Paxil activating or sedating. Comparison of Selective Serotonin Reuptake Inhibitors (SSRIs).



Paxil activating or sedating

Paxil activating or sedating

Antidepressants have some different pharmacological characteristics, this means that patients may respond differently to certain SSRIs or experience different side effects with different drugs. Paroxetine and sertraline have been associated with slightly more cases of nausea.

Sexual dysfunction The SSRIs as a class produce a variety of sexual side effects, including anorgasmia, decreased libido, impotence, and delayed ejaculation. Analysis of the clinical trials suggests that fluvoxamine and fluoxetine are less likely to produce sexual side effects than paroxetine and sertraline. Paroxetine appears to cause the highest rate of sexual dysfunction.

Citalopram has been associated with loss of libido and may be associated with a relatively higher level of sexual dysfunction compared with sertraline. The SSRIs are reported to cause sexual dysfunction in the following descending order of frequency: Paroxetine produces more delay of orgasm or ejaculation than fluvoxamine, fluoxetine and sertraline Weight gain Weight gain is another troubling side effect. The SSRIs vary in their effect on the weight.

Fluoxetine and sertraline have the lowest incidence of weight gain during long-term treatment, paroxetine and citalopram higher Paroxetine may cause a significant weight increase, sertraline may cause modest but nonsignificant weight increase with long-term treatment Of the SSRIs, paroxetine may be responsible for the highest risk of weight gain 9.

Sertraline is generally associated with a small degree of weight loss in the acute phase of treatment. Fluoxetine has potent appetite suppressing effects and may cause modest but nonsignificant weight decrease Predictors for antidepressant-induced weight gain Family history of obesity genetic factors Lower levels of educational attainment Low body mass index at the beginning of antidepressant therapy Effects on sleep SSRIs interfere with sleep architecture.

Fluoxetine, paroxetine, and sertraline delay the onset of REM sleep, and fluoxetine and paroxetine increase awakenings and reduce REM sleep, slow-wave sleep, total sleep time, and sleep efficiency.

In contrast, sertraline minimally increases sleep efficiency and reduces nocturnal wakefulness time, which may benefit depressed patients with sleep disturbances Anticholinergic effects Paroxetine, like the TCAs desipramine and imipramine, has an in vitro affinity for the muscarinic cholinergic receptor.

As a result, 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.

Diarrhea Sertraline and fluoxetine are more frequently associated with diarrhea due to their greater specificity for serotonin receptors, while paroxetine has a lower incidence because of its antimuscarinic effects.

Recently, sertraline has been shown to cause statistically significantly more diarrhea than other SSRIs 7. Anxiety, agitation, insomnia Fluoxetine has been associated with highest rate of anxiety and agitation 1. Escitalopram and paroxetine are less likely to cause insomnia than fluoxetine and sertraline. Escitalopram and citalopram have been associated with low rates of insomnia, anxiety, and other activating side effects.

However, if SSRI-induced agitation has previously occurred, then fluoxetine may not be the drug of choice. Dry mouth Citalopram and paroxetine are more likely to cause dry mouth than escitalopram and fluoxetine. Drowsiness, fatigue Paroxetine has been associated with highest rate of drowsiness, somnolence than other SSRIs.

Headache Sertraline and fluoxetine are associated with higher level of headache. Discontinuation symptoms withdrawal SSRIs aren't considered addictive. However, stopping treatment abruptly or missing several doses can cause discontinuation syndrome accompanied by withdrawal symptoms, including nausea, headache, dizziness, lethargy and flu-like symptoms.

All antidepressants do not have the same type or severity of withdrawal symptoms. Discontinuation syndrome is more common with the SSRIs with shorter half lives and inactive metabolites, such as paroxetine, sertraline, and fluvoxamine.

The incidence of discontinuation syndrome is highest with paroxetine followed by fluvoxamine and sertraline.

Citalopram and fluoxetine have a lower occurrence of withdrawal symptoms Abrupt interruption of antidepressant therapy for days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline, with few symptoms seen with fluoxetine Pregnancy category All SSRIs except paroxetine are classified as pregnancy Category C, meaning that they may not be safe for use during pregnancy. Paroxetine may cause heart defects or serious, life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy.

Drug interactions Marked differences exist between the SSRIs with regard to effects on specific CYP enzymes and, thus, the likelihood of clinically important pharmacokinetic drug-drug interactions. The potency of the SSRIs as inhibitors of the metabolism of the PP2-D6 varies and is reported in descending order of potency as paroxetine, fluoxetine, sertraline, citalopram, and fluvoxamine.

Paroxetine is the most potent inhibitor of the cytochrome P 2D6 enzyme of all antidepressants Fluoxetine and paroxetine are more likely to cause P drug interactions than citalopram and sertraline, particularly in combination with medications metabolized by or inhibiting the cytochrome P 2D6 isoenzyme e. Drug interactions with clinical consequences usually involve combinations of an SSRI with other psychotropics, especially monoamine oxidase inhibitors MAOIs and tricyclic antidepressants, clozapine, lithium, methadone, etc.

This combination may lead to the development of a hyperserotonergic syndrome consisting of excitement, diaphoresis, rigidity, hyperthermia, tachycardia, hypertension, and possibly death.

The severity of this interaction necessitates at least 5 week washout when switching a patient from fluoxetine to an MAOI to allow complete elimination of the fluoxetine. At least 14 days should be allowed after stopping citalopram, escitalopram, paroxetine or sertraline before starting an MAOI. Sertraline, citalopram and escitalopram have the lowest potential for drug interactions among the SSRIs, and are to be preferred in patients on other drugs for general medical conditions or if consideration is given to adding an SSRI to other psychotropic medication.

Initial treatment with fluoxetine or paroxetine may not be preferred for patients in whom a potential for a clinically significant drug-drug interaction exists. Half-life The half-life of a drug is the time required to achieve steady-state plasma concentrations i. Half-life can be used to estimate how long it will take to clear a drug from the body after treatment 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 days and its active metabolite, norfluoxetine, has a half-life of days. In comparison, citalopram, escitalopram, paroxetine, and sertraline have shorter half-lives in the range of 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 treatment discontinuation and makes it easier to discontinue than any of the other SSRIs. Antidepressants with relatively short half-lives are desirable for people with multiple 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 treatment fails or if unfavorable drug reactions occur. Paroxetine and fluvoxamine are more quickly cleared from the body than the other SSRIs. The possible slower onset of antidepressant action of fluoxetine may be owing to a longer time taken to achieve therapeutic plasma concentrations.

In situations where the speed of onset of therapeutic effect is particularly important, such as in severe depression, fluoxetine may not be the SSRI of choice. Patients in whom the long half-life may have advantages and therefore for whom fluoxetine should be considered include those who are poorly compliant and those in whom administration less frequent than daily is contemplated. Sertraline exhibits a sex- and age-dependent half-life. Linear and nonlinear pharmacokinetic One of the important differences to note among the SSRIs is whether their pharmacokinetic properties are linear or nonlinear.

Citalopram, escitalopram and sertraline show linear and dose-proportional pharmacokinetics changes in drug concentration proportional to the change in dose. Plasma concentrations of these drugs are proportional to the daily dose administered and, therefore, predictable. In contrast, fluvoxamine, fluoxetine and paroxetine have non-linear 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 ADEs. Titration of fluoxetine and paroxetine doses may therefore be more difficult than with citalopram, escitalopram and sertraline. Advertisement Protein binding Fluoxetine, paroxetine and sertraline are highly protein bound.

What is the best SSRI? Balancing benefits, side effects, cost Head-to-head comparisons:

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Premature Ejaculation, Antidepressants & Sexual Dysfunction, Sex Drive & Drugs



Paxil activating or sedating

Antidepressants have some different pharmacological characteristics, this means that patients may respond differently to certain SSRIs or experience different side effects with different drugs. Paroxetine and sertraline have been associated with slightly more cases of nausea. Sexual dysfunction The SSRIs as a class produce a variety of sexual side effects, including anorgasmia, decreased libido, impotence, and delayed ejaculation.

Analysis of the clinical trials suggests that fluvoxamine and fluoxetine are less likely to produce sexual side effects than paroxetine and sertraline. Paroxetine appears to cause the highest rate of sexual dysfunction. Citalopram has been associated with loss of libido and may be associated with a relatively higher level of sexual dysfunction compared with sertraline.

The SSRIs are reported to cause sexual dysfunction in the following descending order of frequency: Paroxetine produces more delay of orgasm or ejaculation than fluvoxamine, fluoxetine and sertraline Weight gain Weight gain is another troubling side effect. The SSRIs vary in their effect on the weight. Fluoxetine and sertraline have the lowest incidence of weight gain during long-term treatment, paroxetine and citalopram higher Paroxetine may cause a significant weight increase, sertraline may cause modest but nonsignificant weight increase with long-term treatment Of the SSRIs, paroxetine may be responsible for the highest risk of weight gain 9.

Sertraline is generally associated with a small degree of weight loss in the acute phase of treatment. Fluoxetine has potent appetite suppressing effects and may cause modest but nonsignificant weight decrease Predictors for antidepressant-induced weight gain Family history of obesity genetic factors Lower levels of educational attainment Low body mass index at the beginning of antidepressant therapy Effects on sleep SSRIs interfere with sleep architecture. Fluoxetine, paroxetine, and sertraline delay the onset of REM sleep, and fluoxetine and paroxetine increase awakenings and reduce REM sleep, slow-wave sleep, total sleep time, and sleep efficiency.

In contrast, sertraline minimally increases sleep efficiency and reduces nocturnal wakefulness time, which may benefit depressed patients with sleep disturbances Anticholinergic effects Paroxetine, like the TCAs desipramine and imipramine, has an in vitro affinity for the muscarinic cholinergic receptor. As a result, 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. Diarrhea Sertraline and fluoxetine are more frequently associated with diarrhea due to their greater specificity for serotonin receptors, while paroxetine has a lower incidence because of its antimuscarinic effects. Recently, sertraline has been shown to cause statistically significantly more diarrhea than other SSRIs 7. Anxiety, agitation, insomnia Fluoxetine has been associated with highest rate of anxiety and agitation 1.

Escitalopram and paroxetine are less likely to cause insomnia than fluoxetine and sertraline. Escitalopram and citalopram have been associated with low rates of insomnia, anxiety, and other activating side effects. However, if SSRI-induced agitation has previously occurred, then fluoxetine may not be the drug of choice.

Dry mouth Citalopram and paroxetine are more likely to cause dry mouth than escitalopram and fluoxetine. Drowsiness, fatigue Paroxetine has been associated with highest rate of drowsiness, somnolence than other SSRIs. Headache Sertraline and fluoxetine are associated with higher level of headache.

Discontinuation symptoms withdrawal SSRIs aren't considered addictive. However, stopping treatment abruptly or missing several doses can cause discontinuation syndrome accompanied by withdrawal symptoms, including nausea, headache, dizziness, lethargy and flu-like symptoms. All antidepressants do not have the same type or severity of withdrawal symptoms.

Discontinuation syndrome is more common with the SSRIs with shorter half lives and inactive metabolites, such as paroxetine, sertraline, and fluvoxamine.

The incidence of discontinuation syndrome is highest with paroxetine followed by fluvoxamine and sertraline. Citalopram and fluoxetine have a lower occurrence of withdrawal symptoms Abrupt interruption of antidepressant therapy for days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline, with few symptoms seen with fluoxetine Pregnancy category All SSRIs except paroxetine are classified as pregnancy Category C, meaning that they may not be safe for use during pregnancy.

Paroxetine may cause heart defects or serious, life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy.

Drug interactions Marked differences exist between the SSRIs with regard to effects on specific CYP enzymes and, thus, the likelihood of clinically important pharmacokinetic drug-drug interactions. The potency of the SSRIs as inhibitors of the metabolism of the PP2-D6 varies and is reported in descending order of potency as paroxetine, fluoxetine, sertraline, citalopram, and fluvoxamine. Paroxetine is the most potent inhibitor of the cytochrome P 2D6 enzyme of all antidepressants Fluoxetine and paroxetine are more likely to cause P drug interactions than citalopram and sertraline, particularly in combination with medications metabolized by or inhibiting the cytochrome P 2D6 isoenzyme e.

Drug interactions with clinical consequences usually involve combinations of an SSRI with other psychotropics, especially monoamine oxidase inhibitors MAOIs and tricyclic antidepressants, clozapine, lithium, methadone, etc. This combination may lead to the development of a hyperserotonergic syndrome consisting of excitement, diaphoresis, rigidity, hyperthermia, tachycardia, hypertension, and possibly death. The severity of this interaction necessitates at least 5 week washout when switching a patient from fluoxetine to an MAOI to allow complete elimination of the fluoxetine.

At least 14 days should be allowed after stopping citalopram, escitalopram, paroxetine or sertraline before starting an MAOI.

Sertraline, citalopram and escitalopram have the lowest potential for drug interactions among the SSRIs, and are to be preferred in patients on other drugs for general medical conditions or if consideration is given to adding an SSRI to other psychotropic medication. Initial treatment with fluoxetine or paroxetine may not be preferred for patients in whom a potential for a clinically significant drug-drug interaction exists.

Half-life The half-life of a drug is the time required to achieve steady-state plasma concentrations i. Half-life can be used to estimate how long it will take to clear a drug from the body after treatment 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 days and its active metabolite, norfluoxetine, has a half-life of days. In comparison, citalopram, escitalopram, paroxetine, and sertraline have shorter half-lives in the range of 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 treatment discontinuation and makes it easier to discontinue than any of the other SSRIs. Antidepressants with relatively short half-lives are desirable for people with multiple 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 treatment fails or if unfavorable drug reactions occur.

Paroxetine and fluvoxamine are more quickly cleared from the body than the other SSRIs. The possible slower onset of antidepressant action of fluoxetine may be owing to a longer time taken to achieve therapeutic plasma concentrations. In situations where the speed of onset of therapeutic effect is particularly important, such as in severe depression, fluoxetine may not be the SSRI of choice. Patients in whom the long half-life may have advantages and therefore for whom fluoxetine should be considered include those who are poorly compliant and those in whom administration less frequent than daily is contemplated.

Sertraline exhibits a sex- and age-dependent half-life. Linear and nonlinear pharmacokinetic One of the important differences to note among the SSRIs is whether their pharmacokinetic properties are linear or nonlinear. Citalopram, escitalopram and sertraline show linear and dose-proportional pharmacokinetics changes in drug concentration proportional to the change in dose. Plasma concentrations of these drugs are proportional to the daily dose administered and, therefore, predictable.

In contrast, fluvoxamine, fluoxetine and paroxetine have non-linear 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 ADEs.

Titration of fluoxetine and paroxetine doses may therefore be more difficult than with citalopram, escitalopram and sertraline. Advertisement Protein binding Fluoxetine, paroxetine and sertraline are highly protein bound. What is the best SSRI? Balancing benefits, side effects, cost Head-to-head comparisons:

Paxil activating or sedating

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