Chapter 5. Mood Stabilizers

DOI: 10.1176/appi.books.9781585624119.604374



The term mood stabilizer was first applied to the lithium salts when it became clear that they were effective not only in alleviating mania but also as a prophylaxis against both manic and depressive cycles. Since the introduction of lithium to the United States in 1969 there have been very few drugs approved as "mood stabilizers." However, in recent years new drugs, such as lamotrigine, olanzapine, and aripiprazole, have been approved for the prevention of mania and depression in bipolar disorder. In addition, many medications have been approved for the acute treatment of mania, and the first drugs for the acute treatment of bipolar depression have now also been approved. It is somewhat less clear that any of the anticonvulsants currently used in treating bipolar affective disorder are as deserving of the term mood stabilizer as is lithium. However, the second-generation antipsychotics (SGAs) with clear benefits in the acute treatment and prevention of both mania and depression do appear deserving of such designation.

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Table 5–1. Mood stabilizers: names, formulations, and strengths
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Note. FDA = U.S. Food and Drug Administration; NSAID = nonsteroidal anti-inflammatory drug; SSRI = selective serotonin reuptake inhibitor.

Lithium therapy: overview


Bipolar mania and prophylaxis (FDA indicated)

Depression augmentation

Side effects




Weight gain

Cognitive slowing


Renal function

Dermatological side effects

Memory problems

Safety in overdose

Frequently lethal in blood levels above 3.0 mEq/L and toxic above 1.5 mEq/L. Maintain fluid/electrolyte balance. Gastric lavage; mannitol diuresis vs. hemodialysis for higher blood levels.

Dosage and administration

Start at 300 mg bid or tid and increase total daily dose by up to 300 mg, as needed and tolerated, to blood level of 0.6–1.2 mEq/L for bipolar mania and 0.4–0.8 mEq/L for augmentation.


Sudden discontinuation associated with risk of relapse. Taper over 3 months for bipolar mania if feasible.

Drug interactions

Antipsychotics: may lithium toxicity

Bupropion: may seizure risk

Carbamazepine: neurotoxicity (rare)

Diuretics: lithium levels

Iodide salts: hypothyroidism

Neuromuscular blockers: respiratory depression

NSAIDs: lithium levels

SSRIs: serotonin syndrome (rare)

Theophylline: lithium levels

Urinary alkalinizers: lithium levels

Verapamil: or lithium levels

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Table 5–2. Toxicology of mood stabilizers
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Table 5–3. Anticonvulsant dosages in bipolar illness
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Note. CNS = central nervous system; ER = extended-release; FDA = U.S. Food and Drug Administration; GI = gastrointestinal; IR = immediate-release.

Valproate therapy: overview


Acute mania (FDA approved)

Bipolar prophylaxis (may be effective)

Mixed, rapid-cycling bipolar

Seizure disorders (FDA approved)

Side effects

Weight gain


GI upset

Safety in overdose

Serious effects notable mostly at 20 times normal serum level. Symptoms include nausea, vomiting, CNS depression, and seizures. Manage with gastric lavage, forced emesis, and assisted ventilation.

Dosage and administration

Start IR formulation at 15 mg/kg/day and ER formulation at 25 mg/kg/day in divided doses, up to a maximum of 60 mg/kg. Achieve serum levels of 50–100 g/mL.


Rapid discontinuation increases the risk of rapid relapse in bipolar disorder. Otherwise, discontinuation symptoms are uncommon.

Drug interactions

Drugs that valproate serum levels include:







Drugs that valproate serum levels include:





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Table 5–4. Drug interactions of anticonvulsant mood stabilizers
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Note. CNS = central nervous system; FDA = U.S. Food and Drug Administration; TCAs = tricyclic antidepressants; XR = extended-release.

Carbamazepine therapy: overview


Acute mania (FDA approved for Equetro only)

Mixed, rapid-cycling bipolar (not FDA approved)

Seizure disorders (FDA approved)

Side effects



Fatigue and nausea


Safety in overdose

Serious symptoms may occur at 10–20 times normal serum levels. Symptoms include nausea, vomiting, CNS depression, respiratory depression, and seizures. Management includes gastric lavage, forced emesis, assisted ventilation.

Dosage and administration

For the XR form: 200 mg bid, to therapeutic range of 800–1,200 mg/day. Follow serum levels to 6–10 g/mL.


Carbamazepine has not been associated with a withdrawal syndrome with rapid discontinuation. However, as with other mood stabilizers, rapid discontinuation is associated with an increased risk of rapid relapse. In bipolar patients, decrease dose over 6 months. In nonbipolar patients, dose may be decreased by 25% every 3 days.

Drug interactions

Drugs that may carbamazepine levels include: cimetidine, ciprofloxacin, diltiazem, fluoxetine, fluvoxamine, doxycycline, erythromycin, fluconazole, grapefruit juice, INH (isoniazid), ketoconazole, macrolide antibiotics (erythromycin, clarithromycin, troleandomycin), nefazodone, norfloxacin, prednisolone, propoxyphene, protease inhibitors (e.g., ritonavir), TCAs, valproate, verapamil, and warfarin

Drugs whose blood levels are by coadministration with carbamazepine include: atypical antipsychotics, benzodiazepines, doxycycline, ethosuximide, fentanyl, glucocorticoids, haloperidol, methadone, oral contraceptives, phenothiazines, phenytoin, sertraline, TCAs, and theophylline

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Table 5–5. New anticonvulsants


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