If rapid worsening occurs, it may be a supersensitivity phenomenon.¹ There are two main options: trying a newer antipsychotic (risperidone and clozapine have both been reported helpful in such cases²), or adding an anticonvulsant drug to permit neuroleptic dosereduction.³ Valproate, phenytoin, or (last choice) clonazepam may be added and then another effort to taper the neuroleptic could follow. Carbamazepine has also been used and in theory could be the best choice given its anti-kindling effects in animal models, but pharmacokinetic interactions with neuroleptics make this drug more complicated to use. Plasma levels of neuroleptics are markedly reduced when carbamazepine is added, sometimes by 50-80%. (4) Although this effect may actually be desirable in this clinical situation of excessive neuroleptic dose, it will be difficult to know if any clinical change that occurs is from direct effects of the carbamazepine or the altered metabolism of the neuroleptic. If, nevertheless, you want to use carbamazepine, skip the next paragraph and read a more detailed discussion about how to use it.
The anticonvulsant addition (and, if possible, subsequent tapering of the neuroleptic to a less toxic dose) may result in an acceptable level of recovery for this patient. If it does not, and yet the parkinsonian side effects have become minimal, you have the situation where the patient is having an unsatisfactory response but parkinsonism is mild. Go back two questions to the point where you were asked: "Is there MARKED parkinsonism?" and answer negatively. The algorithm will take you to new assessments and recommendations.
If you plan to use carbamazepine, and haloperidol is the neuroleptic, blood level monitoring may help clarify the role of the carbamazepine. We recommend the following procedure:
1. Raise the original neuroleptic dose to, (or above if necessary), the dose before worsening occurred, if this has not already been done.
2. Obtain a baseline haloperidol level, and monitor it weekly. Add carbamazepine and increase until a full dose/plasma level is obtained. Additional haloperidol may be added if necessary to maintain the haloperidol blood level at baseline levels, as the carbamazepine level increases and induced metabolism of the haloperidol. (4)
3. Once the carbamazepine is at a full level, and the haloperidol level is unchanged from baseline, assess the patient's clinical state. Allow one to three weeks for the hoped-for antikindling effect of the carbamazepine to take place. The patient may improve significantly from this adjunctive treatment. Presuming that the parkinsonian side effects will still be coarse at that point, begin another attempt to taper the haloperidol.
Carbamazepine also stimulates the metabolism of other neuroleptics, but blood level measurements of these neuroleptics are more difficult to interpret. Commercial laboratories do not measure the many active metabolites of these neuroleptics. Therefore, these levels are less indicative of the amount of bioactive drug present. Nevertheless, the clinical effect of adding carbamazepine is likely to be similar, and the potential pharmacokinetic issues should still be kept in mind.
Recommendation #134
