62.2 Bipolar Disorder: Maintenance Pharmacotherapy & Lithium Monitoring

ABFM Family Medicine Certification Study Guide Exam

Track your progress as you read

Finished sections get a check mark.

1 Chapter 1: Exam Structure, Blueprint & Clinical Decision-Making

1.1 Exam Blueprint, FMCLA vs. One-Day Exam & Board Scoring 1.2 Clinical Reasoning, Test-Taking Strategy & Ambiguity Management 1.3 Evidence-Based Medicine & Clinical Practice Guidelines in Primary Care

2 Chapter 2: Healthcare Systems, Practice Management & Quality

2.1 Practice Management, Billing, Coding & Documentation 2.2 Quality Improvement, Patient Safety & Diagnostic Stewardship 2.3 Interprofessional Team-Based Care & Care Coordination

3 Chapter 3: Ethics, Law, Biostatistics & Health Equity

3.1 Medical Ethics, Informed Consent & Surrogate Decision-Making 3.2 Biostatistics, Clinical Epidemiology & Diagnostic Test Interpretation 3.3 Social Determinants of Health, Health Equity & Cultural Humility 3.4 Physician Wellness, Burnout Prevention & Professionalism

4 Chapter 4: Lifestyle Counseling & Behavior Change

4.1 Alcohol Use Screening & Brief Intervention 4.2 Illicit Drug & Cannabis Counseling 4.3 Tobacco & Vaping Cessation Counseling

5 Chapter 5: Nutrition, Physical Activity & Chronic Disease Prevention

5.1 Dietary Counseling for Obesity & Chronic Disease Prevention 5.2 Exercise Prescription & Physical Activity Counseling 5.3 Genetic Risk Assessment & Family History Counseling

6 Chapter 6: Routine Adult Immunizations

6.1 ACIP Adult Respiratory Vaccines: Influenza, COVID-19, RSV & Pneumococcal 6.2 ACIP Adult Non-Respiratory Vaccines: Tdap, Shingrix, HPV & Hep B 6.3 Immunizations in Special Populations: Pregnancy, Asplenia & Immunocompromise

7 Chapter 7: Pediatric Health Maintenance & Surveillance

7.1 Newborn Examination & Early Postnatal Care 7.2 Well-Child Care, Developmental Surveillance & Milestones 7.3 Pediatric & Adolescent Screening: Vision, Hearing, Anemia & Lead 7.4 Pediatric Oral Health, Dental Screening & Fluoride

8 Chapter 8: Behavioral Health & Safety Screening

8.1 Primary Care Depression, Anxiety & Behavioral Health Screening 8.2 Domestic Violence, Intimate Partner Violence & Firearm Safety 8.3 Occupational Health & Recreational Safety Counseling

9 Chapter 9: Adult Preventive Screening: Cardiovascular & Metabolic

9.1 Cardiovascular Disease & Hypertension Screening 9.2 Type 2 Diabetes Screening & Prediabetes Risk Stratification 9.3 Abdominal Aortic Aneurysm & Osteoporosis Screening

10 Chapter 10: Adult Cancer Screening: Breast & Gynecologic

10.1 Breast Cancer Screening & Risk-Assessment 10.2 Cervical Cancer Screening & ASCCP Algorithms 10.3 Skin Cancer Clinical Assessment & Counseling

11 Chapter 11: Adult Cancer Screening: Colorectal, Lung & Prostate

11.1 Colorectal Cancer Screening Modalities & Intervals 11.2 Lung Cancer Screening with Low-Dose CT 11.3 Prostate Cancer Screening & Shared Decision-Making

12 Chapter 12: Sexual Health, Infectious Disease Screening & Contraception

12.1 Sexual Health Counseling & Risk-Reduction Strategies 12.2 STI Screening: Chlamydia, Gonorrhea, Syphilis & Trichomoniasis 12.3 Bloodborne Infectious Disease Screening: HIV & Hepatitis C

13 Chapter 13: Reproductive Life Planning, Lactation & Preoperative Care

13.1 Preconception Planning & Comprehensive Contraception Management 13.2 Lactation Support & Breastfeeding Counseling 13.3 Preoperative Medical Evaluation & Pre-Participation Sports Exam

14 Chapter 14: Emergent Cardiovascular Conditions

14.1 Acute Coronary Syndromes & Myocardial Infarction 14.2 Acute Chest Pain Risk Stratification & Triage 14.3 Acute or Critical Valvular Heart Emergencies

15 Chapter 15: Cardiac Arrhythmias, Heart Failure & Hypertensive Crises

15.1 Acute Atrial & Ventricular Arrhythmias 15.2 Acute Decompensated Heart Failure & Cardiogenic Shock 15.3 Hypertensive Emergency & Urgency Management

16 Chapter 16: Vascular & Thromboembolic Emergencies

16.1 Pulmonary Embolism & Deep Vein Thrombosis 16.2 Acute Aortic Syndromes & Peripheral Vascular Emergencies 16.3 Critical Limb Ischemia & Acute Arterial Occlusion

17 Chapter 17: Neurologic Emergencies: Stroke & Altered Consciousness

17.1 Acute Ischemic Stroke & Intracranial Hemorrhage 17.2 Syncope Evaluation & Status Epilepticus 17.3 Acute Delirium, Encephalopathy & Severe Confusion

18 Chapter 18: Neurologic Trauma & Acute Cranial Emergencies

18.1 Concussion, Moderate-to-Severe TBI & Intracranial Injury 18.2 Thunderclap & Acute Severe Secondary Headaches 18.3 Acute Ophthalmologic Emergencies

19 Chapter 19: Acute Abdominal, Pelvic & Gastrointestinal Emergencies

19.1 Acute Abdominal & Pelvic Pain Triage 19.2 Upper & Lower Gastrointestinal Bleeding 19.3 Acute Hepatic Failure, Cholangitis & Severe Jaundice

20 Chapter 20: Acute Pulmonary & Airway Emergencies

20.1 Acute Hypoxic Respiratory Failure & ARDS 20.2 Severe Community-Acquired Pneumonia & Empyema 20.3 Acute Severe Epistaxis & Airway Obstruction

21 Chapter 21: Acute Traumatic Injuries & Wound Care

21.1 Major Trauma Resuscitation & Initial Assessment 21.2 Burn Assessment, Inhalation Injury & Resuscitation 21.3 Laceration Management, Complex Wounds & Animal Bites

22 Chapter 22: Acute Orthopedic & Musculoskeletal Emergencies

22.1 Acute Ambulatory Fractures & Initial Splinting 22.2 Compartment Syndrome & Major Orthopedic Trauma 22.3 Septic Arthritis & Acute Microcrystalline Crises

23 Chapter 23: Severe Infections, Sepsis & Systemic Emergencies

23.1 Sepsis, Septic Shock & Initial Fluid Resuscitation 23.2 Necrotizing Soft Tissue Infections & Severe CNS Infections 23.3 Anaphylaxis Diagnosis, Epinephrine Dosing & Airway Protection

24 Chapter 24: Metabolic, Endocrine & Electrolyte Emergencies

24.1 Diabetic Ketoacidosis & Hyperosmolar Hyperglycemic State 24.2 Critical Electrolyte Emergencies: Dyskalemias & Dysnatremias 24.3 Severe Calcium Abnormalities & Acute Adrenal Crisis

25 Chapter 25: Hematologic, Urologic & Dental Emergencies

25.1 Severe Symptomatic Anemias & Coagulopathic Emergencies 25.2 Testicular Torsion, Priapism & Acute Urinary Retention 25.3 Urgent Odontogenic Infections & Dental Trauma

26 Chapter 26: Psychiatric, Behavioral & Obstetric/Gynecologic Emergencies

26.1 Suicidal Ideation, Acute Agitation & Behavioral Emergencies 26.2 Acute Physical & Sexual Assault Care 26.3 Life-Threatening Vaginal Bleeding & Ectopic Pregnancy 26.4 Environmental Heat Stroke & Severe Hypothermia

27 Chapter 27: Acute Head, Neck & Neurologic Symptoms

27.1 Primary Acute Headaches: Migraine, Tension & Cluster 27.2 Concussion & Minor Closed Head Injury Evaluation 27.3 Transient Ischemic Attack Evaluation & ABCD2 Risk Scoring

28 Chapter 28: Acute Cranial Nerves, Hearing & Sensory Symptoms

28.1 Peripheral Neuropathies: Bell's Palsy, Carpal Tunnel & Radiculopathy 28.2 Acute Tinnitus, Sudden Sensorineural Hearing Loss & Cerumen Impaction 28.3 Acute Dizziness, Benign Paroxysmal Positional Vertigo & Vestibular Neuritis

29 Chapter 29: Acute Upper Respiratory Tract Infections

29.1 Acute Viral Rhinosinusitis vs. Bacterial Rhinosinusitis 29.2 Acute Pharyngitis: Group A Streptococcus & Centor Criteria 29.3 Acute Otitis Media, Otitis Externa & Serous Effusion

30 Chapter 30: Acute Lower Respiratory Infections & Cough

30.1 Influenza, COVID-19 & Viral Respiratory Syndromes 30.2 Acute Bronchitis & Lower Respiratory Tract Infections 30.3 Ambulatory Community-Acquired Pneumonia

31 Chapter 31: Allergic, Nasal & Non-Infectious Pulmonary Conditions

31.1 Allergic Rhinitis & Acute Non-Anaphylactic Allergic Reactions 31.2 Acute Dyspnea in Ambulatory Care 31.3 Interstitial Lung Diseases & Sarcoidosis Presentation

32 Chapter 32: Acute Chest, Cardiac & Vascular Symptoms

32.1 Palpitations Evaluation & Arrhythmia Triage in Primary Care 32.2 Deep Vein Thrombosis & Superficial Thrombophlebitis 32.3 Ambulatory Hypotension & Orthostasis Evaluation

33 Chapter 33: Acute Upper Gastrointestinal Conditions

33.1 Peptic Ulcer Disease & Gastritis 33.2 Dysphagia, Esophagitis & Acute Esophageal Disorders 33.3 Acute Nausea, Vomiting & Foodborne Illness

34 Chapter 34: Acute Lower Gastrointestinal Conditions

34.1 Acute Infectious Diarrhea & Gastroenteritis 34.2 Acute Constipation & Functional Bowel Changes 34.3 Ano-Rectal Disorders: Hemorrhoids, Fissures, Abscesses & Pruritus Ani

35 Chapter 35: Inflammatory, Functional & Malabsorptive GI Disorders

35.1 Acute Flares of Inflammatory Bowel Disease 35.2 Irritable Bowel Syndrome: Diagnosis, Subtyping & Management 35.3 Celiac Disease & Malabsorption Syndromes

36 Chapter 36: Acute Abdominal, Hepatic & Biliary Disorders

36.1 Ambulatory Abdominal & Pelvic Pain Triage 36.2 Acute Cholecystitis, Biliary Colic & Pancreatitis 36.3 Acute Liver Injury & Viral Hepatitis

37 Chapter 37: Acute Abdominal Wall, Hernias & Dental Conditions

37.1 Abdominal Wall, Inguinal & Ventral Hernias 37.2 Acute Dental Pain, Odontogenic Abscess & Aphthous Ulcers 37.3 Acute Edema: Unilateral vs. Bilateral Diagnostic Evaluation

38 Chapter 38: Acute Infectious Dermatoses

38.1 Bacterial Skin Infections: Impetigo, Cellulitis & Cutaneous Abscesses 38.2 Fungal Skin Infections: Tinea Corporis, Cruris, Pedis & Onychomycosis 38.3 Viral Cutaneous Infections: Herpes Simplex, Zoster & Molluscum Contagiosum

39 Chapter 39: Inflammatory, Allergic & Autoimmune Dermatoses

39.1 Atopic Dermatitis, Contact Dermatitis & Eczematous Flares 39.2 Non-Infectious Rashes: Urticaria, Drug Eruptions & Erythema Multiforme 39.3 Cutaneous Malignancies & Premalignant Lesions: AK, BCC, SCC & Melanoma

40 Chapter 40: Acute Shoulder, Elbow & Upper Extremity Injuries

40.1 Rotator Cuff Pathology, Tendinopathy & Shoulder Impingement 40.2 Lateral & Medial Epicondylitis, Olecranon Bursitis & Elbow Sprains 40.3 Wrist & Hand Soft-Tissue Injuries: De Quervain, TFCC & Finger Sprains

41 Chapter 41: Acute Knee, Ankle & Lower Extremity Injuries

41.1 Meniscal Tears, Ligamentous Knee Injuries & Patellofemoral Pain 41.2 Ankle Sprains, Ottawa Ankle Rules & Achilles Tendinopathy 41.3 Plantar Fasciitis, Shin Splints & Overuse Syndromes

42 Chapter 42: Acute Ambulatory Fractures & Dislocations

42.1 Distal Radius, Scaphoid & Common Upper Extremity Fractures 42.2 Metatarsal, Clavicle & Common Lower Extremity Fractures 42.3 Joint Dislocation Management: Nursemaid's Elbow & Shoulder Subluxation

43 Chapter 43: Acute Axial Musculoskeletal Pain & Falls

43.1 Acute Low Back Pain: Red Flags, Strain & Disc Herniation 43.2 Acute Cervical Strain, Whiplash & Axial Neck Pain 43.3 Evaluation of Falls in Ambulatory & Older Patients

44 Chapter 44: Acute Inflammatory Arthropathies & Generalized Pain

44.1 Acute Inflammatory Arthritis & Spondyloarthropathies 44.2 Myalgias, Rhabdomyolysis & Post-Viral Pain Syndromes 44.3 Acute Non-Headache Pain Management Strategies

45 Chapter 45: Acute Renal, Urinary & Genitourinary Conditions

45.1 Uncomplicated UTI, Pyelonephritis & Acute Urethritis 45.2 Hematuria Workup & Glomerulonephritis 45.3 Nephrolithiasis & Acute Urinary Tract Obstruction

46 Chapter 46: Acute Male Genitourinary & Prostatic Conditions

46.1 Acute Prostatitis, Epididymitis & Orchitis 46.2 Acute Scrotal Pain: Torsion vs Appendage, BPH & Male Genital Emergencies 46.3 Acute Urinary Retention & Incontinence Evaluation

47 Chapter 47: Acute Women's Health & Early Pregnancy Care

47.1 Early Pregnancy Diagnosis, Dating & Initial Complications 47.2 Abnormal Uterine Bleeding & Acute Menstrual Disorders 47.3 Premenstrual Syndrome & Premenstrual Dysphoric Disorder

48 Chapter 48: Breast Disorders, STIs & Pediatric Elimination

48.1 Palpable Breast Mass, Mastitis & Nipple Discharge 48.2 Sexually Transmitted Infections: Diagnosis, Staging & CDC Guidelines 48.3 Pediatric Enuresis & Encopresis

49 Chapter 49: Systemic Signs, Metabolic Dysregulation & Miscellaneous Infections

49.1 Acute Fever, Sepsis Screening & FUO in Primary Care 49.2 Acute Hyperglycemia & Symptomatic Hypoglycemia 49.3 Electrolyte Abnormalities: Mild-to-Moderate Disturbances 49.4 Vector-Borne, Tick-Borne & Rickettsial Illnesses

50 Chapter 50: Chronic Cardiovascular Diseases: Hypertension & Ischemia

50.1 Essential Hypertension Management: 2025 AHA/ACC Guideline & JNC Strategies 50.2 Chronic Coronary Artery Disease & Post-MI Secondary Prevention 50.3 Chronic Heart Failure: HFrEF, HFpEF & Quadruple GDMT

51 Chapter 51: Chronic Vascular, Valvular & Dyslipidemic Diseases

51.1 Peripheral Arterial Disease & Claudication 51.2 Chronic Valvular Heart Disease & Murmur Evaluation 51.3 Lipid Disorders & ASCVD Risk-Based Statin Therapy

52 Chapter 52: Chronic Respiratory Diseases: Asthma & COPD

52.1 Chronic Asthma Management: GINA Stepwise SMART Therapy 52.2 Chronic Obstructive Pulmonary Disease: GOLD Recommendations 52.3 Solitary Pulmonary Nodule Evaluation & Fleischner Society Criteria

53 Chapter 53: Chronic Metabolic Diseases: Diabetes Mellitus

53.1 Type 2 Diabetes Management: ADA Pharmacotherapy Algorithms 53.2 Type 1 Diabetes: Basal-Bolus Insulin, CGMs & Diabetic Complications 53.3 Diabetic Microvascular & Macrovascular Disease Surveillance

54 Chapter 54: Obesity, Nutrition & Metabolic Bone Diseases

54.1 Medical & Behavioral Management of Obesity & Incretin Mimetics 54.2 Osteoporosis & Metabolic Bone Disease: DEXA, FRAX & Antiresorptives 54.3 Nutritional Deficiencies: Vitamin D, B12, Iron & Malnutrition

55 Chapter 55: Chronic Endocrine Disorders

55.1 Primary & Subclinical Hypothyroidism, Hyperthyroidism & Nodules 55.2 Adrenal Disorders: Addison's Disease & Cushing's Syndrome 55.3 Hypercalcemia, Hyperparathyroidism & Pituitary Disorders

56 Chapter 56: Chronic Kidney Disease & Venous Disorders

56.1 Chronic Kidney Disease: KDIGO Staging & Renoprotective Therapy 56.2 Chronic Venous Insufficiency, Stasis Dermatitis & Lymphedema 56.3 Chronic Electrolyte & Acid-Base Management in CKD

57 Chapter 57: Chronic Gastrointestinal & Hepatic Diseases

57.1 Gastroesophageal Reflux Disease, Barrett's Esophagus & Dyspepsia 57.2 Chronic Liver Disease: MASLD/NAFLD, Cirrhosis & Portal Hypertension 57.3 Viral Hepatitis B & C: Long-Term Monitoring & DAA Therapy

58 Chapter 58: Colorectal Surveillance & Chronic Pancreaticobiliary Care

58.1 Post-Polypectomy Colorectal Polyp Surveillance Guidelines 58.2 Chronic Pancreatitis & Exocrine Pancreatic Insufficiency 58.3 Chronic Nausea, Gastroparesis & Functional GI Disorders

59 Chapter 59: Chronic Musculoskeletal & Rheumatologic Disorders

59.1 Osteoarthritis: Hip, Knee & Hand Management 59.2 Spinal Conditions: Spinal Stenosis, Spondylolisthesis & Compression Fractures 59.3 Chronic Myopathies & Fibromyalgia Syndrome

60 Chapter 60: Chronic Neurologic & Neurodegenerative Disorders

60.1 Dementia: Alzheimer's, Vascular & Lewy Body Disease 60.2 Parkinson's Disease & Essential Tremor 60.3 Epilepsy: Chronic Antiseizure Medications & Post-Stroke Care

61 Chapter 61: Chronic Peripheral Nerves, Pain & Sensory Disorders

61.1 Diabetic & Chronic Peripheral Neuropathies 61.2 Chronic Pain Syndromes & Chronic Daily Headaches 61.3 Chronic Tinnitus, Presbycusis & Persistent Dizziness

62 Chapter 62: Chronic Psychiatric Disorders

62.1 Major Depressive Disorder & Generalized Anxiety Disorder 62.2 Bipolar Disorder: Maintenance Pharmacotherapy & Lithium Monitoring 62.3 Adult & Pediatric Attention-Deficit/Hyperactivity Disorder

63 Chapter 63: Chronic Behavioral Health & Neurodevelopmental Conditions

63.1 Chronic Behavioral Conditions: PTSD, OCD & Somatization 63.2 Autism Spectrum Disorder & Intellectual Disabilities 63.3 Eating Disorders: Anorexia Nervosa, Bulimia & Binge Eating

64 Chapter 64: Chronic Substance Use Disorders & Tobacco Cessation

64.1 Alcohol Use Disorder: Pharmacotherapy & Relapse Prevention 64.2 Opioid & Stimulant Use Disorders: MOUD & Harm Reduction 64.3 Longitudinal Tobacco Cessation Pharmacotherapy

65 Chapter 65: Chronic Dermatologic Conditions

65.1 Acne Vulgaris, Rosacea & Seborrheic Dermatitis 65.2 Chronic Plaque Psoriasis & Biologic Therapies 65.3 Chronic Eczema, Hidradenitis Suppurativa & Cutaneous Lupus

66 Chapter 66: Chronic Reproductive, Infectious & Geriatric Special Care

66.1 Chronic Menstrual Disorders, Infertility & Sexual Dysfunction 66.2 Menopause Management & Hormone Replacement Therapy 66.3 Chronic HIV Infection Management & Primary Care Integration 66.4 Gender-Affirming Primary Care & Hormone Therapy 66.5 Advance Care Planning, Palliative Care & End-of-Life Symptom Control

67 Chapter 67: Continuity Care: Sleep, Fatigue, Cancer, Pregnancy & the Adult Preventive Visit

67.1 Chronic Insomnia & Obstructive Sleep Apnea 67.2 Chronic Malaise, Fatigue & ME/CFS 67.3 Primary Care During Cancer Treatment & Survivorship 67.4 Routine Prenatal Care & Longitudinal Pregnancy Management 67.5 The Periodic Adult Health Examination & Medicare Annual Wellness Visit

62.2 Bipolar Disorder: Maintenance Pharmacotherapy & Lithium Monitoring

Key Takeaways Explain This Topic AI

Bipolar I Disorder requires at least one lifetime manic episode lasting at least 7 days or requiring hospitalization, characterized by DIG FAST symptoms; Bipolar II Disorder requires at least one hypomanic episode (lasting at least 4 days without marked impairment, hospitalization, or psychosis) AND at least one major depressive episode.

Systematic screening for bipolar disorder using the Mood Disorder Questionnaire (MDQ) is mandatory in all patients presenting with depressive symptoms before initiating an antidepressant, because antidepressant monotherapy can precipitate acute mania, rapid cycling, or lethal mixed states.

Lithium is the gold-standard maintenance agent that uniquely demonstrates proven anti-suicide efficacy, requiring maintenance serum trough levels of 0.6 to 1.0 mEq/L drawn exactly 12 hours post-dose; routine surveillance mandates monitoring renal function (BUN/creatinine every 6 months), thyroid function (TSH every 6-12 months), and serum calcium annually.

Lithium is eliminated 100% by the kidneys and is heavily reabsorbed in the proximal tubule alongside sodium; toxicity is triggered by volume depletion and medications that reduce renal clearance, most notably thiazide diuretics (which increase lithium reabsorption by 30-50%), NSAIDs, and ACE inhibitors/ARBs.

Emergent hemodialysis is indicated for lithium toxicity when serum levels exceed 4.0 mEq/L regardless of symptoms, or when levels exceed 2.5 mEq/L in the presence of severe neurological signs (seizures, coma, delirium) or acute renal failure.

Last updated: September 2026

Classification and Clinical Spectrum of Bipolar Disorders

Bipolar disorders are recurrent, life-shortening mood disorders characterized by pathological oscillations in mood, energy, psychomotor activity, and cognition. Correct classification is among the most consequential diagnostic tasks in family medicine, as misattributing bipolar disorder to unipolar major depression leads to inappropriate antidepressant monotherapy, precipitating acute manic exhaustion, cycle acceleration, and elevated suicide mortality. THE BIPOLAR SPECTRUM: PHENOTYPIC SPECTRUM

• Disorder Category Obligate DSM-5-TR Diagnostic Criteria & Episode Trajectory
• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════
• Bipolar I Disorder • Requires at least ONE lifetime MANIC EPISODE (lasting >= 1 week or

requiring hospitalization).

• Major depressive episodes are typical throughout life but NOT required.

• Marked occupational/social impairment, psychotic features, or hospitalization.

• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Bipolar II Disorder • Requires at least ONE HYPOMANIC EPISODE (lasting >= 4 consecutive days)

AND at least ONE MAJOR DEPRESSIVE EPISODE.

• Must NEVER have experienced a full manic episode.

• Observable change in functioning, but NO marked impairment, NO psychosis,

and NO psychiatric hospitalization.

• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Cyclothymic Disorder • Persistent fluctuating mood disturbance for at least 2 YEARS in adults

(1 year in children/adolescents).

• Numerous periods of hypomanic symptoms (not meeting full criteria) and

depressive symptoms (not meeting major depressive episode criteria).

• Never symptom-free for > 2 consecutive months.

• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════
• Mania versus Hypomania: The Cardinal Distinctions

The differentiation between full mania and hypomania is absolute and dictates diagnostic classification. While both share identical core symptom domains, they differ dramatically in duration, severity, and clinical complications: MANIC EPISODE VS. HYPOMANIC EPISODE

• Diagnostic Feature Manic Episode (Bipolar I) Hypomanic Episode (Bipolar II)
• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════
• Minimum Duration At least 7 CONSECUTIVE DAYS At least 4 CONSECUTIVE DAYS
• (or any duration if hospitalized) (observable by family/colleagues)
• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Functional Impairment MARKED IMPAIRMENT in social, NO marked impairment in occupational
• occupational, or interpersonal life or social functioning
• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Psychiatric Hospitalization Frequently required to prevent harm NEVER REQUIRED (hospitalization
• to self or others automatically classifies as Mania)
• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Psychotic Features May be present (delusions of grandeur, NEVER PRESENT (psychosis
• paranoia, auditory hallucinations) automatically classifies as Mania)
• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════
• The DIG FAST Mnemonic for Manic/Hypomanic Symptoms

Under DSM-5-TR, an episode requires a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy, accompanied by at least 3 symptoms (or 4 symptoms if the mood is only irritable) from the DIG FAST criteria:

[D] Distractibility : Attention is easily drawn to unimportant, irrelevant external stimuli.

[I] Indiscretion / Impulsivity : Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., unrestrained shopping sprees, sexual indiscretions, reckless driving, foolish financial investments).

[G] Grandiosity : Inflated self-esteem or grandiosity, ranging from uncritical self-confidence to grandiose delusions of divine mission, special powers, or elite celebrity status.

[F] Flight of Ideas : Subjective experience that thoughts are racing, accompanied by rapid, disjointed topic switching on speech examination.

[A] Activity Increase : Substantial increase in goal-directed activity (socially, at work, at school, or sexually) or psychomotor agitation (aimless, non-goal-directed motor pacing).

[S] Sleep Deficit : Decreased need for sleep (distinct from insomnia: the patient sleeps only 2 to 3 hours but awakens feeling completely rested, energized, and ready to conquer the day).

[T] Talkativeness / Pressured Speech : Speech that is rapid, loud, intrusive, and exceedingly difficult to interrupt.

Screening Mandate: The Mood Disorder Questionnaire (MDQ)

Between 20% and 30% of patients presenting with major depressive episodes in primary care actually have an underlying bipolar diathesis. Patients rarely volunteer hypomanic symptoms during a depressive presentation because periods of hypomania are experienced as highly productive and ego-syntonic.

The Board-Style Pearl: The Peril of Antidepressant Monotherapy

Initiating antidepressant monotherapy (SSRIs, SNRIs, TCAs, or bupropion) in a patient with undiagnosed bipolar disorder without a concurrent mood-stabilizing agent carries devastating clinical consequences:

Precipitation of Acute Mania or Hypomania : Antidepressant-induced mood switching occurs in 15% to 40% of bipolar patients exposed to unipolar antidepressants.

Cycle Acceleration & Rapid Cycling : Antidepressants can destabilize mood rhythms, accelerating the patient into rapid cycling (defined as >= 4 distinct mood episodes within a 12-month period).

Induction of Mixed States : Produces a high-arousal state combining severe depressive dysphoria with manic psychomotor agitation and impulsivity—the clinical phenotype with the highest instantaneous risk of completed suicide .

Mandatory Clinical Practice : All primary care patients presenting with depression must be screened with the Mood Disorder Questionnaire (MDQ) . An MDQ is positive if the patient endorses >= 7 of 13 lifetime hypomanic/manic symptoms occurring simultaneously, causing moderate to severe impairment. Any positive MDQ warrants mood stabilizer therapy or psychiatric referral, and strictly precludes unipolar antidepressant monotherapy .

Maintenance Pharmacotherapy: Lithium Carbonate (The Gold Standard)

Lithium carbonate is the premier gold-standard mood stabilizer for the long-term maintenance of Bipolar I Disorder. It demonstrates superior efficacy in preventing both manic and depressive recurrences and possesses unique neuroprotective and antisuicidal properties. THE CARDINAL LIFE-SAVING PROPERTY OF LITHIUM

• Along with Clozapine, Lithium is one of only two psychiatric medications
• DEFINITIVELY PROVEN in randomized controlled trials and large cohort
• studies to substantially REDUCE THE RISK OF COMPLETED SUICIDE

and suicide attempts in bipolar patients.

Renal Handling and Pharmacokinetics of Lithium

Lithium is a monovalent cation with no plasma protein binding and zero hepatic metabolism. It is eliminated 100% unchanged by the kidneys :

Proximal Tubule Reabsorption : Lithium is freely filtered at the glomerulus. In the proximal convoluted tubule, approximately 80% of filtered lithium is reabsorbed , utilizing the same paracellular pathways and sodium-hydrogen antiporters (NHE3) as sodium ions.

The Sodium-Lithium Competition : The proximal tubule cannot distinguish between sodium and lithium. Consequently, any clinical condition or pharmacologic agent that induces hypovolemia, dehydration, or sodium depletion causes the proximal tubule to hyper-reabsorb sodium, simultaneously hyper-reabsorbing lithium , rapidly driving serum lithium concentrations into severe, life-threatening toxic ranges.

Therapeutic Window and Serum Trough Monitoring

Lithium has an extraordinarily narrow therapeutic index. Serum concentrations must be drawn precisely as a 12-hour trough level (exactly 12 hours after the evening dose, typically drawn at 8:00 AM after an 8:00 PM dose) at steady state (4 to 5 days after dose initiation or adjustment):

• Acute Manic Episode Target : 0.8 to 1.2 mEq/L
• Long-Term Maintenance Target : 0.6 to 1.0 mEq/L (In older adults or sensitive patients: 0.4 to 0.8 mEq/L)
• Toxicity Threshold : >= 1.5 mEq/L
• Severe/Life-Threatening Toxicity : > 2.0 to 2.5 mEq/L LITHIUM LABORATORY MONITORING PROTOCOL

• Organ System / Parameter Baseline Testing Requirements Ongoing Routine Surveillance Schedule
• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════
• Serum Lithium Trough Confirm steady state at 4-5 days Every 3 to 6 months in stable patients;
• Level (12-hr trough) after initial dose or titration 1 to 2 weeks after any dose adjustment
• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Renal Function Serum Creatinine, eGFR, BUN, Every 6 months. Monitor for chronic
• (Tubulointerstitial risk) and baseline Urinalysis tubulointerstitial nephropathy and NDI
• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Thyroid Function Serum TSH and Free T4 Every 6 to 12 months. Primary
• (Hypothyroidism / Goiter) hypothyroidism develops in 10-20%
• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Serum Calcium Serum Calcium and Albumin Every 12 months. Evaluates for lithium-
• (Hyperparathyroidism) induced parathyroid hyperplasia / adenoma
• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Cardiac Conduction 12-lead ECG in patients >= 40 years Repeat periodically or if syncope occurs;
• or with known cardiac disease monitors sinus node dysfunction
• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Pregnancy Status Serum or urine hCG in all Repeat immediately if menses delayed;
• females of childbearing potential screen for Ebstein anomaly in pregnancy
• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════
• Long-Term Organ Toxicities & Actionable Management

Thyroid Dysfunction (Hypothyroidism and Goiter) :

Mechanism : Lithium concentrates in the thyroid follicular cells, inhibiting iodine uptake, iodotyrosine coupling, and thyroid hormone release.

Incidence : Primary hypothyroidism develops in 10% to 20% of patients, far more frequently in women.

Clinical Management Pearl : Do NOT discontinue lithium if mood is well controlled ! Instead, continue lithium at the current therapeutic dose and initiate exogenous levothyroxine replacement therapy to normalize TSH.

Renal Dysfunction: Nephrogenic Diabetes Insipidus (NDI) & Chronic Kidney Disease :

Nephrogenic DI : Lithium enters principal cells of the medullary collecting duct via epithelial sodium channels (ENaC), inhibiting adenylate cyclase and downregulating aquaporin-2 water channels . Patients present with profound polyuria (>3 L/day) and polydipsia. Management: If lithium cannot be switched, Amiloride is the drug of choice because it selectively blocks ENaC, preventing further lithium accumulation inside collecting duct cells.

Chronic Tubulointerstitial Nephropathy : Long-term therapy (>10-20 years) can lead to irreversible interstitial fibrosis and tubular atrophy. If eGFR declines progressively below 30-45 mL/min or significant proteinuria develops, deliberate transition to an alternative mood stabilizer is warranted in consultation with nephrology.

Primary Hyperparathyroidism & Hypercalcemia :

Lithium alters the calcium-sensing receptor (CaSR) set-point in the parathyroid glands, stimulating parathyroid hormone (PTH) secretion and inducing multiglandular parathyroid hyperplasia or solitary adenomas. Check annual serum calcium.

Lithium in Pregnancy: The Real-World Risk of Ebstein Anomaly :

Historic teaching described massive risks of Ebstein anomaly (apical displacement of the tricuspid valve leaflets into the right ventricle, causing severe tricuspid regurgitation and 'atrialization' of the right ventricle).

Modern prospective registries demonstrate that the absolute risk is approximately 1 to 2 per 1,000 live births (compared to 1 per 20,000 in the general population). While this represents a 10- to 20-fold relative risk elevation, the absolute risk is far lower than historical estimates.

Perinatal Management : In women with severe, relapsing Bipolar I disorder, lithium may be maintained during pregnancy after rigorous informed consent. Perform a targeted fetal echocardiography and detailed anatomy scan at 18 to 22 weeks gestation. Lithium clearance increases by 30% to 50% during the second and third trimesters, requiring monthly trough monitoring, followed by an immediate dose reduction around delivery to prevent neonatal toxicity.

Lithium Toxicity: Stages, Precipitating Factors & Emergency Management STAGING & PHENOTYPE OF LITHIUM TOXICITY

• Toxicity Stage Serum Level Key Clinical Features & Neurological Findings
• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════
• Mild to Moderate 1.5 to 2.0 mEq/L Coarse resting and intention tremor (vs. fine postural
• Toxicity tremor at baseline), persistent nausea, vomiting, watery

diarrhea, muscular weakness, ataxia, and drowsiness.

• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Severe Toxicity > 2.0 to 2.5 mEq/L Gross confusion, disorientation, delirium, profound
• cerebellar ataxia, hyperreflexia, diffuse myoclonus,

choreoathetosis, seizures, stupor, and acute oliguria.

• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Life-Threatening > 3.5 to 4.0 mEq/L Coma, intractable status epilepticus, cardiovascular
• Toxicity collapse, multiorgan failure, permanent cerebellar injury

(SILENT syndrome), and death.

• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════
• The High-Yield Drug Interactions Triggering Toxicity

In board examinations and clinical practice, lithium toxicity is most commonly precipitated by the addition of common medications that alter renal hemodynamics or sodium handling: PHARMACOLOGIC TRIGGERS OF LITHIUM TOXICITY

• Drug Class & Agents Pathophysiologic Mechanism of Interaction Relative Risk Level
• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════

Thiazide Diuretics Inhibit Na/Cl cotransporter in distal tubule. HIGHEST RISK DIURETIC:

(HCTZ, Chlorthalidone) Induces volume depletion, causing compensatory Increases serum lithium

proximal tubule sodium/lithium reabsorption. levels by 30% to 50%!

─────────────────────────────────────────────────────────────────────────────────────────────────────────

NSAIDs Inhibit renal prostaglandin synthesis, DANGEROUS COMBINATION:

(Ibuprofen, Naproxen, blunting renal vasodilatory tone. Decreases Increases serum lithium

Celecoxib, Indomethacin) renal blood flow and GFR, reducing excretion. levels by 25% to 40%!

(Aspirin & Acetaminophen do not affect GFR).

─────────────────────────────────────────────────────────────────────────────────────────────────────────

ACE Inhibitors & ARBs Dilate efferent arterioles, reducing intra- GRADUAL TOXICITY:

(Lisinopril, Losartan) glomerular filtration pressure and GFR. Causes insidious lithium

accumulation over 1-3 weeks.

─────────────────────────────────────────────────────────────────────────────────────────────────────────

Loop Diuretics (Furosemide) Induce volume contraction; less proximal Moderate risk; monitor levels.

Volume Loss / Dehydration Gastroenteritis, febrile sweating, sauna. High risk; triggers acute toxicity.

• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════
• Emergency Management Algorithm for Lithium Toxicity

Immediate Cessation : Discontinue lithium immediately.

Stat Diagnostic Panel : Obtain serum lithium level, comprehensive metabolic panel (BUN, creatinine, electrolytes), and a 12-lead ECG.

Isotonic Normal Saline Hydration : Administer IV 0.9% Normal Saline at 150 to 200 mL/hr . Saline re-expands intravascular volume, restores renal perfusion, and provides sodium ions to the proximal tubule, competitively promoting urinary excretion of lithium.

Activated Charcoal is Ineffective : Activated charcoal DOES NOT bind monovalent cations like lithium and should never be administered for pure lithium ingestions.

Emergent Hemodialysis : Hemodialysis is the definitive, life-saving modality for severe lithium intoxication.

Absolute Indications for Hemodialysis :

Serum lithium level > 4.0 mEq/L , regardless of the patient's clinical symptoms.

Serum lithium level > 2.5 mEq/L in the presence of severe neurological manifestations (seizures, coma, delirium, myoclonus) or hemodynamic instability.

Serum lithium level > 2.5 mEq/L in patients with acute renal failure, chronic end-stage renal disease, or severe heart failure unable to tolerate vigorous saline hydration.

Patients whose lithium levels rise or fail to decline despite aggressive IV saline hydration.

Note on Dialysis Rebound : Lithium equilibrates slowly between intracellular and extracellular compartments. Serum lithium levels frequently rebound 6 to 12 hours after hemodialysis as intracellular lithium shifts into the vascular space, frequently necessitating a second dialysis session.

Alternative Mood Stabilizers & Second-Generation Antipsychotics ALTERNATIVE MAINTENANCE AGENTS FOR BIPOLAR DISORDER

• Medication Target Levels & Monitoring Clinical Niche & Efficacy Black Box Warnings & Critical Risks
• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════

Divalproex Trough: 50-125 mcg/mL. First-line for acute mania, • HEPATOTOXICITY (microvesicular).

Sodium / Monitor: CBC (platelets), mixed features, and rapid • PANCREATITIS (hemorrhagic).

Valproate LFTs, lipase/amylase, weight. cycling presentations. • EXTREME TERATOGENICITY:

Neural tube defects (spina

bifida), 8-10 pt IQ drop!

• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Lamotrigine No therapeutic drug level. First-line maintenance for • STEVENS-JOHNSON SYNDROME (SJS)

(Lamictal) Strict slow titration: start BIPOLAR DEPRESSION. and Toxic Epidermal Necrolysis.

25 mg daily; slow escalation. Ineffective for acute mania. • Valproate doubles half-life;

must cut dose by 50%!

• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Quetiapine Dose: 300 mg daily at bedtime. FDA-approved monotherapy Metabolic syndrome: weight gain,
• (Seroquel) Monitor: fasting glucose, lipids, for acute bipolar depression hypertriglyceridemia, diabetes;

BMI, annual AIMS exam. and maintenance. sedation and orthostasis.

• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Lurasidone Dose: 20-80 mg daily with food First-line for acute bipolar Minimal metabolic weight gain;
• (Latuda) (>=350 calories). Monitor lipids, depression; pregnancy must take with >=350 kcal meal;

glucose, and AIMS exam. favorable. akathisia and EPS risk.

• ─────────────────────────────────────────────────────────────────────────────────────────────────────────
• Cariprazine Dose: 1.5-3 mg daily. D3/D2 partial agonist; Akathisia, restlessness, EPS;

(Vraylar) Monitor lipids, glucose, AIMS. bipolar depression & mania. long half-life (active weeks).

• ═════════════════════════════════════════════════════════════════════════════════════════════════════════════
• Divalproex Sodium: Teratogenicity & Surveillance Pearls

Divalproex sodium (valproate) is highly effective for euphoric and dysphoric mania, mixed episodes, and rapid cycling. However, its use is heavily constrained by serious toxicities:

Dose-Dependent Thrombocytopenia : Platelet counts must be checked at baseline and periodically; counts <100,000/mcL require dose reduction or discontinuation.

Black Box Hepatotoxicity & Pancreatitis : Monitor transaminases and abdominal pain symptoms. Fatal hemorrhagic pancreatitis can develop unpredictably at any time during therapy.

Extreme Teratogenicity : First-trimester valproate exposure carries a 1% to 2% risk of neural tube defects (lumbar spina bifida) , craniofacial defects, cardiovascular anomalies, and severe neurodevelopmental harm (producing an average 8- to 10-point reduction in childhood IQ and high rates of autism spectrum disorder). Valproate is strictly contraindicated in females of childbearing potential unless all alternative therapies have failed and two forms of reliable contraception are documented.

Lamotrigine: Slow Titration and Stevens-Johnson Syndrome

Lamotrigine is the premier maintenance mood stabilizer specifically for preventing depressive recurrences in Bipolar I and Bipolar II disorder (it lacks efficacy for acute mania).

Black Box Warning for SJS/TEN : The risk of life-threatening Stevens-Johnson syndrome is directly tied to the speed of initial dose titration. Titration must follow a rigid protocol: 25 mg daily for Weeks 1 and 2, then 50 mg daily for Weeks 3 and 4, then 100 mg daily for Week 5, reaching target 200 mg daily at Week 6 .

The Rule of Discontinuation : If a patient misses lamotrigine for more than 5 half-lives (approximately 5 days) , tolerance to the titration is lost. The clinician MUST restart the titration from 25 mg daily rather than resuming the full maintenance dose.

The Critical Valproate Drug Interaction : Valproate potent inhibits lamotrigine glucuronidation, more than doubling the elimination half-life of lamotrigine (from ~25 hours to ~60 hours). When adding lamotrigine to valproate, the lamotrigine starting dose MUST BE REDUCED BY AT LEAST 50% (starting 25 mg every other day) to avoid triggering SJS. Conversely, enzyme inducers (carbamazepine, phenytoin, and estrogen-containing oral contraceptives) double lamotrigine clearance, requiring higher maintenance doses.

Second-Generation Antipsychotics (SGAs) & Metabolic Surveillance

Second-generation antipsychotics play an indispensable role in bipolar management:

Bipolar Depression : Monotherapy with Quetiapine , Lurasidone (taken with >= 350 kcal meal), Cariprazine , or Olanzapine-Fluoxetine combination (OFC) are FDA-approved first-line treatments.

Acute Mania & Maintenance : Aripiprazole, Risperidone, Olanzapine, and Ziprasidone are robust anti-manic agents.

Mandatory Metabolic Surveillance (ADA/APA Consensus Protocol) :

Fasting Plasma Glucose / HbA1c: Baseline, 3 months, then annually.

Fasting Lipid Profile: Baseline, 3 months, then annually.

Body Weight and BMI: Baseline, 4 weeks, 8 weeks, 12 weeks, then quarterly.

Blood Pressure & Waist Circumference: Baseline and annually.

Abnormal Involuntary Movement Scale (AIMS): Every 6 to 12 months to detect early tardive dyskinesia (involuntary choreoathetoid movements of the tongue, face, or extremities).

Loading diagram... Bipolar Maintenance Decision Tree, Lithium Monitoring, and Toxicity Triage Pathway