Use of mood stabilizers for bipolar disorders
By Dr. Abimbola Farinde

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The term mood stabilizer first originated with the use of lithium salts when it was discovered they could assist with alleviating mania. Since the introduction of lithium to the United States in 1969, other drugs have been approved and released into the market as mood stabilizers.

Along with lithium, other mood stabilizers such as lamotrigine, carbamazepine, valproate and atypical antipsychotics such as olanzapine and aripiprazole have been approved for the prevention of mania, acute mania treatment and depression associated with bipolar disorder.

The currently accepted and recognized use for mood stabilizers by the Food and Drug Administration is for the treatment of acute mania and acute bipolar depression, with the goal of stabilizing the existing manic or depressive episode in a timely fashion. If the episode is not effectively treated, it can lead to residual symptoms of mania or depression that can be associated with recurrences of the illness. Mood stabilizers are also considered to be the cornerstone of maintenance therapy, but there is only some evidence to support their use.

Lithium was the first maintenance medication approved for use in bipolar disorder, followed by lamotrigine. Second-generation antipsychotics are now becoming increasingly utilized as maintenance treatment for bipolar disorder as well. The treatment of rapid-cycling bipolar disorder (four or more cycles per year) and mixed states is another use for mood stabilizers.

When it comes to the treatment of rapid-cycling, studies have suggested that divalproex is a good choice. The use of the olanzapine-fluoxetine combination, olanzapine monotherapy, aripiprazole and quetiapine have also shown some efficacy, according to controlled studies, when it comes to reducing the depressive and manic episodes in individual with rapid-cycling bipolar disorder.

It can prove to be quite difficult to treat mixed states of bipolar disorder because it is the manifestation of the combination of depressive and manic features. But with the few studies that have examined the treatment response with mood stabilizer, carbamazepine has shown promise, as well as some second-generation antipsychotics.

Additionally, if certain mood stabilizers are misused, this can prove to be detrimental. Lithium has a narrow therapeutic window, meaning that it does not take much to move from a therapeutic effect to a toxic effect. Lithium can only be started once lab tests are performed, such as monitoring of electrolytes, EKG, urinalysis, thyroid function and complete blood count.

It is quite easy for one to experience an adverse reaction with lithium therapy if it is not used appropriately. This can range from the common (nausea, vomiting, fine hand tremor) to signs of toxicity such as lethargy, tremor, seizures, shock, coma or even death.

When valproate was initially introduced into the market, the major negative associated with its use was the risk of hepatotoxicity and pancreatitis. These conditions can occur with varying degrees of exposure, so it is important that periodic assessment of liver function, amylase and lipase levels are performed. The potential for misuse is not an option when it comes to valproate, because this can potentially turn out to be fatal.

With lamotrigine therapy, caution must be exercised when it is used concurrently with valproate. This can increase lamotrigine concentration, leading to the development of the life-threatening Stevens-Johnson syndrome. One must abide by the strict dosing guidelines that are in place when using lamotrigine therapy.

Newer agents such as antipsychotics, other anticonvulsants (gabapentin, pregabalin, topiramate, tiagabine, oxcarbazepine, levetiracetam, zonisamide and ethosuxide), benzodiazepine, calcium channel blockers, and omega-3 fatty acids are also being used to treat mood disorders. While the newer anticonvulsants do not have as many clinical trials as the older agents, they are being used as augmentation therapy if an individual's current regimen fails to deliver the desired therapeutic effect.

With the growth of the use of mood stabilizers, these agents are also being used for off-label indications. While the FDA does not promote the use of off-label indications, mood stabilizers are being used for other conditions such as the treatment of aggression, augmentation therapy in resistant schizophrenia and post-traumatic stress disorder to name a few. Even though their use is not completely accepted, it is becoming a commonplace practice among clinicians who attempt to find ways to treat clients after all other therapeutic interventions have been unsuccessful.

The long-term risks that can be associated with the use of mood stabilizers can be observed with more notable agents such lithium, which can cause hypothyroidism, goiter and reversible diabetes insipidus. Some individuals can also develop cogwheeling and mild signs of parkinsonism, and there can be the gradual development of slowed mentation and forgetfulness indicating a mental deficit.

Dr. Abimbola Farinde is a clinical pharmacist specialist in psychiatry and geriatrics who graduated from Texas Southern University and earned her Masters of Science in psychology in 2010. She has gained a wealth of knowledge and training with the completion of residency training programs and being in practice for more than five years. She is very interested in sharing her knowledge with other professionals engaged in clinical practice in a variety of settings.