By far the most significant variety of antidepressants marketed lately will be the selective serotonin reuptake inhibitors (SSRIs). The six SSRIs available in the u s an 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 throughout treatment of other psychiatric disorders including dysthymia, premenstrual dysphoria, bulimia nervosa, obesity, borderline personality disorder, alcoholism, painful joints, and migraine headache.
Among the many SSRIs, you can find 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 results in differences among the many SSRIs inside their half-lives, clinical activity, unwanted side effects, and drug interactions. You can find differences between SSRIs that might be clinically significant.
The initial drug throughout SSRI class was Prozac (Fluoxetine), which hit the usa market in 1987. Prozac was FDA approved on December 29, 1987. It really 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 was approved by 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 way of the FDA on December 29, 1992. Paxil is manufactured by GlaxoSmithKline.
Luvox (Fluvoxamine maleate) was succeeding SSRI FDA approved on December 05, 1994. However, at the moment 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 by the FDA on August 14, 2002. Lexapro is manufactured by Forest Pharmaceuticals, Inc. Lexapro is a cleaner, improved version of Celexa.
Mechanism of behavior
Brain health holds discourse 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 inside the brain. This leaves more serotonin available, which boosts neurotransmission (sending of nerve impulses) and improves mood. In due course, the amounts of natural serotonin will rise again, and in some instances the SSRI could possibly be reduced and withdrawn.
Approved indications and uses
SSRIs seem to have been primarily used for the treatment of depression and have been studied for a few indications beyond depression.
Celexa (Citalopram) is indicated of the treatment of:
sadness
Lexapro (Escitalopram) is indicated for remedy for:
major depressive conditions
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 youngsters and adolescents who will be 7 to 17 years aged.
Zoloft (Sertraline) is indicated for remedy for:
major a depressive disorder
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 due to treatment).
Unwanted symptoms & unwanted effects
While SSRIs don't look to differ in overall tolerability, the reported incidences of specific adverse effects vary. Adverse reactions 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 negative effect accociated with consumption of 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 with 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, for example 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 within the acute phase of treatment, whereas paroxetine may cause weight after long-term treatment. Fluoxetine gets the most potent appetite-suppressing effects inside the shortcut 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 usually tend to cause lack of saliva than escitalopram and fluoxetine.
Drowsiness, fatigue. Paroxetine has long been linked to highest rate of drowsiness, somnolence compared to other SSRIs.
Headache. Sertraline and fluoxetine are related to greater level of headache.
Often, antidepressants can be connected with worsening warning signs depression or suicidal thoughts or behavior, particularly early in treatment or after you alter dosage. Be sure you converse with your doctor about any changes in the symptoms. It is necessary to have more careful monitoring firstly 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 in 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 on their protein binding, metabolism, half-lives, if they have linear or nonlinear pharmacokinetics, whether or not they have active metabolites.
Half-life
The half-life of your drug is the duration required to achieve steady-state plasma concentrations (i.e., to metabolize half the dose and lower blood concentrations by 50%). Half-life work extremely well to estimate how long it will take to clear a drug from the body after treatment is discontinued.
Fluoxetine is exclusive for it's long half-life along with the long half-life of its active metabolite norfluoxetine. Fluoxetine has a half-life of 4-6 days and your active metabolite, norfluoxetine, consists of a half-life of 4-16 days. Compared, citalopram, escitalopram, paroxetine, and sertraline have shorter half-lives in the varieties of 20-35 hours, and steady-state concentrations (and therapeutic effect) are reached additional rapidly. The long half-life of fluoxetine may blunt the effects of missed doses or treatment discontinuation and makes it better to discontinue than any of the other SSRIs. On the other hand, fluoxetine requires an anymore washout period in comparison to the other SSRIs (a couple of weeks), particularly when switching to monoamine oxidase inhibitors (MAOIs) or TCA.
Antidepressants with relatively short half-lives are desirable to people with multiple comorbidities and splendid, multiple-drug regimens basically because they encourage once-daily dosing. Short half-life enables physicians to modify much quicker and safely to a substitute antidepressant if treatment fails or if unfavorable drug reactions occur.
Linear and nonlinear pharmacokinetic.
Among the many important differences to make note of among the many SSRIs is actually their pharmacokinetic properties are linear or nonlinear.
Citalopram, escitalopram and sertraline show linear and dose-proportional pharmacokinetics. Plasma concentrations of those drugs are proportional to the daily dose administered and, therefore, predictable. In contrast, 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 cause disproportionate and unpredictable increases in plasma levels, half-lives, and adverse effects. Titration of fluoxetine and paroxetine doses may therefore be more difficult when compared to citalopram, escitalopram and sertraline.
Drug Interactions
The interaction between monoamine oxidase inhibitors (MAOIs) and SSRIs is a vital drug interaction limiting SSRI use. This combination may lead towards the development of a hyperserotonergic syndrome being made of excitement, diaphoresis, rigidity, hyperthermia, tachycardia, hypertension, and possibly death. The severity of this interaction necessitates a minimum of 5 week washout when switching a person from fluoxetine to an MAOI to help complete elimination of a typical fluoxetine. Not less than 14 days really should be allowed after stopping citalopram, escitalopram, paroxetine or sertraline before you begin an MAOI. This difference in washout time between fluoxetine and citalopram, escitalopram, paroxetine and sertraline when switching from an SSRI to an MAOI is one of the key differences between SSRIs.
Author Resource:-
Citalopram, escitalopram and sertraline side effects of Sertraline hold the lowest potential for drug interactions among the SSRIs. Citalopram should be avoided in patients more likely to take overdoses. Sertraline would be Nexium side effectspreferable for cardiac patients taking beta blockers or type IC antiarrhythmic agents.
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