Mood stabilizers treat acute mania and prevent recurrence of mania and depression in bipolar disorder.

ADHD drugs increase dopamine and norepinephrine in the prefrontal cortex, improving attention and impulse control.

Stimulants work within 30–60 minutes; atomoxetine and viloxazine need several weeks; lithium needs about 1–3 weeks for antimanic effect.

Lithium serum levels (trough, 12 hours after the last dose)

Other therapeutic ranges: valproate (mania) about 50–125 mcg/mL (350–870 µmol/L) (epilepsy about 50–100 mcg/mL [350–700 µmol/L]); carbamazepine about 4–12 mcg/mL (17–51 µmol/L).

Lithium

• Early/common: fine hand tremor, thirst, polyuria, nausea, diarrhea, weight gain, metallic taste, acne
• Long term: hypothyroidism and goiter, nephrogenic diabetes insipidus, chronic kidney disease, hypercalcemia (hyperparathyroidism), ECG changes (T-wave flattening, sinus node dysfunction)
• Boxed warning: toxicity is closely related to serum level and can occur at doses near the therapeutic range

Valproate — boxed warnings for hepatotoxicity (highest risk in children under 2 and mitochondrial POLG disorders), pancreatitis, and fetal harm (neural tube defects, lower IQ). Also weight gain, tremor, hair loss, thrombocytopenia, hyperammonemia (lethargy, vomiting, confusion).

Carbamazepine — SJS/TEN (boxed; linked to HLA-B*15:02), aplastic anemia and agranulocytosis (boxed), hyponatremia, dizziness, diplopia, ataxia; strong enzyme inducer; teratogenic.

Lamotrigine — serious rash (SJS/TEN) (boxed), usually in the first 2–8 weeks; dizziness, diplopia; rare hemophagocytic lymphohistiocytosis.

All antiseizure drugs used as mood stabilizers (valproate, carbamazepine, lamotrigine) carry a class warning (not boxed) for suicidal thoughts and behavior — monitor mood.

Stimulants

• Decreased appetite, weight loss, insomnia, headache, stomachache, irritability or "rebound" as the dose wears off
• Increased heart rate and BP; growth slowing in children
• Tics may appear or worsen; rare psychosis or mania
• Methylphenidate: rare priapism; peripheral vasculopathy (cold, painful, color-changing fingers or toes)
• Boxed warning (updated 2023): misuse, abuse, addiction, and overdose
• Children under 6 on extended-release stimulants: higher drug levels, more side effects, clinically significant weight loss (2025 labeling)

Atomoxetine and viloxazine — boxed warning: suicidal thinking in children and adolescents; atomoxetine: rare liver injury, increased HR and BP, nausea; viloxazine: drowsiness, decreased appetite.

Guanfacine and clonidine — sedation, hypotension, bradycardia, dizziness; rebound hypertension if stopped abruptly.

Lithium

• Caution or avoid: significant kidney disease, dehydration or sodium depletion, severe cardiovascular disease, Brugada syndrome
• Drugs that raise lithium levels: thiazide diuretics, ACE inhibitors, ARBs, NSAIDs (except aspirin), metronidazole
• Drugs that lower levels: caffeine, theophylline, osmotic diuretics
• Pregnancy: small risk of cardiac malformation (Ebstein anomaly); plan with the prescriber — do not stop abruptly; levels change markedly in pregnancy and after delivery. Lithium passes into breast milk (infant monitoring if used)

Valproate — contraindicated in liver disease, urea cycle disorders, POLG mitochondrial disease, and for migraine prevention in pregnancy; avoid in people who can become pregnant unless no alternative works, with effective contraception. Interactions: raises lamotrigine levels about twofold (rash risk — the lamotrigine dose is halved); carbapenems sharply lower valproate levels; aspirin raises free valproate; alcohol.

Carbamazepine — contraindicated with MAOIs and bone marrow depression; avoid if HLA-B*15:02 positive unless benefits clearly outweigh risks. Enzyme inducer: lowers the effect of hormonal contraceptives, warfarin, and many other drugs; grapefruit juice raises its levels.

Lamotrigine — estrogen-containing contraceptives lower levels; valproate raises levels.

Stimulants

• Use with or within 14 days of an MAOI (hypertensive crisis)
• Serious structural heart disease, cardiomyopathy, or serious rhythm problems (sudden death risk); uncontrolled hypertension
• Glaucoma, agitation, history of substance misuse (use lower-misuse forms and supervision)
• Decongestants and other sympathomimetics — additive effects

Atomoxetine — contraindicated with MAOIs and in narrow-angle glaucoma, pheochromocytoma, severe cardiovascular disease; strong CYP2D6 inhibitors (fluoxetine, paroxetine) raise levels. Viloxazine — contraindicated with MAOIs and sensitive CYP1A2 substrates (e.g., theophylline).

Alpha-2 agonists — additive effects with other antihypertensives and CNS depressants.

Listed in priority order.

1. Recognize lithium toxicity early — vomiting, diarrhea, coarse tremor, ataxia, slurred speech, confusion. Hold the dose and notify the prescriber; obtain a level.
2. Lithium levels — trough 12 hours after the last dose; about 5 days after starting or any dose change, then every 3–6 months when stable, and whenever illness, dehydration, or new interacting drugs occur.
3. Lithium labs — baseline and periodic creatinine/eGFR, electrolytes (sodium), TSH, calcium, urinalysis; ECG if over 40 or with cardiac disease; pregnancy test. Normal serum sodium 135–145 mEq/L (mmol/L).
4. Fluid and sodium balance — record intake and output; watch for fever, vomiting, diarrhea, sweating, or reduced intake.
5. Valproate — liver tests, CBC with platelets, level; ammonia if lethargic or confused; report abdominal pain (pancreatitis).
6. Carbamazepine — confirm HLA-B*15:02 result before starting in people of Asian ancestry (including Filipino); CBC, sodium, liver tests, level.
7. Lamotrigine — follow the titration schedule exactly; if doses have been missed for about 5 days or more, restart the titration rather than resuming the prior dose; stop and report any rash.
8. Stimulants — BP and pulse at each visit; height, weight, and BMI plotted in children; screen cardiac history (syncope, exertional chest pain, family history of sudden death); check for tics, mood, sleep, and signs of diversion.
9. Atomoxetine/viloxazine — mood and suicidal thinking, especially early; liver symptoms.
10. Alpha-2 agonists — BP and HR; taper to stop.

Lithium

• Drink about 2–3 L of fluid daily; keep salt intake steady — do not start a low-salt diet on your own.
• Report vomiting, diarrhea, heavy sweating, or fever — dehydration raises levels quickly.
• Avoid NSAIDs such as ibuprofen and naproxen unless the prescriber approves; tell every provider you take lithium (diuretics, ACE inhibitors).
• Know toxicity signs: coarse tremor, vomiting, diarrhea, unsteady walking, slurred speech, confusion — hold the dose and seek care.
• Keep blood tests on schedule; take the dose at the same times each day with food.

Valproate, carbamazepine, lamotrigine

• Avoid alcohol; report yellow skin, dark urine, or severe abdominal pain (valproate).
• Report any rash, fever, mouth sores, or blistering at once (lamotrigine, carbamazepine).
• Report fever, sore throat, bruising or bleeding (carbamazepine).
• Use effective contraception; carbamazepine makes hormonal contraceptives less effective. Plan pregnancy with the prescriber.

ADHD drugs

• Give stimulants early in the day to prevent insomnia; give with or after breakfast if appetite is affected; offer a nutritious snack later in the day.
• Swallow long-acting forms whole unless the product allows opening the capsule and sprinkling.
• Store securely; never share or sell — stimulants are controlled substances.
• Report chest pain, fainting, racing heart, hallucinations, new tics, cold or discolored fingers, or an erection lasting more than 4 hours.
• Atomoxetine/viloxazine: report worsening mood or thoughts of self-harm; atomoxetine: report jaundice or dark urine.
• Do not stop guanfacine or clonidine suddenly (rebound high BP).

Lithium toxicity (no antidote)

Toxicity can occur at therapeutic levels in older adults. Management: hold lithium, obtain level, electrolytes, creatinine, and ECG; IV isotonic saline as ordered; activated charcoal does not bind lithium; whole-bowel irrigation for sustained-release overdose; hemodialysis for severe toxicity or kidney failure.

Valproate overdose — CNS depression, hyperammonemia, cerebral edema; L-carnitine is used for hyperammonemia or hepatotoxicity; hemodialysis for severe cases.

Carbamazepine overdose — ataxia, nystagmus, seizures, coma, dysrhythmias (sodium-channel blockade → sodium bicarbonate for wide QRS); multiple-dose activated charcoal may be used.

Stimulant overdose — agitation, hyperthermia, tachycardia, hypertension, dysrhythmias, seizures, psychosis. Treat with benzodiazepines, cooling, and supportive care; no specific antidote.

Clonidine/guanfacine overdose — bradycardia, hypotension, sedation, miosis, respiratory depression (mimics opioid toxicity); atropine for bradycardia; naloxone has variable effect.

• Lithium 0.6–1.2 mEq/L; trough 12 h after dose; toxicity usually above 1.5
• Dehydration, low sodium, thiazides, ACE inhibitors/ARBs, NSAIDs raise lithium
• Lithium long term: hypothyroidism, nephrogenic DI, CKD, hypercalcemia → TSH, creatinine, calcium
• Lithium toxicity: coarse tremor, GI upset, ataxia → hold, fluids, hemodialysis if severe; charcoal does not bind lithium
• Valproate: hepatotoxicity, pancreatitis, neural tube defects, hyperammonemia; doubles lamotrigine levels
• Carbamazepine: HLA-B*15:02 before starting in Asian ancestry; agranulocytosis, hyponatremia, enzyme inducer
• Lamotrigine: any rash → stop and report; restart titration after about 5 days missed
• Stimulants: appetite loss, insomnia, growth monitoring, raised HR/BP; give early in the day; boxed warning for misuse
• No stimulant within 14 days of an MAOI
• Atomoxetine and viloxazine: suicidal-thinking boxed warning
• Guanfacine/clonidine: sedation, bradycardia; taper (rebound hypertension)