Bipolar Disorders

Bipolar Disorders are a group of mental disorders characterized by prolonged periods of excessive elevation in mood with/without depressive episodes. It can be considered as a group of disorders that bridge between the depressive and psychotic disorders.
- Bipolar I Disorder
- Bipolar II Disorder
- Cyclothymic Disorder
- Substance/Medication-Induced Bipolar and Related Disorder
- Bipolar and Related Disorder Due to Another Medical Condition
- Other Specified Bipolar and Related Disorders

Epidemiology

The lifetime prevalence for bipolar I disorder is approximately 0.6%, with equal gender distribution.
Bipolar I disorder is more common in
- high income (1.4%) than low income (0.7%) countries
- Separated, divorced, or widowed individuals have higher rates of bipolar I disorder.
mania more common in men, more depressive episodes in women
onset from childhood 5-6 yo to 50yo, average age of 30yo

Onset

For many people, their first episode was triggered by a major life stressor.
Subsequent episodes have also been linked with a stressful life event.
no specific personality traits are associated with bipolar
most often starts with depression (70%) and is a recurring disorder
most will suffer both depressive & manic episodes (although some only have manic episodes)
manic episodes often have rapid onset (hours/days) but evolves over few weeks
- an untreated manic episode lasts about 3 months (so continue Rx for at least 3/12)
- 90% who have a manic episode are expected to have another
- Need to Dx & Tx early with antipsychotics +/- BZ initially then with mood stabilisers (Li, carbamazepine, valproate) as prognosis worsens with repeated episodes
- After about 5 episodes, the interepisode interval stabilises to about 6-9 months
15% of pts with bipolar have > 4 episodes per year 🡺 ‘rapid cyclers’

Prognosis

Bipolar has poorer prognosis cf MDD
lithium prophylaxis improves the course & prognosis but only 50-60% respond well
Between 6 to 7% of individuals will die by suicide, and suicide is a significant cause of bipolar disorder mortality
poor prognostic factors:
- bad premorbid occupational status
- alcohol & substance abuse
- psychotic features
- depressive features
- interepisode depressive features
- male gender
good prognostic factors:
- short duration of manic episodes
- advanced age at onset
- fewer suicidal thoughts
- lack of comorbid ψ or medical problems
7% do NOT have a recurrence of Sx
45% have more than 1 episode
40% have chronic disorder (most people have about 10 manic episodes in their life)

COURSE & PROGNOSIS:

mood disorders have chronic relapsing courses
once they have had 1^st episode (precipitated by stressors) they are more at risk of 2^nd episode

With DDx, always think:

primary psychiatric condition (SZ, MDD, bipolar, GAD, etc)
secondary psychiatric condition (eg depression secondary to dementia)
secondary to general medical condition (GMC)
secondary to substance-use
organic cause
depressive phase:
- same DDx as for depressive disorder above
manic phase:
- bipolar I
- bipolar II
- cyclothymic disorder
- mood disorder from general medical condition or substance-induced
- consider borderline / narcissistic / histrionic / anti-social personality disorders
- schizophrenia
  - merriment, elation & infectiousness of mood favour mania
  - manic mood, rapid or pressured speech & hyperactivity favour mania
  - onset of mania is often rapid & perceived as a marked sudden change from previous behaviour
catatonic phase:
- can be depressive phase of bipolar I or catatonic schizophrenia
medical conditions – a large variety of medical/neurological conditions & substances can produce similar Sx. In particular, antidepressants can also precipitate mania in some patients! (look at temporal relationship).

Bipolar I Disorder

disorder in which at least one manic episode has occurred
if manic symptoms lead to hospitalization, or if there are psychotic symptoms, the diagnosis is bipolar I
commonly accompanied by at least 1 MDE but not required for diagnosis
time spent in mood episodes: 53% asymptomatic, 32% depressed, 9% cycling/mixed, 6% hypo/ manic

Bipolar II Disorder

disorder in which there is at least 1 MDE, 1 hypomanic episode, and no manic episodes
while hypomania is less severe than mania, bipolar II is not a “milder” form of bipolar I
time spent in mood episodes: 46% asymptomatic, 50% depressed, 1% cycling/mixed, 2% hypo/ manic
bipolar II is often missed due to the severity and chronicity of depressive episodes and low rates o spontaneous reporting and recognition of hypomanic episodes

MANIC EPISODE

abnormally and persistently elevated/expansive/ irritable mood +
abnormally and persistently increased goal-directed activity or energy
lasting ≥1 wk and present most of the day, nearly every day
≥3 of the following symptoms:
- D – distractibility (attention too easily drawn to irrelevant external stimuli)
- I – indiscretion & ↑ participation in pleasurable activities with painful consequences (unrestrained shopping sprees, sexual indiscretions, or foolish business investments)
- G – grandiosity & ↑ self-esteem
- F – flight of ideas or subjective experience that thoughts are racing
- A – activity ↑ goal-directed (socially, work, school, sexually) or ψ-motor agitation
- S – sleep need perceived as ↓
- T – talkativeness & pressure to keep talking

marked impairment in social or occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features

Hypomanic Episode

abnormally and persistently elevated/expansive/ irritable mood +
abnormally and persistently increased goal-directed activity or energy
lasting ≥4 days and present most of the day, nearly every day
≥3 of the following symptoms:
- D – distractibility (attention too easily drawn to irrelevant external stimuli)
- I – indiscretion & ↑ participation in pleasurable activities with painful consequences (unrestrained shopping sprees, sexual indiscretions, or foolish business investments)
- G – grandiosity & ↑ self-esteem
- F – flight of ideas or subjective experience that thoughts are racing
- A – activity ↑ goal-directed (socially, work, school, sexually) or ψ-motor agitation
- S – sleep need perceived as ↓
- T – talkativeness & pressure to keep talking
uncharacteristic change in functioning that is observable by others
but not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization
absence of psychotic features (if these are present the episode is, by definition, manic)

Mixed Features

an episode specifier in mania or depression that indicates the presence of both depressive and manic symptoms concurrently, classified by the disorder and primary mood episode component (i.e. BD, current episode manic, with mixed features)
clinical importance due to increased suicide risk and appropriate treatment
if found in patient diagnosed with major depression, high index of suspicion for BD
while meeting the full criteria for a MDE, the patient has on most days ≥3 of criteria B for a manic episode
while meeting the full criteria for a manic/hypomanic episode, the patient has on most days ≥3 of criteria A for a depressive episode (the following criterion A cannot count: psychomotor agitation, insomnia, difficulties concentrating, or weight changes)

DEPRESSIVE EPISODES:

depressed mood & anhedonia (inability to experience pleasure) are key Sx of depression
pt’s may say that they feel blue, hopeless, down in the dumps or worthless
2/3 of depressed pts contemplate suicide & 10-15% commit suicide (roughly same for SZ)
Once they’ve had a past attempt at suicide, they now have the strongest risk factor for future attempts
Anxiety is a common Sx of depression & affects 90% of depressed patients
Alcohol abuse & somatic Sx (constipation/headaches) often complicate the Tx of depression
Diurnal variation is common (50%) where ↑↑↑ severity in morning & better at night

CHILDREN:
- Sx can include: school phobia, excessive clinging to parents, poor academic performance, substance abuse, anti-social behaviour, sexual promiscuity, truancy & itinerancy
ELDERLY:
- More common than in general population (which is 15-25% women) so prevalence in elderly ranges from 25-50%
- Often correlated with low SES, loss of spouse, concurrent physical illness & social isolation
- Often underdiagnosed & undertreated (perhaps because of ageism accepting it as ‘normal’ for them or also because they present with more somatic complaints)

Mental state Exam	Depression	Mania
Appearance & Behaviour:	generalised psychomotor retardation is the most common Sx (although ψ-motor agitation is seen, esp. in elderly 🡪 agitation is seen as hang wringing & hair pulling) stooped posture, no spontaneous movements downcast or averted gaze, avoiding eye-contact (can appear similar to the psychomotor retardation seen in catatonic schizophrenia) – thus DSM-IV-TR has mood disorders ‘with catatonic features’	Excited, talkative, sometimes amusing & frequently hyperactive Can be grossly psychotic & disorganised & require physical restraints +/- IM sedatives
Speech:	↓ rate, abnormal rhythm, ↓ volume (R/R/V) Respond with single-word answers + delayed response to questions (sometimes minutes!!)	↑↑ rate, rhythm, ↑ volume (R/R/V) Often cannot be interrupted when speaking (very intrusive & rude) Speech is often disturbed & at ↑↑ mania, they can get loosening of associations (derailment), flight of ideas, word salad & neologisms Can be totally incoherent & like that of a person with schizophrenia
Affect, Mood & Feelings:	Depressed mood is the main Sx (50% will deny depressive feelings & don’t particularly appear depressed) Family members/ employers often bring in or send them in because of social withdrawal & generalised decreased activity	Euphoric Can be irritable (esp. if plans not going their way) Low frustration tolerance 🡪 anger & hostility Emotionally labile 🡪 can switch from laughter to irritability to depression in mins/hours
Thought:	negative view of world & of themselves non-delusional thoughts about loss, guilt, suicide & death 10% have thought disorder of stream/production 🡪 thought blocking & profound poverty of content	↑ self esteem & self-aggrandisement (grandiose) Easily distracted & unrestrained + accelerated flow of ideas Delusions occur in 75% of manic pts 🡪 great wealth, special abilities or power
Perception:	if they have delusions/hallucinations 🡺 MDD + psychotic features if grossly regressed – mute, not bathing, soiling 🡺 MDD + catatonic features delusions & hallucinations that are consistent with depressed mood are ‘mood congruent’ mood-congruent delusions include: guilt, sinfulness, worthlessness, poverty, failure, persecution & terminal somatic illnesses (eg cancer & ‘rotting brain’) mood-incongruent delusions involve grandiosity – exaggerated power, knowledge & worth (eg belief that they are being persecuted for being the Messiah	Can get bizarre & mood-incongruent delusions & hallucinations in mania
Judgement & Insight	judgement best assessed by reviewing pt’s actions in recent past & behaviour during interview depressed patient’s insight is often excessive 🡪 overemphasis of Sx, their disorder & life problems can be difficult convincing them that improvement is possible	Impaired judgement is the hallmark of mania pts They may break laws about credit cards, sexual activities & finances (can result in financial ruin!) Very little insight into their disorder (can abuse Dr for trying to stabilise their mood & remove euphoria)
Rapport/ Reliability/ Risk	can be difficult establishing rapport reliability has to be questioned 🡪 can be overly negative about previous response to antidepressants trialled risk & safety – to self & to others (broadly – includes children who may be neglected, elderly, etc), suicidality, homicidality, etc)	Notoriously unreliable in information supplied Lying & deceit are common 🡪 collateral Hx!
Cognition & Sensorium	orientation – most are orientated to time, person & place (T/P/P) but sometimes they don’t have the energy or will to answer 50-75% will have cognitive impairment (depressive pseudo-dementia) – pts complain of ↓ concentration & memory	Minor cognitive deficit (due to diffuse cortical dysfunction) Gross orientation & memory are intact (but can be so euphoric that they answer incorrectly)

Treatment

1. Acute management

A. Mania / Hypomania

First-line monotherapy
- Lithium (target 0.6–1.0 mmol/L)
- Sodium valproate (50–100 mg/L)
- SGAs: quetiapine, olanzapine, risperidone, paliperidone, aripiprazole; ziprasidone or cariprazine only with specialist advice (not PBS for BD)
- Short-term benzodiazepine (e.g. diazepam, lorazepam) for agitation
If severe or psychotic → add an SGA to lithium/valproate from outset.
Second-line: carbamazepine; lithium + valproate; SGA + valproate.
Third-line / refractory / pregnancy: ECT (safe, rapid) ± clozapine in ultra-resistant cases. nps.org.au ranzcp.org

B. Bipolar Depression

First-line	Adjunct / second-line
• Quetiapine 300 mg nocte (IR or XR)	• Lurasidone 20–120 mg with lithium/valproate
• Lithium monotherapy	• Lamotrigine up-titrated to 200 mg (maintenance + BP II)
• Valproate (esp. mixed polarity)	• Electro-convulsive therapy (psychotic, suicidal, pregnancy)

SSRI/SNRI or bupropion only with a mood stabiliser and short courses; stop if switch or rapid cycling occurs. ranzcp.org a ustralianprescriber.tg.org.au

2. Maintenance

Lithium remains gold standard:
- Trough 0.6–0.8 mmol/L (up to 1.0 mmol/L in high-relapse patients).
- Reduces suicide risk ~60 %. australianprescriber.tg.org.au
Alternatives / adjuncts
- Valproate (good for manic polarity, rapid cyclers).
- Quetiapine or olanzapine (weight/metabolic surveillance).
- Lamotrigine (depressive polarity, BP II).
- Aripiprazole or lurasidone for predominantly manic relapse.
Psychosocial: structured psycho-education, CBT or IPSRT, relapse-signature monitoring, family work. cci.health.wa.gov.au

2.1 Mixed states & rapid-cycling

Combine lithium or valproate + an SGA; consider lamotrigine for depressive swings, cautious use of ECT if medication-refractory. Close follow-up every 2–4 weeks until stable. ranzcp.org

2.2 Special situations

Scenario	Key points
Pregnancy	Avoid valproate & carbamazepine (teratogenic). Lithium possible (first-trimester risk), with maternal–fetal cardiology input. Quetiapine considered safest SGA. ECT is non-teratogenic.
Breastfeeding	Lithium generally avoided; quetiapine or olanzapine acceptable; valproate low milk transfer.
Medical comorbidity	Check interactions: ACE-I/ARBs, NSAIDs & thiazides ↑ lithium; CYP3A4 inducers ↓ SGAs / carbamazepine; monitor metabolic syndrome on SGAs.

2.3 Safety & monitoring schedule

Parameter	Baseline	First year	Long-term
Lithium level (12 h post-dose)	✔	q 1–3 mo until stable	q 6 mo (earlier if sick/drug change)
eGFR, U&E	✔	q 3–6 mo	q 6–12 mo
TFTs	✔	6 mo	yearly
Calcium	✔	—	yearly
Weight/BMI, lipids, FBG	✔	3 mo	yearly
FBC/LFTs (valproate/carbamazepine)	✔	3 mo	yearly

Advise patients to maintain hydration; withhold lithium during acute dehydrating illness or when starting interacting medicines. nps.org.au australianprescriber.tg.org.au

Domain	Key actions
Pharmacological prophylaxis	Maintain mood stabiliser ± SGA at the lowest effective dose: • Lithium 0.6-0.8 mmol/L (up to 1.0 mmol/L if highly relapsing) • Sodium valproate 50-100 mg/L (avoid in women of child-bearing potential) • Lamotrigine (depressive polarity, BP II) • Quetiapine / Olanzapine / Aripiprazole (manic polarity)
Psychosocial & lifestyle	Structured psycho-education, CBT or IPSRT, family work, relapse-signature monitoring, sleep hygiene, exercise, weight-gain prevention (metformin ± GLP-1RA if needed).
Comorbidity surveillance	Annual CVD risk, metabolic panel, bone density (if >45 y or on SGAs), smoking/alcohol/drug screen, cancer screening per RACGP Red Book.
Re-assessment cadence	• Stable patient: 3-monthly psychiatric & physical review. • Earlier review after life events, dosage change, pregnancy, or interacting medicines.

4. Chronic lithium toxicity

Aspect	Details
Definitions	Chronic toxicity = gradual accumulation in a long-term user (most common). Acute-on-chronic = overdose on top of steady state.
Precipitating factors	Dehydration, intercurrent illness, acute kidney injury, new interacting drug (NSAID, ACE-I, ARB, thiazide, COX-2 inhibitor), elderly ↓GFR.
Typical serum levels	Often 1.5-2.5 mmol/L (may be toxic at “therapeutic” levels in the elderly or those with CNS disease).
Clinical features	Fine → coarse tremor, new gait ataxia, dysarthria, nystagmus, myoclonus, confusion, lethargy progressing to delirium, seizures; GI symptoms are minimal in pure chronic toxicity.
Initial work-up	• Serum lithium & U&E/eGFR immediately, then q 6 h • FBC, serum osmolality, Ca²⁺, glucose • ECG (T-wave flattening, sinus node dysfunction).
Immediate management	1. Cease lithium. 2. Isotonic saline bolus 10-20 mL/kg, then IV maintenance to target urine output 2-3 mL/kg/h. 3. Stop interacting drugs; correct electrolytes. 4. Admit under medical / toxicology team.
Dialysis criteria (EXTRIP/AusTox)	• Serum Li > 2.5 mmol/L with neurological features or • Serum Li > 4.0 mmol/L regardless of symptoms or • Deteriorating renal function or failure to clear despite hydration. Use intermittent haemodialysis; repeat if rebound >1.0 mmol/L after 6 h.
Supportive care	Airway protection for reduced GCS, benzodiazepines for seizures, avoid phenytoin.
Post-toxicity plan	Review indication. If restarting lithium, aim ≤0.6 mmol/L, once-daily dosing, close fortnightly levels for 3 mo. Provide written sick-day protocol and hydration advice.

5. Chronic complications & mitigation

Complication	Incidence	Prevention / Action
CKD (eGFR decline ~0.7 mL/min/yr)	15–20 % over ≥10 y	Keep trough ≤0.8 mmol/L, once-daily dosing switch if sustained eGFR < 45 mL/min/1.73 m².
Nephrogenic diabetes insipidus	up to 40 %	Night-time dose amiloride 5–10 mg daily if polyuria/polydipsia teach fluid replacement.
Hypothyroidism / goitre	10–20 % (women > men)	Annual TSH replace with thyroxine without stopping lithium.
Hyperparathyroidism / hypercalcaemia	5–10 %	Annual Ca²⁺ / PTH consider endocrine referral.
Weight gain & metabolic syndrome	10–20 %	Diet/exercise plan, screen annually metformin if BMI ≥ 30 kg/m².

6. Relapse‐prevention

Predictors of Relapse

Category	Key factors
Biological	≥4 episodes lifetime mixed polarity rapid cycling residual subsyndromal symptoms comorbid anxiety or SUD female sex (depression relapse) postpartum period.
Treatment-related	Non-adherence abrupt discontinuation (esp. lithium or antipsychotic) drug interactions (lithium + NSAID/thiazide).
Psychosocial	Irregular sleep/work patterns high-EE family environment chronic stress limited social support.

Pillar	What to do
Medication adherence	“No missed doses.” Keep tablets near toothbrush or set phone alarms. Review scripts before they run out.
Psychological therapies	Ongoing supportive psychotherapy, CBT, interpersonal & social rhythm therapy (IPSRT), or family-focused therapy (FFT) – whichever helped most in past episodes.
Daily routine & circadian rhythms	Fixed wake-up / bedtime, regular meals, daylight exposure, scheduled exercise. Use the Social Rhythm Metric card from IPSRT.
Sleep hygiene	>7 h nightly; no screens or caffeine after 8 PM; wind-down ritual (reading, breathing exercises).
Stress-management toolkit	Mindfulness app, 4-7-8 breathing, 10-minute walk, brief CBT worksheet. Post “stress triggers” list on fridge; practise one coping skill daily.
Substance use	Zero recreational drugs; limit alcohol to ≤2 standard drinks on any day; avoid binge drinking.
Early-warning sign log	Keep a mood/sleep journal or app. Add your cues (e.g. poetry bursts, overspending). If two cues appear → follow action plan.
Emergency / crisis plan	Wallet & fridge copies detailing: who to call (GP, psych, 000, Lifeline 13 11 14), what meds to tweak, who holds credit card, who checks in daily.
Social & functional supports	• Vocational rehab or flexible work arrangements • Assess who manages bills if mood shifts • Educate family: brief hand-out on signs & what to say.
Lifestyle anchors	Mediterranean-style diet, 150 min exercise/week, weight and BP check each GP visit.
Sick-day rule (lithium users)	Pause lithium and ring doctor if dehydrated (vomiting/diarrhoea) or starting NSAIDs/ACE-I/thiazides.

2.3 Evidence-based Interventions

Modality	Evidence highlights
Pharmacological prophylaxis	Lithium, valproate, lamotrigine (depressive polarity), quetiapine/olanzapine/aripiprazole. Combination therapy > monotherapy in rapid cycling.
Psychoeducation	RCTs show 40–50 % ↓ relapse, ↑ medication adherence. Delivered 6–8 group sessions or digital modules (e.g. WA-CCI).
CBT (maintenance-focused)	Meta-analysis: modest delay to depressive relapse, best in <12 previous episodes.
IPSRT	Frank et al. RCT: lengthens time to manic & depressive recurrence over 2 y by ~46 %. Works via social rhythm stabilisation
Family-Focused Therapy	Miklowitz trials: ↓ relapse, ↑ med adherence, esp. youth BD.
FFT-HF / multifamily groups	Useful in high-EE households; improves expressed emotion and reduces rehospitalisations.
Vocational rehab / IPS	Supports return to work; stabilises routine; limited RCTs but endorsed in CPG.
Lifestyle/Sleep interventions	Structured exercise, stimulus-control sleep programme; non-randomised data show ↓ hypomanic prodromes.

Monitoring & Early Intervention Framework

Phase	Time-frame	Key tasks
Acute → Continuation (0–6 mo)	Weekly–fortnightly visits; aim residual-symptom free ≥8 wk; document early-warning list.
Maintenance (≥6 mo)	GP + psychiatrist q 3 mo; lithium/TFT/eGFR q 6 mo; psychosocial booster every 6–12 mo; update crisis plan yearly.
Prodrome detected	Increase clinical contact to weekly; pre-agreed dose adjustment (e.g. +100 mg quetiapine or lithium to 0.8–1.0 mmol/L); diary review; involve carer.

Special Populations

Group	Tailored prevention strategy
Pregnancy	If lithium used, aim ≤0.6 mmol/L monthly levels after 20 wks screen sleep CBT-IPSRT helpful CT safe if severe.
Adolescents	Emphasise Family-Focused Therapy school liaison substance use counselling monotherapy preferred.
Rapid-cyclers	Combination lithium + valproate or valproate + SGA consider lamotrigine; review thyroid & substance use.

Key Take-aways

Lithium = gold-standard prophylaxis; suicidality reduction is a bonus.
Psychoeducation + IPSRT/FFT are the best-evidenced psychosocial tools; deliver early.
Sleep / routine disruption is the most modifiable environmental trigger—teach “social rhythm” regulation.
Never stop meds abruptly; plan tapers ≥4 wk, monitor fortnightly.
Integrate GP-psychiatry shared care: 6-monthly labs, annual metabolic screen, crisis plan review.

Quick mnemonic

“MAP-SLEEP”

P lan for crisis

M eds adhere

A larm signs list

P sychological therapy

S leep 7–9 h

L ifestyle routine

E ducate family

E tOH/drugs nil