Diagnostic reassessment and treatment response in schizophrenia.

BACKGROUND: The reasons for poor treatment response in some patients with schizophrenia remain unclear. It is possible that misdiagnosis of nonschizophrenic disorders as schizophrenia could result in suboptimal pharmacotherapy in some patients. METHOD: To assess this possibility, 110 severely ill, chronic patients with a referral diagnosis of schizophrenia were comprehensively assessed and rediagnosed according to DSM-III-R criteria. Global Assessment of Function (GAF) and Clinical Global Impressions (CGI) ratings were made at admission and at discharge from the ward, after the implementation of individualized treatment plans. RESULTS: The diagnosis of schizophrenia was confirmed in 80 patients (73%) and revised to another type of psychotic illness in 30 patients (27%). The GAF and CGI ratings were similar at admission in patients with confirmed and revised diagnoses. All patients improved by the time of discharge (p = .0001); however, patients with a revised diagnosis improved more than those with confirmed schizophrenia (p = .02). Patients with a revised diagnosis were less likely to require continued hospitalization on chronic care wards (p = .004). At admission, medication regimens were similar in the two groups of patients. At discharge, patients with a revised diagnosis were less likely to have received neuroleptics (p = .007) and more likely to have received antimanic drugs (p = .0002) or electroconvulsive therapy (p = .0004). CONCLUSION: These findings from a clinical sample suggest that diagnostic reassessment is an important first step in the management of apparently refractory schizophrenia.

Effect of propranolol and phenothiazines on electrodermal orienting and habituation in schizophrenia.

Bilateral electrodermal orienting responses were measured to repeated auditory stimuli in schizophrenic patients and controls. In 3 studies phasic activity to moderate intensity sounds of patients on no drugs or phenothiazines was predominantly hyper- or hypo-responsive. Controls showed moderate or slow habituation. Propranolol was found to facilitate habituation in slow habituators and to reinstate responses in half of non-responders, especially when given as the sole drug. The effects seldom had a counterpart in changes in non-specific responses or levels of skin conductance. Modulatory influences on stimulus and response processing and on lateral asymmetries in responses may underlie propranolol's efficacy in treating schizophrenia.

DL-propranolol and chlorpromazine following admission for schizophrenia. A controlled comparison.

Similar improvement followed when propranolol and chlorpromazine were randomly used as the first drug after admission. Forty-six patients with florid symptoms of schizophrenia were assigned at random to have either racemic propranolol (24) or chlorpromazine (22). Each individual's drug was adjusted to an optimal dose, and the progress of the groups was followed for 12 weeks. Thirty-five patients remained in the study for 6 weeks, and 27 for 12 weeks. By weeks 6 and 12 the total schizophrenia scores on a modified Brief Psychiatric Rating Scale had improved significantly when the results from both groups were combined. The numbers leaving the study, and the amount and rate of improvement, were similar for both groups, but with a possible advantage to chlorpromazine. Side-effects, which usually were mild, were commoner in the chlorpromazine group.

Active and passive avoidance learning in controls and schizophrenic patients on racemic propranolol and neuroleptics.

Normal controls and schizophrenic patients on propranolol as sole drug or combined with neuroleptics showed superior active and passive avoidance learning to schizophrenic patients who were medicated with conventional neuroleptics only. Active avoidance involved responding quickly, passive avoidance withholding a response to avoid an unpleasant noise and reacting to the appropriate stimulus. This may reflect an improvement brought about by propranolol in the limbic regulation of stimulus and response processes.

Propranolol and blood glucose: simultaneous measurements over a wide range of doses and the effect of propranolol on the glucose tolerance test.

No correlation was found between blood glucose and simultaneous measurements of plasma propranolol concentration in patients with schizophrenia, on a daily dose of 80 mg to 1800 mg of propranolol as an adjunct to phenothiazine medication. The Glucose Tolerance Test (GTT) in ten patients on propranolol and phenothiazines did not differ significantly from those of a matched control group on phenothiazine alone. Two patients with mild diabetes showed no significant change in their GTT after stopping propranolol. These observations accord with the view that relatively high doses of propranolol as an adjunct to phenothiazine medication in schizophrenia are safe from the standpoint of glucose metabolism. This does not apply to the insulin dependent diabetic who is in danger of severe hypoglycaemia when glycogenolysis is blocked by propranolol.

Propranolol as an adjunct to the treatment of schizophrenia.

Propranolol contributed usefully to the practical management of patients with chronic schizophrenia whose florid symptoms had not remitted with major tranquillisers. 14 patients who had received an average equivalent of 954 mg per day of chlorpromazine for 10 years were given, in addition, either propranolol or a placebo for 12 weeks. Both groups had improved by the twelfth week, but the propranolol group had improved significantly more.

Safeguards in the treatment of schizophrenia with propranolol.

Early results for an uncontrolled study of 555 patients with florid schizophrenia suggest that propranolol can be used safely in high dosage, and in a proportion of cases it appears to control schizophrenic symptoms. This method of treatment is now being submitted to controlled trial. Evdence from this uncontrolled study suggests that there was a therapeutic dose range in which symptoms steadily improved as a low dose was ineffective and a high dose, particularly if reached too rapidly, caused toxic effects. Rapid increases (400-800 mg) in the daily total intake when given in divided doses (4 to 10/day) produced gross toxic effects that included ataxia with unprotected falls, drop attacks, visual hallucinations, and confusional states. Severe toxic effects were uncommon when the dose was raised by regular, gradual increments (e.g. by 40-80 mg/day), when propranolol was given twice daily, when the dose was held steady as the patient started to improve, and when the daily total dose was reduced if the fall in pulse rate or blood pressure was excessive, or if there was evidence of toxicity. The observation of gradual, progressive improvement was the most valuable positive guide to the dose of propranolol. All schizophrenic symptoms remitted, at least temporarily, in 26 of 55 patients (in 15 of 17 patients who had been ill for less than one year and in 11 of 38 patients who had been ill for longer than a year). Patients who then stopped propranolol usually relapsed within hours or days.

Differences between behavior therapists and psychotherapists.

Patient-therapist interaction patterns of three experienced behavior therapists and three matched analytically oriented therapists were compared. Each therapist saw ten patients in short-term individual therapy. The more active behavior therapists dominated the conversation in terms of speech time, more frequently offered explicit advice and instructions, gave more direct information, presented their own value judgments, and exerted greater control over the content of the interaction than did psychotherapists. Although both groups provided a warm and accepting atmosphere, behavior therapists showed higher levels of accurate empathy, interpersonal contact, and therapist self-congruence. Patients viewed behavior therapists as more authoritarian and believed that psychotherapists encourage greater independence. It was concluded that the two therapy approaches to patients were consistent with theoretical models of each.

Short-term analytically oriented psychotherapy versus behavior therapy.

Ninety-four outpatients with anxiety neurosis or personality disorder were randomly assigned for four months to a waiting list, behavior therapy, or psychoanalytically oriented therapy. The target symptoms of all three groups improved significantly, but the two treated groups improved equally well and significantly more than those on the waiting list. There were no significant differences among the groups in work or social adjustment; however, the patients who received behavior therapy had a significant overall improvement at four months. One year and two years after the initial assessment, all groups were found to be equally and significantly improved.

Propranolol in the control of schizophrenic symptoms.

All schizophrenic symptoms remitted completely in six out of 14 adults who had not responded to phenothiazine drugs and who were then given propranolol. Another patient improved markedly and four improved moderately. Two had minimal or transient improvement, and one left hospital unchanged after a short, severe, toxic reaction. The six with complete remissions all began to improve within a few days of starting propranolol and the florid symptoms remitted completely after three to 26 days. They were stabilized on a daily dose of 500-3,500 mg of propranolol and at the time of writing had remained well for up to six months. Two patients who stopped propranolol after their symptoms remitted relapsed severely within a few days. Toxic effects (ataxia, visual hallucinations, and confusional states) were related to the rate of increase rather than to the absolute dose of propranolol. After the procedure was modified unwanted effects were usually mild or absent.