Bipolar disorder mania treatment

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. 

Drug treatment is a vital part of the management of bipolar disorder, both during episodes of depression or mania and as prophylaxis thereafter. Patients require explanation and education about the illness and about the treatments available, in order to be able to make informed choices and to avail themselves of the appropriate options fot treatment. 

Depression and mania are both affective disorders but their symptoms and treatments are quite distinct. Mania is expressed as heightened mood, exaggerated sense of self-worth, irritability, aggression, delusions and hallucinations. In stark contrast, the most obvious disturbance in depression is melancholia that often co-exists with behavioural and somatic changes (Table 20.1). Some individuals experience dramatic mood swings between depression and mania. This is known as "bipolar disorder which, like mania itself, is treated with lithium salts or neuroleptics. 

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. 

Table 36-4 includes a summary of current drug therapy for bipolar disorder. An algorithm for treatment of bipolar mania is shown in Table 36-2. 

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... 

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... 

Lamotrigine is effective for the maintenance treatment of bipolar disorder. It is more effective for depression relapse prevention than for mania relapse. Its primary limitation as an acute treatment is the time required for titration to an effective dosage. In addition to maintenance monotherapy, it is sometimes used in combination with lithium or divalproex, although combination with divalproex increases the risk of rash, and lamotrigine dosage adjustment is required.37... 

Treatment of depressive episodes in bipolar disorder patients presents a particular challenge because of the risk of a pharmacologic mood switch to mania, although there is not complete agreement about such risk. Treatment guidelines suggest lithium or lamotrigine as first-line therapy.17,41 Olanzapine has also demonstrated efficacy in treatment of bipolar depression, and quetiapine is under review for approval of treatment of bipolar depression.42 When these fail, efficacy data support use of antidepressants. 

Comorbid conditions must be addressed in order to maximize desired outcomes. For comorbid bipolar disorder and attention-deficit/hyperactivity disorder when stimulant therapy is indicated, treatment of mania is recommended before starting the stimulant in order to avoid exacerbation of mood symptoms by the stimulant. 

Lithium The first drug to be used in the treatment of unipolar mania and bipolar disorder. 

In depressed patients, cortical-hypothalamic-pituitary-adrenal axis hyperactivity can be explained by the hypersecretion of CRF, and secondary pituitary and adrenal gland hypertrophy. Impaired negative feedback at various CNS sites, including the hippocampus and pituitary are also likely to contribute. Downregulation of hippocampal mineralocorticoid receptors and expression is reported in depressed suicides [50]. In bipolar disorder, hyperactivity of the cortical-hypothalamic-pituitary-adrenal axis has been observed [51]. This increase in cortical-hypothalamic-pituitary-adrenal axis activity has also been observed in mixed mood states, mania and in depression in rapidcycling patients. Partial reversal of HPA overactivity is associated with treatment and recovery from depression. 

Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. 

In addition to being effective in the treatment of schizophrenia, clozapine also is effective in the treatment of the manic phase of bipolar disorder. Although not a first-line treatment for mania, clozapine is useful for patients who are not responding well to more traditional treatments. Finally, clozapine is the one antipsychotic proven to help treatment-resistant schizophrenia. Fully one-third of patients who do not respond to other antipsychotics will respond to clozapine. 

Numerous open studies, and seven controlled studies, have shown that valproate is effective in the treatment of acute mania. It has also been claimed to have an antidepressant action. Recent studies have shown that valproate is effective in the long-term treatment of bipolar disorder. 

In contrast to the large number of studies that have investigated lithium as a maintenance treatment for bipolar disorder, relatively few studies have been made of divalproex sodium, despite its widespread use in the acute treatment of mania. There is evidence from one placebo-controlled study in which lithium was compared with divalproex sodium that the latter drug was better tolerated but that the prevention of relapse did not differ between the drugs. It would therefore appear that a switch to divalproex sodium may be particularly useful in bipolar patients who are experiencing... 

Lithium is used in the prophylaxis and treatment of mania and in the prophylaxis of bipolar disorders and recurrent depression. Lithium should be stopped 24 hours before major surgery but the normal dose can be continued for minor surgery, with careful monitoring of fluids and electrolytes. After major surgery, renal function is reduced and this may compromise clearance of lithium. Lithium is a drug with a narrow therapeutic index and it should be avoided if possible in patients with renal impairment. Renal function should be tested before initiating treatment. If lithium is given to patients with renal impairment, a reduced dose should be used and serum lithium concentrations should be monitored closely. 

Bipolar mania - For the treatment of acute manic and mixed episodes associated with bipolar disorder. 

Bipolar mania (ora only) - For the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. Schizophrenia - For the treatment of schizophrenia. 

Bipolar disorder For the maintenance treatment of Bipolar I Disorder to delay the time to occurrence of mood episodes (eg, depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy. 

Neuropsychiatric events Life-threatening or fatal neuropsychiatric events, including suicide, suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior have occurred in patients with and without a previous psychiatric disorder during peginterferon alfa-2b treatment and follow-up. Psychoses, hallucinations, bipolar disorders, and mania have been observed in patients treated with alpha interferons. 

Prevention or treatment of acute mania, manic phase of bipolar disorder (manic-depressive illness) PO 900-l,200mg/day. Maintenance 300mgtwiceaday. May increase by 300mg/dayqlwk. 

Mania in bipolar disorder PO Initially, 40 mg twice a day. May increase to 60-80 mg twice a day on second day of treatment. Range 40-80 mg twice a day. 

Mania. Mania and hypomania can also occur in children and adolescents on SSRIs, and, again, it is not known if there is an added developmental risk (Ven-kataraman et al., 1992). In a fluoxetine treatment study for depression, 3 (of 48) patients developed manic symptoms, even after excluding patients with psychotic depression, bipolar symptoms, or a family history of bipolar disorder (Emslie et al., 1997). In a paroxetine treatment study for depression, 5 adolescents (of 93) were removed for emotional lability and 1 for eupho-ria/expansive mood (Keller et al., 2001). 

Chart reviews and open trials of outpatients with bipolar disorder and bipolar spectrum disorder have been published for 28 risperidone- and 23 olanzapine-treated treated children and adolescents (Frazier et ah, 1999 2001). Significant decreases in mania, depression, and aggression ratings occurred over the course of treatment however, other medications were also used simultaneously. Additional anecdotal information exists for olanzapine (Soutullo et ah, 1999 Chang and Ketter, 2000), quetiapine (Schaller and Behar, 1999), and clozapine (Fuchs, 1994). 

Carlson, G.A. (2000) Very early onset bipolar disorder. Does it Exist in Childhood In Rapoport, J, ed. Onset of Adult Psychopathology—Clinical and Research Advances. APPI Press, pp. 303-332. Carlson, G.A., Bromet, E.J., and Lavelle, J. (1999) Medication treatment in adolescents vs adults with psychotic mania. / Child Adolesc Psychopharmacol 9 221-231. 

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