Behavioral Health

Bipolar I and II disorders: diagnosis and pharmacotherapy

Clinical Overview and When to Suspect Bipolar Disorder

— Depression with early onset (<25), postpartum onset, psychotic features, atypical features (hypersomnia, hyperphagia), or family history of bipolar disorder

— Antidepressant-induced mania/hypomania, rapid mood switching, or treatment-resistant depression (≥3 failed antidepressants)

— Highly recurrent depression (≥5 episodes), brief depressive episodes, mixed features (irritability + agitation + racing thoughts during depression)

— Substance use disorders, gambling, hypersexuality, or unexplained legal/financial crises layered on mood symptoms

Bipolar spectrum = recurrent mood episodes with pathologic elevation (mania/hypomania) alternating with depression; lifetime prevalence ~1% (BP-I), ~1.1% (BP-II), with peak onset late teens to mid-20s.

Bipolar I: at least one manic episode (≥7 days OR any duration requiring hospitalization), psychotic features allowed; depressive episodes typical but not required for diagnosis.

Bipolar II: at least one hypomanic episode (≥4 days, no marked functional impairment, no psychosis, no hospitalization) PLUS at least one major depressive episode. A single manic episode reclassifies as BP-I — permanently.

Cyclothymia: ≥2 years (1 yr in youth) of subthreshold hypomanic and depressive symptoms.

When to suspect in primary care or ED:

Step 3 management: In any adult presenting for "depression," always screen for prior mania/hypomania before starting an antidepressant — the MDQ (Mood Disorder Questionnaire) or direct interview about decreased need for sleep, grandiosity, and goal-directed hyperactivity prevents the classic Step 3 error of unmasking mania with an SSRI.

Comorbidities are the rule, not exception: anxiety disorders (~60%), substance use (~40%), ADHD, migraine, obesity, metabolic syndrome, and elevated cardiovascular mortality (~1.5–2× general population).

Board pearl: Suicide risk is 15–20× general population; lifetime suicide attempt rate ~25–50%. This drives the urgency of accurate diagnosis and lithium consideration (only mood stabilizer with proven anti-suicide effect).

Presentation Patterns and Key History

— Distractibility

— Impulsivity / Indiscretion (spending sprees, hypersexuality, reckless driving)

— Grandiosity / inflated self-esteem

— Flight of ideas / racing thoughts

— Activity increased / psychomotor agitation

— Sleep — decreased need (feels rested after 2–3 hr), distinct from insomnia

— Talkativeness / pressured speech

— Collateral from family (patients lack insight during mania)

— Substance use (stimulants, cocaine, steroids, antidepressant-induced mania)

— Sleep history — reduced need for sleep is the most sensitive early prodrome

— Postpartum timing (mania within 2–4 weeks postpartum is highly specific for bipolar)

— Medication adherence and prior response (lithium responders tend to be familial)

Manic episode (DSM-5, BP-I) — distinct period of abnormally elevated/expansive or irritable mood AND increased energy/activity, ≥1 week (or any duration if hospitalized), with ≥3 of DIGFAST (4 if mood is only irritable):

Mania causes marked impairment, hospitalization, or psychosis; hypomania (BP-II) has same symptoms but ≥4 days, observable change, no marked impairment, no psychosis, no hospitalization.

Mixed features specifier: ≥3 symptoms of the opposite pole during the index episode — high suicide risk, worse prognosis, lithium less effective; consider valproate or atypicals.

Rapid cycling: ≥4 mood episodes/year; more common in women, BP-II, hypothyroidism, antidepressant exposure.

Bipolar depression dominates lifetime symptom burden (BP-I ~3× more depressive than manic time; BP-II even higher) — often atypical: hypersomnia, leaden paralysis, hyperphagia, weight gain.

Key history to extract:

Key distinction: Decreased need for sleep (mania) vs insomnia with fatigue (depression/anxiety) — the manic patient sleeps 2 hours and feels energized; this single question has high yield.

Board pearl: Antidepressant- or stimulant-induced mania that persists beyond the physiologic effect of the agent counts toward a bipolar diagnosis (DSM-5 update).

Physical Exam Findings (and Mental Status Assessment)

— Appearance: flamboyant, brightly colored or disheveled clothing, excessive makeup, poor hygiene if severe

— Behavior: psychomotor agitation, intrusive, hyperactive, difficulty remaining seated

— Speech: pressured, loud, rapid, hard to interrupt; clang associations (rhyming), punning

— Mood/affect: euphoric, expansive, or irritable; labile; can flip to tearful within minutes

— Thought process: flight of ideas, tangentiality, looseness; circumstantial

— Thought content: grandiose delusions (special powers, missions, identity), religious or erotomanic delusions; persecutory in severe mania

— Perception: auditory hallucinations possible (mood-congruent)

— Cognition: distractible, often alert and oriented but inattentive

— Insight/judgment: severely impaired

— Tachycardia, hypertension, hyperthermia → consider stimulant/sympathomimetic intoxication, thyrotoxicosis, NMS, serotonin syndrome

— Tremor, hyperreflexia, clonus → serotonin syndrome or lithium toxicity

— Goiter, lid lag, proptosis → hyperthyroidism mimicking mania

— Dehydration markers (manic patients forget to eat/drink)

— Injuries from impulsivity (lacerations, MVC sequelae, signs of sexual assault)

Bipolar disorder is a clinical diagnosis — no pathognomonic exam finding — but the mental status exam (MSE) is the core "physical exam" and must be documented thoroughly on Step 3 cases.

Manic MSE:

Depressive MSE (bipolar depression): psychomotor retardation OR agitation (mixed features), poor eye contact, low/monotone speech, hopelessness, passive or active SI, mood-congruent delusions in severe episodes.

Vital signs and general exam: assess for medical mimics and complications:

Step 3 management: Always perform a safety assessment — risk to self (suicide, accidental death from impulsivity), risk to others, and ability to care for self (food, shelter, medical needs). This drives the involuntary hold decision and is testable.

Board pearl: Hyperthyroidism can perfectly mimic mania (insomnia, weight loss, agitation, pressured speech) — TSH is mandatory on initial workup.

Diagnostic Workup — Initial Labs and Studies

— CBC, CMP (Na, K, BUN, Cr, glucose, LFTs, Ca) — baseline for lithium, valproate, carbamazepine

— TSH (mandatory — hyperthyroidism mimics mania; hypothyroidism worsens depression and is induced by lithium)

— Urine drug screen (cocaine, amphetamines, PCP, cannabis, synthetic cannabinoids)

— Urine pregnancy test in any female of reproductive age — alters every medication choice

— Lipid panel, HbA1c — baseline before atypical antipsychotics (metabolic syndrome risk)

— HIV, RPR if risk factors or first-episode psychosis (neurosyphilis, HIV encephalopathy can present with mania)

— B12, folate if cognitive symptoms or elderly

— Vitamin D, magnesium (low Mg can precipitate lithium toxicity)

— First episode of mania after age 40 (secondary mania red flag)

— Focal neuro findings, headaches, recent head trauma

— Atypical features, treatment-resistant course, or new cognitive decline

Bipolar diagnosis is clinical; labs serve to (1) exclude medical mimics, (2) baseline before pharmacotherapy, and (3) detect substance contributors.

Initial workup for new manic/hypomanic presentation:

ECG before lithium, ziprasidone, or any QT-prolonging agent — assess QTc, bradyarrhythmia, sinus node dysfunction (lithium contraindicated in sick sinus).

Neuroimaging (MRI brain) — not routine but obtain if:

EEG — if seizure suspicion, atypical episodic features, or post-ictal confusion.

Other targeted testing: ANA if lupus suspected, ceruloplasmin in young patients with neuropsychiatric symptoms (Wilson disease), HIV/syphilis as above.

Key distinction: A "first manic episode after age 40" should trigger workup for secondary mania — stroke (right hemisphere), MS, frontotemporal dementia, brain tumor, HIV, neurosyphilis, steroid- or levodopa-induced.

Board pearl: Always document a baseline weight, BMI, waist circumference, and fasting glucose/lipids before starting an atypical antipsychotic — Step 3 loves the metabolic monitoring vignette at 12 weeks and annually thereafter.

Diagnostic Workup — Advanced and Differential Confirmation

— MRI brain with contrast — right-sided frontal/subcortical strokes, MS plaques, tumors (frontal), neurodegenerative changes

— LP if encephalitis, autoimmune encephalitis (anti-NMDA receptor — young women with psychosis, dyskinesias, autonomic instability), neurosyphilis (VDRL/FTA-ABS), or paraneoplastic syndromes

— Autoimmune panel: anti-NMDA, anti-LGI1, anti-CASPR2, anti-thyroid antibodies (Hashimoto encephalopathy)

— Ceruloplasmin, 24-hr urinary copper, slit lamp — Wilson disease in <40

— Heavy metals if exposure history

— Cortisol, dexamethasone suppression if Cushing suspected

— YMRS (Young Mania Rating Scale) — mania severity

— MADRS or HAM-D — depression

— MDQ — screening tool, NOT diagnostic

— CGI-S/I — Clinical Global Impression

When the picture is atypical, treatment-resistant, or onset is late, expand workup beyond initial screen.

Secondary mania workup (especially first episode >40 or focal findings):

Pharmacogenomics (CYP2D6, CYP2C19, HLA-B1502): not routinely required but HLA-B1502 testing is mandatory before carbamazepine in patients of Asian ancestry to prevent Stevens-Johnson syndrome / TEN. HLA-B*5701 not relevant here.

Rating scales for severity and tracking (Step 3 may reference):

Sleep study — if sleep disturbance disproportionate to mood or comorbid OSA suspected (OSA worsens mood cycling).

Neuropsychological testing — useful in cognitive complaints, distinguishing pseudodementia of depression from neurocognitive disorders, or assessing executive dysfunction.

Step 3 management: Document the specific DSM-5 criteria met, duration, functional impairment, and absence of substance/medical cause — this is the structure expected in psych documentation and in CCS notes.

Board pearl: A patient on levodopa, corticosteroids, interferon, or isotretinoin who develops mood symptoms — always consider iatrogenic mood disorder before diagnosing bipolar; symptoms typically resolve with agent discontinuation.

Acute Episode Triage and Treatment Selection Logic

— Inpatient admission for: danger to self/others, psychosis, severe agitation, inability to care for self, mixed features with high SI, pregnancy with destabilization, or failed outpatient management

— Outpatient intensive (PHP/IOP) for moderate hypomania or bipolar depression without imminent risk

— Routine outpatient for stable maintenance or mild hypomania with insight and support

— Lithium — classic, best for euphoric/classic mania, anti-suicide benefit

— Valproate (divalproex) — better for mixed features, rapid cycling, irritable mania

— Atypical antipsychotics: risperidone, olanzapine, quetiapine, aripiprazole, asenapine, cariprazine, ziprasidone

— Severe mania: combine lithium or valproate plus an atypical antipsychotic — superior response to monotherapy

— Quetiapine monotherapy

— Lurasidone monotherapy or with lithium/valproate (favorable metabolic profile)

— Cariprazine

— Olanzapine + fluoxetine (Symbyax) — effective but metabolic burden

— Lamotrigine — useful for maintenance and depression prevention; titrate slowly (rash/SJS)

First decision: acute episode type — mania, hypomania, bipolar depression, or mixed — drives drug choice.

Second decision: severity and setting:

Third decision: current medications — discontinue antidepressants during acute mania (they perpetuate the episode); taper rather than abrupt stop if on long-term to avoid discontinuation syndrome unless mania is severe.

Acute mania first-line (monotherapy or combination):

Acute bipolar depression first-line:

Avoid antidepressant monotherapy in bipolar depression — risk of switch to mania, especially in BP-I; if used, only with a mood stabilizer and preferentially bupropion or SSRI (avoid TCAs and SNRIs which have higher switch rates).

CCS pearl: In an acute manic CCS case, order: admit to psychiatry, place on involuntary hold if criteria met, suicide/safety precautions, labs (CMP, TSH, UDS, hCG, lithium/valproate level), ECG, then start lithium OR valproate ± atypical, and discontinue any antidepressant.

Board pearl: Lithium is the only agent with demonstrated anti-suicide effect independent of mood stabilization — preferred in patients with prior attempts when not contraindicated.

Pharmacotherapy — First-Line Agents in Depth

— Dose: start 300 mg BID-TID; target trough 0.8–1.2 mEq/L (acute), 0.6–1.0 (maintenance); check level 5 days after dose change, 12 hours post-dose

— Monitoring: TSH, BUN/Cr, Ca every 6–12 months; level every 3–6 months once stable

— Adverse effects: tremor (fine), polyuria/nephrogenic DI, hypothyroidism, hyperparathyroidism, weight gain, acne, Ebstein anomaly in pregnancy (1st trimester), cognitive dulling

— Toxicity (>1.5): coarse tremor, ataxia, confusion, seizures, arrhythmia; NSAIDs, thiazides, ACE-I/ARBs, dehydration raise levels

— Dose: load 20–30 mg/kg/day; target level 50–125 µg/mL

— Monitoring: LFTs, CBC, ammonia if AMS; level periodically

— AEs: weight gain, alopecia, tremor, thrombocytopenia, hepatotoxicity, pancreatitis, hyperammonemia, PCOS; teratogen (neural tube defects, IQ↓) — avoid in women of childbearing potential

— Titrate slowly: 25 mg/day × 2 weeks, 50 × 2 weeks, then up to 200 mg

— SJS/TEN risk — stop at any rash; risk ↑ with valproate co-administration (halve dose) and rapid titration

— Target 4–12 µg/mL; autoinduces its own metabolism (dose ↑ at 2–4 weeks)

— AEs: agranulocytosis, aplastic anemia, SIADH/hyponatremia, SJS (test HLA-B*1502 in Asians), CYP3A4 inducer (lowers OCP, warfarin, many drugs)

— Quetiapine: sedation, weight gain, metabolic — covers mania, depression, maintenance

— Olanzapine: highly effective, worst metabolic profile

— Risperidone: hyperprolactinemia, EPS at higher doses

— Aripiprazole: partial D2 agonist, akathisia, weight-neutral

— Lurasidone, cariprazine: favorable for bipolar depression, lower metabolic burden

— Ziprasidone: QT prolongation — get ECG; take with ≥500 kcal meal

Lithium:

Valproate (divalproex):

Lamotrigine (depression/maintenance, not acute mania):

Carbamazepine:

Atypical antipsychotics — Step 3 favorites:

Step 3 management: Before starting any atypical: weight, BMI, waist, BP, fasting glucose, lipids, AIMS exam for movement disorders; reassess at 12 weeks and annually.

Board pearl: Lithium + NSAID, thiazide, ACE-inhibitor, or dehydration = toxicity; teach patients to hold lithium during acute GI illness and to hydrate aggressively.

Adjunctive and Refractory Treatment Strategies

— Aripiprazole monthly, risperidone biweekly, paliperidone monthly — approved for bipolar I maintenance

— Strong Step 3 favorite for patients with repeated relapses due to nonadherence

— Pregnancy with severe mood episode (safest option)

— Catatonia

— Severe suicidality or refusal to eat/drink

— Treatment-resistant mania, depression, or mixed states

— Patients who previously responded to ECT

— Bilateral > unilateral for severe mania; main AE is transient anterograde and retrograde amnesia

— CBT, IPSRT (Interpersonal and Social Rhythm Therapy) — sleep/circadian stabilization

— Family-focused therapy — reduces relapse

— Psychoeducation — adherence, prodrome recognition

Benzodiazepines (lorazepam, clonazepam) — short-term adjunct for acute agitation, insomnia, and to bridge mood stabilizer onset; avoid long-term use (dependence, disinhibition).

Antipsychotic combinations: for severe or psychotic mania, combine lithium/valproate + atypical (e.g., lithium + risperidone) — outperforms monotherapy.

Long-acting injectables (LAIs) for adherence-limited patients:

Electroconvulsive therapy (ECT) — highly effective; first-line for:

Repetitive TMS — option for bipolar depression in non-acute setting, but evidence weaker than for unipolar depression; avoid in mania (theoretical switch risk).

Clozapine — for refractory mania after failure of multiple agents; requires ANC monitoring (weekly × 6 months, then biweekly, then monthly) due to agranulocytosis risk; also causes myocarditis, seizures, sialorrhea, metabolic syndrome.

Ketamine/esketamine — emerging role in acute suicidality in bipolar depression, but mania switch risk limits routine use; use under specialist guidance with mood stabilizer cover.

Psychotherapy (always pair with pharmacotherapy):

Lifestyle: regular sleep-wake schedule (single most important nonpharmacologic intervention), exercise, avoid alcohol/stimulants, light exposure regulation, shift-work avoidance.

CCS pearl: In a refractory mania CCS case, after lithium + atypical fails, add valproate or switch atypical, and if still failing, order ECT consult — do not just keep stacking medications.

Board pearl: ECT is the most effective treatment for severe bipolar depression and acute mania in pregnancy.

Special Populations — Elderly and Organ Impairment

— May be late-onset (workup for secondary mania: stroke, dementia, tumor, medication) or aging long-standing disease

— Higher sensitivity to all psychotropics — start low, go slow

— Increased risk of falls, delirium, cognitive impairment, drug interactions

— Lithium: narrower therapeutic window; target lower (0.4–0.8 mEq/L), check more often; renal clearance declines with age and dehydration

— Valproate: increased risk of tremor, sedation, hyperammonemia, thrombocytopenia

— Atypicals: boxed warning — increased mortality in elderly with dementia-related psychosis; use cautiously, lowest dose, document risk discussion

— Avoid benzodiazepines (falls, delirium — Beers criteria)

— Lithium is renally cleared — contraindicated or requires significant dose reduction in CKD (eGFR <30); monitor levels more frequently and lower target

— Chronic lithium use itself can cause chronic interstitial nephritis — annual creatinine, urinalysis, eGFR; consider transition if Cr trending up

— Valproate, lamotrigine, carbamazepine, and most atypicals are hepatically metabolized — preferred in renal disease (with adjustments)

— Avoid or carefully dose valproate, carbamazepine (hepatotoxic)

— Lamotrigine: reduce dose in moderate-severe hepatic impairment

— Lithium is safe hepatically (not metabolized by liver)

— Atypicals: most require dose reduction; quetiapine and olanzapine particularly

— Lithium: avoid in sick sinus syndrome; baseline ECG

— Ziprasidone, iloperidone: QT prolongation — avoid with other QT-prolonging agents

— Clozapine: myocarditis (especially first 1–2 months) — monitor troponin, CRP, ECG if symptomatic

Elderly (>65) bipolar:

Renal impairment:

Hepatic impairment:

Cardiac disease:

Step 3 management: In an elderly patient newly manic, order MRI brain, TSH, B12, RPR, and review medication list (steroids, levodopa, dopamine agonists) before assuming primary bipolar disorder.

Board pearl: Lithium dose reduction needed when starting ACE-I, ARB, thiazide, or NSAID — anticipate level rise of 25–40%; recheck within 5–7 days.

Special Populations — Pregnancy, Postpartum, Pediatrics

— Untreated bipolar carries high relapse risk (>70% if mood stabilizer stopped) and adverse outcomes (preterm birth, low birth weight, postpartum psychosis)

— Valproate: contraindicated — neural tube defects (1–2%), facial dysmorphism, IQ reduction (~9 points); also avoid in any woman of childbearing potential without reliable contraception

— Carbamazepine: neural tube defects, craniofacial abnormalities — avoid

— Lithium: Ebstein anomaly (tricuspid valve) — risk ~1/1000–2000 (lower than historically thought); if benefits outweigh, continue with fetal echo at 16–20 weeks, frequent level monitoring (volume expansion lowers level; postpartum diuresis raises it — reduce dose at delivery)

— Lamotrigine: preferred mood stabilizer in pregnancy — lowest teratogenic risk among anticonvulsants

— Atypicals (quetiapine, olanzapine, aripiprazole): generally considered relatively safe; monitor for neonatal EPS, withdrawal

— ECT: safe in all trimesters; preferred for severe episodes

— Bipolar women have highest risk of postpartum psychosis (~25–50% if BP-I) — psychiatric emergency, risk of infanticide/suicide

— Restart or optimize mood stabilizer immediately postpartum; lithium prophylaxis is highly effective

— Breastfeeding: lithium relatively contraindicated (infant levels significant); valproate and carbamazepine compatible; lamotrigine moderate transfer — monitor infant

— Diagnosis requires same DSM-5 criteria; discrete episodes differentiate from ADHD and DMDD (chronic irritability without episodicity)

— FDA-approved agents: risperidone, aripiprazole, quetiapine, asenapine, olanzapine for mania ≥10–13 yrs; lurasidone, olanzapine-fluoxetine for depression

— Lithium approved ≥7 years for mania

— Monitor growth, metabolic parameters, prolactin closely

Pregnancy:

Postpartum:

Pediatrics (children/adolescents):

Step 3 management: In a pregnant patient with acute mania, involve OB and psychiatry, choose ECT or atypical antipsychotic, avoid valproate/carbamazepine absolutely, and discuss informed consent on lithium with documented shared decision-making.

Board pearl: Postpartum psychosis in a BP-I patient = psychiatric emergency, hospitalize, separate from infant initially, treat aggressively (lithium + antipsychotic ± ECT).

Complications and Adverse Outcomes

— Bipolar patients have 1.5–2× cardiovascular mortality, partly disease-related (stress, sleep, lifestyle), partly iatrogenic (atypicals, valproate, lithium)

— Metabolic syndrome prevalence ~35–50%

— Monitor weight, BP, lipids, glucose, HbA1c at baseline, 12 weeks, annually

— Hypothyroidism (~20–30%) — annual TSH; treat with levothyroxine, do not stop lithium

— Nephrogenic diabetes insipidus — polyuria, polydipsia; amiloride can mitigate

— Chronic kidney disease — slowly progressive in long-term users; annual Cr, eGFR

— Hyperparathyroidism, hypercalcemia — annual calcium

— Metabolic syndrome, weight gain, diabetes, hyperlipidemia (olanzapine and clozapine worst)

— Hyperprolactinemia (risperidone, paliperidone) — galactorrhea, amenorrhea, sexual dysfunction, osteoporosis

— EPS, akathisia, tardive dyskinesia — annual AIMS; treat TD with VMAT2 inhibitors (valbenazine, deutetrabenazine)

— Neuroleptic malignant syndrome — hyperthermia, rigidity, autonomic instability, ↑CK; stop agent, supportive care, dantrolene/bromocriptine

— Valproate: hepatotoxicity, pancreatitis, hyperammonemia, thrombocytopenia, PCOS

— Carbamazepine: agranulocytosis, SIADH, SJS

— Lamotrigine: SJS/TEN, HLH (rare)

Suicide: lifetime attempt rate 25–50%; completed suicide 10–15× general population; highest in mixed episodes and depressive phases, early in illness, with comorbid substance use.

Substance use disorders: ~40–60% lifetime — alcohol, cannabis, cocaine, stimulants — worsen course, adherence, and outcomes; integrated dual-diagnosis treatment improves both.

Cardiovascular and metabolic:

Endocrine/renal complications from lithium:

From antipsychotics:

From anticonvulsants:

Cognitive dysfunction: persistent inter-episode cognitive impairment in many patients; medication contribution variable.

Occupational/social: relationship loss, financial ruin from impulsive spending, legal consequences from manic behavior.

Key distinction: Serotonin syndrome (hyperreflexia, clonus, GI symptoms, fast onset) vs NMS (rigidity, hyporeflexia, days-long onset) vs lithium toxicity (coarse tremor, ataxia, confusion).

Board pearl: Tardive dyskinesia is most likely with first-generation antipsychotics but occurs with atypicals too — annual AIMS; first-line treatment is VMAT2 inhibitor (valbenazine).

When to Escalate — Inpatient, Consult, and ICU Triage

— Active suicidal or homicidal ideation with plan/intent

— Mania with psychosis or severe agitation

— Inability to care for self (not eating, not sleeping, dehydration)

— Mixed features with high impulsivity

— Postpartum psychosis

— Severe medication side effects requiring close monitoring (NMS, lithium toxicity, agranulocytosis)

— Failed outpatient stabilization, nonadherence with deterioration

— Imminent danger to self

— Imminent danger to others

— Grave disability — inability to provide for basic needs due to mental illness

— Typical initial hold 72 hours; extension requires judicial review

— Severe lithium toxicity (level >2.5, or symptomatic at lower levels): ICU, IV fluids, hemodialysis if level >4, level >2.5 with renal failure, or severe symptoms

— NMS, serotonin syndrome — ICU, supportive care, agent withdrawal

— Severe valproate toxicity — hyperammonemia → hepatic encephalopathy; L-carnitine

— Agranulocytosis (clozapine, carbamazepine) — stop drug, isolate, G-CSF if febrile

— SJS/TEN — burn/ICU level care, stop offending agent permanently

— Psychiatry for any diagnostic uncertainty, treatment failure, or pregnancy

— Nephrology for lithium-induced CKD trajectory

— Endocrinology for refractory hypothyroidism or hyperparathyroidism

— OB/MFM for pregnant patients

— Cardiology for QT prolongation, lithium + sick sinus

— Toxicology/poison control for overdose

Inpatient psychiatric admission indications:

Involuntary hold criteria (state-specific but general framework):

Medical/ICU admission for:

Consultations:

CCS pearl: In lithium toxicity CCS: stop lithium, IV normal saline aggressively, check level q2–4h, ECG, consult nephrology for HD if level >4 or symptomatic with renal dysfunction. Do not give activated charcoal — lithium does not bind.

Step 3 management: Document the least restrictive setting principle — outpatient if safe, partial hospitalization if intermediate, inpatient only when criteria met. This appears in ethics/safety vignettes.

Board pearl: Lithium toxicity is treated with hemodialysis, not gastric lavage or charcoal — lithium is a small unbound ion freely dialyzable.

Key Differentials — Other Mood/Psychiatric Disorders

— No history of mania/hypomania; key Step 3 trap is mistaking BP-II depression for MDD and starting SSRI monotherapy → switch

— Atypical features, early onset, family history, treatment resistance should trigger bipolar screening

— Mood lability within hours to days, reactive to interpersonal stress; not the discrete sustained episodes of bipolar

— Identity disturbance, fear of abandonment, chronic emptiness, self-harm

— Frequently comorbid with bipolar — treat both

Major depressive disorder (unipolar):

Cyclothymic disorder: ≥2 yrs of fluctuating subthreshold hypomanic and depressive symptoms; never meets full episode criteria.

Disruptive mood dysregulation disorder (DMDD): children 6–18, chronic severe irritability + temper outbursts, not episodic — distinguishes from pediatric bipolar.

Schizoaffective disorder: psychotic symptoms present for ≥2 weeks in the absence of a mood episode, with mood episodes occurring for the majority of the illness duration. In bipolar with psychotic features, psychosis only occurs during mood episodes.

Schizophrenia: prominent and persistent psychosis with negative symptoms; mood symptoms minimal relative to psychotic burden.

Borderline personality disorder (BPD):

ADHD: chronic distractibility, hyperactivity, impulsivity from childhood — not episodic; no euphoria, no decreased need for sleep, no grandiosity. Comorbid with bipolar in ~10–20%.

Generalized anxiety disorder, PTSD: hyperarousal and insomnia can mimic hypomania, but mood is dysphoric/anxious, not elevated, and not goal-directed.

Substance-induced mood disorder: stimulants, cocaine, hallucinogens, steroids, antidepressants — symptoms resolve with discontinuation.

Key distinction: Bipolar mood episodes = discrete, sustained, days-weeks duration with neurovegetative changes; BPD lability = rapid, interpersonally reactive, hours-long. Test favorite.

Step 3 management: When BPD and bipolar are both present, treat the bipolar pharmacologically and the BPD with DBT (dialectical behavior therapy); avoid benzos and stimulants given misuse risk.

Board pearl: Schizoaffective vs bipolar with psychotic features hinges on whether psychosis occurs outside mood episodes — if yes, schizoaffective; if only during, bipolar with psychotic features.

Key Differentials — Medical and Substance Causes

— Hyperthyroidism: insomnia, agitation, pressured speech, weight loss, tremor — TSH

— Cushing syndrome: depression more common than mania; can cause psychosis

— Hypothyroidism: depression, cognitive slowing — TSH

— Pheochromocytoma: episodic anxiety, hypertension, palpitations

— Stroke (right hemisphere, especially frontal/orbitofrontal): secondary mania

— Multiple sclerosis: mood disorders, including mania, in 10–20%

— Frontotemporal dementia: disinhibition, impulsivity, social inappropriateness — often misdiagnosed as late-onset bipolar

— Brain tumors (frontal, temporal): personality and mood changes

— Traumatic brain injury, especially frontal: disinhibition and mood lability

— Seizure disorders (especially temporal lobe): peri-ictal mood changes, post-ictal psychosis

— Huntington disease: psychiatric prodrome

— Neurosyphilis: grandiose delusions, mania, personality change — RPR/FTA-ABS

— HIV encephalopathy, anti-NMDA receptor encephalitis (young women, psychosis, dyskinesias, autonomic instability), Lyme neuroborreliosis

— SLE: psychosis, mood disorders — ANA, anti-dsDNA

— Hashimoto encephalopathy: anti-TPO antibodies, responds to steroids

— Wilson disease (<40, neuropsychiatric), B12 deficiency, hepatic encephalopathy, uremia

— Stimulants (cocaine, amphetamine, methamphetamine), PCP, hallucinogens — acute psychosis/mania

— Steroids: dose-dependent mania, depression, psychosis (>40 mg prednisone)

— Levodopa, dopamine agonists: mania, hypersexuality, gambling

— Interferon: depression with suicide risk

— Isotretinoin: depression (controversial), warn patients

— Antidepressants: switch to mania, especially TCAs and SNRIs

Endocrine:

Neurologic:

Infectious:

Autoimmune:

Metabolic:

Substance/medication-induced:

Key distinction: Secondary mania is suggested by first episode >40, focal neurologic findings, abnormal imaging, atypical features, or temporal relationship to a medication.

Board pearl: Always check TSH, B12, RPR, HIV, urine drug screen, and review medications before settling on a primary bipolar diagnosis — this is the Step 3 "don't miss the medical cause" pattern.

Maintenance Therapy and Long-Term Planning

— Lithium — gold standard, anti-suicide effect, best for classic euphoric bipolar

— Lamotrigine — strong for preventing depressive relapse, weaker for mania prevention

— Quetiapine — covers both poles, but metabolic burden

— Valproate — effective for mixed/rapid cycling; avoid in reproductive-age women

— Aripiprazole, olanzapine, risperidone LAI for adherence concerns

— Do not abruptly stop lithium — rapid discontinuation doubles relapse risk and may reduce future lithium responsiveness; taper over weeks-months

— Communicate with patient that "feeling better" is not a reason to stop

— Pill organizers, family involvement, LAIs, simplified regimens

— Psychoeducation on prodrome recognition (sleep change is the earliest sign)

— Smartphone mood tracking apps

— Sleep regularity — consistent bedtime/wake time, 7–9 hours; sleep loss is the most common mania trigger

— Exercise, Mediterranean diet, limit caffeine

— Abstinence from alcohol, cannabis, stimulants

— Light therapy mornings; avoid bright light evenings

Maintenance pharmacotherapy is lifelong for BP-I after one severe manic episode or two episodes of any kind; strong indication after 1 episode with high risk features (psychosis, suicide attempt, family history).

First-line maintenance:

Combination therapy common: lithium + lamotrigine (bipolar with predominant depression), lithium + atypical (BP-I with breakthrough mania).

Discontinuation guidance:

Antidepressant use in maintenance: controversial; if used, only with mood stabilizer, avoid in rapid cycling, prefer bupropion or SSRI, monitor for switch.

Adherence support:

Lifestyle prescription (write it as you would diabetes management):

Reproductive planning: discuss contraception with all women of reproductive age on valproate/carbamazepine; preconception counseling for those planning pregnancy — switch to lamotrigine, lithium, or atypical before conception when possible.

Step 3 management: Document a relapse prevention plan with patient and family: list of prodromal symptoms, action steps (call clinic, increase contact, medication adjustment), emergency contacts, and crisis line.

Board pearl: Sleep deprivation is both a trigger and a prodrome of mania — maintaining regular sleep is among the highest-yield nonpharmacologic interventions.

Follow-Up, Monitoring, and Rehabilitation

— Acute episode: weekly visits until stable, then biweekly, then monthly

— Stable maintenance: every 3 months

— Lithium level: every 3–6 months once stable; sooner with dose change, new interacting medication, GI illness, dehydration

— Valproate level: as clinically indicated

— TSH, BUN/Cr, Ca: every 6–12 months on lithium

— LFTs, CBC, platelets: every 6–12 months on valproate or carbamazepine

— Carbamazepine level + CBC: more often early (autoinduction, agranulocytosis risk)

— Metabolic panel (weight, BP, fasting glucose, lipids): baseline, 12 weeks, then annually on atypicals

— AIMS exam: every 6–12 months on antipsychotics for tardive dyskinesia

— Annual ECG if on QT-prolonging agents or lithium with cardiac risk

— CBT for bipolar — cognitive restructuring, relapse prevention

— IPSRT — stabilizes social rhythms (sleep, meals, social interactions)

— Family-focused therapy — reduces relapse by improving communication

— Group psychoeducation — improves adherence and outcomes

— Supported employment programs

— Vocational rehabilitation after disruptive episodes

— Social skills training

— NAMI peer support groups

— Treat alcohol/substance use disorders (naltrexone, acamprosate; integrated care)

— Treat anxiety with mood stabilizer cover; avoid SSRI monotherapy

— Cardiovascular risk reduction (smoking cessation, statins, BP control)

— Sleep apnea evaluation if BMI or symptoms suggest

— Recognize prodromes (sleep change, irritability, increased activity)

— Medication adherence and side effect reporting

— Avoid OTC interactions (NSAIDs with lithium, St. John's wort with multiple agents)

— When to call (sleep <4 hr × 2 nights, racing thoughts, SI, rash)

Monitoring cadence:

Symptom tracking: mood charts, sleep logs, YMRS/MADRS at follow-up to objectively trend.

Psychotherapy integration — should be ongoing alongside pharmacotherapy:

Rehabilitation and reintegration:

Comorbidity management:

Patient and family education topics:

Step 3 management: Schedule follow-up within 7 days of psychiatric discharge — this is a CMS quality measure and a Step 3 transition-of-care favorite.

Board pearl: Post-discharge 7-day and 30-day follow-up reduces readmission and suicide risk — explicitly arrange before discharge.

Ethical, Legal, and Patient Safety Considerations

— Acutely manic patients often lack decision-making capacity for psychiatric treatment due to impaired insight, grandiosity, and judgment

— Capacity is decision-specific — patient may have capacity for some decisions but not others; reassess as mood stabilizes

— Document the four elements: understanding, appreciation, reasoning, communicating a choice

— Justified when patient meets state criteria: imminent danger to self, danger to others, or grave disability due to mental illness

— Least restrictive setting principle — choose outpatient over inpatient, voluntary over involuntary when safe

— Patients retain rights even when committed: refusal of specific medications (in most states unless emergency or court-ordered), access to legal counsel, periodic review

— HIPAA permits sharing information with family for treatment purposes even without explicit consent when patient lacks capacity or in emergency

— Encourage release of information when patient is stable to allow family support during future episodes

— Use Columbia Suicide Severity Rating Scale (C-SSRS) or similar

— Means restriction counseling (firearm safety, medication quantities)

— Written safety plan with warning signs, coping strategies, support contacts, crisis line (988)

— Most states require reporting of conditions that impair driving; varies by jurisdiction

— Pilots, commercial drivers, surgeons — work with occupational health, FAA, etc., regarding medication and disease disclosure

— Shared decision-making about teratogenic mood stabilizers — document risks of treatment AND risks of untreated illness

— Both have risks; involve patient, partner, OB, and psychiatry

— 7-day post-discharge follow-up reduces relapse and suicide

— Reconcile medications, especially confirm continuation of mood stabilizer

— Communicate active SI status to outpatient team

Capacity and consent:

Involuntary commitment:

Confidentiality and family involvement:

Tarasoff duty to warn/protect: if patient makes credible threat against identifiable third party, clinician has duty to take reasonable steps — warn potential victim, notify police, hospitalize patient. Varies by state.

Suicide risk and safety planning:

Mandatory reporting: child abuse, elder abuse — applies during manic episodes when caregiving compromised.

Driving and occupational risk:

Pregnancy and informed consent:

Transitions of care (Step 3 emphasis):

Step 3 management: A manic patient refusing treatment with impaired capacity and grave disability — pursue involuntary hold, document capacity evaluation, attempt least restrictive intervention first, and consult psychiatry. Do not simply discharge against medical advice.

Board pearl: The combination of active suicidal ideation + impaired capacity + refusal of treatment justifies involuntary hospitalization — this is the highest-yield ethics vignette in bipolar.

High-Yield Associations and Rapid-Fire Facts

Lithium and the kidney: nephrogenic DI (treat with amiloride), chronic interstitial nephritis, hyperparathyroidism, hypothyroidism — "the lithium quartet."

Lithium toxicity treatment: hemodialysis for level >4, level >2.5 with renal failure or severe symptoms, or refractory to fluids; charcoal does not work.

Lithium interactions raising levels: NSAIDs, thiazides, ACE-I, ARBs, dehydration.

Valproate teratogenicity: neural tube defects, IQ ↓ ~9 points, facial dysmorphism — avoid in women of childbearing potential.

Lamotrigine + valproate: valproate doubles lamotrigine levels — halve lamotrigine dose and slow titration to prevent SJS.

Carbamazepine + Asian ancestry: test HLA-B*1502 before starting (SJS/TEN risk).

Clozapine: agranulocytosis (REMS program), myocarditis (first 2 months), seizures, sialorrhea, metabolic syndrome; used in refractory mania.

Ziprasidone: take with ≥500 kcal meal for absorption; QT prolongation.

Aripiprazole: partial D2 agonist; akathisia common; weight-neutral; impulse control issues (gambling).

Olanzapine: most weight gain and metabolic burden; combined with fluoxetine = Symbyax for bipolar depression.

Quetiapine: only atypical with strong evidence in all three phases — mania, depression, maintenance.

Lurasidone, cariprazine: bipolar depression favorites with low metabolic burden.

Ebstein anomaly: lithium first-trimester exposure — fetal echo at 16–20 wks.

Postpartum psychosis: most strongly associated with bipolar I; emergency.

Antidepressant switch to mania: highest with TCAs and SNRIs; lowest with bupropion and SSRIs.

Rapid cycling: ≥4 episodes/yr; associated with antidepressant exposure, hypothyroidism, female sex.

Mixed features: lithium less effective; valproate and atypicals preferred; high suicide risk.

ECT: first-line in pregnancy with severe episode, catatonia, refractory mania/depression, severe suicidality, prior responder.

Lithium anti-suicide effect: unique among mood stabilizers — favored in patients with prior attempts.

Sleep deprivation: most common precipitant of mania.

First episode >40: think secondary mania — neuroimaging.

DMDD: chronic irritability in children — NOT bipolar.

Schizoaffective: psychosis ≥2 weeks without mood episode.

Step 3 management: Two highest-yield post-discharge orders — follow-up within 7 days and safety plan with means restriction.

Board pearl: Whenever you start an antidepressant for "depression," screen for prior mania first (MDQ or interview) — missing this is the classic Step 3 mistake.

Board Question Stem Patterns

— Diagnosis: acute manic episode, bipolar I

— Best next step: admit, safety precautions, stop any antidepressant, start lithium or valproate + atypical antipsychotic

— Diagnosis: antidepressant-induced switch → bipolar diagnosis emerging

— Best next step: stop sertraline, start mood stabilizer, reconsider as bipolar

— Diagnosis: lithium toxicity

— Best next step: stop lithium and thiazide, IV normal saline, check level, hemodialysis if level >4 or severe

— Answer: HLA-B*1502 testing to prevent SJS/TEN

— Answer: ECT is safest and most effective option

— Answer: lamotrigine (or lithium, quetiapine)

— Answer: MRI brain, comprehensive workup for secondary mania

— Diagnosis: postpartum psychosis — hospitalize, treat aggressively

— Action: switch to lower-metabolic-risk atypical (lurasidone, aripiprazole, cariprazine) and address metabolic syndrome

— Diagnosis: DMDD, not bipolar

— Diagnosis: nephrogenic DI; treatment: amiloride, consider lithium continuation if needed

"30-year-old man brought in by family for 5 days of decreased sleep, grandiose plans, pressured speech, and reckless spending..."

"28-year-old woman with recurrent depression started on sertraline now presents with 5 days of euphoria, racing thoughts, decreased need for sleep..."

"Patient on chronic lithium presents with tremor, confusion, ataxia after starting hydrochlorothiazide..."

"22-year-old Asian woman with bipolar disorder — what to do before starting carbamazepine?"

"Pregnant woman with bipolar I, severe manic episode, refusing medications..."

"BP-II patient with predominant depressive episodes — best maintenance?"

"45-year-old man first manic episode, no prior psychiatric history — next step?"

"Postpartum day 7, BP-I patient with delusions, agitation, confusion..."

"Patient on olanzapine with weight gain 15 lb in 3 months, new HbA1c 7.2%..."

"Adolescent with chronic daily irritability and outbursts, no discrete episodes..."

"Lithium-treated patient with polyuria, polydipsia, normal glucose..."

Step 3 management: Stems emphasizing what to order next, what to monitor, when to follow up, and when to escalate — pick the answer that follows guidelines (7-day post-discharge follow-up, baseline metabolic labs, level monitoring at 5 days post-dose change).

Board pearl: When a stem mentions decreased need for sleep + grandiosity + goal-directed activity + impulsivity ≥ 1 week, it is mania until proven otherwise — start mood stabilizer, not antidepressant.

One-Line Recap

Bipolar disorder is a recurrent episodic mood disorder defined by mania (BP-I) or hypomania plus depression (BP-II), treated acutely with lithium, valproate, or atypical antipsychotics (and quetiapine/lurasidone/lamotrigine for depression), maintained lifelong with mood stabilizers (lithium preferred for anti-suicide effect), monitored with disease-specific labs, and managed with attention to teratogenicity, metabolic side effects, sleep regulation, and post-discharge transitions of care.

Diagnosis pearls: mania ≥7 days (or hospitalization) with DIGFAST symptoms; hypomania ≥4 days without marked impairment; always screen for prior mania before starting antidepressants; first episode >40 → workup secondary mania.

Pharmacotherapy pearls: lithium for classic mania and suicide prevention (target 0.8–1.2 acute, 0.6–1.0 maintenance, monitor TSH/Cr/Ca); valproate for mixed/rapid cycling but never in pregnancy-capable women without contraception; lamotrigine for bipolar depression maintenance (slow titration, watch SJS); quetiapine/lurasidone/cariprazine for bipolar depression; combine mood stabilizer + atypical for severe mania; ECT for refractory cases, pregnancy, catatonia.

Monitoring pearls: lithium level 12 hours post-dose, q3–6 months; metabolic panel baseline, 12 weeks, annually on atypicals; AIMS annually; ECG before lithium/ziprasidone; HLA-B*1502 before carbamazepine in Asians; 7-day post-discharge follow-up reduces relapse and suicide.

Safety pearls: assess suicide risk every visit; involuntary hold criteria require imminent danger or grave disability; postpartum psychosis in BP-I is an emergency; sleep deprivation is the most common manic trigger; NSAIDs, thiazides, and dehydration cause lithium toxicity treated with IV fluids and hemodialysis.

Board pearl: Bipolar disorder is a lifelong illness — accurate early diagnosis, lithium when appropriate, vigilant monitoring, structured psychoeducation, and meticulous transitions of care are the high-yield Step 3 priorities.