Mania mixed

It is common for both the depressive and manic phases to occur simultaneously in what is termed a mixed state or dysphoric mania. During these mixed episodes, the patient s mood is characterized by symptoms of both a depression and mania. Mixed episodes often have a poorer outcome than classic euphoric mania and, as a rule, respond better to certain anticonvulsants and atypical antipsychotic drugs than to lithium. As many as 50% of admissions to inpatient psychiatric facilities for the treatment of manic episodes appear to be for mixed manic states. The recognition... 

Preferred for Euphoric mania Mixed episode Mixed episode... 

Valproic acid, valproate sodium, and (DVP) are carboxylic acid-derivative anticonvulsants. Divalproex sodium is a stable coordination compound consisting of valproic acid and valproate sodium in a 1 1 molar ratio (AHFS, 2000). It is a pro-drug of valproate, dissociating into valproate in the GI tract (AHFS, 2000), and a simple branched-chain carboxylic acid (w-dipropylacetic acid) with antiepileptic activity against a variety of types of seizures (Beydoun et al., 1997). Divalproex sodium has been approved for treating adults with simple and complex absence seizures (Mattson et al., 1992), and for mania. It has shown efficacy across a broad spectrum of BD subtypes (i.e., pure mania, mixed mania, and rapid cycling) (Pope et al., 1991 Bowden et al., 1994). 

Educate family members and the patient about the characteristics of the disorder(s) being treated, e.g., euphoric mania, mixed mania, psychotic mania, severe... 

Resperidone Tablet Syrup Acute mania mixed episode in bipolar-l disorder. 

Published Guidelines and Treatment Protocols. Currently there are no published evidence-based studies that compare different agents and combination therapies for the treatment of acute mania, mixed... 

Few randomized controlled trials have been done to evaluate different approaches for the treatment of acute and recurrent bipolar depression. Nonpharmacologic treatment that may have augmenting effects include phototherapy for seasonal-pattern depression and sleep deprivation for rapid cycling." The use of ECT for severe episodes of mania/mixed episodes, depression, psychotic features (e.g., hallucinations or delusions), or rapid cycling is still considered the best acute treatment approach for those patients who do not respond to first-line mood stabilizers such as lithium and valproate. " ... 

Alternative ECT used for patients with severe mania, mixed states, depression, or psychosis. 

Dysphoric mania, mixed episode, rapid cycling (most probably better than lithium but not as efficient as valproate), part of schizoaffective disorder, comorbid substance abuse, absence of psychosis, obesity... 

J Rapid cycling, dysphoric mania, mixed episode, stable or decreasing number of manic exacerbations... 

BPAD Bipolar I >2 major mood episodes (at least one mania/mixed affective)... 

Reviews A review of quetiapine for the treatment of acute bipolar mania, mixed episodes and maintenance therapy reported the most common adverse events in acute trials were somnolence, sedation, dry mouth, weight gain, dizziness, asthenia, pharyngitis and postural hypotension [210 ]. In the maintenance trials, the most common adverse events were somnolence, upper respiratory tract infection, nasopharyngitis and headache. 

Janicak PG, Rado JT. Quetiapine for the treatment of acute bipolar mania, mixed episodes and maintenance therapy. Expert Opin Pharma-cother 2012 13(ll) 1645-52. 

Bipolar disorder is a mood disorder characterized by one or more episodes of mania or hypomania, often with a history of one or more major depressive episodes.1 It is a chronic illness with a course characterized by relapses and improvements or remissions. Mood episodes can be manic, depressed, or mixed. They can be separated by long periods of stability or can cycle... 

Bipolar I disorder affects men and women equally bipolar II seems to be more common in women. Rapid cycling and mixed mania occur more often in women. Individuals with bipolar disorder commonly have another psychiatric disease with 78% to 85% reporting another Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis during their lifetime. The most common comorbid conditions include anxiety, substance abuse, and eating disorders.2... 

Electroconvulsive therapy (ECT) is the application of prescribed electrical impulses to the brain for the treatment of severe depression, mixed states, psychotic depression, and treatment-refractory mania in patients who are at high risk of suicide. It also may be used in pregnant women who cannot take carbamazepine, lithium, or divalproex. 

Assess for secondary causes of mania or mixed states (e.g., alcohol or drug use)... 

Mild to moderate symptoms of mania or mixed episode... 

Electroconvulsive therapy (ECT) is used for severe mania or depression during pregnancy and for mixed episodes prior to treatment, anticonvulsants, lithium, and benzodiazepines should be tapered off to maximize therapy and minimize adverse effects. 

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... 

Olanzapine Zyprexa 20, 30 mg Tablets 2.5, 5, 7.5, 10, 5-20 mg/day in 1 or 2 doses combination with lithium or valproate for the acute treatment of mania or mixed states for bipolar I disorder. Olanzapine and aripiprazole are approved for relapse prevention as well as for acute therapy... 

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... 

Conventional antipsychotic drugs such as chlorpromazine and haloperidol have long been used in the treatment of acute mania. More recently, atypical antipsychotic drugs including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasi-done have been approved for the treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood-stabilizing drugs.25 Aripiprazole and olanzapine are also approved for maintenance therapy. The combination of olanzapine and fluoxetine is approved for treatment of bipolar depression. Quetiapine is approved for treatment of... 

Mixed mood episodes Symptoms of mania and depression occurring simultaneously or in close juxtaposition. 

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. 

Changes in the sleep-wake cycle or light-dark cycle can precipitate episodes of mania or depression. Bright light therapy can be used for the treatment of winter depression and can precipitate hypomania, mania, or mixed episodes. 

Exercise (regular aerobic and weight training at least three times a week) / The use of electroconvulsive therapy for severe mania or mixed episodes, psychotic depression, or rapid cycling is still considered the best... 

Lithium is the drug of choice for bipolar disorder with euphoric mania, whereas valproate has better efficacy for mixed states, irritable/dysphoric mania, and rapid cycling compared with lithium. 

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. 

Ari pi prazole, olanzapine, quetiapine, risperidone, and ziprasidone are effective as monotherapy or as add-on therapy to lithium or valproate for acute mania. Prophylactic use of antipsychotics can be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed in view of long-term side effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). 

Use in combination with other drugs (e.g, anti-psychotics, lithium, valproate) for the acute treatment of mania or mixed episodes. Use as a short-term adjunctive sedativehypnotic agent. Binds to the benzodiazepine site and augments the action of GABA/, by increasing the frequency of Cl" channel opening which causes hyperpolarization (a less excitable state) and inhibits neuronal firing. 

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. 

Lithium is effective for acute mania, but it may require 6 to 8 weeks to show antidepressant efficacy. It may be more effective for elated mania and less effective for mania with psychotic features, mixed episodes, rapid cycling, and when alcohol and drug abuse is present. Maintenance therapy is more effective in patients with fewer episodes, good functioning between episodes, and when there is a family history of good response to lithium. It produces a prophylactic response in up to two-thirds of patients and reduces suicide risk by eight- to 10-fold. 

Valproate is as effective as lithium and olanzapine for pure mania, and it can be more effective than lithium for rapid cycling, mixed states, and bipolar disorder with substance abuse. It reduces the frequency of recurrent manic, depressive, and mixed episodes. 

B. Does not fulfill criteria for a mixed episode (i.e., no evidence of mania). 

In the bipolar affective disorders (BPADs), periods of normal mood are interspersed with episodes of mania, hypomania, mixed states, or depression. BPAD differs from MDD in that there is a bidirectional natnre to the mood swings and, for many patients, the rate of cycling is more rapid in BPAD than MDD. The phases of BPAD inclnde mania, hypomania, and depression, though mixed states, the simultaneous presentation of symptoms of both mania and depression, are common. 

In contrast to MDD, the bipolar disorders consist of episodes of depression and episodes of hypomania or mania. This poses a problem for treating the depressed phase of this illness, becanse, as noted earlier, antidepressants can trigger hypomania, mania, or mixed dysphoric mania and can increase the freqnency of manic episodes. Therefore, the hallmark of treating BPAD is the nse of mood stabilizers, with and withont snpplemental antidepressant therapy. Please refer to Table 3.16 for a comparison of the traditional mood stabilizers. 

Lithium remains the treatment of choice for bipolar patients who experience classic euphoric episodes of mania. Current evidence suggests that those with mixed episodes or rapid cycling episodes respond preferably to anticonvulsants or atypical antipsychotic drugs. In addition to its use as a mood stabilizer, lithium is effective in converting unipolar antidepressant nonresponders to responders. Finally, lithium may also be an effective treatment for patients with clnster headaches. 

Valproate (Depakote, Depakene). Valproate is an anticonvnlsant that has been demonstrated in multiple controlled clinical trials to be an effective mood stabilizer and, in fact, has obtained FDA approval for the treatment of acute mania. It appears to be particularly effective in bipolar patients who experience mixed episodes or rapid cycling or who have not responded well in the past to lithium. 

Carbamazepine (Tegretol, Equetro). Carbamazepine is another anticonvulsant with documented efficacy in treating BEAD, and was recently FDA approved for this indication. Like valproate, carbamazepine is usually preferred to lithium in cases of mixed mania or rapid cycling. 

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