By far the most significant variety of antidepressants marketed lately will probably be the selective serotonin reuptake inhibitors (SSRIs). The six SSRIs featured in the United States are citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). The most important applications of the SSRIs include unipolar and bipolar major depression and all of the anxiety disorders. However, controlled trials also support the consumption of SSRIs in the treatment of other psychiatric disorders including dysthymia, premenstrual dysphoria, bulimia nervosa, obesity, borderline personality disorder, alcoholism, painful joints, and migraine headache.
Among the list of SSRIs, there exists more similarities than differences. Although all SSRI drugs hold the same the mechanism of action, each SSRI has a slightly different pharmacological and pharmacokinetic characteristics. This encourages differences among the list of SSRIs inside their half-lives, clinical activity, unwanted side effects, and drug interactions. There exists differences between SSRIs that might be clinically significant.
The initial drug in the SSRI class was Prozac (Fluoxetine), which hit the usa market in 1987. Prozac was FDA approved on December 29, 1987. It truly is manufactured by Eli Lilly and Company.
Zoloft (Sertraline hydrochloride) was the 2nd SSRI to come back to market in the United States, and it also was approved from the FDA on December 30, 1991. Zoloft is manufactured by Pfizer Inc.
Paxil (Paroxetine hydrochloride) was the third SSRI to come to market in america and was approved by the FDA on December 29, 1992. Paxil is manufactured by GlaxoSmithKline.
Luvox (Fluvoxamine maleate) was succeeding SSRI FDA approved on December 05, 1994. However, now its marketing status is "Discontinued".
Celexa (Citalopram hydrobromide) was approved because of the FDA on July 17, 1998. Celexa is manufactured by Forest Pharmaceuticals, Inc.
Lexapro (Escitalopram oxalate) will probably be the newest and more selective of the SSRIs approved from the FDA on August 14, 2002. Lexapro is manufactured by Forest Pharmaceuticals, Inc. Lexapro is really a cleaner, improved version of Celexa.
Mechanism of behavior
Brain health exchanges data with itself with the use of special chemicals called neurotransmitters, such as serotonin and norepinephrine. Neurotransmitters carry signals from one nerve cell to a different one. Low levels of serotonin and norepinephrine have not been confirmed to cause depression but it surely widely believed that elevation of those chemicals is associated with improvement in mood in depressed people.
All SSRIs have the same general mechanism of action. SSRIs even try to relieve warning signs depression by blocking the reabsorption (reuptake) of serotonin by certain nerve cells throughout brain. This leaves more serotonin available, which improves neurotransmission (sending of nerve impulses) and improves mood. In the end, the amounts of natural serotonin will rise again, as well as in some instances the SSRI can be reduced and withdrawn.
Approved indications and uses
SSRIs seem to have been primarily used for treating depression and have been studied for some indications beyond depression.
Celexa (Citalopram) is indicated of the treatment of:
gloom
Lexapro (Escitalopram) is indicated for remedy for:
major a depressive condition
generalized anxiety disorder (GAD)
Paxil (Paroxetine) is indicated for your remedy for:
major depressive conditions
obsessive compulsive disorder (OCD)
panic disorder
sad (social anxiety disorder)
generalized anxiety disorder
posttraumatic stress disorder (PTSD)
Prozac (Fluoxetine) is indicated for the remedy for:
major depressive conditions
obsessive-compulsive disorder
moderate to severe bulimia nervosa
panic disorder
in January 2003, Prozac was approved from the FDA for remedy for depression and OCD in children and adolescents who definitely are 7 to 17 years aged.
Zoloft (Sertraline) is indicated for remedy for:
major depressive conditions
obsessive-compulsive disorder
panic disorder
posttraumatic stress disorder
premenstrual dysphoric disorder (PMDD) in grown-ups (newest indication)
social anxiety disorder
Efficacy
Clinical trials comparing an SSRI with another SSRI implies that drugs inside this class are equally efficacious. Each SSRI produces approximately a 60% overall response rate (ie, at least a 50% reduction in symptoms because of treatment).
Unwanted symptoms & unwanted effects
While SSRIs don't look to differ in overall tolerability, the reported incidences of specific adverse effects vary. Uncomfortable side effects that patients experience are frequently mild to moderate and don't require dose reductions or discontinuation. SSRIs possess the following uncomfortable side effects:
Nausea. The foremost coomon symptom accociated with by using SSRIs is nausea. Paroxetine and sertraline seem to have been linked to a bit more cases of nausea.
Sexual dysfunction. Depression itself may cause impotence and all SSRIs are actually associated with impotence during therapy in ladies and men. There might be lesser detrimental effect on sexual function by fluoxetine compared to other agents. Citalopram is connected with lack of libido. Paroxetine tends to make the highest rate of ed.
Anticholinergic effects. Paroxetine causes a higher rate of anticholinergic effects, similar to sandpaper throat, constipation, and cognitive disruption, when compared with other SSRIs. These effects could be particularly difficulties tolerate for elderly or concomitantly medically ill patients.
Weight. The SSRIs vary throughout their effect on the weight. Sertraline is usually involved with a quantity of weight loss inside the acute phase of treatment, whereas paroxetine may cause weight gain after long-term treatment. Fluoxetine has the most potent appetite-suppressing effects inside the shorter term and produces a greater degree of weight loss than paroxetine, sertraline, citalopram, or escitalopram.
Diarrhea. Sertraline and fluoxetine are usually more frequently associated with diarrhea, paroxetine uses a lower incidence.
Anxiety, agitation, insomnia. Fluoxetine continues to be involved with highest rate of hysteria and agitation. Escitalopram and paroxatine are more unlikely to cause insomnia than fluoxetine and sertraline.
Lack of saliva. Citalopram and paroxetine will probably cause sandpaper throat than escitalopram and fluoxetine.
Drowsiness, fatigue. Paroxetine has been involved with highest rate of drowsiness, somnolence compared to other SSRIs.
Headache. Sertraline and fluoxetine are related to greater level of headache.
Often, antidepressants might be connected with worsening indicators of depression or suicidal thoughts or behavior, particularly early in treatment or if you improve dosage. Be sure you converse with your doctor about any changes in the symptoms. It is necessary to have more careful monitoring at the beginning of treatment or on the change in treatment, and you may have to end clonazepam (klonopin) if your symptoms worsen.
Pharmacokinetics
A few of the key differences among SSRIs are set to differences with their pharmacokinetic properties. The one pharmacokinetic parameters shared by all of the SSRIs would be that they are relatively slowly, but completely, absorbed that came from the gut. They differ with regard to their protein binding, metabolism, half-lives, whether they have linear or nonlinear pharmacokinetics, in the event that they have active metabolites.
Half-life
The half-life of the drug is the time essential to achieve steady-state plasma concentrations (i.e., to metabolize half the dose and lower blood concentrations by 50%). Half-life can be utilized to estimate the length of time it involves clear a drug out of your body after treatment is discontinued.
Fluoxetine is different because of its long half-life and the long half-life of that active metabolite norfluoxetine. Fluoxetine uses a half-life of 4-6 days and also its particular active metabolite, norfluoxetine, has a half-life of 4-16 days. In contrast, citalopram, escitalopram, paroxetine, and sertraline have shorter half-lives within the variations of 20-35 hours, and steady-state concentrations (and therapeutic effect) are reached considerably more rapidly. The long half-life of fluoxetine may blunt the results of missed doses or treatment discontinuation and also makes it easier to discontinue than any one of the other SSRIs. However, fluoxetine requires a for much longer washout period compared to the other SSRIs (a few weeks), especially when switching to monoamine oxidase inhibitors (MAOIs) or TCA.
Antidepressants with relatively short half-lives are desirable for people with multiple comorbidities and opulent, multiple-drug regimens because they enable once-daily dosing. A short half-life enables physicians to exchange more rapidly and safely to another antidepressant if treatment fails or if unfavorable drug reactions occur.
Linear and nonlinear pharmacokinetic.
Among the important differences to note among the list of SSRIs is whether their pharmacokinetic properties are linear or nonlinear.
Citalopram, escitalopram and sertraline show linear and dose-proportional pharmacokinetics. Plasma concentrations of them drugs are proportional to your daily dose administered and, therefore, predictable. On the flip side, fluvoxamine, fluoxetine and paroxetine have nonlinear pharmacokinetics. Higher doses may produce much greater increases in plasma drug concentrations than would otherwise be expected. Thus, increasing the dose of paroxetine or fluoxetine can result in disproportionate and unpredictable increases in plasma levels, half-lives, and adverse reactions. Titration of fluoxetine and paroxetine doses may therefore be a bit more difficult compared to citalopram, escitalopram and sertraline.
Drug Activities
The interaction between monoamine oxidase inhibitors (MAOIs) and SSRIs is the main drug interaction limiting SSRI use. This mixture may lead to the development of a hyperserotonergic syndrome being inclusive of excitement, diaphoresis, rigidity, hyperthermia, tachycardia, hypertension, and possibly death. The severity of the interaction necessitates not less than 5 week washout when switching a patient from fluoxetine to an MAOI to let complete elimination of many fluoxetine. A minimum of 14 days should be allowed after stopping citalopram, escitalopram, paroxetine or sertraline before starting an MAOI. This difference in washout time between fluoxetine and citalopram, escitalopram, paroxetine and sertraline when switching because of an SSRI to an MAOI is definitely one of the key differences between SSRIs.
Author Resource:-
Citalopram, escitalopram and sertraline Sertraline side effects have the lowest potential for drug interactions among the list of SSRIs. Citalopram really should be avoided in patients about to take overdoses. Sertraline will be side effects of Nexiumpreferable for cardiac patients taking beta blockers or type IC antiarrhythmic agents.
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