Sertraline hydrochloride is an orally administered selective serotonin reuptake inhibitor (SSRI) antidepressant. It is prescribed for depression and a number of anxiety disorders, including social anxiety disorder (SAD), post-traumatic stress disorder (PTSD), panic disorder, obsessive-compulsive disorder (OCD), and premenstrual dysphoric disorder (PMDD) in adults over age 18. As well, it is approved for OCD in children and adolescents aged 6-17.
The FDA approved the drug, manufactured by Pfizer, for depression in 1992, for OCD in 1996, for PMDD in 2002, and for SAD in 2003.
The mode of action of Zoloft is believed to be linked to its inhibition of CNS neuronal uptake of serotonin. Clinical trials at relevant doses in humans have demonstrated that sertraline blocks the uptake of serotonin into human platelets.
The chronic use of sertraline was found in animals to down-regulate brain norepinephrine receptors, as with other drugs for treating depressive disorder (MDD). Sertraline does not inhibit monoamine oxidase.
Indications and Dosage:
Sertraline is indicated for the treatment of MDD in adults. The efficacy of the drug in treating a major depressive episode was established in six- to eight-week trials of adult outpatients whose diagnoses corresponded to the DSM-III category of MDD.
A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with day-to-day functioning (nearly every day for at least 2 weeks). An episode should include at least 4 of the following symptoms: change in sleep habits, change in appetite, psychomotor agitation or retardation, loss of interest in usual activities or decreased sex drive, increased fatigue, feelings of worthlessness or guilt, slowed thinking or impaired concentration, and suicidal thoughts or behavior.
The initial dose of Zoloft should be administered for MDD and OCD at a dose of 50mg/day, once daily.
For panic disorder, PTSD and SAD, treatment should be initiated with a dose of 25mg/day, once daily. After one week, the dose should be increased to 50mg/day, once daily.
Patients not responding to 50mg/day may benefit from increases up to a maximum of 200mg/day. Given the rapid elimination half-life of Zoloft (24 hours), changes in dosage should not occur at intervals of less than 1 week.
In patients suffering from PMDD, initial treatment should begin with a dose of 50mg/day, either daily throughout the menstrual cycle or limited to the luteal phase of the cycle, depending on the doctor’s assessment. Those not responding to the 50mg/day treatment, benefit may be seen with increases (at 50mg increments/menstrual cycle) up to 150mg/day when dosing throughout the menstrual cycle, or 100mg/day when dosing during the luteal phase of the menstrual cycle. If a 100mg/day dose has been established with luteal phase dosing, a 50mg/day titration step for three days should be utilized at the beginning of each luteal phase dosing period.
Zoloft should be given once a daily, either in the morning or evening.
In children and adolescents, Zoloft should be initially administered with a 25mg/day dose in children ages 6-12, and a once daily dose of 50mg for adolescents age 13-17. Patients not responding may benefit from dose increases up to a maximum of 200mg/day. For children with OCD, their generally lower body weights should be taken into consideration when increasing the dosage, in order to avoid excess dosing. Given the 24 hour elimination half-life of sertraline, dose changes should not occur at intervals of less than 1 week.
Zoloft can have a number of adverse side effects, including asthenia (a feeling of weakness without an actual loss in strength), diarrhea, gas, headache, indigestion, pain, rash, sore throat, tingling sensations, vomiting, problems with vision, insomnia, gastrointestinal disturbances, confusion, dizziness, tremors, delayed ejaculation in men (anorgasmia), and decreased sex drive. It can induce mania or hypomania in a small percentage of individuals. It has also been known to cause minor weight loss.
Less common or rare side effects reported include acne, breast pain or enlargement, fainting, double vision, dry or painful eyes, lightheadedness when standing from a sitting or supine position, difficulties breathing, allergic reaction, altered taste sensation, back pain, changeable emotions, difficulty swallowing, cold clammy skin, cataracts, chest pain, fever, fluid retention, flushing, increased salivation, increased libido, inability to stay seated, hearing problems, frequent urination, hair loss, heart attack, general malaise, hot flushes, low blood pressure, migraine, kidney failure lack of coordination, nasal inflammation, hemorrhoids, hiccups, glaucoma, lack of sensation, light sensitivity, increased salivation, inflammation of the penis, depersonalization (an “unreal” feeling), abnormal dreams/thoughts, hallucinations, paranoia, rapid mood swings, tooth-grinding, worsening of depressive symptoms, memory loss, nosebleed, increased urination at night, ringing in the ears, racing heartbeat, rectal hemorrhage, respiratory infection, skin inflammation or eruptions, edema of the wrists or ankles, irregular heartbeat, twitching, yawn, sleepwalking and vaginal hemorrhage or discharge.
Due to the fact that sertraline is tightly bound to plasma protein, the use of Zoloft in patients taking another drug which is tightly bound to protein, such as digitoxin or warfarin, may cause a shift in plasma concentrations potentially resulting in an adverse effect. Conversely, adverse effects can result from displacement of protein bound Zoloft in other tightly bound drugs.
Patients taking sertraline should not drink alcohol during treatment. Over-the-counter (OTC) remedies should be used with caution. Though none is known to interact with Zoloft, interactions remain a possibility.
Concomitant use of Zoloft with other drugs may produce an increase , decrease or alteration in the effects of either drug. It is especially important to consult your physician before combining sertraline with the following:
- Cimetidine (Tagamet)
- Diazepam (Valium)
- Digitoxin (Crystodigin)
- Flecainide (Tambocor)
- Lithium (Eskalith, Lithobid)
- MAOIs (Nardil, Parnate)
- Other serotonin-boosting drugs like Prozac or Paxil
- Other antidepressants such as Serzone and Elavil
- Propafenone (Rythmol)
- Warfarin (Coumadin)
- Sumatriptan (Imitrex)
- Tolbutamide (Orinase)
If you are taking the oral concentrate form of Zoloft, do not take disulfiram (Antabuse).
Information for Parents and Kids:
Zoloft’s effects during pregnancy have not been adequately studied. For women who are pregnant or may become pregnant, the drug should only be taken during pregnancy if a clear need is established. It is unknown whether Zoloft is found in breast milk, and thus, caution should be exercised when using Zoloft during breastfeeding.
Pregnant women exposed to Zoloft (and other SSRIs or SNRIs) late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. When treating pregnant women with Zoloft in their third trimester, the physician should carefully weigh the potential risks and benefits of treatment. The doctor may consider tapering Zoloft dosage in the third trimester.
In June 2003, the UK banned sertraline for use in children under 18 after studies indicated a link to increasing suicidal rates. Similar concern has been expressed widely in the US, where only fluoxetine (another SSRI) has been officially banned by the FDA for treating depression in minors. However, because the antidepressant-suicide link is correlational, researchers do not know if the increased risk of suicide for those taking antidepressants occurs because the drugs make people suicidal, if suicide occurs because the drugs un-depress people enough to motivate them to actually commit suicide (a popular theory), or because of a third, as yet unknown factor.
Safety and efficacy of sertraline has not been established for children under 6 years of age.
Warnings and Precautions:
Individuals with MDD (both adult and pediatric) may experience worsening of their depression and/or the development of suicidal ideation and behavior or unusual changes in behavior, whether or not they are using antidepressants. There has long been concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients. Antidepressants increased the risk of suicidal thoughts and action in short-term studies in children and adolescents with MDD and other psychiatric ailments.
All pediatric patients taking antidepressants for any indication should be closely observed for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial stages of treatment, or at times of dose changes, either increases or decreases.
Adults with MDD or co-morbid depression in the setting of other psychiatric conditions should be observed similarly for worsening depression and suicidality, especially during the initial stages of drug therapy, or at times of dose changes, either increases or decreases.
Such symptoms as agitation, anxiety, panic attacks, insomnia, irritability, hostility/aggressiveness, impulsivity, hypomania, psychomotor restlessness and mania have been reported in adult and pediatric patients with MDD who have been treated with antidepressants, as well as for other indications, both psychiatric and non-psychiatric. Though no causal link has been established between the emergence of such symptoms and either worsening depression or the emergence of suicidal impulses, there is concern that such symptoms may be precursors to emerging suicidality.
If a decision is made to discontinue Zoloft treatment, the medication should be tapered, as rapidly as is feasible, but while recognizing that abrupt cessation may produce or be linked to certain adverse reactions.
Clinical studies of the use of Zoloft in elderly patients indicate that in persons with MDD, there doesn’t appear to be any overall difference in the pattern of adverse reactions to those reported by younger patients. As with all medications, greater sensitivity of some older persons cannot be ruled out. The only standout difference was the occurrence of urinary tract infection in a percentage of elderly subjects.
As with other SSRIs, sertraline has been associated with cases of clinically significant hyponatremia in the elderly.
Pre-marketing clinical experience with Zoloft did not uncover any tendency for drug-seeking behavior, dependence or withdrawal syndrome. As with any CNS active drug, however, physicians should carefully assess patients for history of drug abuse and observe such individuals closely for signs of misuse or abuse (e.g., development of tolerance, drug-seeking behavior, incrementation of dose).
Over-dosage & Contraindications:
As of 1999, of 1,027 cases of overdose involving sertraline worldwide, alone or in conjunction with other drugs, there were 72 deaths.
Among 634 cases in which sertraline was the only drug ingested, 8 overdoses resulted in fatal outcome, 75 completely recovered, and 27 patients experienced sequelae (a secondary consequence or condition as a result of the overdose) after overdosage to include decreased sex drive, alopecia, difficulty ejaculating (men), fatigue, diarrhea, insomnia, drowsiness (somnolence) and serotonin syndrome. The remaining 524 cases had an undetermined outcome. The most common signs and symptoms seen with non-fatal sertraline overdose were somnolence, vomiting, tachycardia (rapid heartbeat), dizziness, agitation, tremor and nausea.
The largest known ingestion was 13.5 grams in a patient who took Zoloft alone and subsequently recovered. However, another patient who ingested 2.5 grams of sertraline alone experienced a fatal outcome.
Other important adverse occurrences associated with Zoloft overdose (alone or with other drugs) include coma, convulsions, delirium, bradycardia (unusually slow heartbeat), serotonin syndrome, stupor, manic reaction, pancreatitis, hallucinations, hypotension (low blood pressure), hypertension (high blood pressure) and syncope (blackout).
In managing Zoloft overdose treatment should consist of those general measures employed in the management of overdosage of any antidepressant.
An adequate airway should be maintained, along with oxygenation and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients.
Activated charcoal should be administered. Due to this drug’s large volume of distribution, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to have benefit. There are no known antidotes for sertraline.
In managing overdosage, the possibility of multiple-drug ingestion should be kept in mind. The physician may consider contacting a poison control center when treating an overdose.
Concomitant use in patients taking MAOIs is contraindicated. Use of Zoloft in conjunction with pimozide is not recommended. The drug is also contraindicated in patients exhibiting a hypersensitivity to sertraline or any of its active ingredients.
The oral concentration of Zoloft is contraindicated with Antabuse (disulfiram) due to the concentrate’s alcohol content.
Generic Name: sertraline
Chemical Formula: C17H17NCl2•HCl
Routes of Administration: oral
Elimination Half Life: 26 hours
Legal Status: by prescription only