Introduction to Mood Stabilizers and Anticonvulsants

Mood Stabilizers and Anticonvulsants (Antiepileptics) are used to treat both epileptic and nonepileptic disorders such as bipolar disorder.

  • Strictest definition: treats and prevents acute mania and depression
  • Intermediate definition: effective in either acute mania and its prevention OR acute depression and its prevention
  • Broadest definition: effective at either treating or preventing mania OR treating or preventing depression, and does not exacerbate symptoms

Most AEDs have multiple mechanisms of action (MOAs), which include modulation of γ‐aminobutyric acid (GABA)ergic and glutamatergic neurotransmission, and alteration of voltage‐gated ion channels or intracellular signaling pathways.

Why are Antiepileptics Used to Treat Bipolar Disorders?

Bipolar disorder and epilepsy share common features including an episodic course of illness and kindling phenomena. The amygdala plays a role in both disorders as well. However, epilepsy and bipolar disorder are two distinct different diseases.[1]

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.

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.

Comparison of Mood Stabilizers

Divalproex Carbamazepine Oxcarbazepine Lamotrigine
Indications Aggression
Approval in Youth No No No No
Pharmacokinetics Phase II 90% (glucuronidation), mostly 10% Phase I Phase I CYP3A4, 2C19 (autoinducing) Minimal P450 interactions, does not autoinduce, more favourable side effect profile Phase II (glucuronidation)
Monitoring Epival levels, albumin level
Studies Wagner 2009 XR no diff from placebo
Side Effects GI issues, wt 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 Agranulocytosis, aplastic anemia
Teratogen Neural tube defects Neural tube defects
Notes 1. Dose dependent toxicity
Dose independent mortality and toxicity
Pancreatitis
Correlation between Epival and PCOS
DDIs The combination of VPA and LTG might be problematic due to VPA’s inhibition of the LTG major metabolic pathway (glucuronidation) (Garnett, 2002).

In 2008 the FDA issued a healthcare alert about the increased risk (2 per 1000) of suicidal ideation and behaviours with any antiepileptic drug (AED) use.[3][4] However, statistical significance only found in only two antiepileptics (topiramate and lamotrigine) out of the eleven studied, and this broad warning for all AEDs has been criticized.[5] The actual true suicidal risk is yet to be established, but is likely very low, subsequent meta-analyses have found no evidence of increased risk.[6]