Anxiolytics SSRIs

Beginning in the 1960s, ben2odia2epiae anxiolytics and hypnotics rapidly became the standard prescription dmg treatment. In the 1980s, buspkone [36505-84-7] (3), which acts as a partial agonist at the serotonin [50-67-9] (5-hydroxytryptamine, 5-HT) type lA receptor, was approved as treatment for generali2ed anxiety. More recently, selective serotonin reuptake inhibitors (SSRIs) have been approved for therapy of panic disorder and obsessive—compulsive behavior. 

A number of medications used in the treatment of anxiety have effects on serotonin neurotransmission (Ch. 13). These medications include tricyclic antidepressant medications, SSRIs, and monoamine oxidase inhibitors (MAOIs). However, because these medications take weeks to exert their full anxiolytic effects, it is unlikely that blocking the reuptake (and thus increasing synaptic levels) of either serotonin or norepinephrine selectively is responsible for their anxiolytic properties — rather it is suspected that the therapeutic effects are due to changes in gene expression, protein levels, and eventually changes in synaptic connections between neurons. 

Venlafaxine extended release, duloxetine, paroxetine, and escitalopram are FDA approved for treatment of GAD. Sertraline is also effective. Acute response and remission rates are approximately 65% and 30%, respectively. Imipramine may be used when patients fail to respond to selective serotonin reuptake inhibitors (SSRIs). In one trial, diazepam, trazodone, and imipramine had greater anxiolytic activity than placebo. 

As anxiolytics, benzodiazepines have faster onset of effect than SSRIs or antipsychotics. Their use is best limited to short-term situations, although there are likely to be comparable risks of dependence in these populations from all major classes of drugs. 

These drugs increase synaptic serotonin by selectively blocking the serotonin reuptake transporter. In preclinical and human studies acute doses tend to be anxiogenic (Bell and Nutt 1998) but chronic administration has anxiolytic effects, possibly due to downregulation of presynaptic autoreceptors (Blier et al. 1990). There are five SSRIs widely available citalopram, fluoxetine, fluvoxam-ine, paroxetine and sertraline. Escitalopram, the S-enantiomer of citalopram. 

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. 

The SSRIs have supplanted the TCAs as clinical treatment options because of their anxiolytic potential, ease... 

Depression associated with panic attacks may benefit from the combination of an antidepressant-anxiolytic or the use of an SSRI (e.g., fluoxetine or paroxetine), which may have antipanic properties separate from their antidepressant effects. 

In addition to buspirone and the non-barbituate, non-BZP hypnotics, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and other new antidepressants all represent attempts to achieve anxiolytic and hypnotic effects seen with the BZDs, while avoiding their unwanted properties. 

Insomnia is a common comorbid condition with depression, and frequently is made worse by antidepressants, particularly the SSRIs. When insomnia persists despite adequate evaluation and attempts to reduce it by other approaches, it is often necessary to use a concomitant sedative-hypnotic, especially a short-acting nonbenzodiazepine with rapid onset such as zaleplon or zolpidem. At times a benzodiazepine sedative hypnotic such as triazolam or temazepam may be necessary. If anxiety persists during the day and cannot be otherwise managed, it may be necessary to add an anxiolytic benzodiazepine such as alprazolam or clonazepam. Use of sedative-hypnotics and anxiolytics should be short-term whenever possible. 

By the 1990s antidepressants from the serotonin selective reuptake inhibitor (SSRI) class became recognized as preferred first-line treatments for anxiety disorder subtypes, ranging from obsessive-compulsive disorder, to panic disorder, and now to social phobia and posttraumatic stress disorder (Fig. 8—9). Not all antidepressants, however, are afficacious anxiolytics. For example, desipramine and bupropion seem to be of little help in several anxiety disorder subtypes. Documentation of efficacy... 

FIGURE 8-9. By the 1990s the serotonin selective reuptake inhibitors (SSRIs) replaced classical anxiolytics as first-line treatments for anxiety disorder subtypes and for mixtures of anxiety and depression but not for generalized anxiety disorder. 

Treatments include behavioural therapies, anxiolytic drugs and antidepressants such as the SSRIs, fluoxetine or fluvoxamine. 

Acute dystonia is a recognized complication of treatment with antipsychotic drugs and it can also occur with SSRIs and the anxiolytic drug buspirone. 

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