Fluoxetine about

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

It is perhaps not surprising that, even after taking into account pharmacokinetic differences between these drugs, the therapeutic doses of the SSRIs do not parallel their Ki for inhibition of 5-HT reuptake. For instance, citalopram is about a thousand times more selective than fluoxetine for inhibition of 5-HT uptake, and yet their clinically effective doses are similar. In short, not only is their selectivity for the 5-HT transporter in vitro a poor predictor of their efficacy in vivo but it has to be questioned whether any of these compounds actually work by blocking 5-HT uptake alone. 

QUESTION I have two questions about your MBDB discrimination studies. It sounds as though you are doing experiments to investigate whether neuronal stores of serotonin are required for MBDB to be recognized. You mentioned that fluoxetine did not prevent the recognition. 

Citalopram and fluoxetine are antidepressant drugs widely used in human medicine and very persistent in WWTPs. However, there are few studies about the degradation of these pharmaceuticals by fungi and none of them identifies TPs. 

The SSRIs are believed to be more effective for numbing symptoms than other drugs. About 60% of sertraline-treated patients showed improvement in arousal and avoidance/numbing symptoms, but not reexperiencing symptoms. Similar numbers of patients have been shown to improve on paroxetine. Fluoxetine was effective in a placebo-controlled trial, and fluvoxamine was effective in an open trial. 

The most effective treatment for cataplexy is the tricyclic antidepressants, fluoxetine, or venlafaxine. Imipramine, protriptyline, clomipramine, fluoxetine, and nortriptyline are effective in about 80% of patients. 

Relapse prevention with medication has been studied in BN as well as AN. In 1991 Walsh et al. placed bulimics who had a 50% or more reduction in binge eating on desipramine in maintenance treatment. About half of the patients relapsed below the 50% reduction within 4 months, despite continued use of the medication. In a second multicenter collaborative study examining the efficacy of fluoxetine maintenance in bulimic patients who had responded to the drug with a 50% reduction of symptoms, the patients who were maintained on the active drug were significantly less likely to relapse than those who were switched to placebo at the end of the acute treatment phase (Romano, 1999). 

In most cases, SSRIs are the first choice for drugs to combat OCD. Clomipramine, fluvoxamine, fluoxetine, paroxetine, sertraline, and citalopram are all SSRIs that have been proven effective in reducing OCD symptoms. However, in about 40 to 60% of patients, these drugs do not completely alleviate all the symptoms. When this is the case, a second type of drug called a neuroleptic is often added. Neuroleptic drugs, such as haloperidol, clozapine, risperidone, and chlorpromazine... 

TCAs in more serious forms of depression such as melancholic or psychotic depression. Some studies have suggested that the SSRls do not work as well as the TCAs in melancholic depression (Roose et al. 1994]. Likewise, one study has suggested that venlafaxine, a drug with a mechanism of action similar to that of the TCAs, was superior to fluoxetine in the treatment of inpatients with melancholic depression (Clerc et al. 1994]. Still, other metaanalyses have failed to find a difference in the efficacy of SSRls versus TCAs in serious forms of depression [Nierenberg 1994]. Nonetheless, given that most studies have employed TCAs, and some debate exists about the utility of SSRls in severe subtypes, it may be prudent to start with a TCA in most patients until the debate is further resolved. For patients who present a significant suicide risk or who have not been able to tolerate TCAs, the SSRls in combination with a standard antipsychotic appears an effective option. 

Another approach to correct neurotransmission is to inhibit the reuptake of the neurotransmitters into their presvnaptic endings. If the presynaptic reuptake mechanism of a neurotransmitter is blocked then more of the neurotransmitter will stay in the synaptic cleft and be functionally available. Many antidepressant drugs, called reuptake inhibitors , are thought to act via this mechanism. If selective for serotonin they are called selective serotonin reuptake inhibitors (SSRIs, Chapter 1), but if selective for both serotonin and noradrenaline they are called serotonin noradrenaline reuptake inhibitors (SNRIs). Most older antidepressants, such as the tricyclic compounds amitriptyline, imipramine and clomipramine, have little specificity for any of the neurotransmitters fluoxetine, paroxetine, citalopram and a few others are specific for serotonin venlafaxine is a representative of the SNRIs. A more recent mixed-uptake inhibitor is mirtazepine, and some similar compounds are about to be launched. 

Residential treatment appeared the most likely way of making an impact on Carl s crack cocaine use, and plans were made for an admission. This could not happen immediately, and in the meantime Carl was prescribed fluoxetine 20mg per day, and diazepam 20-30mg per day. He was keen to try to withdraw himself from crack without going into hospital, and he and his mother were instructed about his use of the two medications. They were advised that diazepam would reduce anxiety and agitation, and might help relieve craving for crack. 

The prototype SSRI, fluoxetine, differs from other SSRIs in some important respects (Table 30-1). Fluoxetine is metabolized to an active product, norfluoxetine, which may have plasma concentrations greater than those of fluoxetine. The elimination half-life of norfluoxetine is about three times longer than fluoxetine and contributes to the longest half-life of all the SSRIs. As a result, fluoxetine has to be discontinued 4 weeks or longer before an MAOI can be administered to mitigate the risk of serotonin syndrome. 

Some naturally occurring neurotransmitters may be similar to drugs we use. For example, it is well known that the brain makes its own morphine (i.e., beta endorphin), and its own marijuana (i.e., anandamide). The brain may even make its own antidepressants, it own anxiolytics, and its own hallucinogens. Drugs often mimic the brain s natural neurotransmitters. Often, drugs are discovered prior to the natural neurotransmitter. Thus, we knew about morphine before the discovery of beta-endorphin marijuana before the discovery of cannabinoid receptors and anandamide the benzodiazepines diazepam (Valium) and alprazolam (Xanax) before the discovery of benzodiazepine receptors and the antidepressants amitriptyline (Elavil) and fluoxetine (Prozac) before the discovery of the serotonin transporter site. This un-... 

---