Bipolar affective disorder: epidemiology, etiology, clinical features, course, and treatment

01Definition and overview

Bipolar affective disorder is a recurrent illness in which episodes of raised mood and energy (mania or hypomania) and, in most patients, episodes of depression are separated by periods of normal mood. It was Kraepelin's manic-depressive insanity, set against dementia praecox by its episodic course and better outcome.

Mania and hypomania differ in severity, not in kind. A mixed episode has manic and depressive symptoms together or alternating within hours.

The three classifications draw the boundaries differently:

ICD-11 (in force since 2022) also asks for increased activity or energy as well as the change in mood for mania and hypomania, and records the current episode and whether psychotic symptoms are present.

Cyclothymia is a persistent instability of mood from early adult life, with many periods of mild elation and mild depression, none meeting the criteria for an episode; it often goes unrecognised as temperament, and some patients later develop bipolar disorder.

Rapid cycling is four or more mood episodes in a year. Estimates vary widely: it affects about 5 to 33 per cent of patients in a given year and a quarter to two fifths at some time, more often women and those with bipolar II. It is usually a phase rather than a fixed subtype, is linked to hypothyroidism, antidepressants and substance misuse, and responds less well to treatment.

02Etiology and pathophysiology

Bipolar disorder is one of the most heritable psychiatric disorders. Twin studies put the heritability at about 70 per cent, identical twins are concordant far more often than non-identical ones, and first-degree relatives have roughly seven times the general risk, with more depression, schizoaffective disorder and schizophrenia among them too. Genome-wide studies find many common variants of small effect, among the first CACNA1C (a calcium channel gene) and ANK3, overlapping with those of schizophrenia and depression; no single gene causes it.

1. 1

   Vulnerability

   Inherited risk, sometimes with a cyclothymic or hyperthymic temperament, lowers the threshold for mood episodes.
2. 2

   Triggers

   Loss of sleep, childbirth, life events, antidepressants, stimulants, corticosteroids and alcohol set off an episode.
3. 3

   Episode

   Mood, energy, sleep and thinking shift together for weeks to months, then return to baseline.
4. 4

   Kindling

   Early episodes need a trigger and later ones less, so episodes come more often and more on their own; prompt, continuing treatment aims to stop this.

Mania can also be secondary to a physical cause, which is looked for especially when it starts after the age of 50 or with neurological signs:

03Clinical features

Hypomania is the same picture in milder form, without psychosis: more energy, sociability, talkativeness and less sleep, which the patient often enjoys and rarely reports. Bipolar depression looks like unipolar depression but is more often atypical, with oversleeping, overeating and heavy fatigue, and more often psychotic. Mixed states combine depressed mood with racing thoughts, agitation and insomnia, and carry the highest suicide risk.

The first episode is often depressive, so the illness may be treated as recurrent depression for years. Features that raise the suspicion are onset in the teens or early twenties, many short episodes, atypical or psychotic features, postpartum onset, a family history of bipolar disorder and a switch into elation on an antidepressant.

04Diagnosis and management

Assessment

The diagnosis is clinical, built from the history, the mental state and an account from someone who knows the patient, because insight is poor and hypomania is seldom volunteered. The Young Mania Rating Scale measures the severity of mania, and the Mood Disorder Questionnaire screens for past highs in patients with depression.

Investigations look for causes and prepare for treatment: full blood count, kidney function with eGFR, liver and thyroid function, calcium, glucose or HbA1c, lipids, weight and blood pressure, a urine drug screen, a pregnancy test where relevant and an ECG if there is heart disease or an antipsychotic is planned. Brain imaging is done for late onset, atypical features or neurological signs.

Acute mania

1. 1

   Make safe

   Assess risk to the patient and others, finances, driving and children. Admission is often needed, under mental health law when insight is lost. A calm, low-stimulation ward helps; physical health, food and fluids are checked.
2. 2

   Remove triggers

   Any antidepressant is stopped; stimulants and alcohol are addressed, and sleep is protected.
3. 3

   Antipsychotic

   An antipsychotic is the first choice: haloperidol, olanzapine, quetiapine or risperidone. If it does not work at an adequate dose, another of these is tried.
4. 4

   Mood stabiliser

   Lithium is added if the response is not enough, or valproate where lithium does not suit and the patient cannot become pregnant. A patient already on lithium has the level checked and the dose optimised first.
5. 5

   Settle

   A short course of a benzodiazepine such as lorazepam for agitation and sleep. ECT for severe, life-threatening or treatment-resistant mania, and as an option in pregnancy.

In network meta-analyses, antipsychotics act faster and more strongly against mania than mood stabilisers; haloperidol, olanzapine and risperidone are among the most effective, and olanzapine, risperidone and quetiapine are among the best tolerated. Hypomania is treated the same way, usually at home.

Bipolar depression

Antidepressants help bipolar depression less than unipolar depression. On their own they risk a switch into mania or a mixed state and faster cycling, more with tricyclics and venlafaxine than with SSRIs or bupropion, so in bipolar I they are used only with an antimanic drug, and stopped when mixed features or hypomania appear.

Long-term treatment

Long-term treatment is offered after a manic episode, and usually continues for years, often for life. Lithium is the first choice: it prevents both manic and depressive relapses and has the strongest evidence of any treatment for lowering suicide in mood disorders. Valproate added to lithium, or lithium alone, prevented relapse better than valproate alone in a large trial. Where lithium is unsuitable or fails, the options are olanzapine, quetiapine or aripiprazole (more against mania), lamotrigine (more against depression), valproate within its limits, or a long-acting injectable antipsychotic when adherence is the problem.

Pregnancy is planned with the psychiatrist. Lithium carries a small risk of heart malformations and needs closer level monitoring in pregnancy and after delivery, and carbamazepine and valproate are teratogenic. After childbirth about a third of women with bipolar disorder or a past postpartum psychosis relapse; among women with bipolar disorder, about two thirds of those who were off medication in pregnancy relapse, against under a quarter of those who continued it.

Psychological and social care

• Psychoeducation, in groups or individually, teaches the patient and family the illness, its early warning signs and a relapse plan; it reduces relapses.
• Regular sleep and daily routines (interpersonal and social rhythm therapy), family-focused therapy and CBT are offered for relapse prevention.
• Alcohol and drugs are addressed, as they trigger episodes and worsen the course.
• Physical health is checked at least yearly: weight, blood pressure, glucose, lipids and smoking, because antipsychotics and the illness raise the risk of metabolic syndrome.
• An advance statement records what the patient wants done in the next episode; work, money and relationships are protected through the illness.

Suicide risk

Suicide risk is among the highest in psychiatry. It peaks in depressive and mixed episodes, early in the illness and after discharge, and rises with alcohol, previous attempts, hopelessness and a family history of suicide. It is asked about at every contact, and lithium is kept in mind for its protective effect, although an overdose of lithium is itself dangerous.

05Epidemiology

live with bipolar disorder, about 36 million worldwide in 2023

1 in 226peoplelive with bipolar disorder, about 36 million worldwide in 2023

lifetime prevalence of bipolar I and of bipolar II across many countries

0.6 and 0.4per centlifetime prevalence of bipolar I and of bipolar II across many countries

the usual age at onset

about 20yearsthe usual age at onset

Counting milder forms, the bipolar spectrum affects about 2 per cent of people in a lifetime. Bipolar I affects men and women equally; bipolar II and rapid cycling are more common in women, and first episodes tend to be manic in men and depressive in women. Onset is usually between the mid-teens and the mid-twenties, and new onset after 50 is uncommon enough to suggest a physical cause. Several years often pass between the first episode and the correct diagnosis. Most patients also have another disorder at some time, most often an anxiety disorder or alcohol or drug misuse.

06Prognosis

Bipolar disorder is a lifelong, recurrent illness. More than nine in ten people who have one manic episode have further episodes; untreated, many have ten or more in a lifetime, and the intervals tend to shorten over the first few episodes before settling. Episodes last weeks to months, mania usually shorter than depression, and patients spend far more time depressed than manic. Many recover fully between episodes, but a substantial minority keep residual depressive symptoms, cognitive difficulties or poor functioning.

In a large Danish cohort followed for up to 36 years, about 8 per cent of men and 5 per cent of women with bipolar disorder died by suicide, and between a quarter and a half of patients attempt it at some time. On average people with the disorder die about 13 years earlier than the general population, mostly from cardiovascular disease, as well as from suicide and accidents.