Lithium anxiolytics

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

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. 

Melchior CL, Ritzmann RF Dehydroepiandrosterone is an anxiolytic in mice on the plus maze. Pharmacol Biochem Behav 47 437-441, 1994a Melchior CL, Ritzmann RF Pregnenolone and pregnenolone sulfate, alone and with ethanol, in mice on the plus-maze. Pharmacol Biochem Behav 48 893-897, 1994b Melia PI Prophylactic lithium a double-blind trial in recurrent affective disorders. Br J Psychiatry 116 621-624, 1970... 

The benzodioxan ring also serves as the aromatic moiety for one of the ubiquitous analogues of the spirone anxiolytic agents discussed in Chapter 9. In the absence of a specific reference, the requisite intermediate (62-1) could be obtained by reducing the cyano group in nitrile (60-1) with lithium aluminum hydride. Alkylation with the spirone side chain chloride (62-2) would then afford binospirone (62-3). 

In partially responsive or nonresponsive patients, the first issue is to determine whether an individual is truly treatment-resistant, because many receive nontherapeutic doses and the potential for improvement may not be adequately tested. Thus, in some situations, more aggressive treatment (dose increase, augmentation) may be appropriate, if not precluded by adverse effects. In selected cases, it may also be helpful to monitor plasma levels to ensure that they are in a reasonable range (see Pharmacokinetics/Plasma Levels earlier in this chapter). If a patient continues to demonstrate significant symptoms after a sufficient trial (2 to 3 weeks), alternatives to switching to another antipsychotic may include the addition of lithium, an anticonvulsant, or a second antipsychotic agent. An antidepressant or anxiolytic may also be helpful, especially if affective or anxiety symptoms are prominent. 

Other possible uses, not addressed in this study, are the potential benefit of clonidine as an adjunct to lithium or anticonvulsants, possibly serving as a substitute for anxiolytics or antipsychotics, or its benefit in less severe exacerbations of mania. 

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