Psychopharmacology has revolutionised the practice of psychiatry and continues to evolve with developments in psychiatric nosology. It has provided the bridge for elucidating the biology of psychiatric disorders and has refined diagnostic distinctions with the introduction of highly specific agents such as lithium. Prediction in psychopharmacology has enhanced the clinical validity of psychiatric syndromes and has contributed to the delineation of meaningful subgroups, with implications for clinical practice.

All recently completed controlled two-year studies on intermittent, early neuroleptic intervention treatment have failed to compare favourably with studies on maintenance treatment concerning relapse prevention. The reason for this failure is still unclear. Therefore the implicit, but as yet unproven, hypothesis that a relapse can be predicted from prodromal symptoms was tested from the perspective of our German multicentre study. Results demonstrate that this is not the case. Possible reasons for and clinical implications of this negative finding are discussed.

The relationship between early treatment response and CT variables was investigated in 50 consecutively admitted patients with DSM-III schizophrenia. Treatment response was defined as the absolute BPRS improvement during patients' hospital stay and was found to be significantly correlated (P<0.05) with the frontal horn ratio (r = −0.36), ventricular ratio (r = −0.32), width of the third ventricle (r= −0.37), width of the frontal interhemispheric fissure (r = −0.33), and average width of the three largest cortical sulci (r = −0.46). According to the results of multiple regression analysis, 35% of the variance in the treatment response was accounted for by the average width of the three largest cortical sulci, the ventricular ratio and the frontal horn ratio. Thus, cerebral abnormalities associated with poor treatment response do not seem to be limited to one particular morphological site, but involve different brain regions.

Lithium treatment, an approach with well documented efficacy, has recently been losing its treatment value. Lithium continues working, however, for those patients for whom it was proven efficacious; that is, most patients with primary episodic affective disorders. Such responders to lithium prophylaxis can be reliably identified beforehand by a comprehensive clinical assessment. The explanation for the paradox of lithium's lost efficacy lies mostly in the educational bias against a comprehensive patient assessment, and in the shift in diagnostic fashion favouring affective disorders and the treatment methods associated with them in the clinicians' minds.

The search for predictors of outcome has not been particularly rewarding, and the use of lithium remains empirical: a trial of lithium is the most powerful predictor of outcome. However, lithium is a highly specific treatment for bipolar disorder. In non-bipolar affective disorder, factors of interest are correlates of bipolar disorder: mood-congruent psychotic features, retarded-endogenous profile, cyclothymic personality, positive family history of bipolar illness, periodicity, and normality between episodes of illness.

Recent studies have indicated that long-term lithium treatment reduces the expected suicidal activity and overall mortality of patients with affective disorders. Based on the data from the lithium clinics in Berlin and Hamilton (n = 512), a minimum length of two years of continued lithium treatment is needed to reduce the high mortality resulting from affective disorders.

We summarise a series of studies using a MAOI to help establish the validity of a subgroup of depressives referred to as atypical depressives. Patients with reactive mood meeting DSM-III criteria for depressive illness who had associated atypical features (which include hyperphagia, hypersomnolence, leaden paralysis, and rejection sensitivity) were randomised to imipramine, phenelzine and placebo. Non-responders were crossed over, and in all there were over 400 patient trials. Phenelzine consistently was found to be superior to imipramine. Only in trials which included patients lacking atypical, vegetative symptoms was imipramine found to equal phenelzine. We conclude that the researcher and the clinician should consider the relevance of the atypical depressive syndrome.

We describe a double-blind study involving 58 in-patients with major depression (DSM-III). After one week on placebo, the patients were randomly assigned to either levoprotiline or maprotiline treatment for three weeks. In the next three weeks, responders were maintained on the same medication and non-responders were shifted to treatment with the complementary drug. After the initial three weeks' treatment, 31% of levoprotiline patients and 58% of maprotiline patients had responded. Both in the initial three-week treatment period and after shifting non-responders to the complementary drug, there were significant differences in favour of maprotiline. The comparison of properties of different outcome criteria in prediction analyses shows that the final score gives the best agreement with global evaluation; using the delta score (final minus baseline) or ratio score (final/baseline) as the outcome criterion may yield paradoxical results.

We describe the limitations on studying the interactions of drugs of abuse in humans. Two ‘acute’ studies were carried out. In the first study, the administration of alcohol/placebo with cocaine showed the possibility of identifying the euphoric effect of the drugs by the EEG power spectra analysis in terms of enhancement of alpha- and beta-wave activity. The results of the second study, in which cocaine and buprenorphine were administered, show the existence of low-dose interactions and the influence of buprenorphine on craving for cocaine.

Psychiatry and psychopharmacology are no longer aiming to make a decisive breakthrough at the end of the century. Rather than seeking explanations, research workers are looking for ‘predictions’. Three main types of prediction are emerging: a tautological, a heuristic, and an irrelevant one. Few predictions found in the recent literature can be marked as ‘logical’ ones. Nevertheless, predictions play two important roles: they generate new hypotheses that can be falsified in properly designed scientific experiments; they also may serve to falsify given hypotheses. The main recent findings on predictions in psychiatry are briefly summarised.