Mood Stabilizers and Anticonvulsants (Antiepileptics) are used to treat both epileptic and nonepileptic disorders such as bipolar disorder. Lithium is considered the gold standard mood stabilizer for bipolar disorder. Valproic acid can be more effective in patients who do not respond to lithium, and also has a more rapid anti-manic effect than lithium, with a therapeutic benefit usually seen in 3 to 5 days. Other mood stabilizers include newer anticonvulsants (e.g. - carbamazepine, lamotrigine). Of note, atypical antipsychotics are also “mood stabilizers” commonly used in bipolar disorder.
The term mood stabilizer is not strictly defined.
Valproic acid is effective in patients who don’t respond to lithium and has a more rapid antimanic effect than lithium and therapeutic benefit is seen in 3 to 5 days.
Lithium | Valproic Acid (VPA) | Carbamazepine | Oxcarbazepine | Lamotrigine | |
---|---|---|---|---|---|
Indications | Bipolar disorder, depression | Bipolar disorder | Bipolar disorder | Bipolar disorder | Bipolar disorder |
Approval in Youth | No | No | No | No | No |
Pharmacokinetics | Not metabolised, excreted by kidneys | Phase II 90% (glucuronidation), Phase I 10% | Phase I CYP3A4, 2C19 (autoinducing) | Minimal P450 interactions, does not autoinduce, more favourable side effect profile | Phase II (glucuronidation) |
Monitoring | Lithium levels, kidney function, thyroid function | Epival levels, albumin level, liver function | Carbamazepine level, albumin level, liver function | Oxcarbazepine metabolite level, albumin level, liver function | No blood work, but important to monitor for skin rashes due to risk of SJS! |
Side Effects | Tremors, acne, thyroid disorders, hypercalcemia | GI issues, weight gain, hair loss, tremor, PCOS, thrombocytopenia, hair loss, encephalopathy, cognitive dulling[2] | Cognitive dulling, diplopia, nystagmus, vertigo, hyponatremia | Cognitive dulling, hyponatremia | Cognitive dulling |
Adverse Reactions | Renal impairment, nephrotoxicity | Pancreatitis, hepatoxcitity | Agranulocytosis, aplastic anemia, hepatotoxicity, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) | Agranulocytosis, aplastic anemia, hepatotoxicity, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) | Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) |
Teratogen | Ebstein's anomaly (cardiac) | Neural tube defects | Neural tube defects, cleft lip | Neural tube defects, cleft lip | Safe in pregnancy |
Drug-Drug Interactions | ACE inhibitors, angiotensin II receptor antagonists (ARBs), thiazide diuretics, NSAIDs, COX-2 Inhibitors | The combination of VPA with lamotrigine can cause significant and dangerous increases of lamotrigine, due to inhibition of the glucuronidation. | Potent CYP interactions with many drugs. | Many!!! | Most particular with VPA |
Notes | The gold standard treatment for bipolar disorder. | In bipolar disorder, may be better for those with comorbid substance use, or traumatic brain injuries | In bipolar disorder, may be better for those with comorbid substance use, substance use disorder, or a negative family history of bipolar disorder. | Similar to carbamazepine, but has several advantages, including no autoinduction, and much less CYP P450 enzyme interactions | Not useful as an anti-manic agent, and only works for bipolar depression. Takes a long time to titrate due to risk for SJS |