The foremost 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 utilization 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 develop the same the mechanism of action, each SSRI consists of 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 across the usa, 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 the United States 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. Low manner of serotonin and norepinephrine have not been confirmed to cause depression but it surely widely identified that elevation of these chemicals is associated with improvement in mood in depressed people.
All SSRIs hold the same general mechanism of action. SSRIs tend to relieve symptoms of 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 applies
SSRIs have already been primarily utilised 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 treatment of:
major depressive conditions
generalized anxiety disorder (GAD)
Paxil (Paroxetine) is indicated for your remedy for:
major a depressive disorder
obsessive compulsive disorder (OCD)
panic disorder
social anxiety disorder (sad)
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 by 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 your treatment of:
major a depressive disorder
obsessive-compulsive disorder
panic disorder
posttraumatic stress disorder
premenstrual dysphoric disorder (PMDD) in grown-ups (newest indication)
sad (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).
Side effects & unwanted effects
While SSRIs don't look to differ in overall tolerability, the reported incidences of specific uncomfortable side 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 seem to have been connected with erectile dysfunction during therapy in ladies and men. There could be lesser detrimental effect on sexual function by fluoxetine compared with other agents. Citalopram is connected with lack of libido. Paroxetine seems to make the highest rate of impotence.
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 might 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 weightloss 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 more frequently connected 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.
Dry mouth. 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 linked with greater level of headache.
Often, antidepressants can be connected with worsening warning signs depression or suicidal thoughts or behavior, particularly at the outset of treatment or after you alter dosage. Be sure you converse with your doctor about any changes within your symptoms. Yopu must 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 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 as a result of its long half-life and also the long half-life of its active metabolite norfluoxetine. Fluoxetine has a half-life of 4-6 days and your active metabolite, norfluoxetine, uses a half-life of 4-16 days. Compared, citalopram, escitalopram, paroxetine, and sertraline have shorter half-lives throughout range of 20-35 hours, and steady-state concentrations (and therapeutic effect) are reached additional rapidly. The long half-life of fluoxetine may blunt the outcome of missed doses or treatment discontinuation and makes it better to discontinue than any of the other SSRIs. Nevertheless, fluoxetine requires an anymore washout period in comparison to the other SSRIs (a couple of weeks), specially when switching to monoamine oxidase inhibitors (MAOIs) or TCA.
Antidepressants with relatively short half-lives are desirable to people with multiple comorbidities and luxurious, multiple-drug regimens basically because they allow for once-daily dosing. A quick half-life enables physicians to change 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 document among the 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. As opposed, 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 may end up in disproportionate and unpredictable increases in plasma levels, half-lives, and adverse effects. Titration of fluoxetine and paroxetine doses may therefore being more difficult when compared to citalopram, escitalopram and sertraline.
Drug Interactions
The interaction between monoamine oxidase inhibitors (MAOIs) and SSRIs is the most important drug interaction limiting SSRI use. This concoction can lead to your development of a hyperserotonergic syndrome being made of excitement, diaphoresis, rigidity, hyperthermia, tachycardia, hypertension, and possibly death. The severity with this interaction necessitates a minimum of 5 week washout when switching a person from fluoxetine to an MAOI to help complete elimination of your fluoxetine. Not less than 14 days really should be allowed after stopping citalopram, escitalopram, paroxetine or sertraline before you start an MAOI. This difference in washout time between fluoxetine and citalopram, escitalopram, paroxetine and sertraline when switching from an SSRI to an MAOI can be one of the key differences between SSRIs.
Author Resource:-
Citalopram, escitalopram and sertraline side effects of Sertraline develop the lowest potential for drug interactions on the list of SSRIs. Citalopram should really be avoided in patients prone to take overdoses. Sertraline could be Nexium side effectspreferable for cardiac patients taking beta blockers or type IC antiarrhythmic agents.
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