Key Facts

Bipolar disorder is a chronic, relapsing mood disorder with alternating episodes of mania/hypomania and depression. It requires long-term pharmacological management and is associated with significant functional impairment and suicide risk.

Epidemiology

Lifetime prevalence of bipolar disorder is approximately 1-2%. Equal sex distribution (unlike unipolar depression). Mean age of onset is 25 years, but there is typically a 9-year delay to correct diagnosis. Bipolar disorder has a strong genetic component (heritability ~85%).

Aetiology

• Genetic: Heritability ~85%; multiple genes involved (CACNA1C, ANK3, DGKH); concordance in monozygotic twins ~70%
• Neurochemical: Dopamine excess (mania), serotonin/noradrenaline deficiency (depression), glutamate/GABA imbalance
• Neuroanatomical: Prefrontal cortex hypoactivity, amygdala hyperactivity, reduced grey matter volume
• Psychosocial: Life events can trigger episodes; disrupted circadian rhythms; sleep deprivation can precipitate mania

Pathophysiology

• Kindling hypothesis: Repeated episodes lower the threshold for future episodes, eventually occurring spontaneously
• Circadian rhythm disruption: Social rhythm therapy targets this mechanism
• Mitochondrial dysfunction: Emerging evidence of bioenergetic impairment
• Second messenger systems: Lithium inhibits inositol monophosphatase and GSK-3β, modulating intracellular signalling

Mania (≥7 days)

• Elevated or irritable mood — inappropriately cheerful or hostile
• Grandiosity — inflated self-esteem, may be delusional
• Decreased need for sleep — feels rested after 2-3 hours
• Pressured speech — rapid, difficult to interrupt
• Flight of ideas — racing thoughts, loosening of associations
• Distractibility and increased goal-directed activity
• Reckless behaviour — spending sprees, sexual indiscretions, risky investments
• Psychotic features may occur (mood-congruent delusions of grandeur, hallucinations)

Hypomania (≥4 days)

• Similar to mania but milder; no psychosis; social functioning may be enhanced or mildly impaired

Bipolar Depression

• Similar to unipolar depression; often more atypical features (hypersomnia, hyperphagia, leaden paralysis)
• Psychomotor retardation more prominent

Red Flags

• Manic episode with psychotic features — may need urgent admission under Mental Health Act
• Rapid cycling (≥4 episodes/year) — associated with poorer prognosis
• Mixed features (simultaneous manic and depressive symptoms) — high suicide risk
• Lithium level >1.5 mmol/L — toxicity, urgent management

Bedside

• MDQ (Mood Disorder Questionnaire): Screening tool for bipolar disorder
• Risk assessment: Suicide risk, risk to others (especially in mania)
• Functional assessment: Impact on work, relationships, finances
• Collateral history: Essential — patients in mania often lack insight

Bloods

• TFTs: Exclude hyperthyroidism (mania mimic); baseline before lithium (lithium causes hypothyroidism)
• U&Es, eGFR: Baseline renal function (lithium nephrotoxicity)
• Calcium: Lithium can cause hyperparathyroidism
• FBC, LFTs: Baseline for valproate monitoring
• Lithium level: Trough level 12 hours post-dose; target 0.6-0.8 mmol/L maintenance
• Pregnancy test: Before starting valproate (teratogenic)

Special Tests

• ECG: QTc baseline (some mood stabilisers/antipsychotics prolong QT)
• Urine drug screen: Exclude substance-induced presentation
• Neuroimaging: If organic cause suspected (first episode mania in elderly)

Non-pharmacological

• Psychoeducation: Understanding illness, recognising early warning signs of relapse
• CBT for bipolar: Evidence for relapse prevention
• Family-focused therapy: Reduces relapse rates
• Social rhythm therapy: Stabilise daily routines and circadian rhythms
• Advance care planning: Crisis plan, preferences for treatment during episodes

Pharmacological

Acute mania (NICE CG185):

• Stop antidepressants
• First-line: Haloperidol 5-10mg, olanzapine 10-15mg, quetiapine 400-800mg, or risperidone 2-6mg
• If already on lithium/valproate: optimise dose; add antipsychotic if needed
• Severe mania: Consider combination antipsychotic + mood stabiliser

Bipolar depression:

• First-line: Quetiapine 300mg OD (monotherapy) or fluoxetine + olanzapine combination
• Lamotrigine 25mg OD titrated slowly to 200mg (effective for depressive episodes, less for mania)
• Antidepressant monotherapy AVOIDED (risk of manic switch) — if used, always with mood stabiliser

Long-term prophylaxis:

• Lithium: First-line; 400-1200mg OD/BD; monitoring: levels 3-monthly (stable), renal/thyroid 6-monthly
• Valproate: 500-2000mg daily; NOT for women of childbearing potential
• Lamotrigine: Effective for bipolar depression prevention; titrate slowly (SJS risk)
• Olanzapine, quetiapine: If mood stabilisers inadequate/not tolerated

Referral Criteria

• All suspected bipolar disorder — secondary care psychiatry for confirmation and initiation of treatment
• Acute mania — consider crisis team or inpatient admission (may require MHA)
• Treatment resistance — specialist mood disorders service

• Chronic relapsing course: Average 8-10 mood episodes over lifetime
• Suicide: 15-20× general population risk; ~25-50% attempt suicide; ~5-10% die by suicide
• Functional impairment: Even between episodes, cognitive and occupational impairment is common
• Lithium: Reduces suicide risk by approximately 60% and relapse rate by ~40%
• Rapid cycling: Poorer prognosis; lithium less effective — consider valproate (if not contraindicated) or lamotrigine
• Comorbid substance misuse worsens prognosis significantly

Lithium Monitoring Schedule

Lithium Toxicity — Signs by Level

Drugs That Increase Lithium Levels