Inadequate treatment response to des-enkephalin-gamma-endorphin compared with thioridazine and placebo in schizophrenia.

The possibility of an involvement of peptidergic systems in schizophrenia has been under investigation for a number of years. Studies of the efficacy of des-tyr-gamma-endorphin were equivocal; more recent studies with des-enkephalin-gamma-endorphin have reported some activity but the peptide has only been investigated as an adjunct to neuroleptic medication, apart from one very small active reference comparator study. In the multicentre study reported here, 96 patients suffering from schizophrenia (DSM-III with a current exacerbation if chronic) were allocated randomly to double-blind treatment with either des-enkephalin-gamma-endorphin (DE-gamma-E) (Org 5878) 10 mg given as a once daily intramuscular injection for 4 weeks, thioridazine 400 mg orally in 2 divided doses or placebo using a double-dummy technique to preserve blindness. There was a significant advantage for thioridazine compared with placebo registered on all measures at weeks 3 and 4. There was no difference between DE-gamma-E and placebo. There was a significant difference between thioridazine and DE-gamma-E at weeks 3 and 4 registered on the MSS and at week 3 registered on the BPRS. The lack of efficacy of DE-gamma-E suggests that the theories that the endorphins have an important role in schizophrenia have to be revised. The need for well designed placebo controlled studies for assessing efficacy in schizophrenia is emphasized.

Lithium versus placebo in acute depression: a clinical trial.

Thirty-one patients suffering from a major depressive illness were entered into a placebo-controlled double-blind study to determine the effectiveness of lithium carbonate in acute depression. Patients were allocated by minimization to receive either lithium or placebo for 6 weeks in 2 parallel groups without crossover. For ethical reasons patients who showed no satisfactory response could be withdrawn at the discretion of the investigator but this was done without breaking the treatment code. More patients were withdrawn from the placebo group than from the lithium group as treatment failures, but in spite of this there was a significant difference in the depression ratings between the 2 groups at weeks 4 and 5 in favour of the active treatment group (p less than 0.04 and p less than 0.03 respectively).

A double-blind comparison of alprazolam, diazepam and placebo in the treatment of anxious out-patients.

In a double-blind 28-day comparison of alprazolam, diazepam and placebo, alprazolam 1.5-3 mg/day was of equivalent anxiolytic effect to 15-30 mg diazepam/day and there was some evidence of antidepressant activity by alprazolam, but not diazepam, in neurotic depression. No serious side-effects or laboratory abnormalities were encountered.

Comparison of trazodone and mianserin in depressive illness.

In a multi-centre study, the antidepressant efficacy and incidence of on-therapy events of trazodone (100 to 400 mg daily) and mianserin (30 to 120 mg daily) was compared using a double-blind pre-determined randomized parallel group design in depressed patients unresponsive to placebo after a 7-day screening period. Of the 111 patients who entered the study, 27 patients were withdrawn or defaulted. The withdrawal rate was similar between the treatment groups. The results of depression rating scale assessments showed that trazodone and mianserin were similar to each other for efficacy in patients judged to be suffering from severe or mild/moderate depression whether of the endogenous or reactive type. For all on-therapy events, there were no major differences between the treatments, with drowsiness being the most frequently reported side-effect.

Mianserin and doxepin in the treatment of outpatient depression with anxiety.

1 A double-blind group comparative trial was performed comparing mianserin (Bolvidon-Organon) and doxepin (Sinequan-Pfizer) in the treatment of depression with anxiety. 2 Sixty outpatients from two centres were divided into 'high' and 'low' severity groups, based on initial HRS scores, and treated for four weeks. 3 Standard rating scales for depression and anxiety demonstrated a substantial improvement with both drugs. However, no consistent difference in efficacy was found although the 'low severity' group appeared to respond better to mianserin. 4 There was a greater incidence of drug-related side-effects with doxepin treatment.

A double blind comparison of alprazolam, diazepam and placebo in the treatment of anxious out-patients.

The anxiolytic effects of alprazolam, a triazolobenzodiazepine, were evaluated in a double-blind 28-day comparison with diazepam and placebo in 46 out-patients suffering from anxiety states of moderate to severe intensity. Alprazolam 1.5-3 mg per day was found to be of at least equivalent anxiolytic effect to 15-30 mg diazepam per day, and there was evidence of antidepressant activity by alprazolam, but not diazepam, in neurotic depression. Side-effects occurred least often with alprazolam and were minor in nature. Laboratory data showed no changes attributable to alprazolam even in a patient who swallowed 15 capsules (7.5 mg). It was concluded that alprazolam is a safe and effective anxiolytic which is well-tolerated and also shows some antidepressant activity.