As with other drugs it is necessary to look for changes induced by anxiolytics on vital signs, laboratory parameters and adverse events. In return, in a more specific way for anxiolytics, we will look at side effects at the central nervous system level with psychological and physiological battery tests. We will also assess the safety of use of anxiolytics in certain specific conditions, such as overdose or withdrawal and in certain populations such as the elderly, neonates and children. The assessment of safety and side effects, whatever the drug type studied, must come early in the developing process of a drug (phases I, II and III).

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.

This objectives of this study were three-fold: retrospectively evaluate anxiolytic/hypnotic consumption by psychiatric inpatients, identify the risk factors of prolonged intakes, and prospectively measure the impact of hospitalisation on the use of those drugs. Three hundred and seventy-six patients hospitalised in 11 psychiatric departments in the Paris region were studied using a structured interview for the anxiolytic/hypnotic treatments, DSM-III-R criteria, GHQ-12, HAD, Spiegel's questionnaire, COVI's anxiety scale and the CGI. Eighty-five per cent of the patients had taken one anxiolytic/hypnotic or more in the 3 months preceding hospitalisation. Hospitalisation induced little change in anxiolytic/hypnotic use: dosage frequency increased from 77% to 84% between the week preceding hospitalisation and that preceding discharge; 26% of consumers were taking at least two anxiolytics or two hypnotics in the first period vs. 23% in the second. The absence of withdrawal during hospitalisation was related to the high age and a diagnosis of depression rather than schizophrenia, to the existence of continuous intake over the 3 months preceding hospitalisation and to higher drug doses during the 7 days preceding hospitalisation. Prescription of treatment at the end of hospitalisation in previously non-user subjects was related to a higher HAD anxiety score at discharge.

Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART), owing to a high prevalence of psychiatric illness within the population living with HIV, as well as a 7-fold increased risk of HIV infection among patients with psychiatric illness. While ART has been notoriously associated with a multitude of pharmacokinetic drug interactions involving the cytochrome P450 enzyme system, the magnitude and clinical impact of these interactions with psychotropics may range from negligible effects on plasma concentrations to life-threatening torsades de pointes or respiratory depression. This comprehensive review summarizes the currently available information regarding drug–drug interactions between antiretrovirals and pharmacologic agents utilized in the treatment of psychiatric disorders—antidepressants, stimulants, antipsychotics, anxiolytics, mood stabilizers, and treatments for opioid use disorder and alcohol use disorder—and provides recommendations for their management. Additionally, overlapping toxicities between antiretrovirals and the psychotropic classes are highlighted. Knowledge of the interaction and adverse effect potential of specific antiretrovirals and psychotropics will allow clinicians to make informed prescribing decisions to better promote the health and wellness of this high-risk population.

Novel anxiolytics notwithstanding, in the latest fifteen years there have been no major innovations in the treatment of anxiety disorders. Fascinating research is going on, but real breakthroughs will require adequate models of disease, based on the disordered physiology of each type of pathological anxiety. In this brief overview, we will address both the field of potential anxiolytics in 1997, and the development of new experimental models of anxiety disorders.

A survey of the history of psychopharmacotherapy is presented.

In Antiquity some psycho-active plant extracts were already known . Since the rise of chemistry in early nineteenth century, sedative drugs were synthesized first. Since the fifties of this century the four groups of psychotherapeutic drugs proper, anxiolytics, hypnotics, antipsychotics and antidepressants have been discovered.

Astute clinical or preclinical observation and the understanding of coincidences, serendipity, has been the basis of these discoveries. Since the prototypes were discovered, no real breakthroughs have been achieved.

Animal research suggests that central serotonergic neurons are involved in behavioral suppression, particularly anxiety-related inhibition. The hypothesis linking decreased serotonin transmission to reduced anxiety as the mechanism in the anxiolytic activity of benzodiazepines conflicts with most clinical observations. Serotonin antagonists show no marked capacity to alleviate anxiety. On the other hand, clinical signs of reduced serotonergic transmission (low 5-HIAA levels in the cerebrospinal fluid) are frequently associated with aggressiveness, suicide attempts, and increased anxiety. The target article attempts to reconcile such human and animal findings by investigating whether anxiety reduction or increased impulsivity is more Likely to account for animal behavioral changes associated with decreased serotonergic transmission. The effects of manipulating central serotonin in experimental anxiety paradigms in animals (punishment, extinction, novelty) are reviewed and compared with the effects of antianxiety drugs. Anxiety seems neither necessary nor sufficient to induce control by serotonergic neurons on behavior. Further evidence suggests that behavioral effects of anxiolytics thought to be mediated by decreases in anxiety are not caused by the ability of these drugs to reduce serotonin transmission. Blockade of serotonin transmission, especially at the level of the substantia nigra, results in a shift of behavior toward facilitation of responding. This behavioral shift is particularly marked when there is competition between acting and restraining response tendencies and when obstacles prevent the immediate attainment of an anticipated reward. It is proposed that serotonergic neurons are involved not only in behavioral arousal but also in enabling the organism to arrange or tolerate delay before acting. Decreases in serotonin transmission seem to be associated with the increased performance of behaviors that are usually suppressed, though not necessarily because of the alleviation of anxiety, which might contribute to the suppression.

Objective: To examine the current pattern of use of psychotropic medication in Sydney nursing homes and compare this with the pattern noted 5 and 10 years earlier.

Method: Data were recorded from medication cards concerning psychotropic medications prescribed for the 3093 residents in the 51 nursing homes in the Central Sydney Health Area. Documented diagnoses and demographic details were noted from their clinical files.

Results: In late 2003, 47.2% of residents were taking one or more psychotropic drug regularly and another 3.5% had been given “as required” (prn) doses at least once in the preceding 4 weeks. Fewer residents were taking hypnotics (11.3%) and anxiolytics (4.1%) regularly, when compared to 1998, but more were taking antidepressants (20.5%). Selective serotonin reuptake inhibitors were prescribed to 11.4%, venlafaxine to 2.6%, mirtazapine 1.6% and tricyclics to 3.6%. Although the proportion taking antipsychotics had not fallen since 1998, there were over twice as many residents (16.4%) taking atypical neuroleptic medication in 2003 as there were taking conventional neuroleptics (8.1%). Most of them did not have schizophrenia.

Conclusions: There have been further reductions in the use of hypnotics and anxiolytics in Sydney nursing homes, with increased prescription of antidepressants and a striking change towards use of atypical rather than conventional neuroleptic medication.

Anxiety states comprise three components, the subjective, the physiological and the behavioural. Anxiety disorders differ from normal anxiety in that cognitive clues inducing the emotion are covert. Anxiety can be induced by a variety of chemical agents, including the catecholamines, caffeine, lactate and some beta-carbolines. Models can be built up from the standpoints of Schachter, Lader and Matthews, and Clark to provide a cohesive theoretical framework for anxiety and panic disorders. Both pharmacological and psychological treatments are effective in these conditions and the model can incorporate the mode of action of these therapies. The ultimate goal is a holistic concept of anxiety combining the bio-psycho-social approaches.

La notion de posologie optimale des benzodiazépines doit être discutée, Elle varie en effet selon les indications thérapeutiques, les malades et les prescripteurs (praticiens généralistes ou spécialistes). Pour ces produits - dont les posologies idéales demeurent individuelles - la moyenne des posologies optimales n’a guère de signification clinique. En revanche, des courbes «d’utilité thérapeutique» doivent être établies dans chaque indication, en identifiant pour différentes posologies l’importance des effets observés (thérapeutiques et indésirables). Cette connaissance des posologies utiles commence dès les essais préciiniques et ceux de pharmacologie humaine (études pharmacocinétiques et électrophysiologiques comme l’E.E.G. quantitatif en laboratoire de sommeil). Elle est utilement complétée par les essais contrôlés ultérieurs. Les posologies particulièrement étudiées au cours de la phase II vont de celles responsables d’un effet supérieur à celui d’un placebo à celle d’un effet considéré comme «maximal». Cette dermère est plus facilement identifiable pour des produits à effet hypnotique prédominant (à des doses généralement bien supportées) que pour celles à visée anxiolytique. Certains plans expérimentaux revêtent dans ces indications un intérêt particulier, notamment certains protocoles intensifs chez un petit nombre de sujets (volontaires sains, insomniaques situationnels ou chroniques).

Au cours des essais de phase III, plusieurs types d’étude peuvent être envisagés : des groupes parallèles homogènes (quant à la nature de l’insomnie ou de l’anxiété) randomisés où plusieurs posologies présumées efficacies sont comparées mais aussi des essais au cours desquels des doses croissantes sont successivement prescrites de façon codifiée à l’ensemble des patients. C’est en fonction de la gravité de la symptomatologie que l’on définit l’intensité d’un effet secondaire ou résiduel «acceptable» (altération des performances, exploration des fonctions mnésiques, etc…).

Lors de la phase IV, la simple étude des posologies couramment utilisées par les praticiens permet d’élaborer des hypothèses quant aux posologies présumées optimales dans des indications particulières comme l’anxiété généralisée, l’alcoolisme, l’anxiété concomitante des psychoses, l’anxiété des attaques de panique voire celle des affections psychosomatiques.

Mais les seules techniques susceptibles de vérifier ces hypothèses restent des études comparatives randomisées de groupes parallèles de patients traités par différentes posologies.