Bipolar Affective Disorder

Introduction

Bipolar disorder, also known as manic-depressive illness, has been recognised since the time of Hippocrates, who described affected patients as "amic" (manic) and "melancholic". In 1899, Emil Kraepelin formally defined manic-depressive illness and importantly distinguished it from dementia praecox (schizophrenia) by noting that patients with manic-depressive illness lacked the progressive deterioration and dementia that he associated with schizophrenia.

Bipolar affective disorder is a serious mental health condition with a high suicide rate — approximately 25–50% of patients attempt suicide during their lifetime, and 11% complete suicide. It utilises more healthcare resources than depression or most chronic medical conditions. Bipolar disorder is the 6th leading cause of morbidity worldwide.

The lifetime prevalence of bipolar disorder is approximately 0.3–1.5% across the general population. There is no significant racial predilection, and it occurs approximately equally in both sexes. However, rapid cycling (four or more mood episodes per year) is significantly more common in women.

Definition

Bipolar affective disorder is characterised by two or more episodes in which the patient's mood and activity levels are significantly disturbed. This disturbance consists of episodes of elevated mood and increased energy (hypomania or mania) alternating with episodes of lowered mood and decreased energy (depression). Repeated episodes of hypomania or mania alone — without a depressive episode — are still classified as bipolar disorder under ICD-10.

Pathophysiology

The precise pathophysiology of bipolar disorder has not been fully determined, but a significant genetic component is well-established. First-degree relatives of a person with bipolar disorder are approximately 7 times more likely to develop the disorder than the general population. Concordance in monozygotic twins is 40–70%, supporting both genetic and environmental contributions.

Several pathophysiological mechanisms have been implicated:

• Environmental triggers, including psychosocial stress and substance misuse
• Sleep deprivation and circadian rhythm disturbances (sleep disruption can precipitate mania)
• Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis
• Thyroid dysfunction (subclinical hypothyroidism is more common in bipolar disorder)
• Dopaminergic dysregulation (hyperdopaminergia during mania)
• Mitochondrial dysfunction
• Neuroinflammation and altered glutamatergic signalling

Clinical Features

The most common age of onset is between 15–19 years, with a second peak at 20–24 years. Early onset is associated with a more severe course. There is a wide spectrum of symptoms:

Mood Symptoms

• Labile (rapidly fluctuating) mood
• Euphoria or elation
• Irritability (particularly in dysphoric or mixed episodes)

Cognitive Symptoms

• Poor concentration and distractibility
• Racing thoughts (flight of ideas)
• Confusion in severe cases

Psychotic Symptoms (present in approximately 60% of manic episodes)

• Delusions (typically grandiose — e.g. believing they are a famous person, or have special powers or divine mission)
• Hallucinations (auditory more common; may be congruent or incongruent with mood)
• Formal thought disorder

Behavioural Symptoms

• Pressure of speech — rapid, difficult to interrupt
• Reduced need for sleep (often with elevated mood despite sleeping little)
• Increased libido and sexual disinhibition
• Aggression and irritability
• Religiosity (preoccupation with religious themes)
• Catatonia or stupor (in severe cases)
• Hyperactivity and increased goal-directed activity
• Overspending, reckless driving, impulsive business decisions

Depressive Symptoms (during depressive episodes)

• Depressed mood
• Loss of interest and pleasure in most activities (anhedonia)
• Significant weight change or change in appetite
• Hypersomnia or insomnia
• Loss of energy and motivation (fatigue)
• Suicidal thoughts (the depressive phase carries the highest suicide risk)
• Symptoms that cause significant distress or functional impairment

Diagnostic Criteria

Manic episode (ICD-10): Elevated, expansive, or irritable mood for at least 1 week (or any duration if hospitalisation is required), accompanied by three or more of the following — increased self-esteem/grandiosity, decreased need for sleep, pressure of speech, flight of ideas, distractibility, increased goal-directed activity or psychomotor agitation, and excessive involvement in risky activities. The symptoms are sufficient to cause marked functional impairment.

Hypomanic episode (ICD-10): An elevated, expansive, or irritable mood lasting at least 4 consecutive days, of a degree that is distinct from normal but not as severe as mania. No psychotic features. Does not cause severe functional impairment or require hospitalisation.

It is essential to rule out organic causes of mania or hypomania, including: infections (encephalitis, HIV), postoperative delirium, Addison's disease, Cushing's syndrome, thyroid dysfunction (hyperthyroidism), brain tumours, cerebrovascular events (CVA), epilepsy (particularly temporal lobe epilepsy), and substance misuse (cocaine, amphetamines, steroids).

Types of Bipolar Disorder

Bipolar I

Defined by the presence of at least one manic episode, which may or may not alternate with depressive episodes. Manic episodes in Bipolar I are severe enough to cause significant functional impairment and often require hospitalisation. Psychotic features are common during manic episodes. Bipolar I is associated with a high risk of suicide and considerable social and occupational disability.

Bipolar II

Characterised by one or more major depressive episodes and at least one hypomanic episode, but no full manic episodes. Bipolar II does not involve psychotic symptoms and does not typically cause the same degree of functional impairment as Bipolar I during the elevated mood phase. However, the depressive episodes can be severe and are associated with high rates of suicide — arguably higher than in Bipolar I due to the greater proportion of time spent in depression. Bipolar II is often under-recognised and misdiagnosed as unipolar depression.

Differential Diagnoses

• Anxiety disorder (can cause agitation and irritability)
• Schizophrenia (psychotic features may overlap; chronic course differs)
• Schizoaffective disorder (mood symptoms with features of schizophrenia)
• Cushing's disease (hypercortisolaemia causes mood disturbance)
• Hypo- and hyperthyroidism
• Hyperparathyroidism
• Head trauma and brain lesions
• Systemic Lupus Erythematosus (SLE) — cerebral involvement
• Substance misuse (stimulants, steroids)
• Emotionally unstable (borderline) personality disorder

Investigations

• Detailed history (concentrating on triggers, past episodes, family history), physical examination, and Mental State Examination (MSE)
• Blood tests: FBC, U&Es, LFTs, TFTs, VDRL/TPHA (syphilis), HIV, calcium, random glucose, HbA1c, lipid profile
• Drug screen (urine toxicology)
• ECG
• EEG if seizure disorder suspected
• CT or MRI brain if organic cause is suspected or the presentation is atypical
• Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D) to assess severity

Management

A comprehensive needs and risk assessment will determine whether inpatient admission is required. Inpatient care is indicated if there is a significant risk to the patient or others, or if the patient is unable to care for themselves.

Find out about any advance directives the patient has made — including their preference for treatment and medications — and document these in the notes.

Acute Mania

• First-line: oral antipsychotics — olanzapine, quetiapine, haloperidol, or risperidone. These are effective for both the psychotic and behavioural features of acute mania.
• Add a mood stabiliser — lithium or sodium valproate — once the acute episode is controlled.
• Benzodiazepines (e.g. lorazepam) may be used short-term for severe agitation.
• Caution: antidepressants alone should be avoided in acute mania as they can worsen the episode.

Bipolar Depression

• Caution: Antidepressants alone are not recommended in bipolar depression as they can precipitate a manic switch, mixed states, or rapid cycling — particularly without a mood stabiliser on board.
• First-line options in bipolar depression: quetiapine (licensed for bipolar depression), lamotrigine (particularly effective for bipolar II depression and maintenance), or lithium.
• If antidepressants are used, they should always be combined with a mood stabiliser and be used at the lowest effective dose for the shortest possible time.
• CBT for persistent depressive symptoms in addition to pharmacotherapy.

Medications — Mood Stabilisers

Lithium

Lithium remains the gold standard mood stabiliser for bipolar disorder. It is effective in preventing both manic and depressive episodes, and has anti-suicidal properties (it is the only mood stabiliser shown to reduce suicide risk).

• Therapeutic serum level: 0.6–1.0 mmol/L (for maintenance; 0.8–1.2 mmol/L for acute mania). Levels should be checked 12 hours post-dose.
• Evaluate response after 7 days of adequate levels.
• Monitoring (NICE recommendation): Renal function (eGFR, urea, creatinine) and TFTs before starting and every 6 months during treatment; lithium levels every 3–6 months once stable; ECG before starting (in patients with cardiac risk factors).
• Toxicity: Lithium has a narrow therapeutic index. Signs of toxicity (levels above 1.5 mmol/L) include coarse tremor, ataxia, dysarthria, confusion, vomiting, and diarrhoea. Above 2.0 mmol/L: seizures, renal failure, cardiac arrhythmia. Ensure adequate hydration and avoid NSAIDs, ACE inhibitors, and thiazide diuretics (which raise lithium levels).
• Contraindicated in pregnancy (Ebstein's anomaly risk, particularly in the first trimester).

Sodium Valproate

• Therapeutic serum level: 60–120 mg/L for sodium valproate; evaluate response after approximately 3 days for semisodium valproate (Depakote).
• Important MHRA restriction: Sodium valproate must not be prescribed to women of childbearing potential unless there is a Pregnancy Prevention Programme (PPP) in place and the patient uses effective contraception. It is highly teratogenic and causes valproate syndrome in up to 40% of in-utero-exposed children.
• Monitoring: LFTs, FBC, and weight at baseline and regularly thereafter.

Carbamazepine

Carbamazepine can be used as a mood stabiliser but is complicated by its many drug interactions (it is a potent inducer of cytochrome P450 enzymes, reducing the levels of many co-prescribed medications including oral contraceptives, antipsychotics, and antiretrovirals). It is generally reserved for cases where lithium and valproate have failed or are contraindicated.

Lamotrigine

Lamotrigine is particularly effective for the prevention of bipolar depression (less effective for mania). It should not be used as a single first-line agent in the acute phase. Must be titrated slowly to reduce the risk of serious skin reactions (Stevens-Johnson syndrome). Lamotrigine is safer in pregnancy than lithium or valproate.

Atypical Antipsychotics

• Olanzapine — effective for acute mania and as maintenance; monitoring for metabolic syndrome (weight, glucose, lipids) is essential
• Quetiapine — licensed for acute mania, bipolar depression, and maintenance; first-choice for bipolar depression
• Aripiprazole — licensed for acute mania and maintenance (less metabolic side effects)

Other Management Considerations

• ECT if treatment fails or in a life-threatening situation (e.g. manic or depressive stupor)
• Duration of treatment: typically at least 2 years after a first episode, and 5 years or indefinitely in those at high risk of relapse
• Arrange regular monitoring reviews including: weight, BMI, blood pressure, lipid profile, FBC, TFTs, LFTs, glucose, prolactin level, ECG, smoking status, and substance use
• Psychological therapies in the long term: group therapy, family therapy, psychosocial support, CBT (particularly psychoeducation about mood monitoring, recognising early warning signs of episodes, and lifestyle management)