Clinical trials of benzamides in psychiatry

The utility of the benzamides in clinical psychiatry requires further evaluation. Of the four compounds mentioned in this chapter, it seems clear that sulpiride is an effective antipsychotic agent as shown by double-blind trials comparing it with placebo and reference antipsychotics (see Table I). Claimed efficacy for this agent in depression, anxiety, and school-phobia require more intensive evaluation. Sultopride has been reported to have efficacy in a variety of psychiatric syndromes, i.e., manic depressive illness and agitation associated with alcoholic syndromes. Tiapride has reported efficacy in a variety of alcoholic states, agitation associated with medical disease, and movement disorders. Unfortunately, all of the studies on both tiapride and sultopride have been open trials on which the results were based solely on the global clinical impression of the investigator. The total lack of formal diagnostic criteria, adequate study design, small sample size, heterogeneity of diagnosis, and questionable length of time for treatment of these disorders make it impossible to draw any firm conclusions at this time as to the efficacy toward any psychiatric disorder. Metoclopramide, on the other hand, may not only have possible antipsychotic efficacy based on one open study (62,63) but may provide an important clue as to the action of antipsychotics in general. More double-blind studies are indicated to assess its function in acute psychosis. The four compounds do seem to have properties similar to many of the classic antipsychotic agents in view of their common dopamine-blocking activity, antiemetic, sedative, and cataleptic effects. In addition, they have similar spectrum of side effects. Certain effects such as lack of efficacy in dopamine receptor models (for metoclopramide) and questionable differences in sites of action (blocking of dopamine and mesolimbic versus nigral striatal areas for sulpiride) may indicate unique neurochemical effects for these compounds and may provide a clue to allow the investigators to better predict antipsychotic efficacy and draw inferences regarding sites of action and mechanisms underlying neuroleptic activity. The benzamides have been used extensively in France since 1967. Before these drugs can be considered to be effective antipsychotic agents on par with phenothiazines and butyrophenones, further double-blind studies are indicated. These studies would give us a better idea as to whether they fit into the psychiatrist's armanentarium and may allow further insights into the relationship between descriptive psychopathology and neuropharmacology.