Occam’s razor and mood stabilizing drugs for bipolar disorder


Occam’s razor – the simplest explanation is usually the right one. How do mood stabilizers work to stabilize mood?

Lithium can stabilize sodium-dependent transporters and sodium-dependent G-protein coupled receptors in inactive states. Lithium  reduces activity of various sodium-dependent transporters, for example, Na(+)-coupled inorganic phosphate cotransporters (Andrini et al., 2012), Na+/Cl)/glycine cotransport (Pérez-Siles et al., 2011) and the sodium-myo-inositol co-transporter (Willmroth et al., 2007).

Blocking sodium channels is one of the key mechanisms by which anticonvulsants work (Brodie,  2017). Carbamazepine, valproic acid and lamotrigine are anticonvulsants used to treat bipolar disorder (Bowden and Karren, 2006.). Carbamazepine is a sodium channel blocker (Kennebäck et al., 1995). Valproic acid blocks sodium channels (Zanatta et al., 2019). Lamotrigine also blocks sodium channels (Kuo, 1998).

Occam’s razor applied to mood stabilizers – Mood stabilizers work by affecting sodium-dependent transporters and/or sodium-dependent G-protein coupled receptors.

Huge increase in anti-psychotic usage in bipolar disorder in recent years

In the treatment of bipolar disorder anti-psychotics have increasingly become more commonly prescribed, increasing from 12.4% of outpatient visits for bipolar disorder in the 1997-2000 period to 51.4% in the 2013-2016 period.

The page on bipolar disorder of this site both points to why lithium and anti-convulsants work at all while also pointing to why lithium and anti-convulsants are very inadequate treatments for bipolar disorder. Lithium and anti-convulsants target the SMVT but do so poorly where the dysregulation of the sodium-dependent multivitamin transporter (SMVT) is only one factor that gives rise to bipolar disorder.

Anti-psychotics are terrible drugs but many psychiatrists and patients find them preferable to lithium and anti-convulsants.