This patient has an unusual type of resistance to the high-potency neuroleptic, haloperidol. There is no parkinsonism suggestive of central dopamine-2 receptor blockade, and antipsychotic effects are unsatisfactory, but the drug has been accumulating in significant amounts in the patient's plasma. It is in the putative therapeutic range of 5-15 ng/ml. (1) It probably is crossing the blood-brain barrier (2), but all brain dopaminergic systems seem unresponsive. This lack of ability to generate parkinsonian side effects on standard neuroleptics actually predicts poor response to clozapine in neuroleptic-resistant patients. (3) Hence, this is a peculiar and difficult subgroup of patients. (4)
Our strategy for such patients is to first address disabling akathisia, if any, and then assess whether it is the presence of an antiparkinsonian agent that explains the lack of manifest parkinsonism. If so, treatment of the patient will follow the pathway for the usual patient with unsatisfactory response to an adequate trial of a standard, typical neuroleptic. If antiparkinsonian treatment is not the explanation, we will attempt a further increase in the haloperidol blood level, to a maximum of 20 ng/ml, which seems to be the upper limit at which occasional persons will finally respond, before turning (with guarded optimism) to reconsider the atypical antipsychotics.
Click here to go on to the next question
¹Subsyndromal Depressive Syndrome, or Depression NOS in DSM-4, is a major public health problem that produces significant functional impairment. See Judd LL. Socioeconomic burden of subsyndromal depressive syndrome and major depression in a sample of the general population. Am J Psychiatry 1996;153:1411-1417.
²Mason BJ, Kocsis JH, Ritvo EC, Cutler RB. A double-blind, placebo-controlled trial of desipramine for primary alcohol dependency stratified in the presence or absence of major depression. JAMA March 13, 1996;275(10):761-767.
³Gelenberg A. Biological Therapies in Psychiatry Newsletter 1996;19(7):25-26.