Bipolar disorder mood-stabilizing drugs

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

Intrinsic reinforcement. Reinforcement that comes from inside the person. Mood stabilizers. Drugs that treat disorders with mood cycles, such as Bipolar Disorder. 

LITHIUM, MOOD-STABILIZING DRUGS, AND OTHER TREATMENT FOR BIPOLAR DISORDER... 

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

In this way it is not very surprising that most antiepileptics are also used in pain treatment, that several tricyclic antidepressants are used in pain management, and even that some antiepileptics became mood-stabilizing drugs for bipolar disorder. 

Bipolar disorder has a lifetime prevalence of approximately 1%. During pregnancy, untreated bipolar disorder may result in hospitalization, suicidal ideation, violence, loss of employment, malnutrition, and an increased risk of postpartum psychosis. It does not appear that pregnancy provides protection for the risk of recurrence of symptoms. Women who discontinue the use of mood stabilizing drugs abruptly before conception or who have had four or more episodes of recurrence of symptoms have a substantial risk for recurrence during pregnancy. Risk for recurrence in the first 3 to 6 months postpartum has been estimated at 20% up to 80%. Postpartum psychosis may occur in 10% to 20% of women with bipolar disorder. 

Lithium is the first-line drug for the treatment of bipolar disorder, since it is efficacious in acute euphoric mania without psychotic features (beneficial in up to 80% of cases), and for maintenance treatment of bipolar I disorder (mood stabilizer). It has some antidepressant capacity, although this is not well established. 

Carbamazepine (Tegretol) is an anticonvulsant and mood-stabilizing drug used in the treatment of epilepsy and bipolar disorder. It is also used to treat ADD (attention-deficit disorder). It is metabolized... 

Lithium carbonate, Li2C03, was the first mood-stabilizing drug approved by the FDA for the treatment of mania and manic-depressive illness, also known as bipolar disorder. Calculate the percent composition by mass of lithium carbonate. 

The primary treatment for depressive episodes in bipolar disorder is mood-stabilizing agents, often combined with antidepressant drugs. 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

Lithium, several (but not all) anticonvulsants, and most of the atypical antipsychotic medications are approved by the U.S. Food and Drug Administration (FDA) for the treatment of one of more phases of bipolar disorder. These medications are referred to as mood stabilizers, and they are the foundation of treatment for bipolar disorders. However, the skillful treatment of bipolar disorder requires not only the knowledge of how to prescribe one or more of these medications but also the understanding that some medications are preferred for one phase of the illness but not the other or for long-term use but not necessarily acute use. In this chapter, we first review the clinical use of lithium and the anticonvulsants that are definite or probable mood stabilizers. The general properties of atypical anti-psychotics are reviewed in Chapter 4. In this chapter, we expand on the use of these compounds for the treatment of bipolar disorder. Discussion of the treatment of each phase of bipolar disorder concludes the chapter. 

Post and Kramlinger (386) have also suggested that lithium added to carbamazepine may be useful in treatment-resistant mood-disordered patients. One possible basis for this approach is that carbamazepine, which has a tricyclic ring structure similar to imipramine, may sensitize postsynaptic serotonin receptors in a similar way to standard drugs such as imipramine. A mood stabilizer (e.g., lithium, valproate, carbamazepine) plus antidepressant may benefit some rapid cycling or mixed bipolar patients, attenuating the propensity to switch from mania to depression. 

These circumstances have important implications for management because drug treatment of the depressive phase may precipitate a manic episode, rapid cycling, or a more virulent course of the illness ( 3). Thus, if bipolar disorder is known or suspected, patients are best managed acutely, as well as for maintenance/prophylaxis, with a mood stabilizer. An antidepressant should be added only when necessary and for the shortest time frame required to alleviate the depressive symptoms. 

Analogous to the recent progress in antidepressant and antipsychotic drug therapy development the pharmacotherapy of bipolar disorder is also experiencing major advances. Data on the efficacy of mood stabilizers for bipolar disorder focus on the following ... 

Whenever possible, we prefer to treat with a mood stabilizer (e.g., lithium, VPA) alone, because of their specificity for bipolar disorder and to minimize adverse effects. This is particularly true in mild to moderately severe episodes of acute mania. In addition, if the patient can benefit from a single drug during the acute episode, this would support its benefit for maintenance and prophylactic purposes. Further, monotherapy diminishes the chance for potentially significant drug interactions and reduces cost. 

Because lithium has long been the standard treatment for bipolar disorder, it is often the drug of first choice. Increasingly, however, VPA has emerged as a viable alternate first-line therapy. CBZ, marketed as an anticonvulsant, has also been studied and used for its mood-stabilizing properties. There has never been a definitive controlled study, however, comparing the efficacy of lithium with other mood stabilizers in difficult-to-treat manic patients. 

The mood stabilizer lithium was developed as the first treatment for bipolar disorder. It has definitely modified the long-term outcome of bipolar disorder because it not only treats acute episodes of mania, but it is the first psychotropic drug proven to have a prophylactic effect in preventing future episodes of illness. Lithium even treats depression in bipolar patients, although it is not so clear that it is a powerful antidepressant for unipolar depression. Nevertheless, it is used to augment antidepressants for treating resistant cases of unipolar depression. 

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