Mood stabilizer

File:Lithium300mg.jpg

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.

Uses

Mood stabilizers are best known for the treatment of bipolar disorder,<ref name="urlTexas State - Student Health Center">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> preventing mood shifts to mania (or hypomania) and depression. Mood stabilizers are also used in schizoaffective disorder when it is the bipolar type.<ref name="Mayo SCAF Dx">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Examples

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:

Mineral

Lithium

Lithium is the "classic" mood stabilizer, the first to be approved by the US FDA, and still popular in treatment. Therapeutic drug monitoring is required to ensure lithium levels remain in the therapeutic range: 0.6 to 0.8 or 0.8–1.2 mEq/L (or millimolar). Signs and symptoms of toxicity include nausea, vomiting, diarrhea, and ataxia.<ref name=pmid_18789369>Template:Cite journal</ref> The most common side effects are lethargy and weight gain (up to Template:Convert).<ref name="Malhi_2013b">Template:Cite journal</ref> The less common side effects of using lithium are blurred vision, a slight tremble in the hands, and a feeling of being mildly ill. In general, these side effects occur in the first few weeks after commencing lithium treatment. These symptoms can often be improved by lowering the dose.<ref>Kozier, B et al. (2008). Fundamentals Of Nursing, Concepts, Process, and Practice. London: Pearson Education. p. 189.</ref>

Anticonvulsants

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.<ref name=pmid15936730>Template:Cite journal</ref> 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.Template:Citation needed

Valproate

Available in extended release form. This drug can be very irritating to the stomach, especially when taken as a free acid. Liver function and CBC should be monitored. Common side effects include sleepiness, nausea, dry mouth. More serious side effects include liver dysfunction, pancreatitis and polycystic ovary syndrome.<ref name="eMC">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref><ref name="Depakote FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Weight gain is possible.<ref>Template:Cite journal</ref>

Lamotrigine (aka Lamictal)

FDA approved for bipolar disorder maintenance therapy, not for acute mood problems like depression or mania/hypomania.<ref name="FDA Prescribing Information at drugs.com" /> The usual target dose is 100–200 mg daily, titrated to by 25 mg increments every 2 weeks.<ref>Healy D. 2005 Psychiatric Drugs explained 4th ed. Churchill Liviingstone: London p.110</ref> Lamotrigine can cause Stevens–Johnson syndrome, a very rare but potentially fatal skin condition.<ref name="FDA Prescribing Information at drugs.com">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref>

Carbamazepine

FDA approved for the treatment of acute manic or mixed (i.e., both depressed and manic mood features) episodes in people with bipolar disorder type I.<ref name="CBZ PI">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref> Carbamazepine can rarely cause a dangerous decrease in neutrophils, a type of white blood cell, called agranulocytosis.<ref name="CBZ PI" /> It interacts with many medications, including other mood stabilizers (e.g. lamotrigine) and antipsychotics (e.g. quetiapine).<ref name="CBZ PI" /> It is considered second-line for bipolar disorder due to its side effects.<ref>Template:Cite journal</ref>

There is insufficient evidence to support the use of various other anticonvulsants, such as gabapentin and topiramate, as mood stabilizers.<ref name="Ketter2007">Template:Cite book</ref>

Antipsychotics

Some atypical antipsychotics (aripiprazole, asenapine, cariprazine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) also have mood stabilizing effects<ref name=pmid15762830>Template:Cite journal</ref> and are thus commonly prescribed even when psychotic symptoms are absent.<ref name=pmid15762830/>

Other

Omega-3 fatty acids

It is also conjectured that omega-3 fatty acids may have a mood stabilizing effect.<ref name=pmid11152679>Template:Cite journal</ref> Compared with placebo, omega-3 fatty acids appear better able to augment known mood stabilizers in reducing depressive (but perhaps not manic) symptoms of bipolar disorder; additional trials would be needed to establish the effects of omega-3 fatty acids alone.<ref>Template:Cite journal</ref>

Levothyroxine

It is known that even subclinical hypothyroidism can blunt a patient's response to both mood stabilizers and antidepressants. Furthermore, preliminary research into the use of thyroid augmentation in patients with refractory and rapid-cycling bipolar disorder has been positive, showing a slowing in cycle frequency and reduction in symptoms. Most studies have been conducted on an open-label basis. One large, controlled study of 300 mcg daily dose of levothyroxine (T₄) found it superior to placebo for this purpose. In general, studies have shown T4 to be well tolerated and to show efficacy even in patients without overt hypothyroidism.<ref>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</ref> Hypothyrodism is common among bipolar patients regardless of the mood stabilizer used.<ref>Template:Cite journal</ref>

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.<ref name=Geoffroy-2012/> 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.<ref name=Geoffroy-2012/> However, side effects are more frequent and discontinuation rates due to adverse events are higher with combination therapy than with monotherapy.<ref name=Geoffroy-2012>Template:Cite journal</ref>

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. There is a need for caution when treating bipolar patients with antidepressant medication due to the risks that they pose.<ref>Chris Aiken: Antidepressants in Bipolar II Disorder, May 14, 2019. In: psychiatrictimes.com</ref><ref name=Gitlin>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Template:See also Nevertheless, antidepressants are still often prescribed in addition to mood stabilizers during depressive phases. This brings some risks, however, as antidepressants can induce mania (increases risk by 34%),<ref>Template:Cite journal</ref> psychosis (relative risk not reported),<ref>Template:Cite journal</ref> cycle acceleration,<ref name=Gitlin/> 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.<ref name=":0">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/</ref> SSRIs and bupropion appear to have lower chances of switching, while SNRIs and tricyclics are more likely to cause switching. A single large, population based study reports that the manic "switch" risk is not increased over regular mood stabilizer treatment when an antidepressant is combined with a mood stabilizer. When an antidepressant is used alone, the risk is about 3 times the regular value.<ref name=Gitlin/> Gitlin (2018) notes that "the potential issue of worsening suicidality in adolescents and young adults treated with antidepressants [...] both controversial and infrequently seen."<ref name=Gitlin/>

Equally critical is the question of whether adding antidepressant has any effect on bipolar depression. High-quality data is lacking in this field, and simply using different analytical approaches can lead to different conclusions. It's also possible that the effect depends on the mood stabilizer used: one study finds no effect when antidepressant is added to lithium or valporate, but some efficacy when it's added to atypical antipsychotics.<ref name=Gitlin/>

Pharmacodynamics

As mentioned above, "mood stabilizers" do not have a unified mechanism of action; the term simply describes how these drugs can be used.

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.<ref>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.</ref> Lithium is, broadly speaking, neuroprotective.<ref name=Quiroz>Template:Cite journal</ref>

The classical theory of valporate's action involves affecting GABA levels and blocking voltage-gated sodium channels (which would affect the brain's glutamate system).<ref name=Gh2013>Template:Cite journal</ref> It has since been found to have many other cellular effects, such as inhibiting histone deacetylases and increasing LEF1.<ref>Template:Cite journal</ref> It is also neuroprotective.<ref name=Quiroz/>

Carbamazepine is mainly a sodium channel blocker, though it too has other activities.<ref>Template:Cite journal</ref> Lamotrigine is a similar case.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

One possible downstream target of several mood stabilizers such as lithium, valproate, and carbamazepine is the arachidonic acid cascade.<ref name=pmid18347600>Template:Cite journal</ref>

See also

• Treatment of bipolar disorder

External links

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