GC163 I Am A Superman Bipolar Disorder
Bipolar disorder is a chronic mood disorder characterized by episodic fluctuations between mania (or hypomania)—during which grandiose delusions such as believing oneself to be a superhero may occur—and depression, with intervening periods of euthymia.
Bipolar Disorder — "I Am a Superman"
The Big Idea: Bipolar disorder is an episodic mood disorder characterised by pathological mood elevations (mania/hypomania) and depressive episodes, creating enormous personal and public burden. The core clinical challenge is correct diagnosis (both under- and overdiagnosis are harmful), acute treatment of each mood phase, and long-term prophylaxis to prevent neuroprogression and suicide. This lecture by KF Chung (HKU Psychiatry) covers the full arc: classification, diagnosis, differential diagnosis, course, aetiology, pharmacotherapy (with important side effects and drug interactions), special populations (pregnancy/lactation), and psychosocial management. [1]
How it fits into exams and clinical practice:
- Fourth Summative MCQs have directly tested DSM-5 diagnostic criteria for bipolar I (see 2023 Q22 below).
- EMQs often list "Bipolar disorder" as a stem option for mood presentations.
- SAQs test differential diagnosis of mood/psychotic presentations, pharmacotherapy side effects (especially lithium), and screening tools.
- In OSCEs, you may need to take a manic history, assess risk, or counsel a patient/family about mood stabilisers.
Learning Objectives (inferred from slide structure):
- Distinguish normal mood fluctuation from pathological mood states.
- Classify mood disorders per DSM-5.
- Apply DSM-5 criteria for manic, hypomanic, depressive episodes and bipolar I/II.
- Recognise the bipolar spectrum and its clinical relevance.
- Formulate the differential diagnosis of mania.
- Understand under- and overdiagnosis pitfalls.
- Describe aetiology (genetic, biological, environmental).
- Outline the course, staging, and prognostic factors.
- Manage acute mania, acute bipolar depression, and prophylaxis with appropriate pharmacotherapy.
- Identify side effects, drug interactions, and lithium toxicity.
- Manage bipolar disorder in pregnancy and lactation.
- Appreciate psychosocial interventions and the importance of stigma reduction.
Mood disorders are abnormal mood states with other associated features resulting in distress and functional impairment. [1]
Why this definition matters: Everyone's mood fluctuates. The pathological state is distinguished by:
- Pervasiveness — the abnormal mood is sustained, not fleeting.
- Associated features — cognitive, biological, psychomotor symptoms cluster with the mood change.
- Distress and functional impairment — the condition disrupts daily life.
Mood disorder is episodic. [1]
This is a fundamental conceptual point. Unlike personality disorders (which are trait-based and persistent), bipolar disorder is characterised by discrete episodes separated by periods of relative wellness (euthymia). This has implications for diagnosis (you need to identify past episodes via longitudinal history) and treatment (acute vs. maintenance phases differ).
DSM-5 splits mood disorders into two major branches: Bipolar Disorders and Depressive Disorders. [1]
| Bipolar Disorders | Depressive Disorders |
|---|---|
| Bipolar I disorder | Major depressive disorder (single/recurrent) |
| Bipolar II disorder | Dysthymic disorder (persistent depressive disorder) |
| Cyclothymic disorder | Other depressive disorders |
| Other bipolar disorders |
A distinct period of elevated, expansive or irritable mood AND increased goal-directed activity lasting at least 1 week. [1]
Three or more of the following (four if mood is only irritable):
- Inflated self-esteem or grandiosity
- Decreased need for sleep
- Pressured speech
- Flight of ideas / racing thoughts
- Distractibility
- Increased goal-directed activity (socially, at work/school, sexually) / psychomotor agitation
- Excessive involvement in pleasurable activities with high potential for painful consequences (buying sprees, sexual indiscretions, foolish business investments) [1]
Marked impairment in functioning, observable by others, to necessitate hospitalization, OR there are psychotic symptoms. [1]
Not due to alcohol, substance or medical conditions. [1]
Mnemonic for manic symptoms: DIG FAST
- Distractibility
- Indiscretion (pleasurable activities with consequences)
- Grandiosity
- Flight of ideas
- Activity increase
- Sleep decreased
- Talkativeness (pressured speech)
Why "increased goal-directed activity" is in criterion A: DSM-5 added this to the core criterion (not just mood) because some manic patients are predominantly irritable rather than euphoric. You must see the energy/activity component alongside mood change. This prevents mislabelling every irritable patient as manic.
Why psychotic features = mania, never hypomania: If psychotic symptoms are present during a mood elevation, by definition it is a manic episode, not hypomanic. This is a key diagnostic discriminator.
At least 4 days of elevated, expansive, or irritable mood AND increased activity or energy. [1]
3 or more manic symptoms (same list as mania). [1]
Change in functioning observable by others but NOT severe enough to cause marked impairment, NOT necessitating hospitalization, and NO psychotic symptoms. [1]
Often missed by patients and doctors, resulting in delayed diagnosis. [1]
Why hypomania is missed:
- Patients feel good during hypomania — they are productive, confident, sociable. They don't seek help.
- They present during depressive episodes and report only depression.
- Doctors forget to systematically ask about past episodes of elevated mood/energy.
- Result: Bipolar II gets misdiagnosed as MDD → inappropriate antidepressant monotherapy → risk of manic switch.
| Feature | Mania | Hypomania |
|---|---|---|
| Duration | ≥1 week | ≥4 days |
| Symptom threshold | ≥3 (or 4 if irritable only) | Same |
| Functional impairment | Marked | Not marked |
| Hospitalization | Often needed | Not needed |
| Psychotic symptoms | May be present | Never present |
5. DSM-5 Criteria — Bipolar I vs Bipolar II
Presence of one single manic episode already satisfies criteria for bipolar I disorder. [1]
Most cases have both manic and depressive episodes. There is a predominant polarity (more manic or more depressive episodes). [1]
Only 5% have mania without any depressive episodes. [1]
Why a single manic episode suffices: Mania is so distinctive and disruptive that its occurrence signals a fundamentally different illness trajectory from unipolar depression. Even one episode carries a >90% risk of future mood episodes. [1] [5]
At least one hypomanic episode + at least one previous depressive episode. Never has a manic or mixed episode. [1]
Depressive episodes are more common in bipolar II disorder. [1]
Clinical implication: BP II is NOT "milder bipolar." The depressive burden is often greater than in BP I, and long-term impairment can be equivalent. [1]
Exam Trap
A patient who has ever had a full manic episode cannot be diagnosed with Bipolar II — they are Bipolar I by definition, even if they currently present with depression or hypomania. If a BP II patient later develops a manic episode, the diagnosis is reclassified to BP I.
Includes: [1]
- Short duration hypomanic episodes (2–3 days)
- Hypomanic episodes with insufficient symptoms (2–4 symptoms)
- Drug-induced hypomanic episodes with spontaneous remission
Morbidity and impairment are greater in MDD with bipolarity than MDD without bipolarity. [1]
Why this matters: The bipolar spectrum concept captures patients who don't meet full DSM-5 criteria for BP I or BP II but still behave more like bipolar patients biologically and pharmacologically. They may respond poorly to antidepressant monotherapy and may benefit from mood stabilisers. BP spectrum can be mistaken as borderline personality disorder due to frequent mood changes. [1]
- Chronic mood instability with alternating periods of mild elation and mild depression.
- Neither the highs nor lows meet criteria for hypomania or major depression.
- Duration: ≥2 years of fluctuating mood with no symptom-free period > 2 months.
- Significant distress/functional impairment despite subthreshold episodes.
Mood disorders are heterogeneous conditions. Specifiers are used to better understand patient's characteristic and to select appropriate treatment. [1]
| Specifier | Key Features | Clinical Relevance |
|---|---|---|
| With anxious distress | Prominent anxiety symptoms | May need anxiolytic adjunct; worse prognosis |
| With mixed features | Opposite-polarity symptoms during episode | More difficult to treat; worse outcomes [1] |
| With rapid cycling | ≥4 episodes per year | Poor prognosis; lithium less effective; valproate preferred |
| With melancholic features | Near-complete absence of capacity for pleasure | Better response to biological treatments |
| With atypical features | Mood reactivity, weight gain, hypersomnia | More common in BP II depression |
| With psychotic features | Delusions/hallucinations | Mood-congruent vs mood-incongruent |
| With peripartum onset | Severe anxiety, panic attacks. Risk of infanticide | Obstetric emergency; postpartum high-risk period |
| With seasonal pattern | Depression begins in fall/winter, remits in spring | Light therapy may help |
High Yield — Rapid Cycling
10–15% of cases are 'rapid cyclers' — ≥4 episodes/year. [1] Outcomes for mixed episodes and rapid cyclers are worse. Rapid cycling is associated with lithium resistance and may respond better to valproate or lamotrigine.
9. Differential Diagnosis of Manic Episode
Differential diagnosis includes: [1]
- Depressive disorder with irritability and anxious distress
- Psychotic disorder or schizoaffective disorder
- Substance/medication-induced or medical conditions
- Attention deficit and hyperactivity disorder
- Personality disorder with prominent irritability
| Feature | Mania with psychotic features | Schizophrenia |
|---|---|---|
| Mood | Elated or irritable, mood-congruent psychosis | Flat/incongruous affect |
| Delusions | Grandiose, persecutory (linked to grandiosity) | Bizarre, passivity, thought alienation |
| FTD | Flight of ideas (logical links preserved) | Loosening of association, neologism, thought blocking |
| Speech | Pressured, difficult to interrupt | Hesitant, halting |
| Sleep | Decreased need (not tired) | Less prominent |
| Onset | Episodic | Insidious |
| Hallucinations | Mood-congruent (voices about special powers) | Mood-incongruent, often 3rd person running commentary |
| First-rank symptoms | 10–20% may have (usually fleeting) | More prominent and persistent |
Drugs: Steroids, L-dopa, stimulants, antidepressants, ECT (in those with bipolar spectrum disorder) [1] Substances: Cocaine, amphetamine [1] Medical: Frontal lobe lesion, hyperthyroidism, Cushing's syndrome [1]
Why these cause mania:
- Steroids/L-dopa/stimulants/cocaine/amphetamine → increase dopaminergic/noradrenergic transmission → euphoria, psychomotor activation.
- Antidepressants → can "switch" a bipolar patient into mania (this is why antidepressant monotherapy is dangerous in bipolar).
- Frontal lobe lesions → disinhibition, personality change (pseudo-manic presentation).
- Hyperthyroidism → sympathetic overactivity mimicking the biological features of mania (agitation, insomnia, weight loss).
- Cushing's syndrome → cortisol excess → psychiatric manifestations including mania and psychosis.
10. Misdiagnosis: Under- and Overdiagnosis
Hypomanic episode is often overlooked. Patients with BP II are misdiagnosed as having major depressive disorder. [1]
Manic episode with psychotic symptoms misdiagnosed as schizophrenia. [1]
Among 600 patients with bipolar disorder, 69% were initially misdiagnosed and most frequently as major depression, followed by anxiety disorders, substance or alcohol use disorder. [1]
Correct diagnosis and treatment was delayed by 5–7 years on average. [1]
Consequences of underdiagnosis: [1]
- Untreated mood symptoms → increased suicidality, comorbid anxiety and substance use disorders
- Poor QOL, greater functional impairment, increased healthcare cost
- Antidepressant monotherapy is less effective and results in manic switch and cycle acceleration
Due to incorrect understanding of the term "manic" "躁". [1]
Among 180 outpatients previously diagnosed with bipolar disorder, structured interview could not confirm the diagnosis in 43 (33%) of them. [1]
Only 43% of 145 patients with a previous diagnosis of bipolar disorder had the condition confirmed by structured interview. [1]
Consequences of overdiagnosis: [1]
- Unnecessary side effects of mood stabilizers
- Increased sick role and disability claims
Requires informants and collateral information (e.g., medical record) to confirm past history of mania/hypomania. [1]
It is important to follow diagnostic criteria in making psychiatric diagnosis. [1]
History from the patient + Collateral information from informants + Screening tools: [1]
- Mood Disorder Questionnaire (MDQ)
- Hypomania Checklist (HCL-32)
11 items, total score 0–60. [1]
- ≥20 = mania
- ≥12 = hypomania
Items (starred items scored 0–8, others 0–4): [1]
- Elevated mood
- Increased motor activity/energy
- Sexual interest
- Sleep
- Irritability
- Speech (rate and amount)
- Language – thought disorder
- Content
- Disruptive-aggressive behavior
- Appearance
- Insight
Why some items are double-weighted (0–8): Irritability, speech, content, and disruptive-aggressive behaviour are given more weight because they are the features most likely to require acute management (hospitalization, risk to self/others).
BP I: lifetime prevalence 0.3%–1.6%. Bipolar spectrum disorder: 3.7%. [1]
Mean age at onset for first mood episode is about 18 years for BP I, but accurate diagnosis is often delayed by 5–10 years. [1]
83% of cases have > 4 episodes; 43% have > 7 episodes. [1]
One third of patients attempted suicide and 10%–20% died from their illness by suicide. [1]
- Risk factors: past suicidal attempt and prominent depressive symptoms. [1]
9th leading cause of disability-adjusted life years under mental, neurological, and substance use disorders (depressive disorder is the 1st cause). [1]
No gender and ethnic difference. [1]
Risk Factors
Risk factors for bipolar disorder: [1]
- High income countries (may be due to referral bias)
- Low income, separated, divorced, or widowed
- Low care and overprotective parents, poor attachment relationship, childhood abuse
- Family history of bipolar disorder and schizophrenia
- Monozygotic concordance 40–70%
- Lifetime risk in first-degree relatives 5–10%, roughly 7× higher than general population
- No gender and ethnic difference
13. Psychiatric and Medical Comorbidity
Comorbidities are common. Need to treat BOTH bipolar disorder and the comorbid conditions. [1]
Sleep disorder, eating disorder, ADHD, psychotic disorder, anxiety disorder, substance use disorder, personality disorder [1]
Comorbid Anxiety Disorders (vs general population): [1]
| Anxiety Disorder | OR (vs general pop.) |
|---|---|
| Panic disorder | 9.1 |
| OCD | 11.5 |
| GAD | 4.3 |
| Social phobia | 4.1 |
| PTSD | 3.9 |
Prevalence of anxiety disorders in BD is as common as in MDD. [1]
Comorbid Substance Use Disorders: [1]
- Drug abuse/dependence: OR 5.2 vs general population; OR 3.7 vs MDD
- Alcohol abuse/dependence: OR 3.4 vs general population
Drug abuse is more common in BD than in MDD. [1]
Higher risk of cardiovascular and metabolic diseases (obesity, diabetes, hypercholesterolaemia). [1]
Risk factors include: alcohol/substance use, unhealthy diet, physical inactivity, social isolation, unemployment, stress, poor sleep, childhood abuse, side effects of pharmacotherapy (valproate, atypical antipsychotics). [1]
14. Aetiology
Multifactorial approach [1]
79% heritability. [1]
First-degree relatives are at higher risk for bipolar, MDD, and other psychiatric disorders. [1]
Shared genetic risk between bipolar, schizophrenia and autism. [1]
Some overlap with genes involved in circadian rhythm regulation. [1]
Biochemical pathways: especially dopaminergic, second messengers, mitochondrial, HPA axis, and thyroid. [1]
Neuroimaging findings: structural and functional abnormalities. [1]
Infective causes, e.g., Toxoplasma gondii (the associated immune response). [1]
Life events and social support, low care and overprotective parents, poor attachment relationship, childhood abuse, sleep deprivation, circadian and social rhythm disruption. [1]
None of them are specific biomarkers. [1]
Why circadian rhythm matters: Bipolar patients have dysregulated circadian clocks. Sleep deprivation can precipitate mania. Social rhythm disruption (jet lag, shift work, irregular daily routines) destabilises mood. This is why Interpersonal and Social Rhythm Therapy (IPSRT) is an evidence-based psychosocial treatment — it regularises daily routines and sleep-wake cycles.
15. Course of Illness
Most manic episodes recover eventually, but residual symptoms are more common after depressive episodes. [1]
Untreated manic episodes can last 4–6 months (median duration). [1]
Most cases have relapses if they are not put on maintenance pharmacotherapy. [1]
In average, 4 major episodes in the first 10 years, getting more frequent then stabilising at around once per year. [1]
Functional recovery: 43%. Relapse: 40%. [1]
Outcomes for mixed episodes and rapid cyclers are worse. [1]
Chance of relapse is higher in those with previous relapse. [1]
Recognition of prodromes and early treatment can reduce relapse. [1]
Recurrence rate reduces by 50% for maintenance vs. discontinuation. [1]
Stage 1: High-risk group (positive FH) or patients with subsyndromal symptoms [1] Stage 2: Patients with a few episodes and optimal functioning [1] Stage 3: Recurrent episodes and decline in functioning and cognition [1]
Neuroprogression theory: worse prognosis with frequent relapses. Increased risk of future development of dementia. [1]
Why neuroprogression matters: Each relapse causes further neurobiological damage (oxidative stress, inflammation, grey matter loss). This is the strongest argument for aggressive prophylaxis — not just symptom control, but neuroprotection.
Outline of management: [1]
- Correct diagnosis
- Illness acceptance and treatment adherence
- Family psychoeducation
- Pharmacological and psychosocial treatment
- Acute manic episode
- Acute depressive episode
- Maintenance and prophylactic treatment
- Special situations: childbearing-age women, pregnancy, children/adolescents, elderly
- Treatment of psychiatric and medical comorbidity
18. Acute Treatment of Mania and Mixed Episodes
Referral to a specialist for in- or out-patient care is necessary because of aggression, excessive spending and disinhibited behaviour. Insight and judgment are usually impaired early. [1]
Consider hospitalization when: [1]
- Presence of psychotic symptoms (mood-congruent or mood-incongruent)
- Severe overactivity
- Bizarre behaviour
- Excessive spending
- Incoherent speech
- Disorganised thinking
- Mixed episode (more difficult to treat)
First-line Monotherapy:
Lithium, Valproate, Quetiapine, Risperidone, Aripiprazole, Paliperidone ( > 6 mg), Asenapine [1]
Combination (if monotherapy insufficient):
Lithium/Valproate PLUS Atypical antipsychotic [1]
Third-line / Treatment-resistant:
Re-evaluate diagnosis and consider ECT (when rapid response needed, e.g., high violence risk). [1]
Why atypical antipsychotics work in mania: Mania involves dopaminergic overactivity (hence grandiosity, psychomotor agitation, psychosis). Atypical antipsychotics block D2 receptors (controlling psychotic and agitation symptoms) while also modulating serotonin pathways (contributing to mood stabilisation).
Why ECT for mania? ECT has rapid onset of action and is effective for both mania and depression. In treatment-resistant or dangerous presentations (catatonia, high violence risk, refusing oral medications), ECT can be life-saving.
19. Acute Treatment of Bipolar Depression
Because of the recognised risk of switching to manic or mixed episodes and the high risk of suicide, referral to a specialist should be considered. [1]
First line: Quetiapine [1] Second line: Lamotrigine, Lithium, Antidepressants (sertraline, venlafaxine) [1] Third line: Valproate [1]
High Yield — Antidepressants in Bipolar Depression
Avoid antidepressants if possible; if used, limit dose and duration. [1] Antidepressant monotherapy in bipolar depression risks manic switch and cycle acceleration. Always combine with a mood stabiliser if antidepressants are used.
20. Prophylactic (Maintenance) Treatment
Established bipolar disorder with recurrent episodes of mania or depression. [1] Severe single episode with suicidal attempts, psychotic episodes and significant functional impairment. [1] Recurrence rate reduces by 50% for maintenance vs. discontinuation. [1] Gradual discontinuation is better than abrupt discontinuation. [1]
Monotherapy: Lithium or Valproate or Quetiapine [1]
Psychosocial (augmentation): [1]
- Psycho-education
- Cognitive behavioural therapy
- Interpersonal and social rhythm therapy
- Family or carer-focused treatment
- Peer-support
- Intensive case management
Less hostile, more supportive → better drug compliance. [1]
Early onset, greater severity, mixed episodes, repeated episodes, previous hospitalisations, residual symptoms, cognitive impairment, poor insight, side effects of medications, comorbid substance or personality disorder. [1]
21. Pharmacotherapy — Side Effect Profiles
Side effects of Lithium: [1]
| Subjective Effects | Systemic Effects |
|---|---|
| Nausea | Renal dysfunction |
| Polydipsia | Hypothyroidism |
| Polyuria | Poor memory |
| Fatigue | QT prolongation |
| Mild tremor | Teratogenic |
| Narrow therapeutic margin | |
| Moderate weight gain |
Start with low dose long-acting Li. Li level 0.6–1.0 mmol/L (lower maintenance level for patients with renal dysfunction). [1]
Why lithium causes nephrogenic DI: Lithium reduces aquaporin-2 (AQP2) expression in renal collecting ducts → impaired water reabsorption → polyuria and polydipsia. This is a form of nephrogenic diabetes insipidus. [6]
Why lithium causes hypothyroidism: Lithium inhibits thyroid hormone release (blocks iodine uptake and thyroglobulin coupling). Monitor TFTs regularly.
Lithium — The Only Mood Stabiliser That Reduces Suicide
Lithium is still an important drug, given that it is the only mood stabiliser to reduce suicide. [1] This is a frequently tested fact. Even if other drugs are better tolerated, lithium remains first-line for patients with high suicide risk.
Side effects of Valproate: [1]
| Subjective | Systemic |
|---|---|
| Nausea, vomiting, diarrhoea | Significant weight gain |
| Tremor | Hepatic derangement |
| Sleepiness | Haematological abnormalities |
| Hair thinning or loss | |
| Polycystic ovarian syndrome | |
| Teratogenic |
Start with 500 mg/day. Dose within therapeutic range according to response and side effects. [1]
Valproate and Women of Childbearing Age
FDA recommendation: valproate should not be used in female children, adolescents and women of childbearing age unless alternatives are ineffective. [1] This is because valproate is highly teratogenic (neural tube defects, developmental delay) and causes PCOS. This is an absolute exam point.
Side effects of Lamotrigine: [1]
| Subjective | Systemic |
|---|---|
| Headache, fatigue, dizziness, dry mouth | Rash |
| Steven-Johnson Syndrome (Box Warning) |
Well-tolerated drug. Start with 25 mg/day in the first 2 weeks (to avoid SJS). If combined with anticonvulsants, start with 12.5 mg/day. Aim at 50–300 mg/day. [1]
Why the slow titration: Lamotrigine's risk of Stevens-Johnson Syndrome (SJS) is dose-dependent and related to rate of dose escalation. Starting low and going slow (25 mg/day for 2 weeks, then doubling every 2 weeks) dramatically reduces the risk. Valproate inhibits lamotrigine metabolism, so even slower titration (12.5 mg/day) is needed with co-administration.
Lamotrigine is a promising agent for treatment of bipolar depression due to its tolerability and wide therapeutic margin. [1]
| Drug | Acute Mania | Bipolar Depression | Prophylaxis | Key Side Effects | Special Concern |
|---|---|---|---|---|---|
| Lithium | 1st line | 1st line (BP I) | 1st line | Renal, thyroid, tremor, teratogenic | Only drug reducing suicide; narrow TI |
| Valproate | 1st line | 3rd line | 1st line (BP I) | Weight gain, liver, hair loss, PCOS | Avoid in women of childbearing age |
| Lamotrigine | Not used | 1st line (BP I/II) | 1st line (BP II) | SJS (slow titration!) | Best tolerated for depression |
| Quetiapine | 1st line | 1st line (BP I/II) | 1st line | Metabolic syndrome | Versatile across all phases |
| Olanzapine | Used | Not 1st line | Less preferred | Highest metabolic risk | Monitor weight/glucose/lipids |
Baseline investigations in bipolar disorder: [1]
- CBP, LRFT
- TFT
- Fasting glucose and lipid profile
- 24 hr Cr clearance (if history of renal disease)
- Urine for toxicology (if relevant)
- Pregnancy test (if relevant)
- ECG (if relevant)
Why each test:
- CBP — valproate can cause cytopenias
- LRFT — lithium affects kidneys; valproate affects liver
- TFT — lithium causes hypothyroidism; hyperthyroidism is a differential
- Fasting glucose/lipids — atypical antipsychotics cause metabolic syndrome
- Cr clearance — lithium is renally excreted
- Toxicology — exclude substance-induced mania
- Pregnancy test — teratogenicity of multiple drugs
- ECG — lithium causes QT prolongation
Lithium level is raised due to concomitant diuretics, NSAID, Ca²⁺ channel blocker, ACE inhibitors (reduced renal excretion). [1]
Potential negligence claims: doctors prescribing NSAID for flu/pain can result in toxic level of Li. [1]
Valproate level is raised due to concomitant aspirin, anticoagulants, lamotrigine, and other anticonvulsants (hepatic enzyme inhibition). [1]
Carbamazepine is a CYP3A4 inducer: causes reduced levels of oral contraceptives, antipsychotics, benzodiazepines, phenytoin. [1]
Lamotrigine: interacts with other anticonvulsants (acts as enzyme inhibitor and level can be raised). [1]
Exam Favourite — Lithium + NSAID/Diuretic/ACEI
This is a classic drug interaction question. Lithium has a very narrow therapeutic index. Anything that reduces renal blood flow or GFR (NSAIDs, ACEi, diuretics) will decrease lithium excretion → toxicity. Always check lithium levels when co-prescribing these drugs.
Medical emergency. [1] Symptoms: Poor motor coordination, ataxia, muscle twitching, slurred speech, confusion. [1]
Treatment: Stop Li at once, high intake of fluid, osmotic diuresis by using extra NaCl, renal dialysis in severe cases. [1]
Mechanism: Lithium toxicity ( > 1.5 mmol/L) causes progressive neurological dysfunction because lithium substitutes for sodium in neurons, disrupting action potential generation. At toxic levels: coarse tremor → ataxia → seizures → coma → death.
| Lithium Level | Clinical Significance |
|---|---|
| 0.6–1.0 mmol/L | Therapeutic maintenance range |
| 0.8–1.2 mEq/L | Target for acute bipolar depression |
| > 1.5 mmol/L | Toxicity range |
| > 2.0 mmol/L | Severe toxicity (seizures, coma) |
25. Pregnancy and Lactation
No drugs are really "safe" — most drugs belong to class C or D. [1]
| Drug | FDA Category | Risk |
|---|---|---|
| Lithium | D | ×3 abnormalities of all types; ×7 cardiac abnormalities (Ebstein anomaly) |
| Valproate | D | Congenital malformation and developmental delay |
| Lamotrigine | C | Low risk of cleft lip/palate in neonates |
| Quetiapine/Olanzapine | C | Lower risk but not zero |
| SSRI | C | Neonatal withdrawal, PPHN |
| Benzodiazepine | D | Floppy infant syndrome |
Stopping drug will increase the chance of relapse. Stopping drug abruptly even higher. [1]
Postpartum period: high risk of relapse. [1]
A potential area for medical negligence claims. [1]
Clinical approach to pregnant bipolar patient:
- Pre-conception planning is ideal — discuss risks with patient and partner.
- If medication needed, choose lowest risk agent (lamotrigine or quetiapine often preferred).
- If patient is on lithium/valproate, discuss risks and plan taper if appropriate — but never abruptly stop.
- Folate supplementation (esp. if valproate exposure).
- Close monitoring during pregnancy and especially postpartum (highest risk period for relapse/new onset psychosis).
Psychosocial intervention is important for prevention of relapses and overall management of bipolar disorder. [1]
| Intervention | Mechanism / Purpose |
|---|---|
| Psychoeducation | Understanding illness, recognising prodromes, improving adherence |
| CBT | Addressing negative cognitions, relapse prevention |
| Interpersonal and social rhythm therapy | Regularising daily routines and sleep-wake cycles (circadian stabilisation) |
| Family/carer-focused treatment | Reducing expressed emotion, improving communication |
| Peer support | Shared experience, reducing isolation |
| Intensive case management | Coordinating multidisciplinary care for complex cases |
Bipolar disorder is underrecognised and undertreated. [1]
The challenge in long-term management is the prevention of relapses, subsyndromal symptoms and functional disability. [1]
Avoid antidepressants if possible; if used, limit dose & duration. [1]
Lithium is still an important drug, given that it is the only mood stabiliser to reduce suicide. [1]
Atypical antipsychotics look promising as mood stabilisers, but limited by metabolic side effects. [1]
Lamotrigine is a promising agent for treatment of bipolar depression due to its tolerability and wide therapeutic margin. [1]
Psychosocial intervention is important for prevention of relapses and overall management of bipolar disorder. [1]
28. Exam Intelligence
| Trap | Correct Understanding |
|---|---|
| "BP II is milder than BP I" | BP II has equivalent long-term impairment; depressive burden is greater |
| "A single manic episode = recurrent BP" | One manic episode = BP I diagnosis (no need for recurrence or depression) |
| "Hypomania can have psychotic features" | Never — psychotic features = mania by definition |
| "Antidepressants are first-line for bipolar depression" | Wrong — mood stabilisers (Li, lamotrigine, quetiapine) are first-line; ADs risk manic switch |
| "Lithium is safe in pregnancy" | Lithium is FDA category D; ×7 cardiac abnormalities (Ebstein anomaly) |
| "Valproate is OK for young women" | Absolutely contraindicated unless alternatives fail — PCOS, teratogenicity |
| "Rapid cycling means hours of mood change" | Rapid cycling = ≥4 discrete episodes per year (not within a day) |
| "Flight of ideas = loosening of association" | Flight of ideas preserves logical links (mania); loosening of association doesn't (schizophrenia) |
| "Lithium + NSAID is fine" | NSAIDs reduce renal excretion of lithium → toxicity |
| Parameter | Value |
|---|---|
| Manic episode duration | ≥1 week |
| Hypomanic episode duration | ≥4 days |
| Rapid cycling | ≥4 episodes/year |
| Lithium therapeutic range (maintenance) | 0.6–1.0 mmol/L |
| Lithium therapeutic range (acute depression) | 0.8–1.2 mEq/L |
| Lithium toxicity | > 1.5 mmol/L |
| YMRS mania threshold | ≥20 |
| YMRS hypomania threshold | ≥12 |
| BP I prevalence | 0.3–1.6% |
| Bipolar spectrum prevalence | 3.7% |
| Heritability | 79% |
| MZ concordance | 40–70% |
| First-degree relative risk | 5–10% (≈7× general population) |
| Mean age of onset BP I | ~18 years |
| Suicide attempt rate | 1/3 of patients |
| Suicide mortality | 10–20% |
Past Paper Questions
Question: Bipolar affective disorder (BAD) is a common and serious mood disorder. Which of the following is the diagnostic criterion listed in the DSM-V for bipolar I disorder?
A. Irritability must be present. B. Manic symptoms that have lasted for at least 1 week. C. Past or current depressive episodes should be present. D. Patients notice the mood change.
Correct Answer: B
Rationale: Per DSM-5, a manic episode requires symptoms lasting ≥1 week (or any duration if hospitalised). Irritability can be present but is not mandatory (elevated/expansive mood is sufficient) → A is wrong. A single manic episode satisfies BP I criteria without requiring any depressive episode → C is wrong. The change in functioning needs to be observable by others, not necessarily noticed by the patient (especially since insight is impaired) → D is wrong.
Question stem (EMQ): For each of the following patients presenting with the respective symptom, select the MOST LIKELY diagnosis. Options include: A. Adjustment disorder, B. Bipolar disorder, C. Eating disorder, D. GAD, E. MDD, F. OCD, G. Panic disorder, H. PTSD, I. Substance use disorder, J. Undifferentiated psychological distress.
While Q23 specifically tested "constant worrying even when there is no specific threat" (Answer: D — GAD), this EMQ format shows that bipolar disorder is a standard option in Fourth Summative EMQs and could be the answer for presentations involving episodic elevated/irritable mood with increased energy and goal-directed activity.
High Yield Summary
Bipolar I = ≥1 manic episode (≥1 week, marked impairment/psychosis). Bipolar II = ≥1 hypomania (≥4 days, no marked impairment, NEVER psychosis) + ≥1 depressive episode. Hypomania is commonly missed → BP II misdiagnosed as MDD → antidepressant monotherapy → manic switch. Correct diagnosis requires patient history + collateral informants + screening tools (MDQ, HCL-32).
Acute mania: Lithium, valproate, or atypical antipsychotics (quetiapine, risperidone, aripiprazole). Combination if insufficient. ECT for treatment-resistant/dangerous cases.
Acute bipolar depression: Lithium, lamotrigine, or quetiapine first-line. Avoid antidepressant monotherapy. If AD needed, combine with mood stabiliser and limit dose/duration.
Prophylaxis: Lithium, valproate, or quetiapine for BP I; quetiapine, lithium, or lamotrigine for BP II. Probably lifelong. Augment with psychosocial Tx (psychoeducation, CBT, IPSRT, family therapy).
Lithium is the only mood stabiliser proven to reduce suicide. Monitor level (0.6–1.0 mmol/L). Watch for renal dysfunction, hypothyroidism, tremor, teratogenicity (Ebstein anomaly). Interactions: NSAIDs, ACEi, diuretics → ↑lithium → toxicity. Toxicity is a medical emergency: stop Li, fluids, NaCl diuresis, dialysis.
Valproate is contraindicated in women of childbearing age (teratogenicity, PCOS). Lamotrigine must be titrated slowly to prevent SJS. Quetiapine/olanzapine → metabolic syndrome (olanzapine worst).
Pregnancy: No drug truly safe. Lithium (D) — cardiac malformations. Valproate (D) — NTD/developmental delay. Lamotrigine (C) — relatively safer. Never stop abruptly. Postpartum = highest relapse risk.
Neuroprogression: Frequent relapses → cognitive decline → dementia risk. Stage early, treat early, maintain prophylaxis.
Active Recall - Bipolar Disorder
[1] Lecture slides: GC 163. I am a superman Bipolar disorder.pdf (all pages) [2] Lecture slides: CFB (PSY02) Classification and Diagnosis of Psychiatric Illness.pdf (p36) [3] Lecture slides: CFB (PSY01) An introduction to Psychiatry.pdf (p18, p20) [4] Lecture slides: Seminar 2 - Psychopathology - Dr Simon SY Lui_1_9_2025.pdf (p13) [5] Senior notes: Ryan Ho Psychiatry.pdf (p51, p144, p146, p155, p163–164, p169) [6] Senior notes: Block A - Two cases of polyuria and polydipsia.pdf (p5) — lithium and AQP2/nephrogenic DI [7] Past papers: 2023 Fourth Summative MCQ.pdf (Q22) [8] Past papers: 2020 Fourth Summative Assessment MCQ paper.pdf (Q23–27, EMQ Section VI)
GC161 Alcohol And The Brain From Psychiatric To Neuropsychiatric Perspectives
An integrated clinical framework examining alcohol's effects on the brain across both psychiatric manifestations (such as mood disorders, psychosis, and dependence) and neuropsychiatric consequences (including cognitive impairment, Wernicke-Korsakoff syndrome, and alcohol-related brain damage).
GC164 I Am Depressed Mood Disorders
Mood disorders are a category of mental health conditions—including major depressive disorder, persistent depressive disorder, and bipolar disorder—characterized by significant disturbances in emotional state that impair daily functioning.