Mania in bipolar disorder

Mundo E, Walker M, Cate T, Macciar-di F, Kennedy JL. The role of serotonin transporter protein gene in antidepressant-induced mania in bipolar disorder preliminary findings. Arch Gen Psychiatry 2001 58 539-544. 

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. 

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. 

In four instances, the agency has invoked this rule at the time of approval of supplements for new indications for psychotropic drugs already approved for other psychiatric indications. It was noted in the approval letters for these supplements that, since the drugs in question would likely be used in children and/ or adolescents with the newly approved indications, the FDA required the sponsors of these products to conduct studies that would be pertinent to such use in the pediatric population. Since the products were ready for approval in adults, the FDA deferred the required pediatric studies to a future date. Alternatively, sponsors could make an argument for waiver of the requirement. The drug products and indications for which the FDA has required studies under the Pediatric Rule are as follows paroxetine for social anxiety disorder sertraline for post-traumatic stress disorder (PTSD) olanzapine for acute mania in bipolar disorder and fluoxetine in premenstrual dysphoric disorder (PMDD). 

Weisler RH, Keck PE Jr, Swann AC, et al Eixtended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder a multicenter, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 66 323-330, 2005... 

Bowden CL, Grunze H, Mullen J, Brecher M, Paulsson B, Jones M, Vagero M, Svensson K. A randomized, double-bhnd, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder. J Clin Psychiatry 2005 66 111-21. 

Revicki DA, Paramore LC, Sommerville KW, Swann AC, Zajecka JM. Divalproex sodium versus olanzapine in the treatment of acute mania in bipolar disorder health-related quality of life and medical cost outcomes. J Clin Psychiatry 2003 64 288-94. 

Treafmenf may nof only reduce mania buf also prevenf recurrences of mania in bipolar disorder... 

Masoliver F. Menoyo A, Perez V, et al. Serotonin transporter linked promoter (polymorphism) in the serotonin transporter gene may be associated with antidepressant-induced mania in bipolar disorder. Psychiatr Genet 2006 16 25-9. 

Tegretol is prescribed to treat the mania in bipolar disorder, not the depression. Therefore, a depression scale does not indicate anything about the effectiveness of the medication. 

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... 

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. 

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. 

Disturbances of sleep are typical of mood disorders, and belong to the core symptoms of major depression. More than 90% of depressed patients complain of impaired sleep quality [60], Typically, patients suffer from difficulties in falling asleep, frequent nocturnal awakenings, and early morning awakening. Not only is insomnia a typical symptom of depression but, studies suggest, conversely, insomnia may be an independent risk factor for depression. In bipolar disorders sleep loss may also be a risk factor for the development of mania. Hypersomnia is less typical for depression [61] and, in contrast to insomnia, may be related to certain subtypes of depression, such as seasonal affective disorder (SAD). 

As many as 1 in 10 patients experience episodes of mania akin to those seen in bipolar disorder after TBl. Right-sided brain injury, particularly in the frontal lobe or so-called limbic structures, has the greatest potential to produce a secondary mania. The manic symptoms include euphoric or irritable mood, decreased need... 

Psychosis or mania Antidepressants can precipitate manic episodes in bipolar disorder patients during the depressed phase of their illness and may activate latent psychosis in other susceptible individuals. The sustained-release formulation of bupropion is expected to pose similar risks. There were no reports of activation of psychosis or mania in clinical trials conducted in nondepressed smokers. 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

Virtually all anticonvulsants are or have been of interest for the treatment of bipolar disorder. However, the importance of controlled data cannot be understated. For example, gabapentin, an anticonvulsant that initially received much attention as a potential mood stabilizer, was compared with placebo and did not appear to stabilize mood (Frye et al. 2000 Pande et al. 2000). Similar negative results were seen with topiramate in placebo-controlled trials for the treatment of mania. Although these medications might be useful adjuncts in some patients, given the currently expanded pharmacopoeia of medications with positive controlled trial data in bipolar disorder, we do not recommend the primary use of agents that have only case reports as an evidence base or controlled studies with predominantly negative results. 

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. 

Clinical Efficacy in Bipolar Disorder (Especially in Mania)... 

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