Mania acute manic episode

Bipolar mania - For short-term treatment of acute manic episodes associated with bipolar I disorder, as monotherapy or adjunct therapy to lithium or divalproex. 

For more than 40 years, Li+ has been used to treat mania. While it is relatively inert in individuals without a mood disorder, lithium carbonate is effective in 60 to 80% of all acute manic episodes within 5 to 21 days of beginning treatment. Because of its delayed onset of action in the manic patient, Li+ is often used in conjunction with low doses of high-potency anxiolytics (e.g., lo-razepam) and antipsychotics (e.g. haloperidol) to stabilize the behavior of the patient. Over time, increased therapeutic responses to Li+ allow for a gradual reduction in the amount of anxiolytic or neuroleptic required, so that eventually Li+ is the sole agent used to maintain control of the mood disturbance. 

Lithium carbonate is completely absorbed by the gastrointestinal tract and reaches peak plasma levels in 1-2 hours. The elimination half-life is approximately 24 hours. Steady-state lithium levels are achieved in approximately 5 days. Therapeutic plasma levels range from 0.5 to 1.2 mEq/L. Lower plasma levels are associated with less troubling side effects, but levels of at least 0.8 mEq/L are often required in the treatment of acute manic episodes. Therefore, when intolerable side effects have not intervened, treatment of acute mania with lithium should not be considered a failure until plasma levels of 1.0-1.2 mEq/L have been reached and have been maintained for 2 weeks. As discussed at the end of this chapter (see Treatment of Mania or Mixed Episodes ), more severely ill patients may require combination treatment. 

It is well established that monotherapy with various antidepressants or mood stabilizers is relatively ineffective (i.e., they are necessary but not sufficient) for treating mood disorders with associated psychosis. Thus, psychotically depressed patients are best managed with a combination of antipsychotic-antidepressant or with electroconvulsive therapy. Although antipsychotics have a more rapid onset of action than lithium in an acute manic episode, we are unaware of clinical trials that examine the differential effect of antipsychotics or lithium for nonpsychotic versus psychotic mania. This topic is discussed further in... 

Mania can occur in any age group. Acute manic episodes in the elderly may best be managed with high potency neuroleptics. The use of lithium is not contraindicated in the elderly provided renal clearance is reasonably normal. The dose administered should be carefully monitored, as the half-life of the drug is increased in the elderly to 36-48 hours in comparison to about 24 hours in the young adult. The serum lithium concentration in the elderly should be maintained at about 0.5 mEq/litre. It is essential to ensure that the elderly patient is not on a salt-restricted diet before starting lithium therapy. The side effects and toxicity of lithium have been discussed in detail elsewhere (see p. 198 et seq.), and, apart from an increase in the frequency of confusional states in the elderly patient, the same adverse effects can be expected as in the younger patient. 

Although mania has been associated with olanzapine (SEDA-24, 68 SEDA-25, 68 SEDA-26, 62), it has also been used in the treatment of acute mania. In a 12-week, double-blind, double-dummy, randomized trial, 120 patients with bipolar disorder type I hospitalized for an acute manic episode were randomly assigned to either sodium valproate (n = 63) or olanzapine (n = 57) and were followed in hospital for up to 21 days (60). Valproate and olanzapine had similar short-term effects on clinical or health-related quality of life outcomes in bipolar disorder adverse effects that occurred in a higher percentage of olanzapine-treated than valproate-treated patients included somnolence (47% versus 29%), weight gain (25% versus 10%), rhinitis (14% versus 3%), edema (14% versus 0%), and slurred speech (7% versus 0%) no adverse events occurred significantly more often with valproate. 

Lamotngine (Lamictal). Lamotrigine, another anticonvulsant used to treat BPAD, is currently FDA approved for the prevention of both depressive and manic episodes during BPAD maintenance therapy. This represents a shift in the paradigms for BPAD therapy, as medications used to treat acute episodes have also typically been used for antimanic prophylaxis. Lamotrigine is not effective in the acute treatment of mania but has become for many the drug of choice for bipolar depression as well as for prevention of subsequent mood episodes of either polarity. 

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. 

These are usually treated with sedative neuroleptics (as for schizophrenia, above). Treatment must also aim to support the patient socially including for instance advising on legal protection from the financial or other consequences of mania. One of the risks of treatment is the sudden mood swing at the end of the manic episode, with acute depression possibly triggered by the neuroleptics. Because of the concern for the manic episode and symptoms, return to normal is viewed with relief, and the downswing may go un-noticed, with the concomitant suicidal risk. 

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. 

ECT is the only clearly established bimodal therapy in that it is equally effective for both the depressed and manic phases of the disorder. Although the primary indication for ECT is a severe, unremitting, or drug-nonresponsive depressive episode, data from as early as the 1940 s support its use for the treatment of acute mania, particularly manic delirium (242, 243 and 244). Based on clinical experience, we would expect mania to remit rapidly with ECT, whereas lithium can take weeks. Hence, there may be a superiority for E(3T over lithium in the early phases of treatment. What the final outcome would be is more problematic, but clearly, there is a need to further explore the efficacy of ECT in mania. In this light, Schnur and colleagues ( 245) reported on the relationship between various pretreatment symptoms and therapeutic outcome to ECT in 18 manic patients. They found that although severity of mania was not predictive, anger, irritability, and suspiciousness were more characteristic of nonresponders to ECT. 

Two studies have directly addressed the question of lithium s specificity for mania or affective psychosis, as it is sometimes called. In one of these studies a group of 78 patients admitted with an acute psychotic episode diagnosed as mania, schizophrenia or schizoaffective disorder were randomised to receive lithium or chlorpromazine. The authors hypothesised that patients diagnosed as manic would respond better to lithium and those diagnosed with schizophrenia would respond better to chlorpromazine. In contrast they found that there was no difference in the effects of the different drugs on people with different diagnostic labels and that the only discernible effect was the inferiority of lithium in severely disturbed patients (Braden et al. 1982). A similar study published in 1988 claimed to show that lithium had specificity for... 

When patients present in a manic episode, rapid remission of symptoms is required, particularly if the person is psychotic or experiencing severely disruptive behavior. In these cases, use of an antipsychotic medication is usual. These medications may include use of conventional or first generation antipsychotic medications, such as chloipromazine or haloperidol (Table 35.3). Recently, the second generation or atypical antipsycho tics have also shown efficacy in treatment of acute mania (American Psychiati ic Association, 2000). The latter agents are preferred due to their lower likelihood of inducing neuro-... 

The desired outcome for bipolar disorder is to alleviate or shorten the duration of an acute manic, hypomanic, or depressive episode, to maintain good functioning, and to prevent further cycles of mania or depression. The general principles and goals for the management of bipolar disorder are found in Table 68-5. 

Carbamazepine (brand name Tegretol) Originally developed as an anticonvulsant medication. It is used along with other medications such as valproic acid (Depakote or Depakene) to treat individuals suffering from some type of mood disorder (acute mania and bipolar disorders). It is thought to retard the electrochemical process in the nervous system that can set off either convulsions or manic episodes. Also used to treat alcohol withdrawal, cocaine addiction, and emotional disorders. 

Antipsychotic drugs commonly have been used empirically to manage manic and psychotic illness in bipolar disorder patients. Indeed, standard neuroleptics are a mainstay of the treatment of acute mania (only chlorpromazine is FDA-approved for this indication, although haloperidol has also been widely used) and for manic episodes that break through prophylactic treatment with LF or an anticonvulsant. However, the older antipsychotics are not used routinely for long-term prophylactic treatment in bipolar disorder because their effectiveness is untested, some may worsen depression, and the risk of tardive dyskinesia in these syndromes may be higher than in schizophrenia. 

Acute mania as part of bipolar I disorder is supposed to result from overexcitation of limbic neurons. This can arise either from loss of inhibitory tonic orbitofrontal control of limbic neurons or from various intra- and intercellular alterations (the full mechanism is unknown as yet). Manic episodes are often classified into euphoric (classical), dysphoric, mixed (along with clinical manifestations of major depressive disorder), mania with psychotic/catatonic features, and mania with a rapid cycling course of the disease. 

A limited body of evidence indicates that lithium helps atypical mania, schizoaffective disorder, or schizophreniform disorder, both as an acute treatment and for prevention of recurrence. There are younger patients who demonstrate both schizophrenic and manic features early in the course of their illness. When in doubt about the diagnosis, lithium may be preferable for an acute episode because, if successful, it will most likely be an effective prophylaxis as well. Clearly, some patients are so disturbed that the clinician cannot wait until lithium becomes fully effective, and an antipsychotic must be added, but often it can be discontinued after a brief period to determine whether lithium alone is sufficient. 

FIGURE 7—35. Combination treatments for bipolar disorder (bipolar combos). Combination drug treatment is the rule rather than the exception for patients with bipolar disorder. It is best to attempt monotherapy, however, with first-line lithium or valproic acid, with second-line atypical antipsychotics, or with third-line anticonvulsant mood stabilizers. A very common situation in acute treatment of the manic phase of bipolar disorder is to treat with both a mood stabilizer and an atypical antipsychotic (atypical combo). Agitated patients may require intermittent doses of sedating benzodiazepines (benzo assault weapon), whereas patients out of control may require intermittent doses of tranquil-izing neuroleptics (neuroleptic nuclear weapon). For maintenance treatment, patients often require combinations of two mood stabilizers (mood stabilizer combo) or a mood stabilizer with an atypical antipsychotic (atypical combo). For patients who have depressive episodes despite mood stabilizer or atypical combos, antidepressants may be required (antidepressant combo). However, antidepressants may also decompensate patients into overt mania, rapid cycling states, or mixed states of mania and depression. Thus, antidepressant combos are used cautiously. 

Lithium was introduced into modern psychiatric practice in the 1950s and for decades it was the only drug that was thought to have a specific effect on the psychiatric condition known as manic depression. At first it was viewed as a specific treatment for an acute episode of mania and later it was proposed to have prophylactic properties against recurrence of future episodes. It continues to be recommended for the treatment of acute mania, although it is rarely used alone in such circumstances. It is most commonly prescribed for the prophylaxis, or prevention of recurrence, of manic-depressive episodes. 

ANTIMANIC AGENTS are used mainly to treat manic-depressive illness (bipolar disorder), which is characterized by periods of mood normality punctuated by episodes of mania and bouts of depression. The manic phase most often requires acute treatment, and initially ANTIPSYCHOTIC AGENTS, e.g. phenothiazines, will usually be given. Thereafter, a very different psychoactive drug, lithium, may gradually be substituted in most patients, and this can prevent or reduce... 

Lithium and valproate are the mainstays of treatment for both acute mania and prophylaxis for recurrent manic and depressive episodes. Anticonvulsants such as lamotrigine, carbamazepine, and oxcarbazepine and atypical antipsy-chotics such as aripizrazole, olanzapine, risperidone, queti-... 

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