Anxiety disorders with anxiolytics

Pharmacodynamic tolerance to the psychomotor effects of benzodiazepines has been demonstrated after single or multiple doses (File 1985 Greenblatt and Shader 1978 Rosenberg and Chiu 1985). Pharmacodynamic tolerance to the anxiolytic effect (over a 6-month period) has not been demonstrated (Rickels et al. 1983), and clinical experience supports the view that many patients with anxiety disorders require long-term therapy with benzodiazepines or alternative antianxiety agents. An important clinical consequence of tolerance to sedative effects is observed in benzodiazepine overdoses, when patients may initially be... 

Out-patient treatment is substantially cheaper than in-patient management and is generally as effective (Lowman, 1991). A French study on patients with generalized anxiety disorder estimated costs per patient over 3 months to he US 423 for hospitalization, 335 for out-patient services and 43 for medications (Souetre et al, 1994). Comorbid conditions (mostly alcoholism and depression) doubled these direct health-care costs. Over three-quarters of all patients were taking anxiolytic medication. 

It is considered a second-line agent for GAD because of inconsistent reports of efficacy, delayed onset of effect, and lack of efficacy for comorbid depressive and anxiety disorders (e.g., panic disorder or SAD). It is the agent of choice in patients who fail other anxiolytic therapies or in patients with a history of alcohol or substance abuse. It is not useful for situations requiring rapid antianxiety effects or as-needed therapy. 

Abstract The stress-dependence and chronic natnre of anxiety disorders along with the anxiolytic effectiveness of antidepressant drngs snggests that nemonal plasticity may play... 

GABA is formed by the decarboxylation of glutamate, and is the major inhibitory neurotransmitter, hi recent years the GABAa receptor has been identified as the mediator of the anxiolytic and sedative effects of drugs such as alcohol and the benzodiazepines. Abnormahties of this receptor have been identified in humans with anxiety disorders (Nutt and Mahzia 2001). 

The SSRls as a class are now widely considered to be appropriate first-line anxiolytic drugs in particular paroxetine, the most potent 5-HT reuptake blocker, has been licensed in the UK for the treatment of each of the major anxiety disorders. Short-term efficacy has been clearly demonstrated in randomised controlled trials, but in common with other antidepressants, research evidence is lacking for long-term efficacy and necessary duration of treatment. 

Mirtazapine has a novel mechanism of action that in theory should promote anxiolytic effects, although evidence from studies of anxiety disorders is awaited. It increases synaptic release of serotonin and noradrenaline via blockade of presynaptic inhibitory a2-adrenoceptors, as well as blocking post-synaptic 5-HT2 and 5-HT3 serotonin receptors and Hi histamine receptors. Mirtazapine has good efficacy for anxiety symptoms associated with depression (Fawcett and Barkin 1998), and in controlled studies was superior to... 

SSRIs have been approved for the treatment of the majority of anxiety disorders, except agoraphobia and specific phobia. The mechanisms of action responsible for SSRIs anxiolytic activity remain to be fully delineated. Understanding of pre- and postsynaptic receptor regulation with chronic treatment and cross-system effects are critical in furthering our imderstanding of these drugs. Increasing specificity may improve clinical efficacy. 

In patients with panic disorder, basal ANP concentrations are lower when compared to healthy control subjects, but ANP concentrations are faster and more pronounced during experimentally induced panic attacks (Kellner et al. 1995). In line with these findings, there is evidence for an anxiolytic activity of ANP in humans ANP decreases CCK-4-induced panic anxiety in patients with panic disorder (StrOhle et al. 2001) and healthy control subjects, and attenuates HPA system activity by decreasing ACTH and cortisol stimulation (Wiedemann et al. 2001). Modulation of ANP concentrations or nonpeptidergic ANP receptor ligands maybe ultimately used in the pharmacological treatment of anxiety disorders, such as panic disorder. 

---