Clinical methodology for testing of anxiolytic drugs

Diagnostic criteria and classification are changing. It is no longer accept able to include patients with a general diagnosis of ally anxiety, or neuro tic anxiety. Regardless of the reference system used, DSM IV or ICD 10, anx iety disorders are now derailed in separate entities. General anxiety disor der, GAD, which is pivotal for the evaluation of new products, can only be claimed after the elimination of all the others, and is relatively rare. Th e inclusion of such outpatients is further complicated, as comorbidity is f requently associated with GAD - alcoholism, major depression, dysthymia, pe rsonality disorders, somatic disease likely to interfere with patient evalu ation - and leads to exclusions, and also because the requested duration fo r the syndrome, prior to inclusion, is six months, which means six months w ithout psychotropic drugs, including excessive alcohol consumption. As to patient evaluation, the reference scale remains the HAM-A. It should show score above 20 at baseline. It has been designed to assess the level o f anxiety of patients presenting with the diagnosis of anxiety, but not the diagnosis of GAB, and, clearly, in relation to the expected results obtain ed with BZD, which are still the standard reference drugs. The same is true for the other investigator scales and self-rating scales. Moreover, the cr iteria defining clinical improvement are still discussed. More generally, c linical testing in comparison with placebo and reference drugs is particula rly important for anxiolytic drugs. The optimal dose range should be investigated in phase I, evidence of sedat ive or disinhibiting effects, and in phase II, defining the minimal active dose. Longer duration of treatment should be scrutinized in phase III, in order t o cheek on long-term efficacy, recurrences and relapses. The effects of dru g withdrawal should also be studied: withdrawal syndrome, rebound, recurren ce, dependence. It currently looks difficult to market new anxiolytic drugs, and clinical r esearch mainly provides an extension of the indications for antidepressant drugs in anxiety.