Antimanic agents

Keck PE, McElroy SL, Bennett JA (1996a). Health-economic implications of the onset of action of antimanic agents. / Clin Psychiatry 57 (suppl. 13), 13-18. 

In CONCLUSION, lithium is universally accepted as a mood-stabilizing drug and an effective antimanic agent whose value is limited by its poor therapeutic index (i.e. its therapeutic to toxicity ratio). Neuroleptics are effective in attenuating the symptoms of acute mania but they too have serious adverse side effects. High potency typical neuroleptics appear to increase the likelihood of tardive dyskinesia. Of the less well-established treatments, carbamazepine would appear to have a role, particularly in the more advanced stages of the illness when lithium is less effective. 

Well known for their clinical role as antimanic agents, anticonvulsants such as carbamazepine and valproate have also been used in both bipolar and unipolar TRD (Post et al. 1994a, 1994b). In one series. Post et al. (1994a) found a greater response in patients with bipolar (15/40) versus those with unipolar (2/17) TRD. Open studies of valproate also suggest limited antidepressant efficacy, but only a paucity of data with anticonvulsants on TRD exists. More recently, in open trials, lamotrigine (a partial anticonvulsant that inhibits glu-... 

Typical doses of clonazepam have been in the range of 2 to 16 mg/day given on a once or twice per day schedule due to its longer half-life. A major advantage of this anticonvulsant is its relative lack of adverse effects and freedom from laboratory monitoring in comparison with CBZ and VPA. Clonazepam may be more useful when combined with lithium or CBZ rather than as a specific antimanic agent, perhaps supplanting the need for antipsychotics. In this sense, it can be viewed as a behavioral suppressor, rather than a true mood stabilizer (121). 

Limited evidence indicates that the amino acid precursor of 5-HT, l -tryptophan, may be useful, alone or in combination with other antimanic agents to enhance overall efficacy. Contaminants in the production of this agent led to several cases of the eosinophilia myalgia syndrome (EMS) and its removal from the market for several years. 

Maguire J, Singh AN. Clonidine an effective antimanic agent Br J Psychiatry 1987 150 863-864. 

Few clinicians use lithium, an antimanic agent, as primary treatment for depression. However, some have found that lithium along with one of the other antidepressants may achieve a favorable response not obtained by the antidepressant alone. Another potential use of lithium is to prevent relapses of depression. 

Evaluation of potentially useful antimanic agents continues. Studies are in progress to determine whether other novel antipsychotics and anticonvulsants are effective. Omega-3 fatty acids, contained in large amounts in certain fish oils, have been reported in several publications as effective agents as well. Further research on these compounds is needed before determining their true value in antimanic therapy. 

Dilsaver, S. C., A. C. Swann, A. M. Shoaib, T. C. Bowers, and M. T. Halle. 1993. Depressive mania asssociated with non-response to antimanic agents. American Journal of Psychiatry 150 1548-51. 

In manic-depressive and related illnesses, lithium (e.g. lithium carbonate) is the normal treatment for dealing with the manic phase (see antimanic agents), and for preventing certain types of recurrent depression. 

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... 

These findings have important implications for the treatment of bipolar affective disorder. Some agents used to treat partial-complex seizures such as carbamazepine and various valproate formulations have been found to be effective in bipolar affective disorder (Bowden 1995). One such agent, divalproex, is now the most commonly prescribed antimanic agent. These agents may be more effective in subtypes of mania that are not lithium responsive. As noted earlier, African Americans are more often prescribed antipsychotics. Poor tolerance of lithium maybe a factor. Improving access to alternatives to lithium may reduce the need for antipsychotics in some African Americans with mania. 

Antipsychotics are effective antimanic agents. Traditionally they have been first-line agents in acute mania in Europe whereas lithium, anticonvulsants and benzodiazepines... 

Until recently, most studies on antimanic agents were exclusively conducted in patients with bipolar I disorder and euphoric mania, resulting in firm evidence that lithium is especially effective in this type of mania. Valproate shows equal overall efficacy in mania however, fewer studies support its efficacy in euphoric mania compared with lithium. Valproate usually has a more rapid onset of action than lithium as its wide therapeutic window allows loading treatment strategies. Valproate may be the preferred choice in patients with numerous (more than eight) previous manic episodes or more than four depressive episodes, and who... 

Several 9-(phosphonoalkyl)- and 9-(difluoroalkyl)-guanine derivatives (12, X = H or F) have been studied as potential inhibitors of guanylate kinase. The most pronounced effect was observed with n - 5 Phenoxymethylene bisphosphonates (13, where R R and R represent a variety of substituents) were prepared and found to act as inositol phosphatase inhibitors and antimanic agents some inhibited the enzyme with IC50 < 50 pmol 4-(Phosphonomethylphenoxy)-l-carbamoylazetidine-2-ones (14) inhibited human leukocyte elastase for 14 (R R = OEt = 1.2 x 10 moL s (ref. 38). 

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