The P-I-E-N-O Parkinsn's List Drug Database
sertraline / ZoloftTM
ANTIDEPRESSANT:
SSRI: LOW RISK
Description: Sertraline is an oral antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) type. It is similar to fluoxetine and paroxetine. Like these drugs, sertraline is structurally distinct from tricyclic antidepressants and monoamine oxidase inhibitors. Sertraline has one active metabolite and the lowest potential for drug interactions involving CYP2D6 (cytochrome P-450 isoenzyme 2D6) of the SSRIs. Sertraline has also been used in the treatment of obsessive-compulsive disorder (OCD). Sertraline was approved by the FDA in December 1991 for the treatment of major depression. As of May 1995, sertraline is undergoing FDA review for treatment of OCD.
Mechanism of Action: Sertraline potentiates serotonin (5-HT) in the CNS. Sertraline does not affect norepinephrine as do many tricyclic antidepressants. The precise action of SSRIs is not fully understood, but it is believed that sertraline and related agents inhibit reuptake of serotonin at the neuronal membrane. SSRIs have less sedative, anticholinergic, and cardiovascular effects than do the tricyclic antidepressant drugs due to dramatically decreased binding to histamine, acetylcholine, and norepinephrine receptors. Monoamine oxidase is not inhibited by any of the SSRIs. Anticholinergic activity is virtually absent.
Pharmacokinetics: Sertraline is administered orally and is well absorbed following oral administration. The extent of absorption may be somewhat increased by administration with food; the peak concentration may be increased by 25%, and the time taken to attain peak concentration decreased from about 85.5 hours, if administered with food. Sertraline appears to be highly protein-bound (98%), but it does not compete with warfarin or propranolol for binding sites, possibly because its presumed binding site is ›A-acid glycoprotein and not albumin.
Metabolism appears to be hepatic, with first-pass metabolism and minimal renal excretion of unchanged drug. Steady-state levels are achieved after 1 week of normal daily dosage. The elimination half-life is approximately 26 hours. Dosage adjustments are recommended for patients with mild, stable cirrhosis due to the half-life increase from 22 to 52 hours following a single dose.
CONTRAINDICATIONS/PRECAUTIONS: Sertraline should be used with caution in patients with a history of seizure disorders, as well as in debilitated patients or those taking multiple medications, because of the possibility of drug-induced seizure.
Sertraline's effects during electroconvulsive therapy (ECT) have not been evaluated in clinical studies to date. Some clinicians have reported that in rare instances the induced seizure was prolonged in the presence of another SSRI (fluoxetine). Seizures have not been reported during therapy with sertraline, despite overdoses as high as 6,000 mg.
All effective antidepressants can transform depression into mania in predisposed individuals. The usual presentation of this switch is the sudden appearance of insomnia. The antidepressant should be held and appropriate therapy to treat the manic symptoms initiated. Therapeutic doses of lithium (and possibly carbamazepine or valproate) are effective in suppressing the switch process. All antidepressants should be used with caution in depressed patients because of the possibility of suicidal ideation. Close monitoring of the patient is essential during the initial stages of therapy and sertraline prescribed in the smallest quantity consistent with good management.
Sertraline should be used with caution in patients with hepatic disease or severe cardiac disease because metabolism can be delayed. Sertraline half-life can be prolonged from 22 to 52 hours in patients with cirrhosis. Increased plasma levels are obtained after normal doses, and dosage reductions are recommended. The pharmacokinetics of sertraline in patients with renal disease have not been investigated. Either lower doses or a longer dosing interval may be necessary.
Sertraline should be used with caution in patients with severe renal disease because excretion of metabolites can be reduced. Lower doses or less frequent dosing may be necessary.
Sertraline can cause a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) that presents as hypoosmolarity of serum and urine, and hyponatremia. Elderly patients and those receiving diuretics appear to be more at risk.
Patients with diabetes mellitus should be treated with caution because sertraline can dysregulate glucose control. Dose adjustments of hypoglycemics may be necessary.
Sertraline should be used with caution in breast-feeding mothers because of the possibility of excretion of the drug into breast milk. Patients should advise their physician of their intention to breast-feed. Because of its slow elimination, consideration should be given to the possible presence of the drug for a prolonged period after discontinuation of therapy.
Sertraline can cause weight loss. It should be used with caution is patients where weight loss is undesirable.
Sertraline should be used cautiously during pregnancy because full evaluation of its effects has not been undertaken. Sertraline is classified as FDA category B.
DRUG INTERACTIONS: Sertraline potentiates serotonin by inhibiting its neuronal reuptake. Since serotonin is deaminated by monoamine oxidase type A, administration of drugs that can inhibit this enzyme concurrently with sertraline can lead to a serious reaction known as "serotonin syndrome." This reaction may include confusion, seizures, and severe hypertension as well as less severe symptoms. Most MAOIs are non-specific inhibitors of MAO (e.g., furazolidone, pargyline, phenelzine, tranylcypromine) and, since they affect MAO type A, should not be used with sertraline. In addition, selegiline, although selective for MAO type B at usual doses, may inhibit MAO type A at higher doses and should also be avoided in patients receiving sertraline. Finally, procarbazine, an antineoplastic agent, is a weak MAOI and should also be avoided. At least 2 weeks should elapse between the discontinuation of MAOI therapy and the start of sertraline therapy, or vice versa.
Sertraline impairs metabolism of the CYP2D6 (cytochrome P-450 isoenzyme 2D6) pathway at therapeutic doses. This can cause substantial increases in concentrations of other antidepressants metabolized via the same pathway. Plasma concentrations of tricyclic antidepressants, maprotiline, and trazodone can double when used concomitantly with sertraline. Concomitant use of trazodone with sertraline can lead to excessive sedation and unstable gait. When tricyclic antidepressants (amitriptyline, nortriptyline, imipramine, desipramine) have been used concomitantly with sertraline, symptoms of tricyclic toxicity (such as sedation, decreased energy, lightheadedness, psychomotor retardation, xerostomia, constipation, and memory impairment) have been reported. The clinical need for antidepressant polypharmacy is unknown, and it should be undertaken only after careful consideration of alternatives and with careful monitoring.
Sertraline impairs metabolism of the CYP2D6 (cytochrome P-450 isoenzyme 2D6) pathway at therapeutic doses. This can cause substantial increases in concentrations of benzodiazepines metabolized via the same pathway. Fluoxetine, a related agent, has been reported to affect the clearance and plasma concentrations of alprazolam and diazepam, but it had no effect on clonazepam or triazolam. The effects of sertraline on these benzodiazepines are not known.
Sertraline impairs metabolism of the CYP2D6 (cytochrome P-450 isoenzyme 2D6) pathway at therapeutic doses. This can cause substantial increases in concentrations of antipsychotics metabolized via the same pathway. Sertraline can increase the possible risk of adverse effects if used with haloperidol, loxapine, molindone, phenothiazines, pimozide, or thiothixene.
Sertraline decreased the clearance of tolbutamide by 16%. Sertraline did not appear to alter either the protein binding or volume of distribution of tolbutamide. The interaction is believed to be metabolic. Patients should be monitored for increased effects of these drugs if used concomitantly.
Atenolol's œ-adrenergic blocking activity was not altered by the addition of sertraline. The effect of atenolol on sertraline was not evaluated.
Sertraline should be used with caution with other highly proteinbound drugs because it also is a highly protein-bound drug (98%); one highly protein-bound drug can displace the other from their binding sites, leading to increased plasma levels and possible toxicity. Because sertraline is a base, however, it is more likely to bind to ›A-acid glycoprotein than to albumin.
Although no data are available, it is possible that inhibitors of hepatic enzymes such as cimetidine may affect sertraline pharmacokinetics. A significant interaction with cimetidine has been identified for paroxetine, a related agent; sertraline may be similarly affected by cimetidine. Until more data are available, cimetidine should be used cautiously in patients receiving sertraline.
Sertraline can increase the anticoagulant effects of warfarin if used concomitantly. Increases in prothrombin time of 8% have been recorded (p<0.02). Patients should be monitored closely.
While another SSRI (fluoxetine) can increase or decrease lithium concentrations, two doses of sertraline have been shown not to significantly alter lithium concentrations or clearance. Close monitoring of lithium concentrations is advisable, particularly before steady-state has been achieved. Inadequate lithium concentrations (<0.6 mEq/L) can precipitate a conversion to mania in bipolar patients.
Sertraline used concomitantly with tryptophan can cause "serotonin syndrome" (presenting as agitation, restlessness, aggressive behavior, insomnia, poor concentration, headache, paresthesia, incoordination, worsening of obsessive thoughts or compulsive behaviors, nausea, abdominal cramps, diarrhea, palpitations, or chills). Discontinuation of tryptophan usually resolves symptoms. Since sumatriptan is also an agonist at serotonin receptors, it is theoretically possible that a similar reaction could occur if sumatriptran was administered to patients receiving this type of antidepressant.
Cyproheptadine is an antagonist of serotonin in the CNS, and this pharmacologic action opposes the pharmacologic actions of sertraline. Clinically, cyproheptadine reportedly has interfered with the antidepressant and anti-bulimia actions of fluoxetine, an agent related to sertraline, but more data are needed to confim a direct drug-drug interaction. Ondansetron, granisetron, and methysergide also antagonize serotonin (5-HT) receptors, although no drug-drug interactions have been reported with sertraline.
ADVERSE REACTIONS: Insomnia is the most commonly observed CNS adverse effect, occurring in ~16% of patients treated with sertraline; although this is a common symptoms associated with depression. Somnolence, drowsiness, dizziness, tremor, fatigue, and agitation were observed in 6-13% of patients treated with sertraline. Headache was observed in ~20% of patients treated with sertraline, although this rate was almost equal to the placebo group. Approximately 4% of patients report blurred vision.
All effective antidepressants can precipitate a conversion from depression to mania in predisposed individuals. The usual presentation of this switch is the sudden appearance of insomnia. The antidepressant should be held and appropriate therapy to treat the manic symptoms initiated. Therapeutic doses of lithium (and possibly carbamazepine or valproate) are effective in suppressing the switch process.
Gastrointestinal adverse effects are the most problematic adverse effects of serotonin in routine clinical practice. Nausea/vomiting is the most commonly observed, occurring in ~26% of patients treated with sertraline. Diarrhea and xerostomia were observed to occur in 16-18% of sertraline patients. Constipation, dyspepsia, anorexia, and abdominal cramps were observed in 2-8% of patients treated with sertraline. Dysguesia was reported in 1% of patients.
Elevated hepatic enzymes have been reported in approximately 1% of patients during sertraline therapy. Enzyme elevations are assymptomatic, usually occurring within the first 1-9 weeks of therapy.
Angina was observed in ~1% of patients treated with sertraline, although the placebo rate (~2%) was higher than the active treatment group. Palpitations occurred in ~4% of patients treated with sertraline.
Rash (including maculopapular rash, bullous rash) was seen in ~2% of patients treated with sertraline. Other dermatologic effects that occur less frequently include alopecia, xerosis, erythema, photosensitivity, and pruritus, although a causal relationship can not be determined. Diaphoresis has been reported in 8% of patients receiving sertraline.
Sexual dysfunction primarily ejaculation dysfunction (ejaculatory delay ) and orgasm dysfunction (anorgasmia) was observed in ~16% of men and ~2% of women treated with sertraline.
Hyponatremia has been reported with sertraline. Hyponatremia may be associated with transient SIADH. Most cases of hyponatremia were in elderly patients and/or patients on diuretics or who were otherwise volume depleted. This effects appears to be reversible after discontinuation of sertraline.
PATIENT INFORMATION:
What do sertraline tablets do?
Sertraline (ZoloftTM ) is an antidepressant. It helps lift your spirits by treating your depression. Sertraline is one of a new group of medicines that are chemically different from other medicines used for treating depression. If other antidepressants have not helped relieve depression, sertraline may help. Patients who show a good response to sertraline after 8 weeks therapy can continue for a further 8 weeks. Generic sertraline tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take sertraline?
They need to know if you have any of these conditions:
How should I take this medicine?
Take sertraline tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking except on your doctor's advice.
Special precautions for use in children:
This medicine is not for children.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If you miss a dose that you normally take at bedtime to avoid daytime drowsiness and loss of mental alertness, it may be better to miss that dose. Follow your doctor's advice on missed doses. Do not take double or extra doses.
Which other medicines may interact with sertraline?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking sertraline?
Serious side effects with sertraline include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with sertraline include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take sertraline?
Visit your doctor for regular checks on your progress. Continue to take your tablets even if you do not immediately feel better. It can take about 4 weeks before you feel the full effect of sertraline. If you get suicidal thoughts call your doctor at once. If you are going to have surgery, tell your doctor or dentist that you are taking sertraline.
If you have been taking sertraline regularly for some time, do not suddenly stop taking it. You must gradually reduce the dose or your symptoms may get worse. Ask your doctor for advice. Even after you stop taking sertraline it can still affect your body for several weeks; continue to heed all warnings.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how sertraline affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol may interfere with the effect of sertraline. Avoid alcoholic drinks.
Do not treat yourself for coughs, colds or allergies without asking your doctor or pharmacist for advice. Some ingredients can increase possible side effects.
Your mouth may get dry. Chewing sugarless gum or sucking hard candy, and drinking plenty of water will help.
Where can I keep my medicine? Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Throw away any unused medicine after the expiration date.
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