This patient appears to have an inadequate dose, as evidenced by lack of parkinsonian (D2-receptor mediated) side effects, and yet akathisia is limiting the ability to raise the dose to a level that is centrally bioavailable.
The development of akathisia is in itself a marker for a subgroup of patients who have or will have an unsatisfactory response to a neuroleptic.¹ Raising the dose of the neuroleptic is generally not helpful: the response does not improve and the side effects become more intolerable.² Akathisia may appear in the absence of parkinsonian side effects. Farde and colleagues reported that akathisia develops (in susceptible patients) at neuroleptic doses which produce 60-65% occupancy of striatal D2 receptors.³ This is below the 70-80% occupancy at which optimum antipsychotic effects occur with typical neuroleptics.
However, despite these studies, it still seems reasonable for the clinician to at least attempt to reduce the akathisia and, if this is successful, to raise the neuroleptic dose to one which produces mild parkinsonism, (or at least ot a blood level over 5 ng/ml if haloperidol is the neuroleptic being used.) Then, it is possible that antipsychotic effects may follow over the next 2-8 weeks.
¹Levinson D, Simpson G, Singy H, et al. Fluphenazine dose, clinical response,and extrapyramidal symptoms during acute treatment. Arch Gen Psychiatry 1990;47:761-768.
²van Putten T, marder S. Behavioral toxicity of antipsychotic drugs. J Clin Psychiatry 1987;48[9, suppl]:13-19.
³Farde L. Central receptor occupancy and optimal antipsychotic drug treatment. International Congress on Schizophrenia Research. Colorado Springs, Colorado 1993.
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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.