Interaction of chlorpromazine and nortriptyline in patients with schizophrenia

Seven male inpatients suffering from acute schizophrenia were treated with chlorpromazine elixir 100mg 8-hourly for 9 weeks. Nortriptyline 50mg 8-hourly was added during weeks 4, 5 and 6. Plasma chlorpromazine concentrations, antipyrine plasma half-life, blood pressure, pulse rate, pupil size, salivation, handwriting and clinical state were measured at weekly intervals. Plasma chlorpromazine concentrations rose when nortriptyline was added, and the antipyrine plasma half-life was prolonged. Blood pressure dropped on institution of chlorpromazine and dropped further with the addition of nortriptyline. The pulse rate rose in a parallel fashion. Pupil size, salivation and handwriting were diminished by chlorpromazine, but hardly affected further by nortriptyline. The addition of nortriptyline dramatically reversed the therapeutic actions of chlorpromazine, mainly through pharmacodynamic interaction. It is concluded that this combination is potentially deleterious, and must be used with care.