Bipolar disorder treatment with mood stabilizer

Perhaps even more important in children is the issue of bipolar disorder. Mania and mixed mania have not only been greatly underdiagnosed in children in the past but also have been frequently misdiagnosed as attention deficit disorder and hyperactivity. Furthermore, bipolar disorder misdiagnosed as attention deficit disorder and treated with stimulants can produce the same chaos and rapid cycling state as antidepressants can in bipolar disorder. Thus, it is important to consider the diagnosis of bipolar disorder in children, especially those unresponsive or apparently worsened by stimulants and those who have a family member with bipolar disorder. These children may need their stimulants and antidepressants discontinued and treatment with mood stabilizers such as valproic acid or lithium initiated. 

The treatment of bipolar disorder is complex, and depends on the particular phase of illness. The mood stabilizers form the foundation of treatment. These include lithium and the anticonvulsant drugs, valproate, and carbamazepine (Bowden, 1998 McElroy and Keck, 2000 Post, 2000). Recently, lamoh igine has been found effective in some patients (Post, 2000). The goal of treatment with mood stabilizers is reduction of frequency and severity of episodes of depression and mania. 

Bipolar disorder is characterized by episodes of mania or hypomania, which include hyperactivity, decreased need for sleep, and a euphoric or irritable mood. Additionally, persons with bipolar disorder may have episodes of depression similar to those seen in major depressive disorder. The lifetime prevalence of severe bipolar disorder is about 1% and 3-5% if milder cases are included, afflicting men and women equally. Both bipolar disorder and major depressive disorder tend to be episodic, and in the periods of time between episodes, persons may experience few or no symptoms. The etiology of bipolar disorder is predominately genetic, with a 70% concordance in monozygotic twins. The neurobiology of bipolar disorder is less well understood, and few animal models have been developed. Treatment of bipolar disorder usually involves mood stabilizer medications, including lithium, and the anticonvulsants valproate and carbamazepine. At times, antidepressant and antipsychotic medications are also used. 

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... 

Although this is an area in which research is burgeoning, definite evidence of the effectiveness of EFAs in the treatment of mental disorders is lacking. There are some controlled trials of varying methodological quality in adult patients with schizophrenia, and unipolar and bipolar depression, with conflicting results (Fenton et ah, 2000 Maidment, 2000). The most encouraging trial is a preliminary study of 30 patients with bipolar disorder. It found that EFAs concurrent with mood stabilizers reduced the rate of recurrence of episodes (Stoll et al., 1999). 

TREATMENT OF BIPOLAR DISORDER WITH MOOD STABILIZERS... 

Bipolar disorder (manic-depressive illness) is one of the most common of the severe chronic psychiatric disorders. The cyclic mood disorder is characterized by recurrent fluctuations in mood, energy, and behavior encompassing the extremes of human experiences.Bipolar disorder differs from recurrent major depression (or unipolar depression) in that a manic, hypomanic, or mixed episode occurs during the course of the illness. Bipolar disorder is a lifelong illness with a variable course and requires both nonpharmacologic and pharmacologic treatments for mood stabilization. ... 

Approaches for treating bipolar disorder in special populations (e.g., comorbid medical or psychiatric disorders, pregnancy, or breastfeeding) are found in Table 68-9. Patients with comorbid medical conditions or concomitant substance abuse, those over 65 years of age, and pregnant patients may require different treatment approaches. Approximately 20% to 50% of women with bipolar disorder relapse postpartum therefore prophylaxis with mood stabilizers is recommended immediately postpartum to decrease the risk of relapse. ... 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

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

Sprinkle capsule 15, 25 mg Atypical Antipsychotics FDA approved for use in bipolar disorder Aripiprazole Abilify Tablets 5, 10, 15, Dosage should be slowly increased to minimize adverse effects (e.g., 25 mg at bedtime for 1 week, then 25-50 mg/day increments at weekly intervals) 10-30 mg/day once daily acute treatment of mania or mixed episodes due to lack of efficacy used as an adjunctive agent with established mood stabilizers Use as monotherapy or in... 

Lithium was the first established mood stabilizer and is still considered a first-line agent for acute mania and maintenance treatment of both bipolar I and II disorders. It is the only bipolar medication approved for adults and children 12 years and older. Long-term use of lithium reduces suicide risk. Patients with rapid cycling or mixed states may not respond as well to lithium monotherapy as to some anticonvulsants. 

Lamotrigine is effective for the maintenance treatment of bipolar I disorder in adults. It has both antidepressant and mood-stabilizing effects, and it may have augmenting properties when combined with lithium or valproate. It has low rates of switching patients to mania. Although it is less effective for acute mania compared to lithium and valproate, it may be beneficial for the maintenance therapy of treatment-resistant bipolar I and II disorders, rapidcycling, and mixed states. It is often used for bipolar II patients. 

In addition to its acute actions, Li+ can reduce the frequency of manic or depressive episodes in the bipolar patient and therefore is considered a mood-stabilizing agent. Accordingly, patients with bipolar disorder are often maintained on low stabilizing doses of Li+ indefinitely as a prophylaxis to future mood disturbances. Antidepressant medications are required in addition to Li+ for the treatment of breakthrough depression. 

There is strong evidence that bipolar disorder is associated with SUD in adolescents (Wilens et ah, 1999) and that pharmacological interventions are an effective treatment for youth with SUD and bipolar disorder. Two studies, including one randomized controlled study, have reported that mood stabilizers, specifically lithium and valproic acid (Depakote), significantly reduced substance use in bipolar youth (Donovan and Nunes, 1996 Geller et ah, 1998). In addition, these agents are considered effective agents for the treatment... 

Valproate, a simple branched-chain fatty acid, was first reported as a successful treatment for acute mania by Lambert and colleagues in 1966. Following this report, at least 16 uncontrolled trials consistently supported the observation that valproate has acute and long-term mood-stabilizing effects in patients with bipolar disorder (reviewed by Keck et al. 1992a). Recently, five double-blind controlled studies of valproate have been completed that provide definitive evidence of its efficacy in acute mania. 

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