Mood Stabilizers: The First Five

“I am starting to have an idea about the mood stabilizers. There are so many of them. How do I break them down to learn the basics about each one?”  Lily posed this question to Dawn, who had started with an overview of the Mood Stabilizers.  In a previous article entitled, Mood Stabilizers: 5 Things All Clinicians Need to Know, I outlined five essential points about Mood Stabilizers, which can be summarized as:

1. They should be used as a last resort in “rapid and short mood changes”
2. They are divided into three main categories;
3. Lithium and most of the anticonvulsant mood stabilizers are contraindicated in pregnancy;
4. All mood stabilizers are not created equal;
5. Lithium has been shown to be the most effective mood stabilizer.

“Lily, let us move on to the next step and discuss specific mood stabilizers,” responded Dawn.

Below, five Mood Stabilizers are briefly described.

1.     Lithium

Lithium, when compared to other mood stabilizers, has been found to be the most effective when used as a single agent. It has been shown to reduce the risk of suicide, with an incidence as high as 10% in those affected with Bipolar Disorder as well as Major Depressive Disorder, Borderline Personality Disorder, and Schizophrenia. In addition to its efficacy in Bipolar Disorder, Lithium has been used with good effect in treatment resistant Major Depressive Disorder. Like any other medications, Lithium, too, has side effects, which vary based on dose and genetic make-up of the patient or client. Some of the common side effects include increased urination, increased thirst, and hand tremors. At times, they can lead to serious conditions, including Lithium toxicity and hypothyroidism.

2.     Valproic Acid

Also known as Valproate or Sodium Valproate or best known as Depakote, it is used in the treatment of Bipolar Disorder, seizure disorder, and migraines. One advantage of Valproic Acid is its effectiveness in the treatment of mixed state (patients or clients present with both depressive and manic symptoms at the same time), and rapid cycling (individuals with four or more episodes of major depressive disorder or mania in a 12-month period).

Valproic Acid has shown advantage in Bipolar Disorder, where there is also the presence of severe insomnia and anxiety. Because of its good effect on irritability and mood lability (mood changes), it has been used in several situations, including for individuals with low frustration tolerance, who are prone to anger or violence.

In terms of side effects, polycystic ovarian syndrome—a hormonal condition characterized by disruption in menstruation and fertilization—is a concern in women of reproductive age. Other common side effects include and are not limited to nausea or vomiting, dry mouth, and somnolence (sleepiness). Valproic Acid is associated with an increased risk of pancreatitis, an abnormal elevation in liver function tests, and with a decrease in platelets, both of which warrant regular related blood tests. It has a black box warning (strictest warning put on the labeling of prescription drugs by the FDA), because of risks for hepatotoxicity (toxicity of the liver), pancreatitis (inflammation of the pancreas), and fetal abnormalities (birth defects).

Given the black box warning and other serious side effects, Valproic Acid is contraindicated in individuals with acute or chronic liver disease or those with a related family history. It is also contraindicated in individuals with pancreatitis. As an anticonvulsant mood stabilizer, Valproic Acid should not to be given with other anticonvulsants, especially Lamotrigine or Carbamazepine. When used with aspirin and with oral contraceptives, there may be an increase in the amount of Valproic Acid in the blood, which may be toxic; when used with benzodiazepines, like Xanax or Klonopin, there may be increased suppression of the central nervous system; and when used with Zidovudine (a medication used to treat HIV), there may be an increase in the amount of Zidovudine in the blood, which may lead to toxicity.

Lastly, Valproic Acid is included in the World Health Organization’s List of Essentials Medicines. I described this list in our article series, Basic Knowledge of Antipsychotics.  This list contains the most effective and safest medicines needed in a health system.  Valproic Acid is one of the most commonly prescribed anti-seizure medications in the world.

3.     Olanzapine

Also known as Zyprexa, it is both a good antipsychotic and a good mood stabilizer, with the downside remaining its propensity for weight gain and metabolic syndrome, including diabetes, hypertriglyceridemia, and hypertension.  Olanzapine is recommended by the National Institute of Health and Care Excellence (The US National Institute of Health equivalent in the UK) as a first line treatment for acute mania in Bipolar Disorder.  It is also recommended as both a first and second line agent (varying body of authority) for the maintenance treatment of Bipolar Disorder.

4.     Lamotrigine

Also known as Lamictal, its side effects are few, compared to the other mood stabilizers. It also has more of an antidepressant than a manic property but without the risk of causing any manic symptoms or worsening cycling, as I mentioned in our previous article, Mood Stabilizers: The What, 5 Things All Clinicians Need to Know About Them.  If anything, it helps protect against cycling, similar to Valproic Acid. The downside with Lamotrigine is its fame for the risk of causing Stevens Johnson Syndrome, a type of rash, which can be fatal, if not timely or properly treated. If you remember when we spoke about agranulocytosis for Clozapine, in our article series on Clozapine, as an antipsychotic, Stevens Johnson Syndrome for Lamotrigine has the same level of concern, except there is no regular associated blood testing here.

The risk is also smaller than that for agranulocytosis. The trick is to start at a small dose, slowly increase, and continuously educate your patient or client on the risk; and instruct to stop the medication and call the prescribing physician, should he or she notice a rash. Of course, while taking Lamotrigine, a patient or client may develop a rash unrelated to Stevens Johnson, but it is always best to be cautious until proven otherwise. Also similar to Clozapine, if your patient or client misses three consecutive doses of Lamotrigine, he or she will need to start all over again. Going back to the same dose, after missing three or four doses, increases the risk for Stevens Johnson, which is more likely to occur with an initial high dose.

5.     Carbamazepine

Also known as Tegretol, Carbamazepine is an anticonvulsant used in Bipolar Disorder and for neuropathic pain. It shares similar side effects with Valproic Acid, including nausea and drowsiness but has some particular side effects, like skin rash, a decrease in blood cell production and some particular birth defects. Just like Valproic Acid and Lithium, it is on the World Health Organization’s List of Essential Medicines.

“I am starting to have an idea about the mood stabilizers. There are so many of them. How do I break them down to learn the basics about each one?” Lily posed this question to Dawn, who had started with an overview of the Mood Stabilizers.  “Lily, let us move on the next step and discuss the specific mood stabilizers,” responded Dawn.

And, so it went, the first five of the Mood Stabilizers, which I hope you have found helpful and are planning to make use of in your practice, educating your patients and clients, helping to empower them.

References:

1. Yatham LN, Kennedy SH, O’Donovan C, et al. (December 2006). “Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: Update 2007”. Bipolar Disord. 8 (6): 721–39.
2. Selle V, Schalkwijk S, Vázquez GH, Baldessarini RJ (March 2014). “Treatments for acute bipolar depression: Meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics”. Pharmacopsychiatry. 47 (2): 43–52.
3. Perucca E (2002). “Pharmacological and therapeutic properties of valproate: A summary after 35 years of clinical experience”. CNS Drugs. 16 (10): 695–714.
4. Yildiz, A; Guleryuz, S; Ankerst, DP; Ongür, D; Renshaw, PF (2008). “Protein kinase C inhibition in the treatment of mania: A double-blind, placebo-controlled trial of tamoxifen”. Archives of General Psychiatry. 65 (3): 255–63.
5. Ceron-Litvoc D, Soares BG, Geddes J, Litvoc J, de Lima MS (January 2009). “Comparison of carbamazepine and lithium in treatment of bipolar disorder: A systematic review of randomized controlled trials”. Hum Psychopharmacol. 24 (1): 19–28.