A bottle of lithium capsules. Lithium is the prototypical mood stabilizer.

A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, such as bipolar disorder and the bipolar type of schizoaffective disorder.


Mood stabilizers are best known for the treatment of bipolar disorder,[1] preventing mood shifts to mania (or hypomania) and depression. Mood stabilizers are also used in schizoaffective disorder when it is the bipolar type.[2]


The term "mood stabilizer" does not describe a mechanism, but rather an effect. More precise terminology based on pharmacology is used to further classify these agents. Drugs commonly classed as mood stabilizers include:



Many agents described as "mood stabilizers" are also categorized as anticonvulsants. The term "anticonvulsant mood stabilizers" is sometimes used to describe these as a class.[5] Although this group is also defined by effect rather than mechanism, there is at least a preliminary understanding of the mechanism of most of the anticonvulsants used in the treatment of mood disorders.[citation needed]

There is insufficient evidence to support the use of various other anticonvulsants, such as gabapentin and topiramate, as mood stabilizers.[10]



Combination therapy

In routine practice, monotherapy is often not sufficiently effective for acute and/or maintenance therapy and thus most patients are given combination therapies.[15] Combination therapy (atypical antipsychotic with lithium or valproate) shows better efficacy over monotherapy in the manic phase in terms of efficacy and prevention of relapse.[15] However, side effects are more frequent and discontinuation rates due to adverse events are higher with combination therapy than with monotherapy.[15]

Relationship to antidepressants

Most mood stabilizers are primarily antimanic agents, meaning that they are effective at treating mania and mood cycling and shifting, but are not effective at treating acute depression. The principal exceptions to that rule, because they treat both manic and depressive symptoms, are lamotrigine, lithium carbonate, olanzapine and quetiapine.[citation needed]

Nevertheless, antidepressants are still often prescribed in addition to mood stabilizers during depressive phases. This brings some risks, however, as antidepressants can induce mania,[16] psychosis,[17] and other disturbing problems in people with bipolar disorder—in particular, when taken alone. The risk of antidepressant-induced mania when given to patients concomitantly on antimanic agents is not known for certain but may still exist.[18] The majority of antidepressants appear ineffective in treating bipolar depression.[18]

Antidepressants cause several risks when given to bipolar patients. They are ineffective in treating acute bipolar depression, preventing relapse, and can cause rapid cycling. Studies have shown that antidepressants have no benefit versus a placebo or other treatment. Antidepressants can also lead to a higher rate of non-lethal suicidal behavior. Relapse can also be related to treatment with antidepressants. This is less likely to occur if a mood stabilizer is combined with an antidepressant, rather than an antidepressant being used alone. Evidence from previous studies shows that rapid cycling is linked to use of antidepressants. Rapid cycling is defined as the presence of four or more mood episodes within a year's time. Evidence suggests that rapid cycling and mixed symptoms have become more common since antidepressant medication has come into widespread use. There is a need for caution when treating bipolar patients with antidepressant medication due to the risks that they pose. [citation needed]


The precise mechanism of action of lithium is still unknown, and it is suspected that it acts at various points of the neuron between the nucleus and the synapse. Lithium is known to inhibit the enzyme GSK-3B. This improves the functioning of the circadian clock—which is thought to be often malfunctioning in people with bipolar disorder—and positively modulates gene transcription of brain-derived neurotrophic factor (BDNF). The resulting increase in neural plasticity may be central to lithium's therapeutic effects. How lithium works in the human body is not completely understood, but its benefits are most likely related to its effects on electrolytes such as potassium, sodium, calcium and magnesium.[19]

All of the anticonvulsants routinely used to treat bipolar disorder are blockers of voltage-gated sodium channels, affecting the brain's glutamate system. For valproic acid, carbamazepine and oxcarbazepine, however, their mood-stabilizing effects may be more related to effects on the GABAergic system. Lamotrigine is known to decrease the patient's cortisol response to stress.[citation needed]

One possible downstream target of several mood stabilizers such as lithium, valproate, and carbamazepine is the arachidonic acid cascade.[20]

See also



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  2. ^ "Schizoaffective disorder - Diagnosis and treatment - Mayo Clinic". www.mayoclinic.org. Mayo Foundation for Medical Education and Research. Retrieved 10 July 2020.
  3. ^ Marmol, F. (2008). "Lithium: Bipolar disorder and neurodegenerative diseases Possible cellular mechanisms of the therapeutic effects of lithium". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 32 (8): 1761–1771. doi:10.1016/j.pnpbp.2008.08.012. PMID 18789369. S2CID 25861243.
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  9. ^ a b c "EQUETRO(carbamazepine) Package Insert" (PDF). Validus Pharmaceuticals LLC. Retrieved 10 July 2020.
  10. ^ Terence A. Ketter (3 May 2007). Advances in Treatment of Bipolar Disorder. American Psychiatric Pub. p. 42. ISBN 978-1-58562-666-3.
  11. ^ a b Bowden CL (2005). "Atypical antipsychotic augmentation of mood stabilizer therapy in bipolar disorder". J Clin Psychiatry. 66. Suppl 3: 12–9. PMID 15762830.
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  13. ^ Gao, K.; Calabrese, J. R. (2005). "Newer treatment studies for bipolar depression". Bipolar Disorders. 7 (s5): 13–23. doi:10.1111/j.1399-5618.2005.00250.x. PMID 16225556.
  14. ^ AMA Chakrabarti S. Thyroid Functions and Bipolar Affective Disorder. Journal of Thyroid Research. 2011;2011:306367. doi:10.4061/2011/306367. MLA Chakrabarti, Subho. "Thyroid Functions and Bipolar Affective Disorder". Journal of Thyroid Research 2011 (2011): 306367. PMC. Web. 19 May 2017. APA Chakrabarti, S. (2011). Thyroid Functions and Bipolar Affective Disorder. Journal of Thyroid Research, 2011, 306367. http://doi.org/10.4061/2011/306367
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  16. ^ Patel, Rashmi (2015). "Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study". BMJ Open. 5 (12): e008341. doi:10.1136/bmjopen-2015-008341. PMC 4679886. PMID 26667012.
  17. ^ Preda, A; MacLean, RW; Mazure, CM; Bowers MB, Jr (January 2001). "Antidepressant-associated mania and psychosis resulting in psychiatric admissions". The Journal of Clinical Psychiatry. 62 (1): 30–3. doi:10.4088/jcp.v62n0107. PMID 11235925.
  18. ^ a b Amit BH, Weizman A. Antidepressant Treatment for Acute Bipolar Depression: An Update. Depression Research and Treatment [Internet]. 2012 [cited 2013 Jul 18];2012:1–10. Available from: http://www.hindawi.com/journals/drt/2012/684725/
  19. ^ Raber, Jack H. "Lithium carbonate." The Gale Encyclopedia of Mental Disorders, edited by Madeline Harris and Ellen Thackerey, vol. 1, Gale, 2003, pp. 571-573. Gale eBooks, link.gale.com/apps/doc/CX3405700220/GVRL?u=tamp44898&sid=GVRL&xid=9ef84e18. Accessed 20 Jan. 2021.
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