Comparison of Selective Serotonin Reuptake Inhibitors (SSRIs)
Efficacy and effectiveness
Clinical trials comparing one SSRI with another indicate that drugs in this class are equally efficacious. Each antidepressant produces approximately a 60% overall response rate (ie, at least a 50% reduction in symptoms as a result of treatment). However, some differences in the SSRIs efficacy exist.
Escitalopram may be superior in efficacy compared with other SSRIs in the treatment of major depressive disorder2. Also escitalopram has better efficacy in the treatment of severe depression than citalopram4. A major consideration with escitalopram is that it is not yet available in lower-cost generic form. The drug is still under patent. In 2006 Forest Laboratories was granted an 828 day (2 years and 3 months) extension on its patent for escitalopram31. This pushed the patent expiry from December 7, 2009 to March 14, 2012.
Paroxetine, fluoxetine, and sertraline are similar in effectiveness for major depression and depression with high levels of anxiety3,5.
Paroxetine is the only SSRI indicated for all five anxiety disorders in addition to major depressive disorder.
Fluoxetine has a slower onset of antidepressants effect than other SSRIs4. Also, fluoxetine appears to be somewhat less effective, than other drugs in this class24,25.
Sertraline may have a slightly higher rate of response than fluoxetine and paroxetine26. Sertraline has advantages over paroxetine in the treatment of panic disorder27.
Interesting and important fact is that SSRI antidepressants are not interchangeable. Persons who discontinue one SSRI for lack of tolerability or response can be effectively treated with another19.
Discontinuation symptoms (withdrawal)
SSRIs aren’t considered addictive. YET !! However, stopping treatment abruptly or missing several doses can cause withdrawal-like symptoms, including nausea, headache, dizziness, lethargy and flu-like symptoms. This is sometimes called discontinuation syndrome.
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 symptoms10.
Abrupt interruption of antidepressant therapy for 5-8 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 fluoxetine12.
All SSRIs (except paroxetine) are classified as pregnancy Category C, meaning that they may not be safe for use during pregnancy.
Paroxetine (Paxil, Paxil CR) is pregnancy Category D medication. Paroxetine may cause heart defects or serious, life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy.
Selective serotonin reuptake inhibitors differ in their potency and selectivity in inhibiting serotonin reuptake and there may be important effects on other transporters and receptors, indicating that they are not as selective as their manufacturers suggest. It has been proposed, for example, that fluoxetine’s effects on 5-HT2C receptors may underlie a propensity to cause agitation; paroxetine’s affinity for muscarinic receptors causes its increased tendency to produce discontinuation effects; sertraline’s affinity for the dopamine transporter results in a greater efficacy in severe depression; and sertraline’s and fluvoxamine’s affinity for sigma1 opioid receptors is responsible for their efficacy in psychotic depression (Goodnick & Goldstein, 1998a).
The half-life of a drug is the time required to achieve 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 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 2-4 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 treatment discontinuation and makes it easier to discontinue 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 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. In men, the half-life is approximately 30% shorter (22.4 hr) than in females or the elderly (32.1-36.7 hr).
- Celexa Prescribing Information Celexa.com, Forest Pharmaceuticals, Inc.
- Lexapro Prescribing Information Lexapro.com, Forest Pharmaceuticals, Inc.
- Paxil Prescribing Information – Paxil.com, GlaxoSmithKline
- Prozac Prescribing Information Prozac.com, Eli Lilly and Company
- Zoloft Prescribing Information – Zoloft.com, Pfizer Inc.
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Published: May 05, 2007
Last updated: August, 2009