Studies on long-term efficacy and safety should be a main concern in the evaluation of novel antipsychotics. The present paper is a review of important issues related to the design and performance of such trials. The variability of the natural course of schizophrenia, the variability in treatment response, and the variability of actions of different neuroleptics need to be considered. Long-term studies need to address maintenance of efficacy, prevention of relapse and recurrence, health economics, quality of life and a large number of safety issues in order to get approval for new drug applications and reimbursement on expensive new medicines. Assessment instruments for efficacy, tolerability and safety, need to be supplemented with rating scales for various aspects of psychopathology (positive, negative, deficit symptoms), social and work functioning, drug induced mental side effects, quality of life and accounts of total treatment costs.

Long-term (minimum six months) safety and efficacy studies with an anti-anxiety agent are aimed at identifying the emergence of any clinical effects not observed during shorter periods of treatment including the identification of late occurring adverse events, loss of therapeutic benefit, or post-treatment withdrawal effects. There is the need to establish diagnostic criteria for persistent anxiety for patients who truly benefit from long-term therapy. Risk factors predisposing to drug dependence should be assessed prior to continuous use. Ideally, long-term continuous studies should be blinded, comparative and placebo-controlled, with an adequate duration of the withdrawal phase. The treatment response of the elderly in comparison to the overall patient sample should be emphasised.

The acceptability and efficacy of tianeptine were evaluated in three open trials in a total of 549 elderly patients, 426 of whom were treated for 3 months and 188 for 1 year. The therapeutic effect was that expected from an effective antidepressant, with a marked response after treatment for one month. In the geriatric trial, where patients were primarily dysthymic, continuation of treatment after 6 months consolidated the improvement already observed. Tianeptine also had a favorable long-term effect in chronic refractory depression. Drop-outs due to side-effects were few (4.4%), despite the high risk population. All pre-treatment complaints improved on tianeptine. The high frequency of somatic complaints expressed before treatment confirmed the extent to which depression is somatised in the elderly. Concomitant physical disease present in 87% of patients did not restrict the use of tianeptine. The fact that tianeptine has a low incidence of anticholinergic effects and no affinity for either H1 or α1 receptors makes it a particularly easy drug to use in elderly subjects who are sensitive to the side-effects of psychotropic agents.

Evidence from the literature suggests that, on average, 27% of patients with a bipolar disorder (BD) experience a continuous cycling course (CCC) and that this subgroup differs significantly from patients with a noncontinuous cycling course (N-CCC) with respect to sociodemographic characteristics and clinical presentation. The aim of the present paper is to review the studies that evaluated short- and long-term treatment responses in BD patients with CCC. The retrieved studies indicate that CCC is a significant predictor of poor response to long-term treatment with lithium (the odds of a response in the CCC group were 57% less than in the N-CCC group; p<0.01), as well as to polytherapies including lithium and/or an antiepileptic augmented, when necessary, with an antipsychotic and/or antidepressant. The percentage of patients without new episodes during follow-up was significantly lower in the CCC group compared with the N-CCC group (15.4 vs. 37.6% , p<0.01). Compared with patients in the N-CCC group, members of the CCC group had a poorer response and lower remission rates after 12-week antidepressant treatments for a major depressive episode (82.3 vs. 50%, p =0.002; 69.6 vs. 40.9%, p=0.013). These findings, underlining that CCC is a predictor of poor response to short- and long-term treatment in BD, should be interpreted considering the limitations of the reviewed studies (the small sample sizes, the small number of trials and their observational nature, the lack of randomization or placebo controls, and the unblinded nature of the outcomes). Clinical trials and observational studies with larger samples are warranted to confirm the conclusions of our review.