Mood Stabilizers (Lithium)

A first-line treatment, and the only agent here with an antisuicidal property. Lithium is on the first-line list for acute mania in the CANMAT/ISBD and WFSBP guidelines, as reported by StatPearls, and it carries something none of the others do: it "remains the best-supported maintenance treatment," and it remains "the only mood stabilizer consistently associated with reduced suicide mortality across multiple studies"; the nursing text adds that it "possesses unique antisuicidal properties that sets it apart from antidepressants." That property is the disorder-side reason lithium survives its own toxicity profile. Expect 1 to 3 weeks for symptom relief — lithium "may reduce symptoms within one to three weeks" — and expect that a full response is not guaranteed. The therapeutic range is 0.8 to 1.2 mEq/L for acute goals and 0.8 to 1.0 mEq/L for maintenance, per the current FDA label (an older legacy label still in circulation prints a 0.6 floor; the current labeling supersedes it), drawn immediately before the next dose, about 12 hours after the previous one, and re-checked after any dose change, any new interacting medicine, a marked change in strenuous exercise, or any intercurrent illness. Why the safety rules are so strict is pharmacokinetic, not cautionary: lithium is neither protein bound nor metabolized, the proximal tubule reabsorbs 80% of it through sodium transport pathways, and "even minor changes in volume status, renal perfusion, or sodium balance can produce clinically significant changes in serum lithium concentrations." Toxicity most commonly results from reduced renal clearance rather than excessive ingestion, and chronic toxicity is the commonest pattern and is usually unintentional. One labelled interaction runs the other way and is worth a line precisely because it surprises people: “Concomitant use of lithium with an SGLT2 inhibitor may decrease serum lithium concentrations,” and it instructs: “Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.” The label also names a “marked increase or decrease in routinely performed strenuous physical activity (such as an exercise program)” among the situations calling for more frequent levels — primary confirmation of the sweating-and-exercise teaching below. Distinguish the expected from the dangerous: a fine hand tremor, polyuria and mild thirst may persist throughout treatment — a coarse tremor, slurred speech, unsteadiness or confusion is toxicity. Long-term effects that are not toxicity include nephrogenic diabetes insipidus, hypothyroidism from thyroid accumulation, and hyperparathyroidism with hypercalcemia. Contraindicated in renal or cardiovascular disease, severe dehydration or sodium depletion, and in patients receiving diuretics; avoided below a creatinine clearance of 30 mL/min, especially where a low-sodium diet is required. In pregnancy, first-trimester exposure raises the risk of cardiac malformation, particularly Ebstein anomaly; lactation is not advisable. The class page owns the dosing detail; this page teaches why hydration and sodium are drug-safety issues.

A drug cause of hypercalcemia. "Lithium use leads to hypercalcemia by altering the set point at which calcium suppresses parathyroid hormone," and "In most cases, hypercalcemia resolves after discontinuation of lithium."

Valproate or lamotrigine for impulsivity (Open RN). "Impulsivity and behavioral dysregulation may be treated with mood stabilizers (such as valproate and lamotrigine)." For ASPD, StatPearls notes that evidence for medications "is limited and inconsistent, and none are FDA-approved for the treatment of ASPD."

Potent pain control via µ-opioid receptor agonism. Watch for respiratory depression; reverse with naloxone.

Potentiate GABA for anxiety, seizures, and sedation. Additive CNS depression — deadly with opioids.

First-line antidepressants that raise synaptic serotonin. Delayed onset; watch for serotonin syndrome and early suicidality.

Stabilize neuronal firing to prevent seizures. Many are narrow-therapeutic-index — level monitoring and rash vigilance are essential.

A widely used fever/pain reliever with no anti-inflammatory or platelet effect — but hepatotoxic in overdose.

Dopamine-blocking drugs for psychosis. Watch EPS, NMS, metabolic effects — boxed warning in elderly dementia.