Behavioral Health

Acute mania: hospitalization and treatment

Clinical Overview and When to Suspect Acute Mania

— Distractibility, Irresponsibility (risky behavior), Grandiosity, Flight of ideas, Activity increase, Sleep decreased need, Talkativeness/pressured speech

— Young or middle-aged adult brought in by family for not sleeping for days, spending sprees, hypersexuality, religious grandiosity, rapid pressured speech

— Known bipolar I patient who stopped lithium or valproate, started an antidepressant monotherapy, used stimulants/cocaine, or started high-dose corticosteroids

— Postpartum woman within 2–4 weeks with insomnia, agitation, and disorganized thought (rule out postpartum psychosis)

— Elderly patient with first-episode mania >50 — investigate secondary cause (stroke, frontal/temporal lesion, hyperthyroidism, dementia, medication)

Acute mania is a psychiatric emergency defined by a distinct period (≥1 week, or any duration if hospitalization required) of abnormally elevated, expansive, or irritable mood plus increased goal-directed activity/energy, with ≥3 DSM-5 "DIG FAST" symptoms (≥4 if mood is only irritable).

Causes marked functional impairment, psychotic features, or need for hospitalization to prevent harm — this is the threshold distinguishing mania from hypomania (≥4 days, no marked impairment, no psychosis, no hospitalization).

When to suspect on the wards or in clinic:

Bipolar I requires only one lifetime manic episode; depressive episodes are common but not required for diagnosis.

Board pearl: A patient with major depression who develops mania after SSRI initiation gets reclassified as bipolar I (substance/medication-induced mania that persists beyond physiologic effect = bipolar diagnosis per DSM-5).

Step 3 management: Initial outpatient encounter showing florid mania with poor insight and risky behavior → do not "trial outpatient mood stabilizer" — arrange emergency psychiatric evaluation and likely involuntary hospitalization because of impaired judgment and danger to self/others.

Presentation Patterns and Key History

— Duration and trajectory of symptoms (mania classically escalates over days)

— Sleep pattern: "hasn't slept in 4 days and feels great" is near-pathognomonic

— Speech: pressured, tangential, clang associations, flight of ideas

— Behavior: spending, sexual indiscretion, reckless driving, religious/messianic missions

— Substance use: cocaine, methamphetamine, MDMA, synthetic cannabinoids, PCP

— Medication exposures: antidepressants, corticosteroids, levodopa, interferon, isoniazid, stimulants, thyroid hormone

— Past psychiatric: prior depressive or manic episodes, hospitalizations, suicide attempts, family history (bipolar is highly heritable — ~10× risk in first-degree relatives)

— Medical: thyroid disease, head injury, MS, lupus, HIV/neurosyphilis (especially first episode >40–50)

— With psychotic features (mood-congruent grandiose/persecutory delusions or hallucinations) → antipsychotic mandatory

— With mixed features (simultaneous depressive symptoms) → higher suicide risk, avoid antidepressants, favor valproate or atypical antipsychotic over lithium

— Rapid cycling (≥4 episodes/year) → avoid antidepressants; valproate/lamotrigine/atypicals preferred

Core triad in the stem: decreased need for sleep + pressured speech + grandiosity, plus an action that disrupts the patient's life (quit job, drained bank account, drove cross-country, propositioned strangers).

History to obtain — collateral is essential because insight is poor:

Specifiers that change management:

Key distinction: Mania vs schizophrenia — in mania, psychotic symptoms occur only during mood episodes; in schizophrenia, psychosis persists ≥2 weeks without prominent mood symptoms (schizoaffective disorder bridges these).

Board pearl: A bipolar patient on lithium who presents with new mania — always check a lithium level and TSH before assuming nonadherence; subtherapeutic level or new hypothyroidism (lithium-induced) commonly precipitates relapse.

Physical Exam Findings and Safety Assessment

— Disheveled or flamboyantly dressed (bright colors, excessive makeup, religious garb)

— Hyperactive, intrusive, cannot stay seated, may pace

— Diaphoresis, dehydration from poor intake despite high activity

— Tachycardia, hypertension, hyperthermia, mydriasis → suspect stimulant intoxication (cocaine, methamphetamine) or serotonin syndrome / NMS if on serotonergic or antipsychotic agents

— Fever + rigidity + autonomic instability on an antipsychotic → neuroleptic malignant syndrome, stop the drug

— Focal deficits, asymmetric reflexes → stroke, frontal/temporal tumor

— Tremor → hyperthyroidism or lithium toxicity

— Cogwheel rigidity → antipsychotic-induced parkinsonism

— Gait ataxia + dysarthria + coarse tremor → lithium toxicity (check level urgently)

— Mood: euphoric or irritable; affect: labile, expansive

— Thought process: flight of ideas, tangentiality, clang associations

— Thought content: grandiose, persecutory, sometimes suicidal/homicidal

— Perception: mood-congruent hallucinations possible

— Insight and judgment: markedly impaired — anchor for hospitalization decision

Mania is primarily a behavioral/mental status diagnosis, but the exam serves two essential purposes: rule out medical mimics and assess safety/agitation.

General appearance:

Vital signs — every Step 3 stem checks these:

Neurologic exam (critical in first-episode mania, especially >40):

Mental status examination:

Suicide/violence risk screen: active ideation, plan, access to means, prior attempts, command hallucinations, agitation level (use a structured tool such as BARS or Columbia C-SSRS).

CCS pearl: On a CCS case of acute mania, order vital signs, finger-stick glucose, urine toxicology, TSH, BMP, CBC, and a pregnancy test in any female of reproductive age before starting valproate or lithium — these labs anchor both differential and pharmacotherapy choice.

Diagnostic Workup — Initial Labs, Imaging, Toxicology

— CBC, CMP (Na, K, BUN/Cr, glucose, LFTs, Ca) — baseline for valproate (hepatic, thrombocytopenia) and lithium (renal)

— TSH ± free T4 — hyperthyroidism mimics mania; lithium causes hypothyroidism

— Urine drug screen — cocaine, amphetamines, PCP, cannabinoids

— Blood alcohol level

— Urine pregnancy test in any female of reproductive age — valproate, carbamazepine, and lithium are teratogenic

— Urinalysis — UTI in elderly can precipitate delirium mimicking mania

— HIV, RPR/VDRL if first episode, atypical features, or risk factors (neurosyphilis classically causes mania-like presentation)

— B12, folate if cognitive features

— Lithium level (therapeutic 0.6–1.2 mEq/L acute; toxicity >1.5)

— Valproate level (50–125 µg/mL)

— Carbamazepine level (4–12 µg/mL)

— Baseline QTc before starting antipsychotics (especially haloperidol IV, ziprasidone)

— Lithium can cause T-wave flattening/inversion, sinus node dysfunction

— Mandatory in first-episode mania >40, focal neuro signs, head trauma history, or atypical features

— Look for frontal/right-hemisphere lesions, MS plaques, tumor, stroke

Mania is a clinical diagnosis, but every acute presentation gets a medical workup to exclude secondary causes and to baseline for pharmacotherapy.

Initial labs (order on arrival):

Drug levels if on therapy:

ECG:

Neuroimaging (non-contrast CT or MRI):

Board pearl: A 55-year-old man with no psychiatric history develops first-ever manic symptoms — this is not primary bipolar I until proven otherwise. Order MRI brain and a metabolic workup; secondary mania from frontotemporal pathology, stroke, or steroid use is far more likely.

Step 3 management: Always document pregnancy test result before ordering valproate or carbamazepine; failure to do so is a recurrent test-item safety violation.

Diagnostic Workup — Confirmatory and Advanced Studies

— Indicated for episodic behavioral changes, automatisms, postictal confusion, or stereotyped episodes

— Rules out complex partial (temporal lobe) seizures that mimic mania with bizarre behavior and grandiosity

— First-episode mania after age 40–50 → high yield

— Findings suggesting secondary mania: right frontal/temporal stroke, MS plaques, basal ganglia lesions, frontotemporal atrophy, neoplasm

— If fever, meningismus, immunocompromise, rapid cognitive decline, or suspicion of autoimmune encephalitis (anti-NMDA receptor encephalitis classically presents in young women with psychosis, mania, seizures, autonomic instability, orofacial dyskinesias) — send CSF NMDA-R antibodies, paraneoplastic panel, HSV PCR

— 24-hour urinary free cortisol or dexamethasone suppression → Cushing syndrome

— Thyroid antibodies, free T3/T4 → hyperthyroidism, Hashimoto encephalopathy

When the clinical picture is atypical, advanced studies refine the differential and exclude organic mania.

EEG:

MRI brain (preferred over CT for psychiatric workup):

Lumbar puncture:

Endocrine workup if labs suggest:

Neuropsychological testing: reserved for diagnostic clarification of bipolar vs ADHD vs personality disorder, generally outpatient.

Structured diagnostic interviews (MINI, SCID) used in equivocal cases, especially to distinguish bipolar I, bipolar II, schizoaffective, and substance-induced disorders.

Mood charting post-discharge confirms longitudinal pattern and identifies prodromes.

Key distinction: Delirium vs mania — delirium features fluctuating attention, disorientation, abnormal vital signs, visual hallucinations, and reversible cause; mania features preserved orientation, intact attention (though distractible), auditory hallucinations if any, and goal-directed (if chaotic) activity. EEG in delirium shows diffuse slowing; in mania, it's normal.

Board pearl: Young woman with subacute psychiatric symptoms + orofacial dyskinesias + autonomic dysfunction + new seizures → anti-NMDA receptor encephalitis — get LP and screen for ovarian teratoma (pelvic US/MRI); treat with IVIG/steroids/plasmapheresis and tumor removal, not just antipsychotics.

Risk Stratification and First-Line Management Logic

— Step 1: Safety — Is the patient a danger to self/others, gravely disabled, or unable to consent to outpatient care? If yes → involuntary hospitalization.

— Step 2: Medical clearance — Vitals stable? Toxicology and labs reviewed? Pregnancy excluded if relevant?

— Step 3: Acute agitation — Use de-escalation first; if needed, IM antipsychotic ± benzodiazepine (see chunk 7).

— Step 4: Mood stabilization — Initiate or optimize a mood stabilizer and/or atypical antipsychotic.

— Step 5: Address precipitants — Discontinue antidepressants, steroids, stimulants when possible; treat substance withdrawal; correct thyroid.

— Suicidal/homicidal ideation

— Psychotic features impairing reality testing

— Inability to meet basic needs (food, shelter, hydration)

— Severe agitation or aggression

— Failed outpatient management or no support

— Pregnancy with need to change teratogenic regimen

— Severe mania with psychosis: combination — lithium or valproate + atypical antipsychotic (e.g., olanzapine, quetiapine, risperidone, aripiprazole)

— Moderate mania without psychosis: monotherapy — lithium, valproate, or atypical antipsychotic

— Mixed features or rapid cycling: valproate or atypical antipsychotic preferred over lithium

— Pregnancy: prefer antipsychotic (quetiapine, olanzapine); avoid valproate/carbamazepine; lithium possible with informed consent and fetal echo

Decision tree on arrival:

Hospitalization criteria:

Severity-based first-line pharmacotherapy (APA/CANMAT-aligned):

Discontinue: any antidepressant monotherapy (can perpetuate mania), stimulants, steroids when feasible.

CCS pearl: On a CCS case, early orders should include: "admit to psychiatric inpatient unit, suicide/elopement precautions, 1:1 observation if severe, vital signs q4h, mood stabilizer, PRN IM antipsychotic + benzodiazepine for agitation, hold home antidepressant." Advance the clock to monitor response over 24–72 hours before adjusting therapy.

Pharmacotherapy — First-Line Mood Stabilizers and Antipsychotics

— Dose: start 300 mg BID–TID, titrate to level 0.8–1.2 mEq/L for acute mania

— Onset: 5–7 days for mood effect

— Monitor: Cr, TSH, Ca q6 months; level q5–7 days during titration, then steady state

— Toxicity (>1.5): tremor, ataxia, dysarthria, confusion, seizures → hold drug, IV fluids, hemodialysis if severe

— Avoid in: significant CKD, dehydration, NSAIDs/ACEi/thiazides (raise levels)

— Load 20–30 mg/kg for rapid response; target level 50–125 µg/mL

— Monitor: LFTs, CBC (thrombocytopenia, hepatotoxicity, pancreatitis), ammonia if encephalopathy

— Contraindicated in pregnancy (neural tube defects, neurodevelopmental harm — Category X for migraine, avoid in bipolar pregnancy)

— Olanzapine, risperidone, quetiapine, aripiprazole, asenapine, cariprazine, ziprasidone all FDA-approved for acute mania

— Olanzapine: most weight gain/metabolic risk; quetiapine: sedating, useful if insomnia

— Aripiprazole/cariprazine: lower metabolic burden; partial D2 agonists

— First-line: IM olanzapine 10 mg or IM haloperidol 5 mg + lorazepam 2 mg + diphenhydramine 50 mg ("B52")

— Avoid IM olanzapine + IM benzodiazepine together (respiratory depression, hypotension)

Lithium — gold standard for classic euphoric mania, anti-suicidal in bipolar.

Valproate (divalproex) — best for mixed features, rapid cycling, irritable mania, secondary mania.

Carbamazepine — second-line; many drug interactions (CYP3A4 inducer); risk of SJS/TEN (check HLA-B*1502 in Asian patients), agranulocytosis, hyponatremia.

Atypical antipsychotics — first-line for psychotic or severe mania; faster onset than lithium/valproate.

Acute agitation regimen:

Benzodiazepines (lorazepam, clonazepam) — adjunctive for sleep, agitation, catatonia; not monotherapy.

Step 3 management: Discontinue any antidepressant at the time of manic presentation — continuing it prolongs mania and increases mixed/rapid cycling risk.

Board pearl: A bipolar patient on lithium develops polyuria and polydipsia — think nephrogenic diabetes insipidus; confirm with water deprivation test, treat with amiloride and consider switching mood stabilizer.

Refractory Mania, ECT, and Adjunctive Strategies

— Add second-line agent (e.g., add valproate to lithium, or switch antipsychotic class)

— Optimize levels (lithium toward 1.0–1.2; valproate toward 100–125)

— Reassess adherence, drug interactions, occult substance use

— Indications: refractory mania, mania in pregnancy (especially first trimester when teratogens contraindicated), catatonic mania, delirious/malignant mania with hyperthermia and autonomic instability, severe suicidality, inability to tolerate medications

— Course: typically 6–12 sessions, 3×/week, bilateral or right unilateral

— Adverse: transient anterograde amnesia, headache, myalgia; no absolute contraindications, relative cautions for raised ICP, recent MI, unstable aneurysm

— Antidepressant monotherapy (precipitates/maintains mania)

— Lamotrigine for acute mania — too slow to titrate (risk of SJS) and works for bipolar depression, not acute mania

— Gabapentin, topiramate — not effective for acute mania

Combination therapy is the rule for severe or psychotic mania: lithium or valproate + atypical antipsychotic outperforms either alone (response rates ~65–75%).

Switching/adding strategies if no response in 1–2 weeks at therapeutic levels:

Electroconvulsive therapy (ECT) — highly effective and underused; gold standard for treatment-refractory mania.

Clozapine — reserved for severe treatment-resistant bipolar with psychosis; requires ANC monitoring (REMS program) for agranulocytosis.

Adjunctive sleep restoration: benzodiazepine or low-dose sedating antipsychotic; restoring sleep is itself anti-manic.

Avoid in mania:

Substance-induced mania: treat underlying intoxication, supportive care, short-course antipsychotic; do not commit to lifelong mood stabilizer until pattern emerges off substance.

CCS pearl: On a pregnant patient with severe mania and psychosis who cannot tolerate or refuses medications, ECT is the correct order — it is safe across all trimesters with anesthesia and obstetric coordination.

Board pearl: Catatonic features (mutism, posturing, waxy flexibility) during a manic episode → lorazepam challenge first; if refractory, ECT is definitive. Avoid first-generation antipsychotics, which can worsen catatonia and precipitate NMS.

Special Populations — Elderly, Renal, and Hepatic Impairment

— First-episode mania >50 demands neuroimaging and medical workup — secondary mania (stroke, frontotemporal dementia, tumor, medication, hyperthyroidism) is common

— Lower doses, slower titration; "start low, go slow"

— Lithium: reduce dose 30–50%, target 0.4–0.8 mEq/L, monitor renal function more frequently (q3 months), beware drug interactions (NSAIDs, ACEi, thiazides, loop diuretics → toxicity)

— Increased risk of falls, delirium, EPS, anticholinergic toxicity with antipsychotics

— Black-box warning: atypical antipsychotics increase mortality in elderly dementia patients (mostly cardiovascular/infection); use only when benefits clearly outweigh

— Prefer agents with lower anticholinergic burden (aripiprazole, risperidone low-dose)

— Lithium is renally cleared — avoid in eGFR <30; reduce dose and increase monitoring if eGFR 30–60

— Long-term lithium → chronic interstitial nephritis in 10–20% after decades; check Cr q6 months

— Valproate or atypical antipsychotic preferred in CKD

— Valproate and carbamazepine contraindicated in significant liver disease (hepatotoxicity, hyperammonemia)

— Lithium is safe hepatically (renal clearance) — often the preferred mood stabilizer in cirrhosis

— Antipsychotic dosing: reduce olanzapine, quetiapine, risperidone in hepatic dysfunction

— Lithium is dialyzable — dose post-dialysis if used; usually avoided

— Valproate is highly protein-bound, less dialyzed; monitor free fraction

Elderly patients (≥65):

Renal impairment:

Hepatic impairment:

Dialysis patients:

Key distinction: In an elderly patient with acute behavioral change, delirium is far more common than first-episode mania — workup includes infection screen, medication review, electrolytes, and CAM assessment before psychiatric labeling.

Board pearl: Elderly woman on chronic lithium presents with confusion, coarse tremor, ataxia, and Cr bumped from 1.0 → 1.6 after starting hydrochlorothiazide for hypertension — diagnose lithium toxicity, hold lithium, give IV normal saline, dialyze if level >4 or symptomatic.

Special Populations — Pregnancy, Postpartum, and Pediatrics

— Untreated mania is itself harmful (substance use, malnutrition, suicide, obstetric neglect) — do not simply stop all meds

— Valproate: contraindicated — neural tube defects (1–2%), cardiac/craniofacial defects, ~9-point IQ reduction, autism spectrum risk

— Carbamazepine: avoid — neural tube defects, craniofacial anomalies

— Lithium: relative caution — small absolute risk of Ebstein anomaly (~1/1000–2000, RR ~2); obtain fetal echocardiogram at 16–20 weeks; level fluctuates with plasma volume, monitor closely; hold or reduce 24–48 h before delivery to avoid neonatal toxicity

— Lamotrigine and atypical antipsychotics (quetiapine, olanzapine) generally preferred in pregnancy for bipolar maintenance; olanzapine carries gestational diabetes/weight risk

— ECT is safe and indicated for severe/refractory mania in pregnancy

— Lithium is excreted in milk — generally avoided or used with close infant monitoring

— Valproate, carbamazepine, antipsychotics are more compatible

— Postpartum psychosis (1–2/1000 births) is a psychiatric emergency, peaks within 2 weeks of delivery; bipolar women have ~25% risk

— Presents with rapidly fluctuating mood, confusion, hallucinations, infanticidal/suicidal ideation

— Always hospitalize; treat with mood stabilizer + antipsychotic ± ECT; prophylactic lithium postpartum in known bipolar women reduces relapse by ~50%

— Pediatric bipolar I exists but comorbid ADHD overlaps clinically — distractibility, hyperactivity, talkativeness can mimic ADHD

— FDA-approved acute mania agents in pediatrics: risperidone, aripiprazole, quetiapine, olanzapine, asenapine (age ≥10–13); lithium ≥7, valproate off-label

— Monitor metabolic parameters closely

Pregnancy:

Breastfeeding:

Postpartum:

Pediatrics/adolescents:

Step 3 management: Pregnant bipolar patient with active mania → admit, stop valproate/carbamazepine, initiate quetiapine or olanzapine; if severe/psychotic and refractory, ECT. Coordinate with obstetrics for fetal monitoring.

Board pearl: New mother day 10 postpartum with insomnia, paranoia, command hallucinations to harm her infant → postpartum psychosis — emergency admission, separate from infant, antipsychotic + mood stabilizer ± ECT.

Complications and Adverse Outcomes

— Exhaustion, dehydration, rhabdomyolysis from sustained agitation and poor intake

— Trauma from reckless behavior, fights, MVCs

— Aspiration, hyperthermia in delirious/agitated mania

— Suicide and homicide — bipolar I has lifetime suicide risk ~15–20×; mixed features and post-mania depression are highest risk windows

— Lithium toxicity (>1.5 mEq/L): tremor, ataxia, dysarthria, confusion, seizures, arrhythmia; >2.5 is life-threatening → hemodialysis

— Valproate: hepatotoxicity (idiosyncratic, especially <2 yo), pancreatitis, hyperammonemic encephalopathy (treat with L-carnitine), thrombocytopenia, PCOS in women

— Carbamazepine: SJS/TEN (HLA-B*1502 in Asians), aplastic anemia, agranulocytosis, hyponatremia (SIADH), AV block

— Antipsychotics: NMS (fever, rigidity, AMS, autonomic instability, ↑CK), EPS, tardive dyskinesia, metabolic syndrome, QT prolongation, hyperprolactinemia (especially risperidone)

— Clozapine: agranulocytosis, myocarditis, seizures, severe constipation/ileus

— Cognitive decline ("neuroprogression") with each episode

— Marital, occupational, financial ruin

— Substance use disorder comorbidity (~60%)

— Cardiovascular mortality elevated 2× (lifestyle, antipsychotic metabolic effects)

Acute medical complications of mania itself:

Pharmacologic complications:

Long-term outcomes of untreated/recurrent mania:

Switch to depression ("post-manic crash"): high suicide risk; do not rush to antidepressant — optimize mood stabilizer ± quetiapine/lurasidone/cariprazine (FDA-approved for bipolar depression).

Key distinction: NMS vs serotonin syndrome — NMS develops over days with lead-pipe rigidity, hyporeflexia; serotonin syndrome develops over hours with hyperreflexia, clonus, diarrhea. Both can occur in mania patients on combination therapy.

Board pearl: Manic patient on haloperidol + lithium develops fever, rigidity, CK 8000, altered mental status — stop both agents, supportive care, IV fluids, consider dantrolene or bromocriptine; lithium may potentiate NMS risk with antipsychotics.

When to Escalate Care — ICU, Consults, Inpatient Triage

— Danger to self/others, grave disability, severe psychosis, treatment-refractory outpatient course

— Need to initiate or change teratogenic medications (pregnancy)

— Substance co-intoxication requiring monitored withdrawal

— Lithium toxicity with neurologic symptoms or level >2.5 → dialysis

— NMS or serotonin syndrome with hyperthermia/autonomic instability

— Delirious/malignant mania (hyperthermia, dehydration, rhabdomyolysis, autonomic instability) — life-threatening; ECT may be lifesaving

— Severe valproate-induced hyperammonemic encephalopathy or hepatic failure

— SJS/TEN from carbamazepine/lamotrigine — burn unit

— Suicide attempt with medical sequelae (overdose, trauma)

— Psychiatry — primary management

— Internal medicine/hospitalist — medical comorbidities, pregnancy comanagement

— OB/MFM — pregnant patients

— Neurology — first-episode mania with focal signs, suspected encephalitis, seizures

— Toxicology/poison control — overdose, drug-induced mania, lithium toxicity

— Social work — housing, finances, custody (manic spending sprees, child safety)

— Ethics committee — capacity disputes, involuntary treatment with medication

— Mood stabilization, no active SI/HI, restored sleep, return of insight

— Stable medication regimen with side-effect tolerability

— Identified outpatient psychiatrist with follow-up within 7 days of discharge (CMS quality metric)

Inpatient psychiatric admission (standard for acute mania) when:

Medical ICU admission when:

Consults to obtain on the ward:

Transition triggers from inpatient to PHP/IOP:

CCS pearl: When a manic CCS patient develops fever and rigidity, immediately stop antipsychotic, order CK, transfer to ICU, start IV fluids and cooling, and consult psychiatry — do not "watch overnight." Delay in NMS recognition is a recurring exam pitfall.

Step 3 management: Document medical decision-making capacity every time involuntary medication or hospitalization is enacted; capacity is decision-specific, not global.

Key Differentials — Other Primary Psychiatric Disorders

— Hypomania (≥4 days, no marked impairment, no psychosis, no hospitalization) + at least one major depressive episode

— Never a full manic episode — if it occurs, reclassify as bipolar I

— ≥2 years of fluctuating hypomanic and depressive symptoms not meeting full episode criteria

— Major mood episode (manic or depressive) concurrent with schizophrenia-like psychosis, plus ≥2 weeks of psychosis without mood symptoms

— Psychosis dominates; mood symptoms are absent or brief relative to total illness duration

— Psychosis only during depression; no manic history

— Chronic from childhood, no episodic mood elevation, no decreased need for sleep, no grandiosity

— Common comorbidity with bipolar — overlap can confuse pediatric diagnosis

— Mood instability is interpersonally triggered, lasts hours not days, no decreased need for sleep, chronic identity disturbance, self-harm

— Often misdiagnosed as bipolar II; affective lability ≠ episodic mood elevation

— Symptoms emerge during or within 1 month of use of stimulants, hallucinogens, steroids, antidepressants, levodopa

— If symptoms persist beyond physiologic effect of substance → reclassify as primary bipolar

— Hyperarousal, insomnia, restlessness can superficially mimic; no grandiosity, no goal-directed behavioral excess

Bipolar II disorder:

Cyclothymic disorder:

Schizoaffective disorder:

Schizophrenia:

Major depressive disorder with psychotic features:

ADHD:

Borderline personality disorder:

Substance/medication-induced bipolar disorder:

Anxiety disorders, OCD, PTSD:

Key distinction: Bipolar mood lability vs borderline personality: bipolar episodes last days–weeks with autonomous shifts; borderline mood shifts are reactive and resolve within hours. Treatment differs — borderline is primarily DBT/psychotherapy, not mood stabilizers as first line.

Board pearl: A patient with "mood swings several times daily" reactive to interpersonal conflict is borderline PD, not rapid-cycling bipolar; mislabeling exposes the patient to lifelong unnecessary mood stabilizers.

Key Differentials — Medical and Substance-Induced Mimics

— Hyperthyroidism / thyroid storm: tachycardia, tremor, weight loss, heat intolerance, irritability — check TSH on every new mania

— Cushing syndrome: steroid excess can cause mania, depression, or psychosis

— Pheochromocytoma: paroxysmal HTN, anxiety, agitation

— Stroke (especially right frontal/temporal, caudate, thalamic) → secondary mania

— Multiple sclerosis plaques in frontal regions

— Frontotemporal dementia — disinhibition, grandiosity, social impropriety in 50–70 yo

— Brain tumor (frontal lobe, hypothalamus)

— Temporal lobe / complex partial seizures

— Traumatic brain injury — frontal disinhibition

— Huntington disease — early psychiatric features

— HIV (especially late-stage), neurosyphilis (general paresis with grandiose delusions), HSV encephalitis, Lyme, anti-NMDA receptor encephalitis (paraneoplastic, ovarian teratoma)

— Hypoglycemia, hyponatremia, hypercalcemia, hepatic encephalopathy, uremia, B12 deficiency

— Corticosteroids (dose-dependent, often within 2 weeks)

— Antidepressants (SSRIs, TCAs, SNRIs) — switch to mania in undiagnosed bipolar

— Levodopa, dopamine agonists

— Interferon-alpha, isoniazid

— Thyroid hormone replacement in excess

— Stimulants (amphetamines, methylphenidate)

— Anabolic steroids

— Cocaine, methamphetamine, MDMA, PCP, synthetic cannabinoids, hallucinogens

— Alcohol withdrawal can mimic agitation but with autonomic hyperactivity, tremor, seizures

Endocrine:

Neurologic:

Infectious:

Metabolic/toxic:

Medications causing secondary mania:

Substances of abuse:

Delirium — fluctuating attention, disorientation, often visual hallucinations, identifiable medical trigger; always exclude before diagnosing primary mania in inpatients or elderly.

Key distinction: Steroid-induced mania typically presents 5–14 days into therapy, dose-related (>40 mg prednisone equivalent), and resolves with taper; treat acutely with antipsychotic ± mood stabilizer, taper steroid as medically feasible.

Board pearl: A patient on prednisone 60 mg for lupus flare becomes euphoric, sleepless, grandiose — steroid-induced mania; reduce steroid dose if possible, start olanzapine or risperidone, avoid valproate due to potential interaction with immunosuppression.

Discharge Planning, Maintenance, and Secondary Prevention

— Euthymia or near-baseline mood for ≥48–72 hours

— Sleep restored to ≥6 hours

— No active SI/HI; insight returning

— Stable medication regimen with documented tolerability

— Established outpatient follow-up within 7 days (psychiatry) — a CMS quality measure

— Safety plan in place; family/support involved in psychoeducation

— Lithium: first-line for classic euphoric mania, anti-suicidal (reduces suicide ~60%); target 0.6–0.8 mEq/L maintenance

— Valproate: mixed/rapid-cycling phenotype, men or non-childbearing women

— Quetiapine, olanzapine, aripiprazole, risperidone LAI, asenapine, cariprazine — atypicals for maintenance, especially if psychotic features or poor adherence (use long-acting injectables for adherence problems)

— Lamotrigine: best for bipolar depression prevention, not anti-manic

— Combination therapy common

— Antidepressant monotherapy

— Chronic benzodiazepines (dependence, falls)

— Sleep hygiene — protected 7–9 hours; sleep loss is a primary manic trigger

— Social rhythm therapy / IPSRT, CBT for bipolar, family-focused therapy reduce relapse

— Substance use disorder treatment (alcohol, cannabis, stimulants)

— Mood charting and prodrome recognition (decreased sleep, increased energy, irritability)

— Bipolar patients have 2× cardiovascular mortality; aggressive metabolic screening, lipid/glucose control, smoking cessation, BP management integrated with psychiatric care

Discharge readiness criteria:

Maintenance pharmacotherapy (lifelong for bipolar I after first manic episode in most guidelines):

Avoid long-term:

Lifestyle/behavioral interventions:

Vaccinations, primary care:

Step 3 management: At discharge, schedule the first outpatient psychiatry visit within 7 days, primary care within 30 days, provide medication reconciliation list, suicide safety plan, and crisis line; document family involvement when patient consents.

Board pearl: Lithium reduces all-cause and suicide mortality in bipolar — when a stable patient asks to stop after years of euthymia, counsel that discontinuation carries ~50% relapse risk within 6 months, especially with rapid taper; if stopping, taper over ≥4 weeks.

Follow-Up, Monitoring, and Rehabilitation

— Psychiatry: within 7 days, then weekly × 4 weeks, then biweekly, then monthly once stable

— Primary care: 30 days, then per metabolic/comorbidity needs

— Therapist: weekly individual ± family therapy

— Lithium: level + Cr + TSH at 1 week post-initiation/dose change, then q3 months × 1 year, then q6 months; Ca annually

— Valproate: level + LFTs + CBC at 1 week, 1 month, then q3–6 months; ammonia if symptomatic

— Carbamazepine: level + CBC + LFTs + Na at 1, 3, 6 months then annually; HLA-B*1502 in Asians before starting

— Atypical antipsychotics: weight, BP, fasting glucose, lipids, A1c at baseline, 3 months, then annually (ADA/APA monitoring guideline); AIMS exam for tardive dyskinesia every 6 months (annually for atypicals)

— Prolactin if symptomatic (especially risperidone)

— ECG for QT-prolonging agents (ziprasidone, IV haloperidol)

— Vocational rehab, return-to-work planning (gradual reentry)

— Financial recovery: power-of-attorney arrangements for relapses; counsel on prior manic spending

— Driving evaluation if cognitive/medication impairment

— CBT for bipolar — relapse prevention, medication adherence

— Family-focused therapy — reduces relapse ~50% in adolescents

— Interpersonal and social rhythm therapy (IPSRT) — stabilizes circadian rhythms

— Psychoeducation — patient and family recognition of prodromes

— Once-daily dosing when possible

— Long-acting injectable antipsychotics (aripiprazole, risperidone, paliperidone) for nonadherent patients

— Pillbox, smartphone reminders, family involvement

Follow-up cadence post-discharge:

Medication monitoring schedule:

Functional rehabilitation:

Psychotherapy modalities with bipolar evidence:

Adherence strategies:

Key distinction: Annual AIMS exam is mandatory for any patient on antipsychotics; tardive dyskinesia is often irreversible — early detection allows switching to clozapine or valbenazine/deutetrabenazine treatment.

Board pearl: A bipolar patient on long-term lithium develops eGFR drop from 75 → 45 over 5 years — lithium-induced chronic interstitial nephritis; nephrology consult, consider switching to valproate or antipsychotic, but weigh suicide-protective benefit of lithium.

Ethical, Legal, and Patient Safety Considerations

— Requires evidence of mental illness + danger to self, danger to others, or grave disability; standards vary by US state

— Initial emergency hold typically 72 hours; extension requires judicial review

— Document specific behaviors, statements, and risk assessment — not just diagnostic labels

— Manic patients often lack capacity for treatment decisions because of impaired insight, judgment, and risk appreciation

— Capacity is decision-specific — a patient may lack capacity to refuse antipsychotic but retain capacity for other choices

— Four elements: understanding, appreciation, reasoning, expression of choice

— Generally requires court order or surrogate consent except in emergency (imminent danger)

— Document failure of less-restrictive alternatives (de-escalation, oral PRN)

— Child or elder abuse/neglect suspicion — including custodial concerns when a parent with active mania cannot safely care for children

— Tarasoff duty to warn/protect identifiable third parties when patient makes credible threats (varies by state)

— Driving impairment — many states require reporting of conditions causing unsafe driving; counsel patient and document

— Family collateral can be received without violating HIPAA; sharing patient information requires consent except for safety

— Adolescents: parental notification varies by state and condition

— Suicide and elopement precautions, contraband screening, 1:1 observation when indicated

— Restraint and seclusion: least restrictive, time-limited, q15-min monitoring, debrief required, document medical necessity

— Highest suicide risk in the 30 days post-discharge — ensure 7-day follow-up, crisis hotline, safety plan, lethal-means counseling (firearms, medication access)

— Informed consent for teratogenic agents in women of reproductive age — document discussion, contraception, fetal echo plan if lithium chosen in pregnancy

Involuntary hospitalization (civil commitment):

Capacity assessment:

Involuntary medication:

Mandatory reporting:

Confidentiality nuances:

Patient safety on the unit:

Transition-of-care risk:

Reproductive ethics:

Step 3 management: A manic patient refuses lithium, lacks capacity, and family agrees with treatment — in most US states you may treat in emergency, but for ongoing involuntary medication you need a court order or hospital ethics/legal process; do not coerce, document each step.

Board pearl: Manic patient with custody of a 3-year-old who is being left unsupervised → mandatory CPS report, even if therapeutic alliance is at stake.

High-Yield Associations and Rapid-Fire Facts

DIG FAST mnemonic = distractibility, irresponsibility, grandiosity, flight of ideas, activity, sleep ↓, talkativeness

Mania ≥1 week (or any duration if hospitalized) vs hypomania ≥4 days

One manic episode = bipolar I for life

Bipolar I lifetime suicide risk ~15–20%; lithium is anti-suicidal

Postpartum psychosis = bipolar relapse until proven otherwise; 25% risk in bipolar women postpartum

Antidepressant + undiagnosed bipolar → manic switch

First-episode mania >40–50 → image the brain; rule out secondary cause

Lithium toxicity triad: tremor, ataxia, confusion; treat with IV fluids ± hemodialysis

Valproate = mixed/rapid cycling, teratogen (NTDs, ↓IQ), hepatotoxic, pancreatitis, PCOS

Carbamazepine: HLA-B*1502 in Asians (SJS), aplastic anemia, SIADH, CYP3A4 inducer

Lamotrigine: bipolar depression maintenance — not acute mania; titrate slowly (SJS)

Quetiapine, lurasidone, cariprazine, olanzapine-fluoxetine — FDA-approved bipolar depression

ECT: refractory, catatonic, pregnant, suicidal, or delirious mania

NMS: fever, rigidity, ↑CK, autonomic instability — stop antipsychotic

Tarasoff: duty to warn/protect identifiable third party

7-day follow-up post-discharge is a CMS quality metric and reduces suicide

Atypical antipsychotic metabolic monitoring: weight/BP/glucose/lipids at baseline, 3 months, annually

AIMS every 6–12 months for any antipsychotic

Long-acting injectables for nonadherence

Right frontal/temporal stroke → secondary mania

Anti-NMDA receptor encephalitis → young woman, psychosis, orofacial dyskinesias, ovarian teratoma

Steroid-induced mania: prednisone >40 mg, 5–14 days in; treat with antipsychotic, taper steroid

Lithium + thiazide/NSAID/ACEi → toxicity

Step 3 management: Always stop the antidepressant at the time of manic presentation.

Board pearl: Bipolar I patient on lithium for 20 years with stable mood asks about stopping — counsel that abrupt discontinuation carries 50% relapse risk within 6 months and elevated suicide risk; if stopping, taper ≥4 weeks with close monitoring.

Board Question Stem Patterns

— 28-year-old man brought by family after 5 days without sleep, spending savings on a startup, speaking rapidly, claiming chosen by God. Vitals normal, tox screen negative. Answer: Admit; start lithium (or valproate) + atypical antipsychotic; stop any antidepressant.

— Patient with "depression" on sertraline develops grandiosity, decreased sleep, hypersexuality. Answer: Reclassify as bipolar I; discontinue sertraline; start mood stabilizer.

— Stable bipolar patient on lithium starts HCTZ for HTN; develops tremor, ataxia, confusion; level 2.4. Answer: Hold lithium and thiazide, IV normal saline; hemodialysis if level >4 or severe symptoms.

— Pregnant woman with bipolar on valproate in first trimester has manic relapse. Answer: Stop valproate; switch to quetiapine or olanzapine; consider ECT if severe; fetal anatomy scan; folate.

— 62-year-old, no psychiatric history, develops disinhibition, grandiosity, sleeplessness. Answer: MRI brain, TSH, RPR/HIV; do not assume primary bipolar.

— Asthma patient on prednisone 60 mg develops euphoria, sleeplessness, racing thoughts day 8. Answer: Reduce steroid if possible, add olanzapine or risperidone.

— Manic patient on haloperidol develops fever, rigidity, CK 9000. Answer: Stop haloperidol, IV fluids, cooling, dantrolene or bromocriptine, ICU.

— Day 10 postpartum mother with paranoid delusions about her infant. Answer: Hospitalize, separate from infant, antipsychotic + mood stabilizer ± ECT.

— Floridly manic patient refusing lithium, denies illness. Answer: Assess capacity (likely lacks); in emergency may treat; for ongoing involuntary medication, obtain court order.

— Stabilized inpatient on lithium + quetiapine ready for discharge. Answer: Schedule psychiatry follow-up within 7 days, lithium level + Cr + TSH labs, safety plan, family psychoeducation.

Pattern 1 — Classic acute mania presentation:

Pattern 2 — Antidepressant-induced switch:

Pattern 3 — Lithium toxicity:

Pattern 4 — Pregnancy and mania:

Pattern 5 — First-episode "mania" >50:

Pattern 6 — Steroid-induced mania:

Pattern 7 — NMS in a manic patient:

Pattern 8 — Postpartum psychosis:

Pattern 9 — Capacity and refusal:

Pattern 10 — Discharge planning:

Step 3 management: Default test answer for acute mania = mood stabilizer + atypical antipsychotic + stop antidepressant + admit.

One-Line Recap

Rapid recap bullets:

Acute mania is a psychiatric emergency requiring hospitalization, initiation of a mood stabilizer (lithium or valproate) plus an atypical antipsychotic if psychotic/severe, discontinuation of any antidepressant, exclusion of secondary medical/substance causes (especially in first-episode mania >40), and a structured discharge plan with psychiatry follow-up within 7 days.

Diagnose by DIG FAST + ≥1 week duration or hospitalization; one manic episode = bipolar I for life

Work up every case with CMP, TSH, urine tox, pregnancy test, drug levels, ECG; image the brain in first-episode >40 or atypical features

Treat acutely with combination mood stabilizer + atypical antipsychetic; severe/refractory/pregnant/catatonic → ECT; agitation → IM olanzapine or haloperidol + lorazepam (not olanzapine + IM benzo together)

Avoid antidepressant monotherapy, lamotrigine for acute mania, valproate/carbamazepine in pregnancy, and lithium in significant CKD or with concurrent thiazides/NSAIDs/ACEi

Special populations: lithium target 0.4–0.8 in elderly; quetiapine/olanzapine or ECT in pregnancy; postpartum psychosis = emergency separation from infant

Monitor: lithium level/Cr/TSH q6 months; valproate level/LFTs; atypical metabolic panel at baseline, 3 months, annually; AIMS for tardive dyskinesia

Maintain lifelong mood stabilizer after first manic episode; lithium reduces suicide ~60%

Discharge with 7-day psychiatry follow-up, safety plan, family psychoeducation, lethal-means counseling — the post-discharge month is the highest-risk window

Ethics: involuntary hospitalization for danger/grave disability; capacity is decision-specific; Tarasoff duty for credible threats; mandatory CPS report if child safety compromised by parental mania

CCS pearl: The high-yield order set is — admit psychiatry, suicide/elopement precautions, CMP/CBC/TSH/UDS/pregnancy test/ECG, mood stabilizer + atypical antipsychotic, PRN agitation regimen, stop antidepressant, advance clock 48–72 h, then reassess and arrange 7-day follow-up.