Act as a World-Class Professor of General Medicine, Clinical Pharmacology, Pathology, and Medical Education. Teach me MANIA disease in a simple, exam-oriented, and clinically practical manner. For every disease, follow this format: 1. Definition - One-line exam definition - Simple explanation 2. Causes (Etiology) - Common causes - Important risk factors 3. Types / Classification - Brief explanation of each type 4. Pathophysiology - Step-by-step flowchart with arrows - Easy to understand 5. Clinical Features - Symptoms - Signs - Explain why important symptoms occur 6. Key Symptoms That Suggest the Diagnosis - Hallmark symptom - Classic clinical clues - Red flag findings 7. Laboratory Investigations Create a table: Investigation | Expected Finding | Clinical Significance Include: - CBC - Biochemistry - Disease-specific tests - Imaging findings if relevant 8. Differential Diagnosis Create a comparison table: Disease | Similar Features | Differentiating Features 9. Short Clinical Case Example format: "A 55-year-old male presents with chest pain radiating to the left arm, sweating, and breathlessness. ECG shows ST elevation in leads II, III, and aVF. Troponin-I is elevated." Diagnosis: Reasoning: Provide only 1–2 short high-yield cases. 10. Treatment A. Non-Pharmacological Treatment B. Pharmacological Treatment Create a table: Drug | Drug Group | Mechanism of Action | Indication | Dose | Major Adverse Effects For every disease mention: - Drug of Choice (DOC) - First-line drugs - Alternative drugs - Emergency drugs (if applicable) 11. Clinical Pearls - Important bedside clues - High-yield exam facts - Viva points 12. Common Diagnostic Mistakes - Frequently missed findings - Common confusion with other diseases - How to avoid errors 13. 5-Minute Revision Summary Definition → Causes → Pathophysiology → Symptoms → Investigations → Treatment → Complications Teaching Rules: - Use simple English. - Explain like teaching a final-year medical student. - Use tables and flowcharts. - Focus on practical diagnosis and treatment. - Focus on exam-oriented points. - Mention standard drug doses whenever possible. - Keep the explanation concise but complete.
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I now have all the information needed to compile the full, authoritative teaching document. Here it is:
MANIA - Complete Medical Teaching Guide
Sources: Kaplan & Sadock's Synopsis of Psychiatry | Kaplan & Sadock's Comprehensive Textbook of Psychiatry | Stahl's Essential Psychopharmacology | The Maudsley Prescribing Guidelines (15th Ed.) | Harrison's Principles of Internal Medicine 22E | Goodman & Gilman's Pharmacological Basis of Therapeutics
1. DEFINITION
One-Line Exam Definition
Mania is a distinct period of abnormally and persistently elevated, expansive, or irritable mood with increased goal-directed activity or energy, lasting at least 7 days (or any duration if hospitalization is required), causing marked functional impairment.
Simple Explanation
Imagine the brain's "accelerator" stuck at full throttle. The person feels invincible, needs no sleep, talks nonstop, spends recklessly, and may lose touch with reality. This is not just "being happy" - it is a dangerous, pathological state that can destroy careers, relationships, and lives.
2. CAUSES (ETIOLOGY)
Primary (Idiopathic)
- Bipolar I Disorder - the most common cause of a full manic episode
- Bipolar II Disorder - causes hypomania, not full mania
Secondary (Organic) Causes - "MANIC" Mnemonic
| Category | Examples |
|---|---|
| Medications | Antidepressants (most common trigger), steroids, stimulants (cocaine, amphetamines), levodopa, isoniazid |
| Alcohol/Substances | Cocaine, amphetamines, alcohol withdrawal |
| Neurological | TBI, epilepsy (temporal lobe), stroke (right hemisphere), multiple sclerosis, Huntington's |
| Infectious / Inflammatory | Encephalitis (HSV), SLE, HIV |
| Conditions (Medical) | Hyperthyroidism, Cushing's syndrome, Vitamin B12 deficiency |
Important Risk Factors
- Family history of bipolar disorder (strongest genetic risk - concordance ~60-80% in monozygotic twins)
- Postpartum period (highest risk window in women)
- Sleep deprivation (major trigger)
- Substance use
- Age of onset: typically 15-25 years (mean age ~21)
- Social stress, life events (especially those with goal-attainment significance)
3. TYPES / CLASSIFICATION
| Type | Key Feature | Exam Clue |
|---|---|---|
| Bipolar I | At least 1 full manic episode (with or without depression) | Hospitalization often needed |
| Bipolar II | Hypomania (not full mania) + major depressive episode | No hospitalization, no psychosis |
| Cyclothymia | Hypomanic + subsyndromal depressive symptoms for ≥2 years, never meeting full criteria | "Soft" bipolar |
| Manic episode with psychotic features | Delusions/hallucinations during mania | Mood-congruent (grandiose) most common |
| Mixed episode | Full manic + ≥3 depressive symptoms simultaneously | Highest suicide risk |
| Rapid cycling | ≥4 mood episodes per year | More common in women; poor prognosis |
| Secondary mania | Due to medical cause/substance | Always exclude first |
4. PATHOPHYSIOLOGY
Step-by-Step Flowchart
GENETIC PREDISPOSITION (family history, multiple genes)
+
TRIGGERING FACTOR (stress, sleep loss, substance, antidepressant)
|
↓
NEUROTRANSMITTER DYSREGULATION
↑ DOPAMINE activity (euphoria, psychosis, grandiosity)
↑ NOREPINEPHRINE (increased energy, arousal, reduced sleep)
SEROTONIN dysregulation (mood instability)
↓ GABA (reduced inhibition → disinhibition)
|
↓
SECOND MESSENGER SYSTEM DISRUPTION
Abnormal inositol phosphate signaling (PKC pathway overactive)
Abnormal G-protein coupling
[Note: Lithium works HERE - inhibits inositol monophosphatase]
|
↓
HPA AXIS DYSFUNCTION
Elevated cortisol → worsens mood instability
|
↓
LIMBIC SYSTEM HYPERACTIVATION
Amygdala overactivity → emotional lability
Prefrontal cortex hypoactivity → poor judgment, impulsivity
|
↓
CLINICAL MANIFESTATIONS:
Elevated/irritable mood → Decreased sleep need → Grandiosity
→ Pressured speech → Racing thoughts → Distractibility
→ Reckless behavior → (if severe) Psychosis
Key Insight: Lithium works by inhibiting inositol monophosphatase (depleting free inositol), dampening the overactive PKC second-messenger cascade. Valproate stabilizes sodium channels and enhances GABA. Antipsychotics block D2 receptors directly.
5. CLINICAL FEATURES
The DIG FAST Mnemonic (DSM-5 Symptoms - need ≥3, or ≥4 if mood is only irritable)
| Letter | Symptom | Why It Occurs |
|---|---|---|
| D - Distractibility | Cannot focus, easily sidetracked | Prefrontal cortex dysfunction |
| I - Impulsivity / Reckless behavior | Spending sprees, sexual indiscretions, risky investments | ↓ Impulse control; dopamine reward overactivation |
| G - Grandiosity | Feels special, all-powerful, chosen by God | ↑ Dopamine → reward/self-esteem circuits overactivated |
| F - Flight of ideas | Thoughts racing, jumping topic to topic | ↑ Norepinephrine → thought acceleration |
| A - Activity increase / Psychomotor agitation | Non-stop planning, projects, restlessness | ↑ Dopamine + norepinephrine → motor drive |
| S - Sleep decreased (without fatigue) | Sleeps 2-3 hrs and feels rested | ↑ Norepinephrine → wakefulness |
| T - Talkativeness (pressured speech) | Rapid, loud, difficult to interrupt | ↑ Dopamine → verbal output centers |
Plus the core mood criterion: Abnormally elevated, expansive, or irritable mood + increased energy for ≥7 days.
Signs on Examination
- Loud, rapid, pressured speech
- Tangential or circumstantial thought
- Elevated mood or lability/irritability
- Decreased need for sleep
- Grandiose or paranoid delusions (75% of manic patients)
- Visual or auditory hallucinations (mood-congruent usually)
- Psychomotor agitation, hyperactivity
- Distractible on cognitive testing
- Impaired judgment and insight
- Occasionally: physical aggressiveness requiring restraint
Severity Spectrum
Hypomania (4 days, no impairment) → Mania (7+ days, impaired) → Mania with Psychosis (most severe)
6. KEY SYMPTOMS THAT SUGGEST THE DIAGNOSIS
Hallmark Symptom
Elevated/euphoric or irritable mood + decreased need for sleep + grandiosity - this triad is virtually pathognomonic.
Classic Clinical Clues
- Patient who "hasn't slept in 3 days but feels great"
- Suddenly spending large sums of money or starting multiple businesses simultaneously
- Hypersexuality in someone with no prior history
- Pressured speech that cannot be interrupted
- Loud, goal-directed but fruitless activity
- Previous depressive episodes in history
Red Flag Findings (Require Urgent Assessment)
- Psychosis - delusions/hallucinations (requires hospitalization)
- Mixed features - highest suicide risk (depressive + manic symptoms together)
- Rapid cycling - ≥4 episodes/year, poor treatment response
- Violence or agitation - may need emergency sedation
- First manic episode >50 years old - always suspect organic/secondary cause
- Medication-induced mania (antidepressant-triggered) - do not re-expose
7. LABORATORY INVESTIGATIONS
| Investigation | Expected Finding in Mania | Clinical Significance |
|---|---|---|
| CBC | Usually normal; leukocytosis if agitated/stressed | Rule out infection causing secondary mania |
| Electrolytes (Na, K) | Low sodium may worsen lithium toxicity | Baseline before starting lithium |
| Renal function (Cr, BUN, eGFR) | Normal baseline expected | Mandatory before lithium; lithium is nephrotoxic |
| Thyroid function (TSH, T4) | Hyperthyroidism can cause mania; lithium causes hypothyroidism | Screen before and during lithium therapy |
| LFTs | Normal baseline | Valproate is hepatotoxic - baseline + monitoring |
| Serum Lithium level | Acute mania: target 0.8-1.2 mEq/L | Narrow therapeutic index; toxicity >1.5 mEq/L |
| Valproate level | Target 50-125 mcg/mL (acute mania: up to 120 mcg/mL) | Monitor for hepatotoxicity and thrombocytopenia |
| Serum glucose, lipid profile | May be abnormal with atypical antipsychotics | Metabolic monitoring for olanzapine/quetiapine |
| Urine drug screen | Cocaine, amphetamines, cannabis positive | Rule out substance-induced mania |
| Blood alcohol | May be elevated | Alcohol intoxication/withdrawal can mimic mania |
| Serum B12 / Folate | Low B12 can cause mood symptoms | Rule out secondary cause |
| MRI Brain | Usually normal in primary mania | If first episode >50 years, new onset without family history, or focal neurological signs |
| EEG | Normal or nonspecific | Consider if temporal lobe epilepsy suspected |
| CSF (if encephalitis suspected) | WBC elevated in viral encephalitis | HSV encephalitis can cause manic-like psychosis |
| CBC platelets | Thrombocytopenia with valproate | Monitor on valproate therapy |
| Beta-hCG (women of childbearing age) | Rule out pregnancy | Both lithium and valproate are teratogenic |
8. DIFFERENTIAL DIAGNOSIS
| Disease | Similar Features | Differentiating Features |
|---|---|---|
| Schizophrenia | Psychosis, disorganized behavior, agitation | No prominent mood elevation; hallucinations more prominent and mood-incongruent; no return to full baseline; chronically flat affect |
| Schizoaffective Disorder | Both psychosis and mood symptoms | Psychosis persists even when mood is normal (≥2 weeks); required for diagnosis |
| ADHD | Distractibility, hyperactivity, impulsivity | Chronic onset from childhood; no episodic course; no grandiosity, no decreased sleep need, no psychosis |
| Substance intoxication (cocaine, amphetamines) | Euphoria, grandiosity, decreased sleep, psychosis | Urine drug screen positive; resolves within hours-days of abstinence |
| Hyperthyroidism | Agitation, insomnia, distractibility, pressured speech | Elevated T3/T4, low TSH; weight loss, heat intolerance, tachycardia; no true grandiosity |
| Major Depression with agitation | Irritability, restlessness | No elevated mood, no grandiosity, no decreased sleep need; suicidal ideation more prominent |
| Personality disorder (Borderline, Narcissistic) | Impulsivity, grandiosity, recklessness | Chronic pattern, not episodic; mood shifts within hours (not days-weeks); triggered by interpersonal events |
| Delirium | Agitation, confusion, sleep disturbance | Acute onset, fluctuating consciousness, medical cause, disorientation; abnormal EEG |
| TBI-related mood disorder | Irritability, disinhibition, mood lability | History of head trauma; neuroimaging may show lesions; more frontal lobe features |
9. SHORT CLINICAL CASES
Case 1
A 24-year-old male engineering student is brought to the emergency department by his family. For the past 8 days, he has been sleeping only 2 hours per night but claims to feel energetic and "unstoppable." He has withdrawn ₹2 lakhs from his savings to "invest in a business that will make him a billionaire." He speaks rapidly without pause, jumps between topics, and believes he has been "chosen by God" to solve the world's energy crisis. On exam, he is distractible, loud, and cannot complete cognitive tasks. There is no drug use. His mother mentions he had a "depressive episode" 2 years ago.
Diagnosis: Manic episode, Bipolar I Disorder (with mood-congruent grandiose delusions)
Reasoning: ≥7 days of elevated mood + decreased sleep without fatigue (not insomnia) + grandiosity + pressured speech + flight of ideas + goal-directed activity + reckless spending = full DSM-5 manic episode. Prior depressive episode confirms Bipolar I. No substance use rules out secondary cause.
Case 2
A 38-year-old woman on sertraline for depression presents with sudden onset of 5 days of elevated mood, reduced sleep, making expensive purchases online, and talking "a mile a minute." She has never had such an episode before. She is not suicidal and remains functional but her husband says she is "completely unlike herself."
Diagnosis: Antidepressant-induced manic/hypomanic episode (SSRI-induced mood switch)
Reasoning: Temporal relationship to antidepressant initiation + manic features emerging during antidepressant therapy = classic medication-induced mania. Management requires stopping the antidepressant and initiating mood stabilizer. This episode should not be counted as evidence of Bipolar I per DSM-5 unless symptoms persist beyond the physiological effect of the drug.
10. TREATMENT
A. Non-Pharmacological Treatment
- Hospitalization - mandatory if: risk to self/others, psychosis, severe functional impairment, rapid cycling, inability to care for self
- Sleep regulation - dark, quiet environment; enforced rest schedule (reducing sleep deprivation is itself therapeutic)
- Remove precipitants - stop any antidepressants, stimulants, or substances
- Structure and limit-setting - consistent, calm behavioral boundaries
- Psychoeducation (after acute phase is controlled):
- Mood charting / relapse signature recognition
- Importance of medication adherence
- Identifying personal triggers
- Family therapy - crucial for relapse prevention
- Cognitive Behavioral Therapy (CBT) for Bipolar - evidence-based for maintenance
- Interpersonal and Social Rhythm Therapy (IPSRT) - protects circadian rhythm
- Restrict financial access during acute mania (legal guardian if needed)
B. Pharmacological Treatment
Drug of Choice (DOC)
- Acute mania: Lithium carbonate (gold standard; most evidence) OR Valproate (faster onset, preferred in mixed/rapid cycling)
- Maintenance/prophylaxis: Lithium (proven anti-suicide effect, reduces all-cause mortality)
- Mania with acute agitation: IM Haloperidol or IM Olanzapine + Benzodiazepine (lorazepam)
Pharmacological Treatment Table
| Drug | Drug Group | Mechanism of Action | Indication | Dose | Major Adverse Effects |
|---|---|---|---|---|---|
| Lithium carbonate ⭐ DOC | Mood stabilizer | Inhibits inositol monophosphatase (IP₃ pathway); modulates G-protein signaling; increases serotonin synthesis | Acute mania + maintenance + anti-suicidal | Acute: 900-1800 mg/day in divided doses (target: 0.8-1.2 mEq/L) Maintenance: 600-1200 mg/day (target: 0.6-1.0 mEq/L) | Tremor (fine), polyuria, polydipsia, hypothyroidism, weight gain, renal impairment (long-term), teratogen (Ebstein's anomaly), narrow therapeutic index |
| Sodium Valproate (Divalproex) | Anticonvulsant / Mood stabilizer | Enhances GABA activity; blocks voltage-gated sodium channels; inhibits PKC | Acute mania (especially mixed/rapid cycling); valproate preferred over lithium in mixed states | 750-3000 mg/day (target level: 50-125 mcg/mL; acute mania: up to 120 mcg/mL) | Hepatotoxicity, thrombocytopenia, alopecia, weight gain, tremor, pancreatitis, major teratogen (neural tube defects) - avoid in women of childbearing age |
| Haloperidol | Typical antipsychotic | D2 receptor blockade | Acute agitation; mania with psychosis; rapid control | IM: 5-10 mg; can repeat every 30-60 min up to 30 mg/day. Oral: 5-20 mg/day | EPS (acute dystonia, akathisia, Parkinsonism), tardive dyskinesia, NMS, QTc prolongation |
| Olanzapine | Atypical antipsychotic | D2 + 5-HT2A blockade | Acute mania monotherapy OR adjunct (second-line per CANMAT) | 10-20 mg/day oral; 10 mg IM for agitation | Weight gain, metabolic syndrome, sedation, glucose dysregulation - most metabolically toxic atypical |
| Risperidone | Atypical antipsychotic | D2 + 5-HT2A blockade | First-line acute mania (CANMAT); adjunct with lithium/valproate | 2-6 mg/day oral | EPS (more than other atypicals), hyperprolactinemia, weight gain |
| Quetiapine | Atypical antipsychotic | D2 + 5-HT2A + H1 blockade | First-line acute mania; also effective for bipolar depression | 400-800 mg/day (mania) | Sedation, weight gain, metabolic effects, orthostatic hypotension |
| Aripiprazole | Atypical antipsychotic (partial D2 agonist) | Partial D2 agonist + 5-HT1A agonist + 5-HT2A antagonist | First-line acute mania; good metabolic profile | 15-30 mg/day | Akathisia, insomnia, nausea, GI upset - best metabolic profile among atypicals |
| Carbamazepine | Anticonvulsant | Blocks Na+ channels; reduces neuronal firing | Second-line acute mania; alternative when lithium/valproate fail | 400-1600 mg/day (target: 4-12 mcg/mL) | Autoinduction (reduces its own levels), aplastic anemia, Stevens-Johnson syndrome (HLA-B*1502 in Asians), teratogen, CYP450 inducer |
| Lorazepam | Benzodiazepine | GABA-A potentiation | Adjunct for acute agitation; sedation in emergency | 1-2 mg IM/IV PRN, repeat every 30-60 min | Sedation, respiratory depression, dependence; avoid as monotherapy for mania |
| Clonazepam | Benzodiazepine | GABA-A potentiation | Adjunct to reduce agitation while waiting for mood stabilizer onset | 0.5-2 mg TID | As lorazepam; tolerance can develop |
| Lamotrigine | Anticonvulsant | Blocks Na+ channels; reduces glutamate release | Not effective for acute mania - used for bipolar depression and maintenance | 25-200 mg/day (slow titration) | Stevens-Johnson syndrome (if titrated too fast), rash, dizziness |
Treatment Algorithm
ACUTE MANIC EPISODE
|
↓
MILD-MODERATE (no psychosis, no danger)
→ Lithium OR Valproate monotherapy (first-line)
→ OR: Risperidone / Quetiapine / Aripiprazole monotherapy
|
↓
MODERATE-SEVERE (psychosis, impaired ADLs)
→ Lithium OR Valproate + Atypical Antipsychotic (combo)
|
↓
SEVERE AGITATION / EMERGENCY
→ IM Haloperidol 5-10 mg + IM Lorazepam 2 mg
→ OR: IM Olanzapine 10 mg (do NOT give IM olanzapine + IM benzodiazepine together → fatal hypotension)
|
↓
MAINTENANCE (after acute episode resolves)
→ Continue lithium (first-choice) or valproate
→ Add CBT / IPSRT
→ Psychoeducation
11. CLINICAL PEARLS
Bedside Clues
- A patient who "slept only 2 hours and feels fantastic" - this decreased sleep without fatigue is the single most reliable clinical marker distinguishing mania from anxiety or insomnia
- Manic patients often resist treatment because they enjoy the high and lack insight
- The first symptom of a manic relapse is often sleep disturbance - this is the earliest warning sign
- Postpartum mania (days 3-7 after delivery) is a psychiatric emergency - rapid escalation to psychosis is common
- Delusions occur in 75% of manic patients - grandiose and mood-congruent most common
High-Yield Exam Facts
- Bipolar I requires at least 1 manic episode - depressive episode not required for diagnosis
- Bipolar II requires at least 1 hypomanic + 1 depressive episode - a full manic episode rules out Bipolar II and upgrades diagnosis to Bipolar I
- Hypomania duration: ≥4 consecutive days vs. Mania: ≥7 days (or any duration if hospitalized)
- Rapid cycling = ≥4 episodes/year, more common in women, antidepressants can trigger it
- Lithium therapeutic range: 0.8-1.2 mEq/L (acute), 0.6-1.0 mEq/L (maintenance)
- Lithium toxicity signs: coarse tremor, ataxia, confusion, nausea - toxic >1.5 mEq/L, dangerous >2.0 mEq/L
- Do NOT give lamotrigine for acute mania - it is for bipolar depression prevention only
- Do NOT use antidepressant monotherapy in bipolar disorder - can trigger mania/rapid cycling
- Valproate is preferred over lithium in: mixed features, rapid cycling, substance comorbidity, and patients who need faster onset
- Lithium has a unique anti-suicidal effect - proven to reduce suicide risk in bipolar disorder
- ECT is effective for severe, treatment-resistant, or pregnant manic patients
- The mnemonic for mania criteria: DIG FAST
Viva Points
- Q: Why does lithium cause polyuria? → Nephrogenic diabetes insipidus - lithium blocks ADH action on collecting ducts
- Q: What is the teratogenic risk of lithium? → Ebstein's anomaly (tricuspid valve malformation)
- Q: What is Ebstein's anomaly? → Downward displacement of tricuspid valve into RV
- Q: What is the anti-manic mechanism of valproate? → Enhances GABA, blocks Na+ channels, inhibits PKC
- Q: What is the most dangerous adverse effect of carbamazepine in Asians? → Stevens-Johnson syndrome (associated with HLA-B*1502 allele)
12. COMMON DIAGNOSTIC MISTAKES
| Mistake | Why It Happens | How to Avoid It |
|---|---|---|
| Diagnosing schizophrenia instead of mania with psychosis | Psychotic features are prominent, mood elevation is missed or attributed to grandiosity in schizophrenia | Always ask about the MOOD component first; if delusions are mood-congruent (grandiose), think mania |
| Missing secondary mania | First episode, no family history, unusual age (>50 years) | Always order TFTs, urine drug screen, MRI brain in first episodes, especially age >50 |
| Antidepressant-induced mania missed | Patient on SSRIs/SNRIs for "depression" suddenly becomes "better and energetic" - seen as treatment success | Beware the patient who becomes "too good" on antidepressants - a switch to hypomania/mania |
| ADHD vs. mania confusion | Both have distractibility, hyperactivity, impulsivity | ADHD: onset in childhood, chronic, no episodic course, no grandiosity, no decreased sleep need |
| Hypomania mistaken for normal | Patient functional, pleasant, "feeling great" | Duration ≥4 days + behavioral change noted by others + not typical for them = hypomania |
| Missing mixed episode | Patient appears mainly depressed with some agitation | Specifically ask about concurrent ↑ energy, ↓ sleep, racing thoughts during depressive phase - mixed = highest suicide risk |
| Borderline Personality vs. Bipolar II | Both have mood swings, impulsivity, emotional lability | BPD: mood shifts over hours (interpersonally triggered), chronic pattern; Bipolar II: mood episodes lasting days-weeks |
| Stopping lithium abruptly | Patient feels well and stops | Abrupt lithium discontinuation causes rebound mania - taper slowly over weeks |
13. FIVE-MINUTE REVISION SUMMARY
MANIA
│
├── DEFINITION
│ Abnormally elevated/expansive/irritable mood + increased energy
│ ≥7 days + marked functional impairment (or any duration if hospitalized)
│
├── CAUSES
│ Primary: Bipolar I disorder
│ Secondary: Cocaine/amphetamines, antidepressants, steroids,
│ hyperthyroidism, TBI, SLE, epilepsy
│
├── PATHOPHYSIOLOGY
│ ↑Dopamine + ↑Norepinephrine → Hyperactivated limbic system
│ ↓GABA → disinhibition
│ PKC/inositol pathway overactivation
│ → Elevated mood, ↓sleep need, grandiosity, psychosis
│
├── SYMPTOMS (DIG FAST + elevated mood)
│ Distractibility, Impulsivity, Grandiosity, Flight of ideas,
│ Activity increase, Sleep decreased (without fatigue), Talkativeness
│
├── INVESTIGATIONS
│ Lithium level: target 0.8-1.2 mEq/L (acute)
│ Valproate: 50-125 mcg/mL
│ TFTs, RFTs, LFTs (before starting drugs)
│ Urine drug screen (rule out cocaine/amphetamines)
│ MRI brain (if age >50 or focal signs)
│ Beta-hCG in women (both lithium + valproate are teratogenic)
│
├── TREATMENT
│ Acute (mild-moderate): Lithium OR Valproate (DOC)
│ Acute (with psychosis): Lithium/Valproate + Atypical antipsychotic
│ Emergency agitation: IM Haloperidol + IM Lorazepam
│ Maintenance: Lithium (anti-suicide effect)
│ Never use: Antidepressant monotherapy / Lamotrigine for acute mania
│
└── COMPLICATIONS
Suicide (mixed > depressive > manic episodes)
Psychosis and violence
Financial ruin, relationship breakdown
Substance abuse (50% comorbidity)
Lithium toxicity (tremor, ataxia, confusion, renal failure)
Valproate hepatotoxicity / teratogenicity
Rapid cycling (often antidepressant-triggered)
Bipolar I: 90% have ≥1 recurrence → lifelong mood stabilizer needed
Recent Evidence Note (PubMed 2024-2026): A 2025 network meta-analysis (PMID 39128561) confirmed that in pediatric mania, antipsychotics and antiepileptics/lithium have broadly similar efficacy, supporting individualized selection. A 2024 systematic review (PMID 38750644) confirmed lamotrigine is effective for bipolar depression prevention but not acute mania - reinforcing the guideline message above.
Sources: Kaplan & Sadock's Synopsis of Psychiatry | Kaplan & Sadock's Comprehensive Textbook of Psychiatry | Maudsley Prescribing Guidelines 15th Ed. | Harrison's Principles of Internal Medicine 22E | Goodman & Gilman's Pharmacological Basis of Therapeutics
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