Anxiolytics paroxetine

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. 

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. 

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. 

StrOhle A, Pasini A, Romeo E, Hermann B, Spalletta G, di Michele F, Holsboer F, Rupprecht R (2000) Fluoxetine decreases concentrations of 3a,5a-tetrahydrodeoxycorticosterone (3a,5a-THDOC) in major depression. J Psychiatr Res 34 183-186 StrOhle A, Kellner M, Holsboer F, Wiedemann K (2001) Anxiolytic activity of atrial natriuretic peptide in patients with panic disorder. Am J Psychiatry 158 1514-1516 StrOhle A, Romeo E, di Michele F, Pasini A, Yassouridis A, Holsboer F, Rupprecht R (2002) GABAA receptor modulatory neuroactive steroid composition in panic disorder and during paroxetine treatment. Am J Psychiatry 159 145-147 StrOhle A, Romeo E, di Michele F, Pasini A, Hermann B, Gajewsky G, Holsboer F, Rupprecht F (2003) Induced panic attacks shift GABAA receptor modulatory neuroactive steroid composition. Arch Gen Psychiatry 60 161-168 Szapiro G, Vianna MRM, McGaugh JL, Medina JH, Izquierdo I (2003) The role of NMDA glutamate receptors, PKA, MAPK, and CAMKII in the hippocampus in extinction of conditioned fear. Hippocampus 13 53-58... 

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. 

Antidepressant drugs, however, might have direct anxiolytic effects. That is, certain antidepressants such as paroxetine (Paxil) or venlafaxine (Effexor) can help reduce anxiety independent of their effects on depression.1,47 These antidepressants have therefore been advocated as an alternative treatment for anxiety, especially for people who cannot tolerate the side effects of traditional anxiolytics, or who might be especially susceptible to the addictive properties of drugs like the benzodiazepines.1,9,46 Moreover, antidepressants such as paroxetine or venlafaxine are now considered effective as the primary treatment for several forms of anxiety, including generalized anxiety disorder, social phobia, and panic disorder.4,29,53 Antidepressants, either used alone or in combination with antianxiety drugs, have become an important component in the treatment of anxiety. 

Paroxetine has mild anticholinergic actions that can enhance the rapid onset of anxiolytic and hypnotic efficacy but also cause mild anticholinergic side effects... 

Paroxetine. In the structure of paroxetine (Paxih.J amino group, protonated in vivo could H-bond with IK -CHj-O- unshared elcxtruns. A /S-arylamine-like strucKii with an extra aryl group results. The compound is a itr-highly. selective SERT. As expected, it is an effectiveanliil pres.sant and anxiolytic. 

Venlafaxine extended-release, a serotonin-norepinephrine reuptake inhibitor (SNRI), alleviates anxiety in patients with and without co-morbid depression. The reduction in psychic symptoms of anxiety and tension is not accompanied by significant reductions in somatic symptoms. Venlafaxine (dosed once daily) was effective at doses of 150 and 225 mg for 2 months in patients with GAD, and efficacy was maintained for an additional 6 months of therapy." Paroxetine was significantly more effective than placebo at achieving response in 62% and 68% of patients at 20 and 40 mg daily, respectively, after 2 months. Remission occurred in 30% and 36% of patients taking 20 and 40 mg of paroxetine, respectively." Escitalopram was more efficacious than placebo in three 8-week trials in patients with GAD. In a four paraUel-group comparison, diazepam and trazodone were found to be equivalent in anxiolytic activity (remission rates of 66% and 69%, respectively) compared with placebo (47% remission rate), but rmipramine s rate of remission (73%) exceeded that of the other three treatments. ... 

---