Mood stabilizer

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

Contents

Uses

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]

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. [3] The most common side effects are lethargy and weight gain (up to 2 kilograms (4.4 lb)). [4] 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. [5]

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. [6] 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 ]

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. [7] [8] Weight gain is possible. [9]
Lamotrigine (aka Lamictal)
FDA approved for bipolar disorder maintenance therapy, not for acute mood problems like depression or mania/hypomania. [10] The usual target dose is 100–200 mg daily, titrated to by 25 mg increments every 2 weeks. [11] Lamotrigine can cause Stevens–Johnson syndrome, a very rare but potentially fatal skin condition. [10]
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. [12] Carbamazepine can rarely cause a dangerous decrease in neutrophils, a type of white blood cell, called agranulocytosis. [12] It interacts with many medications, including other mood stabilizers (e.g. lamotrigine) and antipsychotics (e.g. quetiapine). [12] It is considered second-line for bipolar disorder due to its side effects. [13]

There is insufficient evidence to support the use of various other anticonvulsants, such as gabapentin and topiramate, as mood stabilizers. [14]

Antipsychotics

Some atypical antipsychotics (aripiprazole, asenapine, cariprazine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) also have mood stabilizing effects [15] and are thus commonly prescribed even when psychotic symptoms are absent. [15]

Other

Omega-3 fatty acids
It is also conjectured that omega-3 fatty acids may have a mood stabilizing effect. [16] 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. [17]
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. [18] Hypothyrodism is common among bipolar patients regardless of the mood stabilizer used. [19]

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. [20] 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. [20] However, side effects are more frequent and discontinuation rates due to adverse events are higher with combination therapy than with monotherapy. [20]

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. [21] [22] [23]

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%), [24] psychosis (relative risk not reported), [25] cycle acceleration, [22] 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. [26] 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. [22] Gitlin (2018) notes that "the potential issue of worsening suicidality in adolescents and young adults treated with antidepressants [...] both controversial and infrequently seen." [22]

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. [22]

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. [27] Lithium is, broadly speaking, neuroprotective. [28]

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). [29] It has since been found to have many other cellular effects, such as inhibiting histone deacetylases and increasing LEF1. [30] It is also neuroprotective. [28]

Carbamazepine is mainly a sodium channel blocker, though it too has other activities. [31] Lamotrigine is a similar case. [32]

One possible downstream target of several mood stabilizers such as lithium, valproate, and carbamazepine is the arachidonic acid cascade. [33]

See also

Categories

Related Research Articles

<span class="mw-page-title-main">Bipolar disorder</span> Mental disorder that causes periods of depression and abnormally elevated mood

Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that each last from days to weeks. If the elevated mood is severe or associated with psychosis, it is called mania; if it is less severe and does not significantly affect functioning, it is called hypomania. During mania, an individual behaves or feels abnormally energetic, happy, or irritable, and they often make impulsive decisions with little regard for the consequences. There is usually, but not always, a reduced need for sleep during manic phases. During periods of depression, the individual may experience crying, have a negative outlook on life, and demonstrate poor eye contact with others. The risk of suicide is high. Over a period of 20 years, 6% of those with bipolar disorder died by suicide. 40-50% overall and 78% of adolescents engaged in self-harm. Other mental health issues, such as anxiety disorders and substance use disorders, are commonly associated with bipolar disorder. The global prevalence of bipolar disorder is estimated to be between 1–5% of the world's population.

Bipolar I disorder is a type of bipolar spectrum disorder characterized by the occurrence of at least one manic episode, with or without mixed or psychotic features. Most people also, at other times, have one or more depressive episodes. Typically, these manic episodes can last at least 7 days for most of each day to the extent that the individual may need medical attention, while the depressive episodes last at least 2 weeks.

<span class="mw-page-title-main">Mania</span> State of abnormally elevated or irritable mood, arousal, and/or energy levels

Mania, also known as manic syndrome, is a psychiatric behavioral syndrome defined as a state of abnormally elevated arousal, affect, and energy level. During a manic episode, an individual will experience rapidly changing emotions and moods, highly influenced by surrounding stimuli. Although mania is often conceived of as a "mirror image" to depression, the heightened mood can be dysphoric as well as euphoric. As the mania intensifies, irritability can be more pronounced and result in anxiety or anger.

<span class="mw-page-title-main">Mood disorder</span> Mental disorder affecting the mood of an individual, over a long period of time

A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where the main underlying characteristic is a disturbance in the person's mood. The classification is in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD).

A psychiatric or psychotropic medication is a psychoactive drug taken to exert an effect on the chemical makeup of the brain and nervous system. Thus, these medications are used to treat mental illnesses. These medications are typically made of synthetic chemical compounds and are usually prescribed in psychiatric settings, potentially involuntarily during commitment. Since the mid-20th century, such medications have been leading treatments for a broad range of mental disorders and have decreased the need for long-term hospitalization, thereby lowering the cost of mental health care. The recidivism or rehospitalization of the mentally ill is at a high rate in many countries, and the reasons for the relapses are under research.

Schizoaffective disorder is a mental disorder characterized by symptoms of both schizophrenia (psychosis) and a mood disorder, either bipolar disorder or depression. The main diagnostic criterion is the presence of psychotic symptoms for at least two weeks without prominent mood symptoms. Common symptoms include hallucinations, delusions, disorganized speech and thinking, as well as mood episodes. Schizoaffective disorder can often be misdiagnosed when the correct diagnosis may be psychotic depression, bipolar I disorder, schizophreniform disorder, or schizophrenia. This is a problem as treatment and prognosis differ greatly for most of these diagnoses. Many people with schizoaffective disorder have other mental disorders including anxiety disorders.

<span class="mw-page-title-main">Lamotrigine</span> Medication used for bipolar disorder, epilepsy, & many seizure disorders

Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut syndrome. In bipolar disorder, lamotrigine has not been shown to reliably treat acute depression in any groups except for the severely depressed; but for patients with bipolar disorder who are not currently symptomatic, it appears to reduce the risk of future episodes of depression.

<span class="mw-page-title-main">Oxcarbazepine</span> Anticonvulsant medication

Oxcarbazepine, sold under the brand name Trileptal among others, is a medication used to treat epilepsy. For epilepsy it is used for both focal seizures and generalized seizures. It has been used both alone and as add-on therapy in people with bipolar disorder who have had no success with other treatments. It is taken by mouth.

Biological psychiatry or biopsychiatry is an approach to psychiatry that aims to understand mental disorder in terms of the biological function of the nervous system. It is interdisciplinary in its approach and draws on sciences such as neuroscience, psychopharmacology, biochemistry, genetics, epigenetics and physiology to investigate the biological bases of behavior and psychopathology. Biopsychiatry is the branch of medicine which deals with the study of the biological function of the nervous system in mental disorders.

<span class="mw-page-title-main">Mixed affective state</span> Medical condition

A mixed affective state, formerly known as a mixed-manic or mixed episode, has been defined as a state wherein features and symptoms unique to both depression and (hypo)mania, including episodes of anguish, despair, self doubt, rage, excessive impulsivity and suicidal ideation, sensory overload, racing thoughts, heightened irritability, decreased "need" for sleep and other symptoms of depressive and manic states occur either simultaneously or in very short succession.

The emphasis of the treatment of bipolar disorder is on effective management of the long-term course of the illness, which can involve treatment of emergent symptoms. Treatment methods include pharmacological and psychological techniques.

<span class="mw-page-title-main">Bipolar disorder in children</span>

Bipolar disorder in children, or pediatric bipolar disorder (PBD), is a rare mental disorder in children and adolescents. The diagnosis of bipolar disorder in children has been heavily debated for many reasons including the potential harmful effects of adult bipolar medication use for children. PBD is similar to bipolar disorder (BD) in adults, and has been proposed as an explanation for periods of extreme shifts in mood called mood episodes. These shifts alternate between periods of depressed or irritable moods and periods of abnormally elevated moods called manic or hypomanic episodes. Mixed mood episodes can occur when a child or adolescent with PBD experiences depressive and manic symptoms simultaneously. Mood episodes of children and adolescents with PBD are different from general shifts in mood experienced by children and adolescents because mood episodes last for long periods of time and cause severe disruptions to an individual's life. There are three known forms of PBD: Bipolar I, Bipolar II, and Bipolar Not Otherwise Specified (NOS). The average age of onset of PBD remains unclear, but reported age of onset ranges from 5 years of age to 19 years of age. PBD is typically more severe and has a poorer prognosis than bipolar disorder with onset in late-adolescence or adulthood.

Bipolar II disorder (BP-II) is a mood disorder on the bipolar spectrum, characterized by at least one episode of hypomania and at least one episode of major depression. Diagnosis for BP-II requires that the individual must never have experienced a full manic episode. Otherwise, one manic episode meets the criteria for bipolar I disorder (BP-I).

<span class="mw-page-title-main">Lithium (medication)</span> Mood-stabilizing psychiatric medication

Certain lithium compounds, also known as lithium salts, are used as psychiatric medication, primarily for bipolar disorder and for major depressive disorder. Lithium is taken orally.

<span class="mw-page-title-main">Hypomania</span> Mental health condition

Hypomania is a psychiatric behavioral syndrome characterized essentially by an apparently non-contextual elevation of mood that contributes to persistently disinhibited behavior.

Bipolar disorder is a mental disorder with cyclical periods of depression and periods of elevated mood. The elevated mood is significant and is known as mania, a severe elevation that can be accompanied by psychosis in some cases, or hypomania, a milder form of mania. During mania, an individual behaves or feels abnormally energetic, elated, or irritable. Individuals often make poorly thought out decisions with little regard to the consequences. The need for sleep is usually reduced during manic phases. During periods of depression, there may be crying, a negative outlook on life, and poor eye contact with others. The risk of suicide among those with the illness is high at greater than 6 percent over 20 years, while self-harm occurs in 30–40 percent. Other mental health issues such as anxiety disorders and substance use disorder are commonly associated. Also known as manic depression. People with bipolar disorder experience the whole spectrum of emotional feelings from unimaginable grief to full blown euphoria whereas normal people experience only a section of the spectrum of emotional feelings somewhere between extreme grief and extreme happiness.

Antimanic drugs are psychotropic drugs that are used to treat symptoms of mania. Though there are different causes of mania, the majority is caused by bipolar disorder, therefore antimanic drugs are mostly similar to drugs treating bipolar disorder. Since 1970s, antimanic drugs have been used specifically to control the abnormal elevation of mood or mood swings during manic episodes. One purpose of antimanic drugs is to alleviate or shorten the duration of an acute mania. Another objective is to prevent further cycles of mania and maintain the improvement achieved during the acute episode. The mechanism of antimanic drugs has not yet been fully known, it is proposed that they mostly affect chemical neurotransmitters in the brain. However, the usage of antimanic drugs should be consulted with a doctor or pharmacist due to their side effects and interactions with other drugs and food.

Epigenetics of bipolar disorder is the effect that epigenetics has on triggering and maintaining bipolar disorder.

References

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