A mood stabilizer is a psychiatric medication used to treat characterized by intense and sustained mood swing, such as bipolar disorder and the bipolar type of schizoaffective disorder.
Uses
Mood stabilizers are best known for the treatment of
bipolar disorder,
preventing mood shifts to
mania (or
hypomania) and depression. Mood stabilizers are also used in schizoaffective disorder when it is the bipolar type.
Examples
The term "mood stabilizer" does not describe a mechanism but 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.
[Kozier, B et al. (2008). Fundamentals Of Nursing: Concepts, Process, and Practice. London: Pearson Education. p. 189.]
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.
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.
- Valproate
- Available in extended-release form. This drug can be very irritating to the stomach, especially when taken as a free acid. Requires regular and full blood count monitoring. Common side effects include sleepiness, nausea, and dry mouth. More serious side effects include liver dysfunction, pancreatitis, and polycystic ovary syndrome.
- Lamotrigine (brand name Lamictal)
- FDA-approved for bipolar disorder maintenance therapy, not for acute mood problems like acute depression or mania, including hypomania.
[Healy D. 2005 Psychiatric Drugs explained 4th ed. Churchill Liviingstone: London p.110] Lamotrigine can cause Stevens–Johnson syndrome, a very rare but potentially fatal skin condition.
- Carbamazepine
- FDA-approved for the treatment of acute manic and mixed (i.e., having a mix of depressed and manic mood features) episodes in people with bipolar I disorder.
There is insufficient evidence to support the use of various other anticonvulsants, such as gabapentin and topiramate, as mood stabilizers.
Antipsychotics
Some atypical antipsychotics (
aripiprazole,
asenapine,
cariprazine,
lurasidone,
olanzapine,
paliperidone,
quetiapine,
risperidone, and
ziprasidone) also have mood-stabilizing effects and are thus commonly prescribed even when
psychotic symptoms are absent.
Other
- Omega-3 fatty acids
- It is also conjectured that omega-3 fatty acids may have mood-stabilizing effects.
- 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 a 300 mcg daily dose of Levothyroxine found it superior to placebo in the setting of bipolar disorder. In general, studies have shown T4 to be well tolerated and to show effectiveness even in patients without overt hypothyroidism.
[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 Hypothyroidism is common among patients with bipolar disorder regardless of the mood stabilizer used.
Combination therapy
In routine practice, monotherapy is often insufficiently effective for acute and/or maintenance therapy. Thus, most patients are placed on combination therapy.
[ Combination therapy (e.g., an atypical antipsychotic with lithium or valproate) has demonstrated better effectiveness over monotherapy in the control of manic episodes, as well as the prevention of relapse.][ However, side effects are more frequent and discontinuation rates are higher due to adverse events with combination therapy than with monotherapy.]
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.[Chris Aiken: Antidepressants in Bipolar II Disorder, May 14, 2019. In: psychiatrictimes.com]
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%),[ 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.][Amit BH, Weizman A. Antidepressant Treatment for Acute Bipolar Depression: An Update. Depression Research and Treatment Internet. 2012 cited;2012:1–10. Available from: http://www.hindawi.com/journals/drt/2012/684725/] 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.[ Gitlin (2018) notes that "the potential issue of worsening suicidality in adolescents and young adults treated with antidepressants ... both controversial and infrequently seen."][
]
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.[
]
Pharmacodynamics
As mentioned above, "mood stabilizers" do not have a unified mechanism of action; the term simply describes how these drugs can be used.
Lithium's precise mechanism of action 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.[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.] Lithium is, broadly speaking, neuroprotective.
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).[
]
Carbamazepine is mainly a sodium channel blocker, though it too has other activities.
One possible downstream target of several mood stabilizers such as lithium, valproate, and carbamazepine is the arachidonic acid cascade.
See also
-
Treatment of bipolar disorder
Categories
External links
