Acute manic episode

Treatment of Manic—Depressive Illness. Siace the 1960s, lithium carbonate [10377-37-4] and other lithium salts have represented the standard treatment of mild-to-moderate manic-depressive disorders (175). It is effective ia about 60—80% of all acute manic episodes within one to three weeks of adrninistration. Lithium ions can reduce the frequency of manic or depressive episodes ia bipolar patients providing a mood-stabilising effect. Patients ate maintained on low, stabilising doses of lithium salts indefinitely as a prophylaxis. However, the therapeutic iadex is low, thus requiring monitoring of semm concentration. Adverse effects iaclude tremor, diarrhea, problems with eyes (adaptation to darkness), hypothyroidism, and cardiac problems (bradycardia—tachycardia syndrome). 

Zhang, H. Y., Shu, L., Li, H. F. et al. (2006). Risperidone versus haloperidol in treatment of acute manic episodes of bipolar 1 disorder a randomized double-blind controlled multicenter study. Journal of Chinese Psychiatry, 39(1), 33-7. 

Aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone are FDA approved for the treatment of acute manic episodes in bipolar I disorder. 

Combination therapy In combination with lithium or valproate for the short-term treatment of acute manic episodes associated with bipolar I disorder. 

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. 

Mukherjee S, Sackeim HA, Schnur DB Electroconvulsive therapy of acute manic episodes a review of 50 years experience. Am J Psychiatry 151 169-176, 1994 Muller AA, Stoll K-D Carbamazepine and oxcarbamazepine in the treatment of manic syndromes studies in Germany, in Anticonvulsants in Affective Disorders. Edited by Emrich HM, Okuma T, Muller AA. Amsterdam, Excerpta Medica, 1984, pp 139-147... 

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... 

Clonazepam. Case reports and one small double-blind study indicate that oral clonazepam may be useful for psychotic agitation when combined with lithium or an antipsychotic (see also the section Management of an Acute Manic Episode in Chapter 10) ( j,7.0, 175). 

Paradoxically, ECT is equally useful in both the acute manic and depressive phases of bipolar disorder, constituting the only truly bimodal therapy presently available. For example, in their literature review, Mukherjee et al. ( 51) found that ECT was associated with marked clinical improvement or remission in 80% of patients undergoing treatment for an acute manic episode. This is not the case for lithium, valproate, or CBZ, which, at best, have relatively weak acute antidepressant effects. Drug therapies may also induce a switch from a depressed to a manic phase, whereas ECT can control both phases of the illness. 

Mukherjee S, Sackheim HA, Schnur DB. Electroconvulsive therapy of acute manic episodes a review of 50 years experience. Am J Psychiatry 1994 151 169-176. 

Manaqement of an Acute Manic Episode Primary Mood Stabiiizers... 

Halman et al. (491) conducted a retrospective chart review on 11 patients who were HIV-positive and presented with an acute manic episode. Whereas the six patients with abnormal MRI findings demonstrated intolerance to standard drug treatment (i.e., lithium, conventional neuroleptics), all benefited from a trial with an anticonvulsant (e.g., valproate, CBZ, clonazepam). 

Lithium is readily absorbed from the gastrointestinal tract and completely distributed throughout all the tissues in the body. During an acute manic episode, achieving blood serum concentrations between 1.0 and 1.4 mEq/L is desirable. Maintenance doses are somewhat lower, and serum concentrations that range from 0.5 to 1.3 mEq/L are optimal. 

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. 

Bipolar affective disorder (acute manic episode) ... 

Patients with bipolar disorder frequently require multiple medications or changes in therapy. For example, antianxiety agents are helpful in reducing anxiety and agitation, especially in patients who refuse antimanic or antipsychotic agents. Likewise an added antipsychotic is more effective than lithium alone in acute manic episodes that include significant psychomotor activity and delusions or hallucinations. Ongoing treatment with antipsychotics after the manic episode is resolved is often not necessary. However, it is not uncommon for a refractory patient to require a combination of mood stabilizers, an antidepressant, and an antipsychotic. 

Quetiapine fumarate is a dibenzapine derivative that has antipsychotic effects, apparently caused by dopamine and serotonin receptor blockade in the CNS. It is indicated in the treatment of schizophrenia and as short-term treatment of acute manic episodes associated with bipolar 1 disorder, as either monotherapy or adjunct therapy to lithium or divalproex. 

Carbamazepine may also be effective in specific cases of acute manic episode. Good prognostic signs for carbamazepine are ... 

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