Carbamazepine neuroleptic drugs

Plasma concentrations of neuroleptic drugs can be lowered by carbamazepine, and patients should be monitored for reduced efficacy (638). 

A 54-year-old man who had been taking neuroleptic drugs for about 30 years developed neuroleptic malignant syndrome within 3 days of taking add-on carbamazepine (400 mg/day) (639). 

This syndrome does not appear to have been described with carbamazepine alone, and it was speculated that its pathogenesis could involve rebound cholinergic activity after a reduction in plasma neuroleptic drug concentrations by carbamazepine. 

Oxcarbazepine is a weaker enzyme inducer than carbamazepine. When it is substituted for carbamazepine, plasma concentrations of concomitant drugs, such as valproate and neuroleptic drugs, can rise, owing to deinduction, leading to potential toxicity (17,18). 

Other drugs that are reported to have beneficial effects but which have not undergone such extensive evaluation as the neuroleptics or carbamazepine include the calcium channel antagonists such as verapamil. A small open study has suggested that the alpha2 adrenoceptor agonist clonidine may... 

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. 

Drugs such as barbiturates and carbamazepine induce certain enzymes and will then trigger faster breakdown of some concomitantly used antipsycho-tics and antidepressants. In contrast, paroxetine, fluoxetine and fluvox-amine, acting by different mechanisms, inhibit the breakdown of other concomitantly administered drugs such as benzodiazepines, antidepressants, antiepileptics and neuroleptics (Table 5.1). 

There is little evidence that lithium is superior to other drugs with sedative actions for the treatment of acute mania. Benzodiazepines, neuroleptics and anticonvulsants have all been tried in mania and none have been found to be inferior to lithium. Two small studies of clonazepam in mania found it was superior to lithium (Chouinard 1988 Chouinard, Young, Annable 1983). All new- and old-generation neuroleptics have been found to be more effective than placebo (Perlis et al. 2006). Comparisons of lithium with the sedative anticonvulsants carbamazepine and sodium valproate show similar effects (Bowden et al. 1994 Freeman et al. 1992 Lerer et al. 1987 Small et al. 1991). 

Lithium is rarely used as the only treatment for acute mania, a practical acknowledgment of its limitations. If it is used at all it is combined with a neuroleptic and other sedatives are frequently prescribed as well. Trials comparing effects of lithium and carbamazepine in acute mania reveal that substantial doses of benzodiazepines or barbiturates were used in addition to the study drugs (Freeman et al. 1992 Small et al. 1991). However the belief in lithium s specificity for manic depression means it is still deemed an effective treatment and it is still recommended for mild to moderate cases of mania (National Institute for Clinical Excellence 2006). 

Although phenothiazines, clonidine, carbamazepine, y-hydroxybutyric acid, and valproic acid may reduce symptoms of alcohol withdrawal, their ability to prevent seizures or delirium tremens has yet to be proven, and in fact, the phenothiazines may lower the seizure threshold. Other drugs used to treat symptoms of alcohol withdrawal include other barbiturates, alcohol itself, sympatholytics such as atenolol, thiamine, magnesium, and other neuroleptics such as haloperidol. At the time of this writing, gabapentin is being compared to lorazepam for acute alcohol withdrawal in a phase II clinical trial. 

C. Clinical Use Lithium carbonate is used in the treatment of bipolar affective disorder (manic-depressive disease). Maintenance therapy with lithium decreases manic behavior and reduces both the frequency and the magnitude of mood swings. Drug therapy with neuroleptics or benzodiazepines may also be required at the initiation of lithium treatment. Antidepressant drugs may be required adjunctively during maintenance. Alternative drugs of value in bipolar affective disorder include carbamazepine, clonazepam, gabapentin, and valproic acid. 

C. Chronic use has been associated with bone marrow depression, hepatitis, renal disease, cardiomyopathy, hyponatremia, and exfoliative dermatitis. Carbamazepine has also been implicated in rigidity-hyperthermia syndromes (eg, neuroleptic malignant syndrome and serotonin syndrome) in combination with other drugs. 

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