How do Zoloft and Sertraline differ
Depression - New Serotonin Reuptake Inhibitors: Low Risk of Interactions with Sertraline
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The specific serotonin reuptake inhibitor (SSRI) sertraline recently received approval as an antidepressant in Germany. Sertraline is sold by the Pfizer company as Zoloft® and in cooperation with the Boehringer Ingelheim company as Gladem®. As Prof. Walter E. Müller (Frankfurt) explained, SSRIs have a high specificity for serotonergic receptors. The lack of or little interaction with other receptor systems results in better tolerability and lower toxicity of SSRIs compared to classic tricyclic antidepressants.
For sertraline, the ratio of serotonin to noradrenaline reuptake inhibition is 840. Only citalopram, at 3,400, is even more selective than sertraline. The selectivity factor for fluoxetine is 54, for fluvoxamine 160 and for paroxetine 280.
Sertraline does not have any relevant interactions with other receptors. The antagonistic effect on the sigma receptor, which causes a slight neuroleptic effect, may be advantageous. Overall, there are no functionally significant differences between the various SSRIs. However, some pharmacokinetic differences are clinically relevant, as Müller emphasized.
The half-life of sertraline is around 25 hours. Clinically at steady state, the metabolite desmethyl sertraline is only responsible for a small proportion of the serotonin reuptake inhibition of ten percent. Thus, sertraline is a well controllable substance. It takes about one week to reach steady state or to wash out of the plasma after discontinuation of the medication.
With some other SSRIs, the already longer half-life in steady state is extended even further due to the potent and long-lasting effect of the metabolite. Weeks pass by, and you have to wait, for example, if you want to use an MAO inhibitor.
The low risk of interactions for sertraline is clinically advantageous. It is due to the fact that sertraline hardly interacts with various cytochrome P450 isoenzymes. Fluoxetine and paroxetine, for example, significantly inhibit the isoenzyme 2D6, via which, among other things, tricyclic antidepressants, haloperidol, beta blockers or propafenone are metabolized. In contrast, sertraline only slightly blocks this isoenzyme.
Fluoxetine also significantly inhibits other isoenzymes such as 2C9 and 2C10, via which, for example, phenytoin and tolbutamine are metabolized. Fluvoxamine in turn inhibits the isoenzymes 1A2 and 2C19, via which tricyclic antidepressants, clozapine, propranolol, theophylline, hexobarbital, diazepam or propranolol are metabolized. Sertraline has been evaluated in more than 25 clinical studies, including 20 double-blind controlled studies, in a total of over 12,000 patients. Doses of 50 mg, 100 mg and 200 mg sertraline once daily showed the same therapeutic efficacy in studies with fixed doses. Overall, it can be concluded that sertraline is at least as effective as other SSRIs or tricyclic antidepressants. Older patients or patients with severe depression also respond well to the substance. Tolerance is no worse in older patients than in younger ones. This is a significant advantage over tricyclics, which are usually less tolerated by older patients.
In preventing recurrence, sertraline is at least as effective as tricyclic antidepressants. The effect of 50 mg in acute maintenance therapy corresponds to that of 20 mg fluoxetine. However, fluoxetine more often leads to activating side effects such as anxiety, restlessness and insomnia.
In two German studies on inpatients and outpatients with major depression, sertraline was just as effective as amitriptyline, but significantly better tolerated, as reported by the head of the study, Prof. Hans-Jürgen Müller (Munich).
Dr. med. Angelika Bischoff
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