own can be tried.

• If patients are already taking lithium, the level should be checked and the dose increased as necessary. If this fails, fluoxetine combined with olanzapine or quetiapine can be added., The fluoxetine can be omitted if the patient prefers.

• For patients already on valproate, a similar approach should be taken to people who are on lithium.

• Patients may also require psychological therapy.

• Review psychological and pharmacological treatments within four weeks of the acute episode. Options include long-term treatment (in which case review in 3-6 months) or stopping treatment. If treatment is stopped, the patient should be counselled about reporting early symptoms of recurrence.

• Long-term pharmaceutical options may include lithium with or without valproate, or if the patient does not want regular monitoring, various combinations or sole use of valproate, quetiapine and olanzapine.

Treatment of an acute mixed episode
During an acute mixed episode antidepressants should be avoided and the aim should be to try to stabilise patients on mood-stabilising or antipsychotic medication (as above).

Long-term treatment in secondary care to prevent relapse or recurrence

After each acute episode of mania or bipolar depression, a discussion should be had with the patient and/or carer about the nature and course of the disorder, treatment options, the risk of relapse after stopping treatment and the risks and benefits of pharmacological and psychological therapy. Risks may be particularly relevant in women of child-bearing age. Factors to take into account include:

• The severity and frequency of episodes.

• Previous response to therapy.

• Symptoms between episodes.

• Relapse triggers, warning signs of relapse and coping strategies.

• Potential length of treatment and review arrangements.

Provide clear written information about bipolar disorder, including the information for the public from the National Institute for Health and Care Excellence (NICE). Ensure there is enough time to discuss options and concerns.⁴

Options available include:

• Pharmacological:
  

  • Lithium should be considered first-line, with the addition of valproate if ineffective. Lithium is the most effective long-term treatment for bipolar disorder.

  • Valproate or olanzapine should be considered for patients intolerant of lithium or who are not prepared to undergo regular monitoring.

  • Do not use valproate in women of child-bearing age without appropriate caution.

  • Alternatives include lamotrigine and carbamazepine.

  • Lithium will require monitoring of levels and monitoring of renal function and thyroid function. Patients need to be advised of adequate rehydration and the dangers of suddenly stopping treatment.

  • Long-term therapy usually continues for two years but may be needed for as long as five years.

  • If medication is stopped, patients should be made aware of early warning symptoms of recurrence. Medication should be tailed off gradually (unless acute toxicity develops). Mood should be monitored for two years after treatment is stopped.

• Cognitive behavioural therapy, interpersonal therapy or behavioural couples therapy may be appropriate.

• NICE provides a link to an evidence-based manual to a psychological intervention that has been developed specifically for bipolar disorder.⁴

• Psychosocial education may be beneficial but evidence is weak.²⁰ Various methods are available, including teaching coping strategies and managing communication difficulties. Psychosocial interventions are particularly important for paediatric and adolescent patients, to provide families with an understanding of symptoms, course and treatment.

Treatment of rapid cycling¹⁷

• Year prevalence of rapid cycling among all bipolar patients ranges between 5-33.3%, while lifetime prevalence ranges between 25.8-43%.

• It is associated with a longer course of illness, an earlier age at onset, more illegal drug and alcohol abuse and increased suicidality.

• NICE recommends treating rapid cycling bipolar disorder in the same way as other types of bipolar disorder, as there is currently no strong evidence to suggest that it should be treated differently.⁴

Other treatments⁴

• Topiramate and gabapentin are not recommended by NICE.

• Electroconvulsive therapy (ECT): NICE guidelines mention that ECT can provide rapid improvement of symptoms in severe cases of mania if all other options have been unsuccessful. However, the effect is short-lived.

• Transcranial magnetic stimulation: this is not recommended by NICE.

Monitoring patients⁴

Once patients begin treatment they should be reviewed at least weekly and then annually once they are stable. Special attention should be paid to lipid levels, plasma glucose, weight, use of tobacco, alcohol and other illicit drugs and monitoring of blood pressure. Regular questioning about side-effects and suicidal ideation should occur.

Mania in special groups⁴

Children and adolescents

The diagnosis of bipolar disorder in young patients is similar to that for adults but mania must be present. Another feature which makes the diagnosis is euphoria present on most days. Irritability may aid the diagnosis but is not necessary. The treatment in children and adolescents is essentially the same as in adults but should be initiated under mental health specialists. Aripiprazole has been recommended for moderate-to-severe manic episodes in adolescents with bipolar I disorder for up to 12 weeks in adolescents aged 13 and older.²¹

Pregnancy²²

Pregnancy is a potentially hazardous time for women with bipolar disorder. Relapse rates are high (23%) during pregnancy, with recurrence and relapse rates as high as 52% postpartum.²³ All women with a history of bipolar disorder should be under specialist psychiatric care whilst pregnant and in the post-partum period;⁸ all professionals involved should be vigilant for any deterioration in mental health.

Complicating things, medications used for mania in child-bearing women may have an impact on a developing fetus. Women must be given clear advice about this risk and how to minimise it, including contraceptive advice.

Women with bipolar disorder who are planning a pregnancy should be referred to a specialist perinatal mental health service (if available) or a community mental health service for an assessment and discussion around drug treatment.⁸ Treatment decisions are complex and have to carefully balance the risk of relapse and mental ill-health in the mother against the risk to the fetus from ongoing drug treatment. Women may be advised to stay on the same medication, to switch to another drug treatment, or to stop or reduce the dose of their medication.

Women with bipolar disorder who become pregnant should also be referred to a specialist perinatal mental health service without delay. Generally, it is inadvisable to stop medication suddenly, as this does not necessarily remove the risk of fetal malformations, and may pose major risks to the mother's health.²⁴ Decisions about continuing, stopping, or changing medications should be made as soon as possible on discovering a pregnancy. These must be individualised, with specialist perinatal psychiatry input.

No specific anti-manic medication is licensed in pregnancy. If a pregnant women develops mania then low doses of antipsychotics can be used.

Elderly

Bipolar disorder may present in elderly patients. Organic disorders, such as strokes and thyroid disorders, need to be excluded. Older patients should be treated as above. Older patients are more likely to develop sudden depression after recovery from a manic episode and need close follow-up. Elderly patients are also more likely to develop side-effects and have drug interactions.

Prognosis

Bipolar disorder requires lifelong treatment and management.⁸ The natural course of bipolar disorder usually includes periods of remission with frequent relapse. This occurs most commonly when adherence to treatment is poor.

• A person with bipolar disorder will experience an average of approximately 10 episodes during their lifetime, although there is a large degree of interindividual variation.

• The risk of recurrence in the 24 months after an episode (50%) is especially high compared with other psychiatric disorders.²⁵ There is a 75% chance of recurrence within four years of an episode.

• Poor prognosis is associated with:

  • Substance dependency.

  • Psychotic features.

  • Depression symptoms.

  • Interepisode depression.

  • Male gender.

• Lithium prophylaxis improves prognosis in about 50% of patients.²⁵ About 45% of patients have a chronic disorder. The mean number of episodes of mania is 9, and the range is 2-30. More episodes indicate a poorer prognosis.

• People with bipolar affective disorder are at higher risk of suicidal ideation and attempts, which lead to a poorer prognosis.

• Mortality is higher among people with bipolar disorder, with the standardised mortality ratio for cardiovascular disease reported to range from 1.2 to 3.0, and that for suicide ranging from 14.0 to 23.4.⁸