High doses of diazepam improve neuroleptic-resistant chronic schizophrenic patients

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Abstract
According to the two currently most popular biological hypotheses, schizophrenic symptoms result from a hyperactivity in dopaminergic neurotransmission or from a hypoactivity in GABAergic neurotransmission. Since diazepam is known to reduce dopamine release and to potentiate GABA, the possible beneficial effects of diazepam were tested in ten hospitalized chronic schizophrenic patients who were resistant to standard neuroleptic treatment. High doses of diazepam, up to 200 mg/day initially, but smaller maintenance doses (less than 55 mg/day diazepam in eight of the ten patients) were added to the previous neuroleptic medication of these patients. The diazepam dose was adjusted daily to avoid oversedation. The effects of diazepam treatment on the mental status were assessed weekly for 12 weeks by the Brief Psychiatric Rating Scale (BPRS), the physician's Clinical Global Impressions Scale (CGI), and the Psychotic inpatient Profile Scale (PIP). For additional documentation, videotapes of mental status interviews were obtained at baseline and during diazepam treatment. These videotapes were rated blind by an independent psychiatrist. The addition of diazepam produced a marked improvement in three, a moderate improvent in four, a mild improvement in one and no change in two of the ten patients. Four of the ten patients were so much improved that they were discharged from the hospital. No side effects were noted, except for one patient who became confused and disoriented on 160 mg diazepam/day. Oversedation was avoided in the other patients, whose maximum daily dose of diazepam was 100 mg or higher, by reducing the diazepam dose within 1 week after the maximum daily dose was reached. It is concluded that diazepam may be of use in the treatment of schizophrenia and that further controlled clinical studies are warranted.