Journal of Family Practice - Do antidepressant medications relieve chronic low back pain?
Depression is frequently undertreated, This is unfortunate, since 70 to 80 percent of patients with this common debilitating illness respond to treatment.[1] Because depression is a biologically heterogeneous group of illnesses, rather than a single disease, patients respond differently to different drugs.
Serotonin reuptake inhibitors such as fluoxetine (Prozac) and sertraline (Zoloft) have become part of the medical armamentarium for the treatment of depression. They have joined other drugs that are used to treat depression, including monoamine oxidase inhibitors (MAOIs), lithium, methylphenidate (Ritalin), trazodone (Desyrel), bupropion (Wellbutrin) and the tricyclic antidepressants.
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After fluoxetine, tricyclic agents are the most commonly prescribed antidepressants, and they are the standard against which new drugs are measured. When the highest acceptable dose of the initial drug is not effective or when that drug produces intolerable side effects, it is often possible to achieve a satisfactory response by trying a different drug or a combination of drugs. In this situation, sertraline may be the drug of choice.
Mechanism of Action
The mechanism of action of all antidepressants is unknown. In depression, the principal biochemical abnormality appears to be impaired metabolism of one or more central amines or peptide neurotransmitters and their receptor sites.
Sertraline inhibits the reuptake of serotonin and, thus, increases the concentration of this neurotransmitter in the central nervous system. In contrast, tricyclic antidepressants and MAOIs not only increase the concentration of serotonin in the central nervous system, but they also increase the levels of norepinephrine and dopamine.
Pharmacokinetics
Sertraline is more than 97 percent bound to serum protein in rats and dogs.[2,3] Little information is available on the distribution of this drug in humans.
Based on the data from animal studies,[2,3] it appears that sertraline undergoes extensive first-pass metabolism in the liver, resulting in a much less potent desmethyl metabolite. No information has been published on the route of excretion of sertraline and its metabolites, beyond the fact that in animal studies no unchanged drug has been found in the bile or urine.
Blood levels of sertraline peak five to eight hours after an oral dose. The half-life of this drug is approximately 24 hours. With continued daily dosing, the steady state concentration is reached in one week. In comparison, the steady-state concentration of fluoxetine is not achieved until the drug has been taken daily for three weeks.
Dosage
Sertraline is available in 50- and 100-mg scored tablets, and the starting dosage is 25 to 50 mg per day. As necessary, the dosage can be increased, up to a maximum of 200 mg per day. However, the daily dose should not be increased more than once a week. The wholesale costs of sertraline and other antidepressants are fisted in Table 1. [TABULAR DATA 1 OMITTED]
Clinical Use
DEPRESSION
In both double-blind and placebo-controlled studies,[1,4] sertraline was found to be as effective as amitriptyline in the treatment of depression. Both the amitriptyline group and the sertraline group had an equal number of patients who withdrew because of intolerable side effects. ultracet. However, among those who continued in the study, the amitriptyline group had a significantly greater incidence of side effects.
In separate studies,[4,5] sertraline was well tolerated and was effective in elderly patients with depression. When the drug was given to a healthy group of elderly volunteers for nine days, it was found to have no effect on psychomotor performance.[6] In another study,[7] sertraline was found to have no electrocardiographic effects. Because of its low side-effect profile, sertraline may be the best choice in selected elderly patients.
Sertraline has not been tested in pregnant women, nursing mothers or children; therefore, its use is not advised in these populations. Since there have been no published studies on sertraline therapy in patients with renal or hepatic disease, the drug should be used cautiously in these groups and patients should be closely monitored.
Seizures can occur in patients who are being treated with tricyclic antidepressants or MAOIs. There have been no reports of seizures associated with the administration of sertraline; however, patients with known seizure disorders were excluded from the clinical trials.
According to information from the manufacturer, sertraline has been shown to interact with drugs such as digoxin (Lanoxin) and warfarin (Coumadin, Panwarfin). These drugs are highly bound to protein, and coadministration with sertraline increases their effect. Similar effects can be expected when sertraline is administered with any drug that binds extensively to protein. Conversely, highly protein-bound drugs can increase the effects and side effects of sertraline. Sertraline also decreases the clearance of tolbutamide (Orinase) and diazepam (Valium).
