Paroxetine indications

H]MDMA interacted with multiple sites in rat brain. A low affinity pH]MDA binding site (apparent Kd>1.0 mM) was found to be resistant to boiling of the synaptosomal preparation for 15 minutes. This site was saturable, as indicated by a 30 pereent inhibition of [ H]MDA binding to boiled synaptosomes by 1.0 mM MDA and a 56 pereent inhibition of the binding by 0.1 mM of the serotonin uptake bloeker paroxetine. The indication of a saturable, nonspecific binding site for [ H]MDA in boiled membranes necessitated that we use boiled tissue to assess nonspecific binding in all subsequent experiments. 

The utilization of IR spectroscopy is very important in the characterization of pseudopolymorphic systems, especially hydrates. It has been used to study the pseudopolymorphic systems SQ-33600 [36], mefloquine hydrochloride [37], ranitidine HC1 [38], carbovir [39], and paroxetine hydrochloride [40]. In the case of SQ-33600 [36], humidity-dependent changes in the crystal properties of the disodium salt of this new HMG-CoA reductase inhibitor were characterized by a combination of physical analytical techniques. Three crystalline solid hydrates were identified, each having a definite stability over a range of humidity. Diffuse reflectance IR spectra were acquired on SQ-33600 material exposed to different relative humidity (RH) conditions. A sharp absorption band at 3640 cm-1 was indicative of the OH stretching mode associated with either strongly bound or crystalline water (Fig. 5A). The sharpness of the band is evidence of a bound species even at the lowest levels of moisture content. The bound nature of this water contained in low-moisture samples was confirmed by variable-temperature (VT) diffuse reflectance studies. As shown in Fig. 5B, the 3640 cm-1 peak progressively decreased in intensity upon thermal... 

Lorazepam is a short-acting benzodiazepine indicated for use in relieving anxiety and insomnia. Lorazepam may also be administered perioperatively to alleviate pain and in status epilepticus. Imipramine is a tricyclic antidepressant, paroxetine is a selective serotonin re-uptake inhibitor, venlafaxine is a serotonin and adrenaline re-uptake inhibitor and moclobemide is a reversible monoamine oxidase inhibitor. Imipramine, paroxetine, venlafaxine and moclobemide are all classified as antidepressants. 

It is remarkable that better enantioselectivities are achieved when CALB-catalyzed acylations of the alcohol are carried out in organic solvent rather than in water. Excellent enantioselectivities are obtained when the process is carried out with vinyl esters [22]. However, in some cases the use of vinyl or alkyl esters as acyl donors has the drawback of the separation of the ester (product) and the alcohol (substrate). A practical strategy to avoid this problem is the use of cyclic anhydrides [23]. In this case an acid is obtained as product, which can be readily separated from the unreacted alcohol by a simple aqueous base-organic solvent liquid-liquid extraction. This methodology has been successfully used for the synthesis of (-)-paroxetine as indicated in Scheme 10.11 [24]. 

Bruxism mainly occurs in stage 2 sleep and REM sleep (Bader et ah, 1977). A relationship to stress and anxiety has been suggested, but the disorder can be chronic without apparent association with stress (Faulkner, 1990 Pierce et ah, 1995). It has been suggested that the central dopaminergic system may be involved in the modulation of sleep bruxism (Lobbezoo et al., 1997). Case reports indicate that bruxism can be induced by the SSRI paroxetine (Romanelli et al., 1996). The mechanism remains unclear possibilities include sleep disturbance, serotonergic-mediated inhibition of dopamine manifesting as akathisia, and SSRI-induced anxiety. SSRI-induced bruxism may respond to therapy with buspirone (Ellison et al., 1993). 

The prototypical serotonin reuptake inhibitor (SRI) medication is the non-selective agent clomipramine, a tricyclic antidepressant (TCA). The Selective SRIs (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalo-pram (Celexa). The Food and Drug Administration (FDA) approved clinical indications for these medications are described in Table 22.1. 

In four instances, the agency has invoked this rule at the time of approval of supplements for new indications for psychotropic drugs already approved for other psychiatric indications. It was noted in the approval letters for these supplements that, since the drugs in question would likely be used in children and/ or adolescents with the newly approved indications, the FDA required the sponsors of these products to conduct studies that would be pertinent to such use in the pediatric population. Since the products were ready for approval in adults, the FDA deferred the required pediatric studies to a future date. Alternatively, sponsors could make an argument for waiver of the requirement. The drug products and indications for which the FDA has required studies under the Pediatric Rule are as follows paroxetine for social anxiety disorder sertraline for post-traumatic stress disorder (PTSD) olanzapine for acute mania in bipolar disorder and fluoxetine in premenstrual dysphoric disorder (PMDD). 

Some evidence indicates that social phobia responds to SSRls, and case reports and studies with fluoxetine [B. Black et al. 1992 Van Ameringen et al. 1993), fluvoxamine [Mendels et al. 1995), paroxetine [Pitts et al. 1996 Ringold 1994), and sertraline [Katzelnick et al. 1995) have reported positive results. Although the full details of these studies have not been published, it seems that SSRls might well prove, in due course, to be effective treatments for social phobia. At the moment, the only treatment licensed for social phobia is moclobemide, which is a reversible inhibitor of monoamine oxidase-A [Nutt and Montgomery 1996 Versiani et al. 1992), and it is possible that it... 

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

Van Laar, M.W., Volkerts, E.R., Verbaten, M.N., et al. Differential effects of amitriptyline, nefazodone and paroxetine on performance and brain indices of visual selective attention and working memoiy. Psychophannacology 162, 351-363, 2002. 

Zimelidine was the first serotonin reuptake inhibitor available for clinical use, but in 1982 was withdrawn worldwide because of its toxicity ( 110). Despite this initial setback, five members of this class have been marketed in the United States and various countries around the world citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). All except fluvoxamine have marketed indications in the United States for the treatment of major depression. Fluvoxamine is marketed in the United States for the treatment of obsessive-compulsive disorder rather than major depression, although it is marketed in a number of other countries for major depression. 

All SSRIs have an antipanic effect. Their advantages are limited adverse effects and lack of toxicity. Because of more acceptable adverse effect profiles, the SSRIs are usually the drugs of choice. Several studies consistently indicate that SSRIs such as fluoxetine, sertraline, paroxetine, fluvoxamine, as well as agents such as clomipramine and trazodone, all possess antipanic efficacy, although the last may be less effective than imipramine ( 24, 105, 106, 107, 108 and 109). 

The selective serotonin reuptake inhibitors (SSRIs) represent a chemically diverse class of agents that have as their primary action the inhibition of the serotonin transporter (SERT) (Figure 30-3). Fluoxetine was introduced in the United States in 1988 and quickly became one of the most commonly prescribed medications in medical practice. The development of fluoxetine emerged out of the search for chemicals that had high affinity for monoamine receptors but lacked the affinity for histamine, acetylcholine, and adrenoceptors that is seen with the tricyclic antidepressants (TCAs). There are currently six available SSRIs, and they are the most common antidepressants in clinical use. In addition to their use in major depression, SSRIs have indications in GAD, PTSD, OCD, panic disorder, PMDD, and bulimia. Fluoxetine, sertraline, and citalopram exist as isomers and are formulated in the racemic forms, whereas paroxetine and fluvoxamine are not optically active. Escitalopram is the S enantiomer of citalopram. As with all antidepressants,... 

The earliest and unfortunately still one of the commonest treatments of social phobia is self-medication with alcohol. The behaviorally disinhibiting actions of alcohol allow many social phobics to engage in social contacts that would otherwise be impossible. Legitimate therapeutic drugs for social phobia are now being discovered at a fast pace (Fig. 9—7). In fact, one of the SSRIs (paroxetine) already has been formally approved for use in the treatment of social phobia, and several other SSRIs and antidepressants are rapidly accumulating evidence of their efficacies in this condition as well. Specifically, studies of all five SSRIs (paroxetine, fluvoxamine, fluoxetine, sertraline, and citalopram) have indicated their efficacy in social phobia. Currently, SSRIs are considered first-line treatments for social phobia. 

Inhibitors obtained from in vitro data include a number of compounds with different selectivities and specificity toward this enzyme. Most of them have not been tested for their in vivo effects and some may also inhibit other enzymes (ticlopidine, fluvoxamine, miconazole, nefazodone, paroxetine, etc.). This query did not yield any additional inhibitors. A summary of substrates (including partial ones) and inhibitors is shown in Table 1 and indicates that clopidogrel and ticlopidine, whose effects have been well documented in vivo and in vitro, are effective inhibitors of CYP2B6 and can be used in an in vivo DI program. 

In these trials, hostile events are found to excess in both adults and children on paroxetine compared with placebo, and are found across indications, and both on therapy and during withdrawal. The rates were highest in children with obsessive compulsive disorder (OCD), where the odds ratio of a hostile event was 17 times greater (95% confidence interval [Cl], 2.22-130.0). 

On March 2, 2004, the Canadian Medical Association Journal reported on a 1998 internal GSK document that had been leaked to it (Kondro et al., 2004). The memorandum advised staff at the international drug giant GlaxoSmithKline (GSK) to withhold clinical trial finds in 1998 that indicated the antidepressant paroxetine... had no beneficial effect in treating adolescents. ... 

The suit provided an analysis of efficacy in GSK s trials, indicating that the drug was often no better than placebo. In an analysis of safety, it found that several combined studies showed that possibly suicide-related behaviors were approximately two times more likely in the paroxetine group than the placebo group. It disclosed that in five studies, GSK coded suicidal thinking and acts, as well as mood swings, crying and similar behaviors, as emotional lability. ... 

Fluoxetine (Prozac /Lilly), paroxetine (Paxil /GlaxoSmithKilne), and sertraline (Zoloft /Pfizer) are selective serotonin reuptake inhibitors (SSRIs) and are useful in the treatment of depression. These agents potentiate the pharmacological actions of the neurotransmitter serotonin by preventing its reuptake at presynaptic neuronal membranes. In addition to its SSRI properties, venlafaxine (EfFexor /Wyeth-Ayerst) also appears to be a potent inhibitor of neuronal norepinephrine reuptake and a weak inhibitor of dopamine reuptake thereby enhancing the actions of these neurotransmitters as well. Venlafaxine is indicated for use in anxiety and depression. 

Of the SSRIs, paroxetine is the agent most likely to cause weight gain however, in this study the authors reported no change in body mass index during the 3 months of treatment, suggesting a more direct effect of paroxetine on metabolism. Further work will be needed to see if similar metabolic effects are associated with other SSRIs and in patients with other treatment indications. 

Treatment is poorly researched there have been few properly controlled trials and almost all open trials have been conducted on small numbers of patients long after the causative incident. The wide range of drugs that has been reported to provide some benefit includes benzodiazepines, TCAs and MAOIs paroxetine (SSRI) (20-50 mg/day p.o.) is now licenced for this indication in the UK. The preferred treattnent immediately following the... 

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