Refractory mania

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. 

Electroconvulsive therapy (ECT) has been described in the treatment of refractory mania in two prepubertal children (Hill et al., 1997). Rey and Walter (1997) have also summarized the literature on juvenile ECT, including its use in mania in adolescents (also see Chapter 30 in this volume). 

Schaller, J.L., and Behar, D. (1999) Quetiapine for refractory mania in a child. J Am Acad Child Adolesc Psychiatry 38 498-499. 

Clozapine also has been shown to benefit schizoaffective and bipolar patients with treatment-refractory mania ( 54) patients with Parkinson s disease and those with other neurological disorders with psychoses, such as Huntington s disease. Although clozapine has been shown to be an effective agent in the elderly, its usefulness in this population is limited because of its anticholinergic, sedative, cardiovascular, and potentially toxic effects on the bone marrow ( 55). In a study of 12 elderly female psychotic patients on clozapine (maximal daily dose, 300 mg), for example, five were taken off clozapine because of postural hypotension, one had a nonfatal episode of agranulocytosis, and one had leukopenia ( 56). 

Calabrese JR, Kimmel SE, Woyshville MJ, et al. Clozapine for treatment-refractory mania. Am J Psychiatry 1996 153 759-764. 

Treatment of refractory mania A randomised, double-blind, placebo-controlled study of the efficacy of 3 weeks of adjunctive nasal spray calcitonin (200 lU per day) for treating refractory mania (N = 46) did not support the use of nasal calcitonin for this indication [7 ]. Rhinorrhoea and nasal inflammation were reported more commonly in the treatment group (6/22) than in the placebo group (2/24). 

Vik A, Ravindran A, Shiah 1, Wong H, Walji N, Lam RW, et al. A double-blind, placebo-controUed study of adjimctive calcitonin nasal spray in acute refractory mania. Bipolar Disord 2013 15(4) 359-64. 

Fourth, if response is inadequate, consider ECT for mania with psychosis or catatonia 6 or add clozapine for treatment-refractory illness Fifth, if response is inadequate, consider adding adjunctive therapies8... 

Mood stabilisers are used to regulate the cyclical change in mood characteristic of bipolar disorder, since they can attenuate both manic and depressive phases. Their main use is as a prophylactic for manic depression and unipolar mania. However, they can also be administered concomitantly with antidepressants for refractory (non-responsive) unipolar depression. 

Anxiety disorders adjunct in treatment-refractory psychosis and in mania severe agitation severe insomnia MDD + anxiety akathisia... 

Brunet et al. (1990), in an open study, reported positive antimanic effects of nimodipine in six patients with acute mania. Our results showed a much lower response rate, ffowever, our patients were much more refractory by history, were treated in a tertiary referral research center, and generally showed a higher incidence of rapid, ultrarapid, and ultradian cycling patterns than in more traditional studies. Our results, however, are consistent with those of Manna (1991), who reported equal long-term efficacy of nimodipine and lithium monotherapy and greater efficacy on a combination of the two drugs than on either drug alone. 

Goodnick PJ. Risperidone treatment of refractory acute mania [Letter]. J din Psychiatry 1995 56 431-432. 

Carbamazepine has been considered to be a reasonable alternative to lithium when the latter is less than optimally efficacious. The mode of action of carbamazepine is unclear, and oxcarbazepine is not effective. Carbamazepine may be used to treat acute mania and also for prophylactic therapy. Adverse effects (discussed in Chapter 24) are generally no greater and sometimes less than those associated with lithium. Carbamazepine may be used alone or, in refractory patients, in combination with lithium or, rarely, valproate. 

In 28 patients who had responded to lithium treatment of mania or schizoaffective mania and who had recurrences after withdrawal, there were equally good responses to retreatment with lithium (461). These findings add to the evidence that lithium discontinuation-induced refractoriness is the exception rather than the rule. However, the issue of whether post-withdrawal refractoriness to reintroduction of lithium is a real phenomenon and, if so, how often it occurs continues to be debated (462). Three patients failed to respond to the reintroduction of lithium, despite having had sustained beneficial responses before withdrawal (463). 

Bipolar depression affects 1% of the general population, and treatment resistance is a significant problem. The addition of pindolol can lead to significant improvement in depressed patients who are resistant to antidepressant drugs, such as selective serotonin reuptake inhibitors or phenelzine. Of 17 patients with refractory bipolar depression, in whom pindolol was added to augment the effect of antidepressant drugs, eight responded favorably (95). However, two developed transient hypo-mania, and one of these became psychotic after the resolution of hypomanic symptoms. In both cases transient hypomanic symptoms resolved without any other intervention, while psychosis required pindolol withdrawal. 

Newer anticonvulsants such as levetiracetam and zonisamide have several published case reports or open trials showing efficacy in mania and treatment-refractory rapid cycling, but it is too early to predict whether they have a place in either acute or maintenance... 

For patients who experience a breakthrough episode, the medication dose should first be optimized. When first-line medications at optimal dose fail to control symptoms, recommended treatment options include the addition of another first-line medication. Alternative treatment options include adding carbamazepine or oxcarbazepine in lieu of an additional first-line medication, adding an antipsychotic if not already prescribed, or changing from one antipsychotic to another. Of the antipsychotics, clozapine may be particularly effective for treatment of refractory illness. Electroconvulsive therapy (ECT) may also be considered for patients with severe or treatment-resistant illness. In addition, ECT is a potential treatment for patients with mixed episodes or for severe mania experienced during pregnancy. 

Lithium is used for prophylaxis mmanicldcpre. i.sive illness. It is also used in the treatment of acute mania, but. because it may lake seveniJ days for the antimanic effect to develop, an antipsychotic drug i.s usually preferred for acutely disturbed patients. Lithium is used as an antidepressant in comhinaiion with tricyclics in refractory patients. 

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