Bipolar and Related Disorders

Seminar notes in 14 parts. Aligned to DSM-5-TR and ICD-11. Read alongside Kaplan & Sadock's, the Oxford Handbook of Psychiatry and the Maudsley Prescribing Guidelines. Doses are for orientation only: always check the current Kenya MoH guidelines and the BNF/formulary before prescribing.

Quick map: mood vs affect → normal vs abnormal mood → classification → mania → hypomania → major depressive episode → BP I vs BP II → cyclothymia → primary vs secondary → investigations → acute mania → bipolar depression → maintenance → what happens if untreated.

1. Define mood and affect. How are they different?

• Mood is the pervasive, sustained emotional state a person reports about themselves over days or weeks. Think of it as the climate. Described by the patient: "I have been low for weeks", "I feel on top of the world".
• Affect is the emotional expression the examiner observes in the interview, moment to moment. Think of it as the weather. Seen in facial expression, tone of voice, posture, gesture.
• Both are recorded in the mental state examination (MSE): mood in the patient's own words, affect by the clinician's description.

Describing affect: range (full, restricted, blunted, flat), mobility (labile = rapid shifts), reactivity (does it change with the topic?), congruence (does it fit the thoughts and the mood?), appropriateness.

Why it matters: mood and affect can disagree. A patient may say "I am fine" (mood) with a flat, tearful affect (depression), or be elated in mood with an irritable, labile affect (mania).

Key terms: euthymia = normal mood; elation = pleasurable, increased; euphoria = intense, unwarranted elation; dysphoria = unpleasant mood; anhedonia = loss of pleasure; lability = rapid, unstable shifts; blunted/flat = reduced/absent emotional expression.

2. Normal variations in mood

Feelings are not symptoms. Everyone is happy, sad, excited, irritable and confident at times. Judge a mood against nine questions:

1. Intensity — proportionate and tolerable, or overwhelming?
2. Duration — hours to a few days (normal) versus a week or more (mania), four days or more (hypomania), two weeks or more (depression).
3. Context — does it make sense for the situation (a funeral, a graduation)?
4. Proportionality — is the reaction in proportion to the trigger?
5. Change from usual functioning — is this a clear change from this person's baseline?
6. Clustering with other symptoms — is it alone, or with sleep change, energy change, appetite, concentration, speech, thoughts?
7. Distress — to the patient or those around them.
8. Impairment — work, school, relationships, self-care.
9. Risk — to self (suicide, recklessness) or others.

The clinical rule: a mood becomes a symptom when it is excessive, prolonged, out of context, a change from baseline, clustered with other symptoms, and causes distress, impairment or risk.

3. Classification of bipolar and related disorders

DSM-5-TR (Bipolar and Related Disorders):

• Bipolar I disorder — at least one manic episode.
• Bipolar II disorder — at least one hypomanic episode and at least one major depressive episode; never a manic episode.
• Cyclothymic disorder — chronic fluctuating mood for 2+ years, never meeting full criteria for an episode.
• Substance/medication-induced bipolar and related disorder.
• Bipolar and related disorder due to another medical condition.
• Other specified and unspecified bipolar and related disorder.

ICD-11 (6A60–6A62): 6A60 bipolar type I, 6A61 bipolar type II, 6A62 cyclothymia.

Specifiers: with anxious distress · with mixed features · with rapid cycling (4 or more episodes in 12 months) · with melancholic features · with atypical features · with mood-congruent or mood-incongruent psychotic features · with catatonia · with peripartum onset · with seasonal pattern.

Epidemiology (orientation): lifetime prevalence of bipolar I about 1%, the whole spectrum about 2–4%. Onset typically late teens to early twenties. Bipolar I affects men and women equally; bipolar II and rapid cycling are more common in women. Heritability is high (about 70–80%); a first-degree relative raises risk roughly tenfold.

4. Clinical features of mania

DSM-5-TR criteria:

• A. A distinct period of abnormally and persistently elevated, expansive or irritable mood and abnormally increased goal-directed activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalisation is needed).
• B. During this period, 3 or more of the following (4 if the mood is only irritable), to a significant degree:
  • Grandiosity or inflated self-esteem
  • Decreased need for Sleep (feels rested after 3 hours)
  • More Talkative or pressured speech
  • Flight of ideas or racing thoughts
  • Distractibility
  • Increase in goal-directed Activity or psychomotor agitation
  • Involvement in risky activities (spending, sexual indiscretion, foolish investments, reckless driving)
  • (Mnemonic: GST FDAI, or the classic DIG FAST.)
• C. Marked impairment in functioning, or hospitalisation is needed to prevent harm, or there are psychotic features.
• D. Not due to a substance or another medical condition. A full manic episode that emerges during antidepressant treatment and persists beyond its physiological effect counts as mania.

Mental state examination in mania:

• Appearance: brightly or flamboyantly dressed, may be dishevelled.
• Behaviour: overactive, intrusive, disinhibited, may be hostile.
• Speech: pressured, loud, rapid, difficult to interrupt; clang associations, punning, rhyming.
• Mood and affect: elated, expansive or irritable; labile.
• Thought: flight of ideas; grandiose ideas that may be delusional.
• Perception: mood-congruent hallucinations in severe cases.
• Cognition: distractible; insight poor.

Severe mania: psychotic features (grandiose, persecutory or religious delusions), catatonia, exhaustion and dehydration ("delirious mania").

5. Clinical features of hypomania

• Same symptoms as mania but less severe and shorter:
  • Lasts at least 4 consecutive days.
  • An unequivocal change in functioning that is uncharacteristic of the person and observable by others.
  • Not severe enough to cause marked impairment or need hospitalisation.
  • No psychotic features. (If psychotic or hospitalised, it is mania by definition.)
• Patients often feel better than well: more energetic, creative, confident, sociable, productive. They rarely seek help and may not admit a problem, so collateral history is essential.
• Early warning signs: sleeping less without feeling tired, talking more, more projects, spending, irritability.
• Hypomania can be missed: patients present for the depressions, so always ask: "Have you ever had a period of several days when you felt unusually high or energetic, needed little sleep and were doing much more than usual?"

6. Clinical features of a major depressive episode

• At least 5 of the following 9 symptoms in the same 2-week period, including at least one of the first two:
  1. Depressed mood most of the day (irritable in children and adolescents)
  2. Markedly reduced interest or pleasure (anhedonia)
  3. Significant weight or appetite change
  4. Insomnia or hypersomnia
  5. Psychomotor agitation or retardation (observable)
  6. Fatigue or loss of energy
  7. Worthlessness or excessive guilt
  8. Poor concentration or indecisiveness
  9. Recurrent thoughts of death, suicidal ideation, plan or attempt

(Mnemonic: SIG E CAPS.)

• Causes distress or impairment; not due to a substance or medical condition.
• Features that point toward bipolar rather than unipolar depression: early age of onset (before 25), many episodes, atypical features (hypersomnia, increased appetite, leaden paralysis), psychomotor retardation, psychotic depression, postpartum episodes, family history of bipolar disorder, a history of antidepressant-induced switch or poor response to antidepressants.
• Melancholic features: loss of reactivity, diurnal variation (worse in the morning), early morning waking, marked retardation, guilt.
• Depression is the dominant, most disabling pole in bipolar disorder, with a high suicide risk.

7. Bipolar I versus bipolar II disorder

Take-home: bipolar II is not "mild bipolar". The depressive burden, suicide risk and functional impairment are equal to or greater than bipolar I.

8. Cyclothymic disorder

• A chronic, fluctuating mood disturbance with many periods of hypomanic symptoms that do not meet criteria for a hypomanic episode, and many periods of depressive symptoms that do not meet criteria for a major depressive episode.
• Duration at least 2 years (1 year in children and adolescents); the symptoms are present at least half the time and the person is never symptom-free for more than 2 months.
• Never met criteria for a manic, hypomanic or major depressive episode.
• Causes significant distress or impairment; not due to a substance or medical condition.
• Often seen as a "moody, unpredictable, unreliable" temperament, with unstable relationships and work.
• 15–50% progress to bipolar I or II, so follow up. Substance use is common.
• Management: psychoeducation, regular sleep and routine, avoid substances, psychotherapy (CBT, IPSRT); mood stabiliser if impairing or progressing. Avoid antidepressant monotherapy.

9. Primary versus secondary bipolar: differential diagnoses

Primary bipolar disorder: the mood disorder is the diagnosis (no direct physiological cause); onset usually late teens to 30s; family history.

Secondary (organic) mania, or bipolar disorder due to another cause, needs to be excluded, especially with a late first episode (over 40–50), no family history, acute onset, atypical features, neurological signs or confusion.

Psychiatric differentials:

• Unipolar major depression (no manic or hypomanic episode ever)
• Schizoaffective disorder and schizophrenia (psychosis outlasts mood symptoms)
• ADHD (chronic since childhood, no distinct episodes)
• Borderline personality disorder (reactive, brief affective shifts, chronic instability)
• Anxiety disorders, PTSD, delirium, agitation, agitated depression
• Disruptive mood dysregulation disorder (children)
• Cyclothymia (subthreshold)
• Substance-induced mood disorder

10. Basic investigations in suspected bipolar disorder

Bipolar disorder is a clinical diagnosis. Investigations are there to exclude medical causes, to establish baselines before treatment and to monitor.

Clinical:

• Full history including collateral (family, friends), past episodes, family history, substance use, medication history and suicide and violence risk.
• MSE and physical and neurological examination.
• Rating scales: Young Mania Rating Scale (YMRS), Mood Disorder Questionnaire (MDQ) (screening), PHQ-9 for depression.

Laboratory:

• FBC, U&E/creatinine (eGFR), LFTs, calcium, glucose and HbA1c, lipid profile.
• TSH/thyroid function (hyperthyroidism mimics mania; lithium causes hypothyroidism).
• HIV test, syphilis serology (VDRL/TPHA), B12 and folate.
• Urine drug screen and alcohol level.
• Pregnancy test in all women of childbearing age (before valproate or lithium).

Other:

• ECG (baseline QTc before antipsychotics, lithium).
• Weight, BMI, waist circumference, blood pressure (antipsychotic and mood stabiliser monitoring).
• CT or MRI head if first episode after 40–50, focal neurological signs, head injury, confusion or atypical course.
• EEG if seizures are suspected.

Before starting lithium: U&E/eGFR, TSH, calcium, ECG (if cardiac risk or over 50), pregnancy test, weight. Before valproate: LFTs, FBC and platelets, pregnancy test (and contraception counselling).

11. Principles of acute mania treatment

1. Safety first. Assess risk to self, others and from reckless behaviour. Consider admission, including involuntary admission under the Kenyan Mental Health Act (as amended) when there is a risk and no insight. Check capacity.
2. Reduce stimulation: quiet, calm environment; limit visitors; firm, consistent, non-confrontational approach.
3. Stop antidepressants, stimulants and other triggers; treat any medical cause; fluids, nutrition and sleep (mania causes exhaustion and dehydration).
4. Drug treatment:
   • First-line: an antipsychotic (olanzapine, risperidone, quetiapine, aripiprazole; haloperidol is also effective) or a mood stabiliser (lithium or valproate). Severe mania often needs antipsychotic + mood stabiliser, because lithium and valproate take 1–2 weeks to work.
   • Agitation and insomnia: short-term benzodiazepine (lorazepam or diazepam).
   • Emergency rapid tranquillisation: haloperidol IM (with an anticholinergic) or lorazepam; avoid IM olanzapine together with a parenteral benzodiazepine (respiratory and cardiac depression).
5. ECT for severe, life-threatening, treatment-resistant mania, catatonia, or in pregnancy.
6. Monitor side effects (extrapyramidal, metabolic, QTc, lithium levels).
7. Psychoeducation and early planning for maintenance as the episode settles.

12. Principles of bipolar depression treatment

• Bipolar depression is not treated like unipolar depression. Do not use an antidepressant alone (risk of switching to mania or hypomania, rapid cycling and mood destabilisation).
• Optimise the existing mood stabiliser first (check adherence and levels).
• Evidence-based options:
  • Quetiapine (about 300 mg at night).
  • Lurasidone or cariprazine (where available).
  • Olanzapine–fluoxetine combination.
  • Lamotrigine: modest in acute depression but strong for prevention of depression.
  • Lithium.
• If an antidepressant is added (an SSRI or bupropion, not a tricyclic), it should be with an antimanic agent (lithium, valproate or an antipsychotic) and with close monitoring for switching. Stop it soon after remission.
• ECT for severe, psychotic or suicidal depression or when drugs have failed.
• Psychological treatment: psychoeducation, CBT, interpersonal and social rhythm therapy (IPSRT), family-focused therapy.
• Suicide risk assessment at every visit. Remove means; engage family.

13. Maintenance treatment and relapse prevention

Aims: prevent relapse of both poles, prevent suicide, restore functioning and quality of life.

Duration: continue for at least 2 years after an episode; long-term or lifelong after two or more episodes, a severe episode, or high suicide risk.

Drug options:

• Lithium is the gold standard: reduces mania, depression and suicide.
  • Target level 0.6–0.8 mmol/L (higher for those who relapse), 12 hours after the last dose; check 5–7 days after starting or changing dose.
  • Monitor: lithium level every 3 months in year 1 then every 6 months; U&E/eGFR, TSH and calcium every 6 months; weight.
  • Side effects: tremor, thirst and polyuria (nephrogenic diabetes insipidus), weight gain, hypothyroidism, hypercalcaemia (hyperparathyroidism), GI upset, chronic kidney disease. Ebstein's anomaly is a small teratogenic risk.
  • Toxicity (narrow therapeutic index): coarse tremor, vomiting, diarrhoea, ataxia, dysarthria, confusion, seizures. Raised by dehydration, NSAIDs, ACE inhibitors/ARBs and thiazides.
  • Stop slowly (over at least 4 weeks): abrupt withdrawal causes rebound mania.
• Valproate: effective for mania and prophylaxis. Avoid in women of childbearing potential (major malformations and neurodevelopmental harm). Monitor LFTs, FBC; levels 50–125 mg/L.
• Lamotrigine: best for preventing depression. Titrate slowly (risk of Stevens–Johnson syndrome); valproate roughly doubles its level (halve the dose).
• Atypical antipsychotics: quetiapine, olanzapine, aripiprazole; long-acting injectables (risperidone, aripiprazole, paliperidone) help adherence. Monitor weight, glucose, lipids, prolactin and QTc.
• Carbamazepine is an alternative (many drug interactions, including with antiretrovirals and the pill).

Relapse prevention:

• Adherence: the commonest cause of relapse; explore beliefs, side effects, insight; involve family.
• Regular sleep and daily routine (social rhythm), avoid shift work and sleep deprivation.
• Avoid alcohol, khat, cannabis and other substances.
• Mood charting and an early warning sign plan (a written relapse signature and who to call).
• Treat comorbid anxiety and substance use; manage physical health (metabolic syndrome).
• Pregnancy planning: review medicines before conception; specialist input.
• Support groups, family psychoeducation, community and primary care follow-up.

14. Consequences of untreated bipolar disorder

• Suicide: among the highest of any psychiatric disorder. Roughly a third to a half of patients attempt suicide at least once, and estimates of lifetime death by suicide range widely (about 4–19%). The risk is many times that of the general population and highest in depressive and mixed states and soon after discharge.
• Relapse and recurrence, more frequent and severe over time (the "kindling" idea), with rapid cycling and treatment resistance.
• Psychosis, catatonia, exhaustion and death in severe mania.
• Cognitive decline and impaired executive function.
• Comorbidity: substance use disorders, anxiety, personality problems.
• Physical health: cardiovascular disease, diabetes and metabolic syndrome; 10–20 years reduced life expectancy.
• Social and economic: loss of job, school dropout, debt and financial ruin from manic spending, relationship and family breakdown, divorce, homelessness.
• Legal and safety: violence, reckless driving, criminal charges, risky sexual behaviour (including HIV and unplanned pregnancy).
• Repeated hospitalisation, stigma, and heavy caregiver burden.
• Treatment delay is common (often 5–10 years), and misdiagnosis as unipolar depression (and treatment with antidepressants alone) can make the illness worse.

Pharmacology at a glance

Tap a drug name for its full card (how it works, adverse effects, cautions, dose), then use Back to this note to return to this spot. Condition guide: bipolar disorder drugs.

Never treat bipolar depression with an antidepressant alone: the switch risk is real.

Revision checklist

• Mood vs affect: climate vs weather; subjective vs objective
• Nine questions that separate normal mood from illness
• DSM-5-TR classification and the main specifiers
• Mania criteria (1 week, 3 of 7 symptoms, or 4 if irritable) vs hypomania (4 days, no psychosis, no hospitalisation)
• Major depressive episode: 5 of 9 over 2 weeks
• BP I (mania) vs BP II (hypomania + depression, never mania)
• Cyclothymia: 2 years, never a full episode
• Secondary causes: thyroid, steroids, khat, HIV, syphilis, stroke, efavirenz, isoniazid
• Baseline tests, especially before lithium and valproate
• Acute mania: antipsychotic ± mood stabiliser, benzodiazepine, safety, ECT
• Bipolar depression: quetiapine / lurasidone / lamotrigine; no antidepressant alone
• Lithium monitoring, toxicity and interactions; valproate in women of childbearing age
• Untreated: suicide, relapse, physical illness, social ruin

Practice questions

1. A 24-year-old man has not slept for 4 nights, speaks rapidly, believes he is chosen to lead the country and has spent his salary on a car. He has had two depressive episodes before. The most likely diagnosis is: A. Bipolar II disorder · B. Bipolar I disorder, current manic episode · C. Cyclothymic disorder · D. Schizophrenia · E. Hyperthyroidism Answer: B. Mania (impairment, grandiosity, reduced sleep, risk) with prior depression.

2. A woman with bipolar I is planning a pregnancy. Which drug should be avoided? A. Lithium · B. Quetiapine · C. Sodium valproate · D. Olanzapine · E. Lamotrigine Answer: C. Valproate has the highest teratogenic and neurodevelopmental risk.

3. A patient on lithium presents with coarse tremor, vomiting, diarrhoea and ataxia after starting ibuprofen for back pain. The most likely cause is: A. Lithium withdrawal · B. Lithium toxicity from NSAID interaction · C. Serotonin syndrome · D. Neuroleptic malignant syndrome · E. Thyrotoxicosis Answer: B. NSAIDs reduce lithium clearance.

4. A patient with bipolar disorder is severely depressed. Which approach is inappropriate? A. Optimise the mood stabiliser · B. Quetiapine · C. Lamotrigine for prevention · D. Fluoxetine as the only treatment · E. ECT if suicidal Answer: D. Antidepressant monotherapy risks a switch to mania and rapid cycling.

5. Which finding best separates hypomania from mania? A. Elevated mood · B. Decreased need for sleep · C. Increased energy · D. No marked impairment, no psychosis and no need for hospitalisation · E. Pressured speech Answer: D.