Learning Objectives
By the end of this session, the learner will be able to identify the primary mood stabilizers used for Bipolar I Disorder, explain the molecular mechanism of Lithium, and recognize the high-yield toxicities and drug interactions associated with Lithium therapy.
1. Overview of Treatment
Bipolar I Disorder involves at least one manic episode. Treatment is often a combination of pharmacology, psychotherapy, and potentially ECT.
| Drug Class | Examples | Clinical Role |
|---|---|---|
| Mood Stabilizers | Lithium, Valproic acid, Carbamazepine. | Maintenance and acute mania. |
| Atypical Antipsychotics | Quetiapine, Lurasidone. | Acute mania and bipolar depression. |
| Anticonvulsants | Lamotrigine, Valproic acid. | Maintenance and depression prevention. |
2. Lithium: Mechanism of Action
Lithium interferes with intracellular signaling by disrupting the phosphoinositide (PI) cycle.
| Mechanism | Biochemical Result | Impact |
|---|---|---|
| Inositol Monophosphatase | Blocks the recycling of inositol. | Decreased  levels. |
| Adenylyl Cyclase | Inhibition of enzyme activity. | Decreased cAMP levels. |
| GSK-3 Inhibition | Blocks Glycogen Synthase Kinase-3. | Modulates neuroprotective pathways. |
3. Lithium Toxicity & Side Effects
Lithium has a narrow therapeutic index. Because it is a small ion, it affects multiple organ systems, necessitating frequent serum monitoring.
| Organ System | Side Effect | High-Yield Detail |
|---|---|---|
| Neurologic | Tremor | Very common; often managed with propranolol. |
| Renal | Nephrogenic DI | Blocks  receptors; treat with Amiloride. |
| Thyroid | Hypothyroidism | Can cause a compensatory goiter; check TSH levels. |
| Teratogenic | Ebstein Anomaly | Malformed tricuspid valve (“atrialized” right ventricle). |
4. Critical Drug Interactions
Lithium is cleared entirely by the kidneys. Interactions that decrease the glomerular filtration rate (GFR) or alter sodium handling are extremely dangerous.
Factors that Increase Lithium Levels:
- NSAIDs (Except Aspirin) decrease renal blood flow.
- Thiazide Diuretics: Cause sodium loss, which triggers the kidney to reabsorb more Lithium.
- ACE Inhibitors / ARBs: Disrupt renal autoregulation and clearance.
Clinical Pearls:
- Diabetes Insipidus Treatment: Amiloride is the drug of choice because it prevents Lithium from entering the collecting duct cells via the ENaC channel.
- Monitoring: Serum Lithium levels must be kept between 0.6–1.2 mEq/L. Levels above 1.5 mEq/L can cause ataxia, confusion, and seizures.