Study guide
11.3 Bipolar Disorder, Mood Stabilizers & Lithium Toxicity
ABIM Internal Medicine Exam
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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy
0.1 Exam Format, Question Types & the 2026 Blueprint 0.2 Eligibility, Registration, Fees & Exam-Day Logistics 0.3 Scoring, the Passing Standard & Score Reports 0.4 Building a Blueprint-Weighted Study Plan
2 Chapter 1: Cardiovascular Disease (14% of Exam)
1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection
3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)
2.1 Diabetes Mellitus: Diagnosis, Glycemic Targets & Pharmacotherapy 2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications 2.3 Thyroid Function Testing & Hypothyroidism 2.4 Thyrotoxicosis, Thyroid Storm & Thyroid Nodules 2.5 Adrenal & Pituitary Disorders 2.6 Hypercalcemia, Hypocalcemia & Disorders of Mineral Metabolism 2.7 Osteoporosis & Paget Disease of Bone 2.8 Ovarian, Testicular & Reproductive Endocrine Disorders 2.9 Hypoglycemia, Endocrine Tumors, Polyglandular Syndromes & Severe Hypertriglyceridemia
4 Chapter 3: Gastroenterology & Hepatology (9% of Exam)
3.1 Esophageal Disease 3.2 Stomach & Duodenal Disease and Gastrointestinal Hemorrhage 3.3 Inflammatory Bowel Disease 3.4 Celiac Disease & Irritable Bowel Syndrome 3.5 Diverticular Disease & Colorectal Cancer Screening 3.6 Viral Hepatitis, Steatotic & Alcohol-Associated Liver Disease 3.7 Cirrhosis & the Complications of Portal Hypertension 3.8 Acute Pancreatitis 3.9 Chronic Pancreatitis & Biliary Tract Disease 3.10 Inherited, Autoimmune & Drug-Induced Liver Disease 3.11 Small Intestinal Disease, Ischemia & Gastrointestinal Complications of HIV
5 Chapter 4: Infectious Disease (9% of Exam)
4.1 Lower Respiratory Tract Infections & Sepsis Syndromes 4.2 Viral Respiratory Pathogens & Tuberculosis 4.3 Central Nervous System Infections 4.4 Skin, Soft Tissue, Bone & Joint Infections 4.5 Infective Endocarditis & Cardiovascular Infection 4.6 Clostridioides difficile & Catheter-Related Bloodstream Infection 4.7 HIV Diagnosis, Antiretroviral Therapy & Prevention 4.8 Opportunistic Infections & Sexually Transmitted Infections 4.9 Fever of Unknown Origin, Neutropenic Fever & Toxic Shock 4.10 Travel-Related Illness, Vector-Borne Disease & Outbreaks 4.11 Infection Prevention, Nosocomial Infection & Postexposure Prophylaxis 4.12 Rheumatic Fever, Poststreptococcal Disease, Enteric & Hepatic Infections
6 Chapter 5: Pulmonary Disease (9% of Exam)
5.1 COPD: Diagnosis, GOLD Classification & Initial Pharmacotherapy 5.2 Interventions That Reduce COPD Mortality & Exacerbation Management 5.3 Asthma: Diagnosis, Stepwise Therapy & Status Asthmaticus 5.4 Interstitial Lung Disease & Idiopathic Pulmonary Fibrosis 5.5 Sarcoidosis, Hypersensitivity Pneumonitis & Occupational Lung Disease 5.6 Pulmonary Embolism: Diagnosis, Risk Stratification & Anticoagulation 5.7 Pulmonary Hypertension & Sleep-Disordered Breathing 5.8 Acute Respiratory Distress Syndrome & Mechanical Ventilation 5.9 Pleural Disease, Empyema & Pneumothorax 5.10 Bronchiectasis, Cystic Fibrosis & Restrictive Lung Disease 5.11 Evaluation of Cough, Dyspnea, Hemoptysis & the Solitary Pulmonary Nodule
7 Chapter 6: Rheumatology & Orthopedics (9% of Exam)
6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease
8 Chapter 7: Hematology (6% of Exam)
7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation
9 Chapter 8: Medical Oncology (6% of Exam)
8.1 Breast, Lung, Colorectal & Prostate Cancer 8.2 Oncologic Emergencies 8.3 Genitourinary & Gynecologic Malignancies 8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary 8.5 Complications of Cancer & Its Treatment 8.6 Cancer Prevention, Survivorship & Psychosocial Care
10 Chapter 9: Nephrology & Urology (6% of Exam)
9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria
11 Chapter 10: Neurology (4% of Exam)
10.1 Acute Ischemic Stroke: Syndromes & Reperfusion 10.2 Transient Ischemic Attack, Secondary Prevention & Hemorrhagic Stroke 10.3 Headache & Facial Pain 10.4 Seizures, Epilepsy & Movement Disorders 10.5 Multiple Sclerosis & Neuromuscular Junction Disorders 10.6 Motor Neuron Disease & Acute Peripheral Neuropathy 10.7 Cranial Neuropathies & Neuro-Ophthalmology 10.8 Peripheral Neuropathies, CNS Tumors & Other Neurologic Disorders
12 Chapter 11: Psychiatry & Behavioral Health (4% of Exam)
11.1 Major Depressive Disorder & Medical Mimics 11.2 Antidepressant Pharmacotherapy & Treatment-Resistant Depression 11.3 Bipolar Disorder, Mood Stabilizers & Lithium Toxicity 11.4 Anxiety, Stress-Related & Obsessive-Compulsive Disorders 11.5 Alcohol Use Disorder & Withdrawal 11.6 Pharmacotherapy for Alcohol & Opioid Use Disorder 11.7 Toxidromes, Psychiatric Emergencies & Suicide Risk Assessment 11.8 Psychotic, Somatic Symptom, Factitious & Personality Disorders 11.9 Eating Disorders, Sleep Disorders & Sexual Health
13 Chapter 12: Dermatology (3% of Exam)
12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses 12.2 Acne, Rosacea & Cutaneous Infections 12.3 Herpes Zoster & Autoimmune Blistering Diseases 12.4 Nodules, Tumors & Cutaneous Oncology 12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions 12.6 Pigment Disorders, Alopecia, Nail Disease & Photosensitivity 12.7 Vascular Dermatoses, Environmental Injury & Cutaneous Signs of Systemic Disease
14 Chapter 13: Obstetrics & Gynecology / Women's Health (3% of Exam)
13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications
15 Chapter 14: Geriatric Syndromes (3% of Exam)
14.1 Comprehensive Geriatric Assessment & Frailty 14.2 Falls, Gait Assessment & Polypharmacy 14.3 Urinary Incontinence & Pressure Injuries in Older Adults 14.4 Mild Cognitive Impairment, Dementia & Its Subtypes 14.5 Delirium & the Pharmacotherapy of Cognitive Disorders 14.6 Palliative Care, Hospice & Advance Care Planning 14.7 Chronic Wounds, Nutrition, Swallowing, Constipation & Hip Fracture 14.8 Sensory Impairment, Dizziness, Elder Mistreatment & Care Settings
16 Chapter 15: Allergy & Immunology (2% of Exam)
15.1 Anaphylaxis: Recognition & Emergency Management 15.2 Urticaria & Angioedema 15.3 Drug Allergy, Desensitization & Adult Immunodeficiency 15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions 15.5 Rhinitis, Conjunctivitis, Eosinophilic & Mast Cell Disorders
17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology
16.1 The USPSTF Framework & Evidence-Based Cancer Screening 16.2 Cardiovascular & Metabolic Screening and Primary Prevention 16.3 Adult Immunization & Vaccines in Special Populations 16.4 Clinical Epidemiology, Biostatistics & Study Design
18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)
17.1 Principles of Bioethics & Decisional Capacity 17.2 Informed Consent, Treatment Refusal & Special Scenarios 17.3 Surrogate Decision-Making, Advance Directives & Confidentiality 17.4 Patient Safety Science, Medical Error & Diagnostic Reasoning 17.5 Quality Improvement Methods, Health Disparities & Health Equity
19 Chapter 18: Perioperative Medicine & Medical Consultation
18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications
20 Chapter 19: Ophthalmology (1% of Exam)
19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease
21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)
20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders
11.3 Bipolar Disorder, Mood Stabilizers & Lithium Toxicity
Key Takeaways Explain This Topic AI
Bipolar I requires a manic episode, while bipolar II requires hypomania with a major depressive episode and no history of mania.
Lithium toxicity is precipitated by volume depletion, non-steroidal anti-inflammatory drugs, thiazides and angiotensin-converting enzyme inhibitors.
Severe lithium toxicity with neurologic impairment or kidney failure is treated with hemodialysis.
Lithium causes nephrogenic diabetes insipidus, chronic tubulointerstitial disease and hypothyroidism, requiring periodic monitoring.
Valproate is contraindicated in people who may become pregnant because of neural tube defects and adverse neurodevelopmental outcomes.
Last updated: August 2026
1. Bipolar Disorder: Classification, Mood Stabilizers & Lithium Toxicity
Bipolar disorder is characterized by pathological fluctuations in mood, energy, and activity levels. Accurate differentiation from unipolar depression is critical, as incorrect pharmacotherapy can trigger life-threatening mania.
Diagnostic Distinction: Bipolar I vs. Bipolar II vs. Cyclothymia
Diagnostic Category Diagnostic Criteria & Episode Characteristics Psychosis & Hospitalization Functional Impairment
Bipolar I Disorder >=1 Lifetime Manic Episode (major depressive episode is common but not required for diagnosis). Manic episode: Distinct period of abnormally and persistently elevated, expansive, or irritable mood + increased goal-directed activity lasting >= 1 week (or any duration if hospitalization is necessary), with >=3 DIG FAST symptoms (>=4 if mood is irritable) Psychotic features (delusions, hallucinations) may be present ; frequently requires emergent hospitalization Severe impairment in social, occupational, or interpersonal functioning
Bipolar II Disorder >=1 Hypomanic Episode AND >=1 Major Depressive Episode ; must NEVER have had a full manic episode. Hypomanic episode: Lasts >= 4 consecutive days with >=3 DIG FAST symptoms; clear change from baseline observable by others NO psychotic features ; does NOT require hospitalization Unequivocal change in functioning, but does NOT cause severe social or occupational impairment
Cyclothymic Disorder Chronic, fluctuating mood disturbance lasting >= 2 years in adults (>=1 year in adolescents) with numerous periods of hypomanic symptoms and depressive symptoms that do not meet full criteria for hypomania or major depression No psychosis; no hospitalization Mild-to-moderate chronic distress and functional impairment DSM-5 Manic Symptom Mnemonic: "DIG FAST"
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- D — Distractibility (attention easily drawn to unimportant external stimuli)
I — Indiscretion / Impulsivity (excessive involvement in high-risk activities: spending sprees, sexual indiscretions, reckless driving)
- G — Grandiosity (inflated self-esteem, delusions of special power, wealth, or identity)
- F — Flight of ideas (subjective experience that thoughts are racing; rapid topic shifting)
A — Activity increase (increased goal-directed activity socially, at work, or sexually) or psychomotor agitation
- S — Sleep decreased need (feels fully rested and energized after only 2 to 3 hours of sleep)
- T — Talkativeness (pressured, rapid, loud speech that is difficult or impossible to interrupt)
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CRITICAL ABIM BOARD SAFETY RULE: Antidepressant Monotherapy in Bipolar Disorder Initiating antidepressant monotherapy (SSRIs, SNRIs, TCAs, Bupropion) in a patient with Bipolar I or Bipolar II disorder is strictly contraindicated . Antidepressant monotherapy carries a high risk of precipitating an acute switch into mania or hypomania , triggering mixed states, or accelerating rapid cycling (>4 mood episodes/year). In bipolar depression, mood stabilizers or approved atypical antipsychotics must always be used as first-line therapy.
- First-Line Mood Stabilizer Pharmacology & Monitoring
- 1. Lithium Carbonate
Mechanism of Action: Alters transmembrane cation transport; inhibits inositol monophosphatase (depleting neuronal second-messenger PIP2); inhibits Glycogen Synthase Kinase-3 (GSK-3beta); promotes neurogenesis and neuroprotection.
Efficacy: Gold-standard mood stabilizer for acute mania, bipolar maintenance, and bipolar depression; proven to reduce suicide mortality and completed suicide rates by >5-fold in bipolar and recurrent unipolar depression.
Therapeutic Serum Levels (12-hour trough level):
- Acute Mania: 0.8 to 1.2 mEq/L
- Long-Term Maintenance: 0.6 to 0.8 mEq/L (elderly: 0.4 to 0.6 mEq/L)
Mandatory Baseline & Routine Monitoring:
Renal Function (BUN, Serum Creatinine, eGFR): Lithium is 100% cleared by the kidneys; monitor every 3-6 months.
Thyroid Function (TSH, Free T4): Lithium inhibits thyroid hormone synthesis and release (causes benign goiter and hypothyroidism in 15-20% of patients; manage by adding Levothyroxine, do not discontinue lithium ).
Serum Calcium: Lithium alters calcium-sensing receptors, causing hyperparathyroidism and hypercalcemia ; monitor annually.
Urinalysis: Screen for Nephrogenic Diabetes Insipidus (NDI) (polyuria, polydipsia, low urine osmolality <300 mOsm/kg despite water deprivation; lithium enters principal cells via ENaC channels and disrupts aquaporin-2 expression; treated with Amiloride which blocks ENaC, plus thiazides/indomethacin).
Baseline 12-Lead ECG: T-wave flattening, sinus node dysfunction.
Pregnancy Test (beta-hCG): First-trimester exposure carries an elevated risk of Ebstein Anomaly (apical displacement of the tricuspid valve leaflets, atrialization of the right ventricle, tricuspid regurgitation; absolute risk ~1 in 1000 live births vs 1 in 20,000 baseline).
Lithium Toxicity Clinical Manifestations & Hemodialysis Triggers
Toxicity Severity & Serum Level Clinical Signs & Neurological Manifestations Precipitating Factors & Drug-Drug Interactions Management Protocol
Mild-to-Moderate Toxicity ; (1.5 to 2.0 mEq/L) Coarse hand tremor, muscular weakness, ataxia, dysarthria, sluggishness, lethargy, persistent nausea, vomiting, watery diarrhea Dehydration, volume depletion, fever, reduced oral fluid intake, low-sodium diets Discontinue lithium; obtain stat serum lithium level, CMP, and ECG; administer IV 0.9% Normal Saline at 150-200 mL/h to restore GFR
Moderate-to-Severe Toxicity ; (2.0 to 2.5 mEq/L) Coarse tremor, profound ataxia, hyperreflexia, muscle fasciculations, myoclonus, confusion, delirium, visual hallucinations, flat affect Drug Interactions that Impair Renal Lithium Excretion: ; 1. NSAIDs (ibuprofen, naproxen, celecoxib; reduce renal prostaglandin synthesis -> decrease renal blood flow and GFR); 2. ACE Inhibitors & ARBs (lisinopril, losartan; decrease GFR); 3. Thiazide Diuretics (hydrochlorothiazide, chlorthalidone; promote sodium loss in distal tubule -> compensatory proximal reabsorption of Na and Li); (Note: Aspirin and Sulindac have minimal effect on lithium levels) ICU admission; aggressive IV 0.9% Normal Saline volume resuscitation; continuous telemetry; avoid forced diuresis with loop diuretics
Severe Life-Threatening Toxicity ; (> 2.5 mEq/L or > 4.0 mEq/L) Seizures, status epilepticus, non-convulsive status, generalized hypertonia, stupor, coma, ventricular arrhythmias, circulatory collapse, acute oliguric renal failure, death Severe acute overdose, acute-on-chronic ingestion, severe renal failure EMERGENT HEMODIALYSIS INDICATIONS: ; 1. Serum Lithium Level > 4.0 mEq/L regardless of clinical symptoms.; 2. Serum Lithium Level > 2.5 mEq/L in the presence of severe neurological toxicity (seizures, coma, marked delirium) or acute renal failure.; 3. Hemodynamically unstable patient or lithium levels continuing to rise despite IV saline hydration. (Note: Continue HD until level is <1.0 mEq/L; monitor for post-dialysis rebound release from intracellular stores)