This patient has a neuroleptic-resistant psychosis - the neuroleptic has been demonstrated to be centrally bioavailable but response level has been unsatisfactory after a trial of reasonable length. Dose increases, and alternative Standard, Typical Neuroleptics* are unlikely to be of benefit.¹ The possible use of alternative antipsychotics** which may have superior efficacy in some patients will be explored shortly. Before this, however, we check (in the next question) to see if akathisia is a major factor that may be contributing to neuroleptic resistance. If so, it is possible that this problem could be addressed and that there may be further steps to take before concluding that this neuroleptic trial is complete.
What might be the biological basis for the treatment resistance of these patients? They are getting CNS D2 blockade, but it is not working (adequately) on the psychosis. It may be that some neurochemical or neurostructural defect has developed to prevent the benefits from occurring. The patient may need to work the dopamine system indirectly, perhaps through the serotonin system. This is one theory of how the new generation of antipsychotics may work.² The presence of parkinsonism during unsuccessful treatment of patients with neuroleptics predicts good response to clozapine.²
*[listed alphabetically] chlorpromazine (Thorazine), fluphenazine (Prolixin), haloperidol (Haldol), thiothixene (Navane), trifluoperazine (Stelazine) and perphenazine (Trilafon)
**[listed alphabetically] olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal)
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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.