Epidemiology^[1]

• International studies suggest a lifelong prevalence rate of bipolar disorder of 0.3-1.5%.^[1]
• A UK study suggested that between 3.3 and 21.6% of primary care patients with unipolar depression may have an undiagnosed bipolar disorder.^[2]
• There is no overall gender predilection, although rapid cycling bipolar disorder (more than four episodes a year) are more common in women.
• Relatives of people with bipolar disorder are seven times more likely to have bipolar disorder themselves.
• Anxiety and substance misuse are common associated conditions.

Types of bipolar disorders

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 This has now mainly been superseded by division into bipolar disorder types I and II, based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) classification, which are also used in the National Institute for Health and Clinical Excellence (NICE) guidelines.^[3]

• Bipolar I: this type presents with manic or mixed episodes and both are required for the diagnosis. 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.

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.^[4]

Presentation^[1]

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:

• 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.

In severe cases there may be grandiose delusions (eg belief that they are world leaders or monarchs), auditory hallucinations, delusions of persecution and lack of insight. The lack of insight is very dangerous as patients are unable to see the need for them to change their behaviour.

Hypomanic phase

Hypomania is a lesser degree of mania with persistent mild elevation of mood and increased activity and energy but without hallucinations or delusions. There is also no significant effect on functional ability.^[4][5]

Depressive phase

In the depressive phase, patients experience low mood with reduced energy. Patients have no joy in daily activities and have negative thoughts. They lack facial expressions and have poor eye contact and may be tearful and unkempt. Low mood is worse in the mornings and is disproportionate to the circumstances. There may be feelings of despair, low self-esteem and guilt for which there may be no clear reason. There may be weight loss, reduced appetite, altered sleep pattern with early morning wakening and loss of libido.

In severe cases there may be delusions of persecution or illness or impending death. Patients may become unwell through self-neglect, eg not eating or drinking.

Psychosocial functioning

Bipolar disorder can have a detrimental effect on psychosocial functioning. It is important to ask specifically about relationship difficulties and work difficulties.^[6]

Diagnosis^[1]

The International Statistical Classification of Disease and Related Health Problems (known as ICD) 'ICD-10' requires at least two episodes in which a person's mood and activity levels are significantly disturbed (one of which must be mania or hypomania).^[7] In comparison, the DSM-IV requires only one episode and divides bipolar disorder into types I and II.^[3] ICD-10 further divides bipolar disorder into:

• Currently hypomanic
• Currently manic
• Currently depressed
• Mixed disorder
• In remission

Three of the following symptoms confirm mania:

• Grandiosity/inflated self-esteem.
• Decreased need for sleep.
• Pressured speech.
• Flight of ideas (rapidly racing thoughts and frequent changing of their train of thought).
• Distractibility.
• Psychomotor agitation.
• Excessive involvement in pleasurable activities without thought for consequences (eg spending spree resulting in excessive debts).

There may also be psychotic symptoms, eg delusions and hallucinations. The manic episode is mixed if there are associated depressive symptoms.

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.^[4][8]

Differential diagnosis^[2]

• Hyperthyroidism or hypothyroidism.
• Anorexia nervosa.
• Cerebrovascular event.
• Dementia.
• Other psychiatric disorders, eg schizophrenia.
• Acute drug withdrawal or illicit drug ingestion.

Management^[1][3]

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.

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.

The following are 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.

Psycho-education about the condition and cognitive behavioural therapy - eg identify triggers and how to avoid them - have been shown to benefit patients with bipolar disorder. These methods can lead to stabilisation of mood and can be followed by supportive psychotherapy.^[4][10]

Pharmacological management

Patients who present with an acute episode should be followed up once a week initially and then every 2-4 weeks for the first few months.

For the management of a manic episode see separate Mania and Hypomania article.

The following represents a summary of current guidance on the management of bipolar disorder:^[3][4]

Treatment of a subsequent acute manic episode

• If patients are already on an antipsychotic and develop a further manic episode then either the dose of the antipsychotic should be increased or it should be substituted with lithium or valproate. Valproate should not be used routinely in females of child-bearing potential and, if it is used, then patients need to be counselled about alternative forms of contraception.
• If patients have a further manic episode on lithium, the levels should be checked and the dose increased if possible, or an antipsychotic can be added.
• If the patient is on valproate then the dose should be increased until symptoms abate or side-effects prevent further increases, in which case an antipsychotic should be added (eg olanzapine, quetiapine or risperidone).
• Patients who have responded poorly to these drugs in the past may be on carbamazepine and, if they have a further manic episode, then addition of an antipsychotic may help.

Rarely, rapid tranquilisation of patients with mania is required. This can be achieved with intramuscular olanzapine, lorazepam or haloperidol. However, these methods do not provide a long-term solution. See separate article Rapid Tranquilisation.

Treatment of an acute depressive episode

• 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 Mental Health Act or Common Law may need to be invoked. See separate article Compulsory Hospitalisation 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 anti-manic medication.
• Mild depression may not require any specific therapy and patients should be reviewed initially on a 1-2-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).
• If depression develops rapidly in a patient already on anti-manic medication then consider increasing the dose of the anti-manic drug or adding a second agent (as above).
• However, occasionally depression may not respond and then an antidepressant along with anti-manic medication can be used - usually for moderate-to-severe depression. Avoid antidepressants if there has been a recent manic or hypomanic episode, or rapid mood fluctuations or rapid cycling - in these cases try to increase the dose of the anti-manic medication or add a second agent, eg lamotrigine.
• Antidepressants should be started at low doses to prevent the risk of switching into a manic episode. The choice of antidepressant is selective serotonin reuptake inhibitors (SSRIs), as they are less likely to cause switching to mania in comparison to tricyclic antidepressants. Fluoxetine is probably first-line, followed by sertraline or citalopram. If patients are on non-antipsychotic anti-manic drugs, ie valproate or lithium, then quetiapine can also be used.
• If patients do not respond to a combination of antidepressants and anti-manic medication then the dose of the antidepressant can be increased or patients can be switched to an alternative antidepressant. If patients are not already on lithium or antipsychotic medication then these should be considered.
• Patients may also require psychological therapy.
• Antidepressants should be stopped once the depressive symptoms have been absent for more than eight weeks. Importantly, patients should still continue anti-manic drugs.

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 anti-manic medication (as above).

Long-term treatment to prevent relapse or recurrence

Long-term therapy needs to be considered for all patients who have had a manic episode. NICE guidance states that long-term therapy should be considered if a patient experiences two or more episodes of mania in bipolar I disorder, or if suicidal ideation is present, or if there is significant functional impairment, or if there are frequent episodes of mania in bipolar II disorder. NICE guidelines mention three areas which require attention in order to manage mania in the long term:^[3]

• Pharmacological - lithium or olanzapine or valproate.
  • If symptoms continue then either the patient can be switched to an alternative monotherapy, or a second agent from the above list can be added.
  • If symptoms still continue then the patient should be referred to a mental health specialist. Medications that might be used in this situation are lamotrigine (especially in bipolar II disorder) or 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 chronic depression or recurrent episodes of depression are a feature then patients should be considered for SSRIs, cognitive behavioural therapy, quetiapine or lamotrigine. These should be initiated under a mental health specialist. These should not be used if the patient has recently had an episode of mania or hypomania. In bipolar II disorder with multiple episodes of depression, lamotrigine should be used for long-term treatment.
• Psychological counselling.
• Psychosocial education.^[6]

Treatment of rapid cycling

• 10-20 % of patients with bipolar disorder have rapid cycling which is defined as four or more cycles of depression and mania a year, with no intervening asymptomatic episodes.^[4][8]
• Patients with rapid cycling should have their thyroid function tested. If they are on antidepressants these should be stopped. Anti-manic therapy should be optimised and compliance checked. First-line therapy is a combination of lithium and valproate and, if this fails, lithium alone can be used.^[3] Lithium withdrawal or toxicity may also cause rapid cycling and levels should be checked.

Other treatments

• Clonazepam, topiramate and gabapentin have been used in acute mania but 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.^[3]
• Transcranial magnetic stimulation: this is not recommended by NICE.

Monitoring patients^[3]

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 groups^[3]

Children and adolescents

The diagnosis of mania in young patients is similar to that for adults but mania must be present. Other features which make the diagnosis are 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.

Pregnancy

Medications used for mania in child-bearing women may have an impact on the fetus if they become pregnant. Therefore, thorough advice about contraception and the risks of becoming pregnant must be discussed.^[4] Drugs, such as carbamazepine, valproate and lamotrigine, have to be stopped if patients become pregnant.

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. Disorders, such as cerebrovascular accidents 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^[3]

• Manic episodes last between two weeks and 4-5 months, whilst depressive episodes are usually longer, eg six months. 90% of patients will experience more than one episode of mania.
• As patients become older, the time between episodes becomes shorter in duration.
• Unfortunately, only 20% achieve 5-year stability with good social and personal outcome.
• There is a high lifetime suicide risk in patients with bipolar disorder. 25-56% present at least one suicide attempt during their lifetime and 15% to 19% die from the attempt.^[11] Lithium has been shown to reduce the risk of suicide and number of suicide attempts in bipolar disorder.^[12]