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Objectives: Rituximab is an effective treatment in patients with established rheumatoid arthritis (RA). The objective of the IMAGE study was to determine the efficacy of rituximab in the prevention of joint damage and its safety in combination with methotrexate (MTX) in patients initiating treatment with MTX. Methods: In this double-blind randomised controlled phase III study, 755 MTX-naïve patients with active RA were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX. The primary end point at week 52 was the change in joint damage measured using a Genant-modified Sharp score. Results: 249, 249 and 250 patients were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX, respectively. At week 52, treatment with rituximab 2×1000 mg + MTX compared with MTX alone was associated with a reduction in progression of joint damage (mean change in total modified Sharp score 0.359 vs 1.079; p=0.0004) and an improvement in clinical outcomes (ACR50 65% vs 42%; p

A 4-week clinical trial, including a 1-week placebo washout period, assessed the antipsychotic activity of naltrexone in 'newly admitted', actively hallucinating, chronic schizophrenics. Chronic naltrexone administration was found to benefit 2 patients and to be of no value in 3 patients. Responsive patients differed from non-responders by the presence of hallucinations despite adequate neuroleptic maintenance therapy and an appropriate response to pathological hallucinatory experience. On the basis of these findings, the possibility of a naltrexone-responsive schizophrenic subgroup was considered.

In a double-blind comparative clinical study, both thiothixene and haloperidol were found to be effective agents for rapid tranquilization of manic and schizophrenic patients. While no statistically significant difference in any of the psychopathological areas which may create a psychiatric emergency was found, results of this study provide further substantiation of the notion that thiothixene has favorable effects on anergia .

The aim of the present studies was to further delineate the role of striatal and limbic dopaminergic versus limbic noradrenergic blockade in the pharmacologic and perhaps therapeutic action of antipsychotic drugs. Metoclopramide shares many properties of antipsychotic neuroleptic drugs, including the production of extrapyramidal side effects, but is not an efficacious antipsychotic agent. This drug was a potent blocker of dopamine (DA) receptors in both striatum and limbic forebrain (comparable in potency to that of chlorpromazine) as evidenced from the increase in homovanillic acid in both brain structures. In contrast, metoclopramide was a weak inhibitor of the norepinephrine (NE) receptor-coupled adenylate cyclase system in the limbic forebrain. Molindone, which is reported not to block DA-sensitive adenylate cyclase, was a potent in vivo blocker of DA receptors in both striatum and limbic forebrain and also inhibited markedly the cyclic AMP response to NE in the limbic forebrain. The phenothiazine derivative, thiethylperazine, was also a potent blocker of DA receptors in both brain areas and displayed an IC50 for NE blockade in the limbic forebrain comparable to that of chlorpromazine. The present results support the view that the ability and potency of drugs to block DA receptors parallels their ability and potency to cause extrapyramidal symptoms in man. Moreover, these results suggest that the blockade of NE receptor-coupled adenylate cyclase systems in brain may be relevant to both the pharmacologic and therapeutic activity of antipsychotic drugs.

Twenty-three patients who completed a four-week, double-blind, clinical trial of bromperidol versus haloperidol were treated with bromperidol for eight additional weeks in a continuation study. Over 87 percent of patients maintained their improved status or showed further improvement. Extrapyramidal signs were frequent, but required discontinuation of treatment in only two patients.

Therapeutic and adverse effects of three dosages (1, 20 and 100 mg daily) of flutroline, a new gamma-carboline with a preclinical pharmacological profile similar to active neuroleptic agents, were compared in a double-blind clinical trial in 25 newly-admitted schizophrenic patients. Therapeutic effects and extrapyramidal signs were seen at the 20 and 100-mg daily dosages, but not at the 1-mg dosage. Serum prolactin levels were significantly elevated only at the 100-mg daily dosage.