13.3 Mood Stabilizers

Mood Stabilizers

Mood stabilizers are the foundation of bipolar disorder treatment. They reduce the frequency and severity of both manic and depressive episodes, helping patients maintain a more stable baseline. Lithium remains the gold standard, but several anticonvulsants serve as important alternatives. For nurses, the priority with these drugs is understanding their narrow safety margins and the monitoring required to keep patients safe.

Key Features of Mood Stabilizers

Lithium works through several mechanisms: it modulates neurotransmitter systems (serotonin, dopamine, and glutamate), provides neuroprotective effects by increasing brain-derived neurotrophic factor (BDNF), and inhibits glycogen synthase kinase-3 (GSK-3), an enzyme involved in mood regulation and neuroplasticity. No single mechanism fully explains its effectiveness, but the combined result is reduced cycling between mania and depression.

Anticonvulsants are used as alternatives or adjuncts to lithium. Each one stabilizes mood through a different pathway:

• Valproic acid and carbamazepine enhance GABA neurotransmission, which calms neuronal excitability. They also modulate dopamine and serotonin systems.
• Lamotrigine blocks voltage-gated sodium channels, stabilizing neuronal membranes and reducing glutamate release. This mechanism makes it particularly effective for preventing depressive episodes rather than manic ones.

Effects of Lithium and Anticonvulsants

Lithium

• Prevents both manic and depressive episodes and is the only mood stabilizer with strong evidence for reducing suicide risk
• Common side effects: nausea, diarrhea, fine hand tremor, weight gain, polyuria (increased urination), and polydipsia (increased thirst)
• Serious long-term concerns: hypothyroidism and nephrogenic diabetes insipidus (the kidneys lose the ability to concentrate urine)
• Has a very narrow therapeutic index (therapeutic range: 0.6–1.2 mEq/L). Even small increases above this range can cause toxicity
• Drug interactions to watch: NSAIDs, ACE inhibitors, and thiazide diuretics all decrease lithium excretion, raising serum levels toward toxicity. Dehydration and low sodium intake have the same effect

Valproic acid

• Effective for manic episodes and rapid cycling (four or more mood episodes per year)
• Side effects: nausea, vomiting, weight gain, hair thinning
• Serious risks: hepatotoxicity (especially in the first 6 months), pancreatitis, and teratogenicity (Category X; causes neural tube defects). Pregnancy must be ruled out before starting
• Interacts with aspirin, warfarin, and other anticonvulsants by competing for protein binding sites

Carbamazepine

• Also effective for manic episodes and rapid cycling
• Side effects: dizziness, drowsiness, nausea, blurred vision
• Serious risks: agranulocytosis (dangerously low white blood cells) and aplastic anemia, both rare but potentially fatal
• A potent liver enzyme inducer (CYP450), meaning it speeds up the metabolism of many other drugs. It reduces the effectiveness of oral contraceptives, warfarin, and other anticonvulsants. Patients on oral contraceptives need to use a backup method of birth control

Lamotrigine

• Most useful for preventing depressive episodes and rapid cycling (less effective for acute mania)
• Side effects: dizziness, drowsiness, headache
• The critical risk is rash, which can progress to Stevens-Johnson syndrome (SJS), a life-threatening skin reaction. To minimize this risk, the dose must be titrated very slowly over several weeks. Any new rash should be reported immediately
• Valproic acid increases lamotrigine levels (raising SJS risk), while carbamazepine decreases them. Dose adjustments are needed when combining these drugs

Pharmacokinetics and Safety Considerations

The narrow therapeutic index of lithium is the single most important safety concept here. The therapeutic range is 0.6–1.2 mEq/L, and toxicity begins around 1.5 mEq/L. Signs of lithium toxicity progress in stages:

1. Mild toxicity (1.5–2.0 mEq/L): increased tremor, nausea, diarrhea, muscle weakness, drowsiness
2. Moderate toxicity (2.0–2.5 mEq/L): confusion, ataxia (unsteady gait), slurred speech, severe GI symptoms
3. Severe toxicity (>2.5 mEq/L): seizures, coma, cardiac arrhythmias, renal failure

Anything that causes dehydration or sodium depletion can push lithium levels up, because the kidneys reabsorb lithium in place of sodium. This includes vomiting, diarrhea, excessive sweating, fever, and low-sodium diets.

Other pharmacokinetic considerations:

• Valproic acid is highly protein-bound, so drugs that compete for binding sites (like aspirin) can increase its free concentration
• Carbamazepine induces its own metabolism (autoinduction), meaning doses often need to be increased after the first few weeks
• Mood episodes themselves can affect adherence. Patients in a manic phase may feel they don't need medication, while depressive episodes can reduce motivation to take it

Nursing Care for Mood Stabilizer Patients

Assessment

• Evaluate mental status, mood, behavior, and medication adherence at each encounter
• Review current medications for potential drug interactions (especially new NSAIDs, diuretics, or antibiotics)
• Check baseline and ongoing labs as appropriate for each drug:
  • Lithium: serum lithium level, renal function (BUN, creatinine), thyroid function (TSH)
  • Valproic acid: serum drug level, liver function tests (LFTs)
  • Carbamazepine: CBC with differential (watching for agranulocytosis), LFTs
  • Lamotrigine: no routine serum levels needed, but monitor skin closely for rash

Monitoring

• Draw lithium levels 8–12 hours after the last dose (typically as a morning trough level). Frequency depends on stability but is often weekly during initiation, then every 1–3 months once stable
• Valproic acid levels are also monitored regularly (therapeutic range: 50–125 mcg/mL)
• Track mood, behavior, and treatment response over time. Document any emerging side effects
• Watch for signs of toxicity, especially with lithium: new-onset tremor, GI complaints, or confusion

Interventions

• Administer medications as prescribed and with food if GI side effects are an issue
• Hold lithium and notify the provider if the patient shows signs of toxicity or if lab values are above the therapeutic range
• Collaborate with mental health professionals for comprehensive care planning
• Advocate for dosage adjustments when side effects are affecting quality of life or adherence

Patient Education for Mood Stabilizers

• Adherence is essential. Mood stabilizers prevent episodes; they don't just treat symptoms in the moment. Stopping medication, even when feeling well, significantly increases relapse risk
• Never stop abruptly. Sudden discontinuation can trigger rebound mania or withdrawal symptoms. Any changes should be done gradually under provider guidance
• Stay hydrated and maintain normal sodium intake. This is especially critical for lithium. Patients should drink adequate water daily and avoid crash diets or sudden changes in salt consumption
• Report side effects early. Persistent nausea, new tremors, unusual fatigue, or any rash (especially with lamotrigine) should be reported right away
• Keep up with blood work. Regular lab monitoring is not optional with these medications. It's how providers catch problems before they become dangerous
• Inform all healthcare providers about mood stabilizer use, including dentists and urgent care providers, because of the potential for drug interactions
• Maintain healthy routines. Regular sleep schedules, consistent exercise, and stress management all support mood stability alongside medication
• Provide information about additional resources: therapy options, peer support groups, and crisis hotlines for times when symptoms break through