Psych meds 101: Mood stabilizers

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Lithium has been around for many years. It works via a number of different mechanisms, including regulating genetic expression of various neuron-related factors, and boosting activity of the calming neurotransmitter GABA. GABA counterbalances the excitatory neurotransmitter glutamate. Lithium is effective for both mania and depression, and has been shown to decrease the risk of suicide.


These medications were initially developed as anti-seizure medications, but have since come to be used as mood stabilizers. They affect signalling between nerve cells by acting at voltage-sensitive ion channels that allow sodium/calcium to flow in and out of neurons, and they also boost GABA neurotransmission.

Valproic acid/divalproex

These are essentially the same molecule, but divalproex can be formulated into an enteric-coated tablet that decreases stomach upset. Valproic acid is effective for mania, but it is less clear how effective it is for bipolar depression. Dosing is targeted to reach a blood level of 350–700 µmol/L.


Carbamazepine is most clearly effective for mania. It affects the liver’s cytochrome P450 system, leading to interactions with a number of different medications. It can also decrease the reliability of oral contraceptives.


Lamotrigine is not effective for bipolar mania, and works best for the prevention of bipolar depression. It interacts with both valproic acid and carbamazepine, requiring adjustments in dose. It must be initiated slowly to decrease the risk of Stevens-Johnson syndrome, a type of severe rash.


There are other anticonvulsants that have been tried in bipolar disorder but don’t necessarily have strong evidence to support their use. These include levatiracetam and topiramate. Gabapentin does not appear to be effective.

Atypical antipsychotics

The mechanism by which atypical antipsychotics have a mood stabilizing effect is not entirely clear, but may be related to their action at the 5HT2a serotonin receptor and resultant effects on glutamate, dopamine, norepinephrine, and serotonin signalling. They are useful for both bipolar mania and depression. Examples include lurasidone, aripiprazole, quetiapine, and olanzapine (which can be combined with the SSRI antidepressant fluoxetine for bipolar depression).

Role of antidepressants

There are two key problems with antidepressants in bipolar disorder: they don’t work particularly well, and there is a risk of triggering mania. The International Society for Bipolar Disorder task force on antidepressant use found that evidence for antidepressant use is limited and weak, and as a result they could not broadly endorse the use of antidepressants in bipolar disorder. An exception is fluoxetine, which is effective when used in tandem with olanzapine.

In conclusion…

I hope that this has all made sense and shone some new light on mood stabilizers. If you have any questions please feel free to shoot them my way!

Written by

Mental health blogger | MH Nurse | Living with depression | Author of 3 books, latest is Managing the Depression Puzzle |

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