Zoloft Side Effects - chronicle Of Ssris - Selective Serotonin Reuptake Inhibitors
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The most principal class of antidepressants marketed in up-to-date years is the selective serotonin reuptake inhibitors (Ssris). The six Ssris ready in the United States are citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). The traditional uses for the Ssris comprise unipolar and bipolar major depression and all of the anxiety disorders. However, controlled trials also maintain the use of Ssris in the medicine of other psychiatric disorders together with dysthymia, premenstrual dysphoria, bulimia nervosa, obesity, borderline personality disorder, alcoholism, rheumatic pain, and throbbing head headache.
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Among the Ssris, there are more similarities than differences. Although all Ssri drugs have the same the mechanism of action, each Ssri has a slightly distinct pharmacological and pharmacokinetic characteristics. This leads to differences among the Ssris in their half-lives, clinical activity, side effects, and drug interactions. There are differences in the middle of Ssris that could be clinically significant.
The first drug in the Ssri class was Prozac (Fluoxetine), which hit the United States shop in 1987. Prozac was Fda beloved on December 29, 1987. It is man-made by Eli Lilly and Company.
Zoloft (Sertraline hydrochloride) was the second Ssri to come to shop in the United States, and it was beloved by the Fda on December 30, 1991. Zoloft is man-made by Pfizer Inc.
Paxil (Paroxetine hydrochloride) was the third Ssri to come to shop in the United States and was beloved by the Fda on December 29, 1992. Paxil is man-made by GlaxoSmithKline.
Luvox (Fluvoxamine maleate) was the next Ssri Fda beloved on December 05, 1994. However, now its marketing status is "Discontinued".
Celexa (Citalopram hydrobromide) was beloved by the Fda on July 17, 1998. Celexa is man-made by Forest Pharmaceuticals, Inc.
Lexapro (Escitalopram oxalate) is the newest and most selective of the Ssris beloved by the Fda on August 14, 2002. Lexapro is man-made by Forest Pharmaceuticals, Inc. Lexapro is a cleaner, improved version of Celexa.
Mechanism of action
The brain communicates with itself through the use of special chemicals called neurotransmitters, such as serotonin and norepinephrine. Neurotransmitters carry signals from one nerve cell to another. Low levels of serotonin and norepinephrine have not been proven to cause depression but it widely believed that elevation of these chemicals is associated with revision in mood in depressed people.
All Ssris have the same general mechanism of action. Ssris seem to comfort symptoms of depression by blocking the reabsorption (reuptake) of serotonin by obvious nerve cells in the brain. This leaves more serotonin available, which enhances neurotransmission (sending of nerve impulses) and improves mood. In due course, the levels of natural serotonin will rise again, and in some instances the Ssri can be reduced and withdrawn.
Approved indications and uses
Ssris have been primarily used for the medicine of depression and have been studied for several indications covering of depression.
Celexa (Citalopram) is indicated for the medicine of:
depression
Lexapro (Escitalopram) is indicated for the medicine of:
major depressive disorder
generalized anxiety disorder (Gad)
Paxil (Paroxetine) is indicated for the medicine of:
major depressive disorder
obsessive compulsive disorder (Ocd)
panic disorder
communal anxiety disorder
generalized anxiety disorder
posttraumatic stress disorder (Ptsd)
Prozac (Fluoxetine) is indicated for the medicine of:
major depressive disorder
obsessive-compulsive disorder
moderate to severe bulimia nervosa
panic disorder
in January 2003, Prozac was beloved by the Fda for the medicine of depression and Ocd in children and adolescents who are 7 to 17 years of age.
Zoloft (Sertraline) is indicated for the medicine of:
major depressive disorder
obsessive-compulsive disorder
panic disorder
posttraumatic stress disorder
premenstrual dysphoric disorder (Pmdd) in adults (newest indication)
communal anxiety disorder
Efficacy
Clinical trials comparing an Ssri with someone else Ssri indicate that drugs in this class are equally efficacious. Each Ssri produces approximately a 60% overall response rate (ie, at least a 50% allowance in symptoms as a succeed of treatment).
Adverse reactions & side effects
While Ssris do not appear to differ in overall tolerability, the reported incidences of exact adverse effects vary. Adverse effects that patients palpate are commonly mild to moderate and do not want dose reductions or discontinuation. Ssris possess the following adverse effects:
Nausea. The most coomon side succeed accociated with use of Ssris is nausea. Paroxetine and sertraline have been associated with slightly more cases of nausea.
Sexual dysfunction. Depression itself may cause sexual dysfunction and all Ssris have been associated with sexual dysfunction during therapy in men and women. There may be lesser detrimental succeed on sexual function by fluoxetine compared to other agents. Citalopram has been associated with loss of libido. Paroxetine appears to cause the top rate of sexual dysfunction.
Anticholinergic effects. Paroxetine causes a higher rate of anticholinergic effects, such as dry mouth, constipation, and cognitive disruption, compared with other Ssris. These effects may be particularly difficult to tolerate for elderly or concomitantly medically ill patients.
Weight. The Ssris vary in their succeed on the weight. Sertraline is ordinarily associated with a small degree of weight loss in the acute phase of treatment, whereas paroxetine can cause weight gain after long-term treatment. Fluoxetine has the most potent appetite-suppressing effects in the short term and produces a greater degree of weight loss than paroxetine, sertraline, citalopram, or escitalopram.
Diarrhea. Sertraline and fluoxetine are more often associated with diarrhea, paroxetine has a lower incidence.
Anxiety, agitation, insomnia. Fluoxetine has been associated with top rate of anxiety and agitation. Escitalopram and paroxatine are less likely to cause insomnia than fluoxetine and sertraline.
Dry mouth. Citalopram and paroxetine are more likely to cause dry mouth than escitalopram and fluoxetine.
Drowsiness, fatigue. Paroxetine has been associated with top rate of drowsiness, somnolence than other Ssris.
Headache. Sertraline and fluoxetine are associated with higher level of headache.
In some cases, antidepressants may be associated with worsening symptoms of depression or suicidal thoughts or behavior, particularly early in medicine or when you change your dosage. Be sure to talk to your physician about any changes in your symptoms. You may need more true monitoring at the beginning of medicine or upon a change in treatment, or you may need to stop the medication if your symptoms worsen.
Pharmacokinetics
Some of the key differences among Ssris are due to differences in their pharmacokinetic properties. The only pharmacokinetic parameters shared by all the Ssris is that they are relatively slowly, but completely, absorbed from the gut. They differ with regard to their protein binding, metabolism, half-lives, either they have linear or nonlinear pharmacokinetics, either they have active metabolites.
Half-life
The half-life of a drug is the time required to accomplish steady-state plasma concentrations (i.e., to metabolize half the dose and lower blood concentrations by 50%). Half-life can be used to estimate how long it will take to clear a drug from the body after medicine is discontinued.
Fluoxetine is unique because of its long half-life and the long half-life of its active metabolite norfluoxetine. Fluoxetine has a half-life of 4-6 days and its active metabolite, norfluoxetine, has a half-life of 4-16 days. In comparison, citalopram, escitalopram, paroxetine, and sertraline have shorter half-lives in the range of 20-35 hours, and steady-state concentrations (and therapeutic effect) are reached much more rapidly. The long half-life of fluoxetine may blunt the effects of missed doses or medicine discontinuation and makes it easier to end than any of the other Ssris. On the other hand, fluoxetine requires a much longer washout period than the other Ssris (several weeks), particularly when switching to monoamine oxidase inhibitors (Maois) or Tca.
Antidepressants with relatively short half-lives are desirable for population with complicated comorbidities and complex, multiple-drug regimens because they allow for once-daily dosing. A short half-life enables physicians to switch more rapidly and safely to an alternative antidepressant if medicine fails or if unfavorable drug reactions occur.
Linear and nonlinear pharmacokinetic.
One of the important differences to note among the Ssris is either their pharmacokinetic properties are linear or nonlinear.
Citalopram, escitalopram and sertraline show linear and dose-proportional pharmacokinetics. Plasma concentrations of these drugs are proportional to the daily dose administered and, therefore, predictable. In contrast, fluvoxamine, fluoxetine and paroxetine have nonlinear pharmacokinetics. Higher doses may yield much greater increases in plasma drug concentrations than would otherwise be expected. Thus, addition the dose of paroxetine or fluoxetine can succeed in disproportionate and unpredictable increases in plasma levels, half-lives, and adverse effects. Titration of fluoxetine and paroxetine doses may therefore be more difficult than with citalopram, escitalopram and sertraline.
Drug Interactions
The interaction in the middle of monoamine oxidase inhibitors (Maois) and Ssris is the most important drug interaction limiting Ssri use. This compound may lead to the improvement of a hyperserotonergic syndrome consisting of excitement, diaphoresis, rigidity, hyperthermia, tachycardia, hypertension, and perhaps death. The severity of this interaction necessitates at least 5 week washout when switching a patient from fluoxetine to an Maoi to allow unblemished elimination of the fluoxetine. At least 14 days should be allowed after stopping citalopram, escitalopram, paroxetine or sertraline before beginning an Maoi. This dissimilarity in washout time in the middle of fluoxetine and citalopram, escitalopram, paroxetine and sertraline when switching from an Ssri to an Maoi is one of the key differences in the middle of Ssris.
Citalopram, escitalopram and sertraline have the lowest possible for drug interactions among the Ssris. Citalopram should be avoided in patients likely to take overdoses. Sertraline would be preferable for cardiac patients taking beta blockers or type Ic antiarrhythmic agents.
Taking thioridazine with paroxetine or fluoxetine may cause serious heart problems.
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