Zoloft (sertraline) vs. Paxil (paroxetine): What's the difference?
- Zoloft (sertraline) and Paxil (paroxetine) are selective serotonin reuptake inhibitor (SSRI) type antidepressants used to treat depression, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder (PMDD).
- Zoloft is also used to treat panic disorder.
- Side effects of Zoloft and Paxil that are similar include drowsiness/sleepiness, sleep problems (insomnia), nausea, constipation, loss of appetite, headache, diarrhea, dry mouth, and increased sweating.
- Side effects of Zoloft that are different from Paxil include nervousness, dizziness, tremor, skin rash, upset stomach, abnormal ejaculation, decreased interest in sexual activity, and weight loss.
- Side effects of Paxil that are different from Zoloft include anxiety and weakness.
- Do not stop using Zoloft or Paxil suddenly, or you could have unpleasant withdrawal symptoms.
What are Zoloft and Paxil?
Zoloft (sertraline) is a selective serotonin reuptake inhibitor (SSRI) type antidepressant used to treat depression, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), social anxiety disorder, panic disorder, and premenstrual dysphoric disorder (PMDD). Other SSRIs include paroxetine (Brisdelle, Paxil, Paxil CR, Pexeva), citalopram (Celexa), fluoxetine (Prozac, Sarafem), and fluvoxamine (Luvox CR). Experts believe depression may be caused by disturbances in the balance between serotonin and other neurotransmitters. Drugs such as Zoloft may restore the chemical balance among neurotransmitters in the brain. SSRIs block the reuptake of serotonin, therefore changing the level of serotonin in the brain. A serotonin balance is reached between attachment to the nearby nerves and reuptake.
Paxil (paroxetine) is a selective serotonin reuptake inhibitor (SSRI) antidepressant used to treat depression, OCD, PTSD, PMDD, and social anxiety disorder. Other SSRIs include fluoxetine (Prozac), citalopram (Celexa), and sertraline (Zoloft). Paxil affects the neurotransmitter serotonin in the brain. Many experts believe an imbalance among neurotransmitters is the cause of depression. Paxil works by preventing the reuptake of serotonin by nerve cells after it has been released. Since reuptake is an important mechanism for removing released neurotransmitters and terminating their actions on adjacent nerves, the reduced uptake caused by Paxil increases free serotonin that stimulates nerve cells in the brain.

QUESTION
Depression is a(n) __________ . See AnswerWhat are the side effects of Zoloft and Paxil?
Zoloft
WARNING
- As demonstrated in short-term studies, antidepressants increased the risk of suicidal thinking and behavior (suicidality) in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of Zoloft or any other antidepressant in a child or adolescent must balance this risk with the clinical need for the antidepressant. Patients who are started on therapy should be closely observed for clinical worsening, suicidal thoughts, or unusual changes in behavior.
The most common side effects of Zoloft are:
- Sleepiness
- Nervousness
- Insomnia
- Dizziness
- Nausea
- Tremor
- Skin rash
- Constipation
- Upset stomach
- Loss of appetite
- Headache
- Diarrhea
- Abnormal ejaculation
- Decreased interest in sexual activity
- Dry mouth
- Increase in sweating, known as diaphoresis
- Weight loss
Possible serious side effects of Zoloft include:
- Irregular heartbeats
- Serious allergic reactions
- Worsening of depression
- Serotonin syndrome
- Hyponatremia
- Abnormal bleeding
- Priapism (prolonged erection)
- Decreased liver function
- Suicidality
- Activation of mania in patients with bipolar disorder
Important side effects are irregular heartbeats, allergic reactions, and activation of mania in patients with bipolar disorder.
If Zoloft is discontinued abruptly, some patients experience side effects such as:
- Abdominal cramps
- Fatigue
- Nausea
- Vomiting
- Diarrhea
- Headaches
- Lightheadedness
- Dizziness
- Diminished appetite
- Flu-like symptoms
- Sweating
- Chills
- Sleep disturbances
- Memory impairment
A gradual dose reduction of Zoloft is recommended when therapy is discontinued.
Paxil
WARNING
- Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of Paxil or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be closely observed for clinical worsening, suicidality, or unusual changes in behavior.
Common side effects of Paxil are:
- Nausea
- Headaches
- Anxiety
- Insomnia
- Drowsiness
- Constipation
- Weakness
- Dry mouth
- Sweating
- Diarrhea
- Loss of appetite
Other important side effects include:
- Increased blood pressure
- Seizures
- Sexual dysfunction
Some patients may experience withdrawal reactions upon stopping Paxil. Symptoms of withdrawal include:
- Anxiety
- Nausea
- Nervousness
- Insomnia
The dose of paroxetine should be gradually reduced when therapy is discontinued.
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What is the dosage of Zoloft vs. Paxil?
Zoloft
The recommended dose of Zoloft is 25 to 200 mg once daily. Treatment of depression, OCD, panic disorder, PTSD, and social anxiety disorder is initiated at 25 to 50 mg once daily. Doses are increased at weekly intervals until the desired response is seen.
The recommended dose for PMDD is 50 to 150 mg every day of the menstrual cycle or for 14 days before menstruation.
Sertraline may be taken with or without food.
Paxil
The recommended dose is 20 to 60 mg daily of immediate release tablets or 12.5 to 75 mg daily using controlled release tablets. Paxil is given as a single daily dose, usually in the morning. As with all antidepressants, the full effect may not occur until after a few weeks of therapy.
Doses for obsessive-compulsive disorders and panic disorders are often higher than those for depression. Doses often are adjusted to find the optimal dose.
Elderly patients, debilitated persons, and patients with certain kidney or liver diseases may need lower doses because they metabolize and eliminate Paxil more slowly and, therefore, are prone to develop high blood levels and toxicity.

SLIDESHOW
Learn to Spot Depression: Symptoms, Warning Signs, Medication See SlideshowWhat drugs interact with Zoloft and Paxil?
Zoloft
All SSRIs, including Zoloft, should not be taken with any of the monoamine oxidase inhibitor (MAOI) class of antidepressants, for example
- isocarboxazid (Marplan),
- phenelzine (Nardil),
- tranylcypromine (Parnate),
- selegiline (Eldepryl, Emsam, Elazar), and
- procarbazine (Matulane).
Other drugs that inhibit monoamine oxidase include
- linezolid (Zyvox) and
- intravenous methylene blue.
Such combinations may lead to confusion, high blood pressure, tremor, hyperactivity, coma, and death. (A period of 14 days without treatment should lapse when switching between Zoloft and MAOIs.) Similar reactions occur when Zoloft is combined with other drugs -- for example, tryptophan, St. John's wort, meperidine (Demerol, Meperitab), tramadol (ConZip, Synapryn FusePaq, Ultram) -- that increase serotonin in the brain.
Cimetidine (Cimetidine Acid Reducer, Tagamet HB ) may increase the levels in blood of Zoloft by reducing the elimination of Zoloft by the liver. Increased levels of Zoloft may lead to more side effects.
Zoloft increases the blood level of pimozide (Orap) by 40%. High levels of pimozide can affect electrical conduction in the heart and lead to sudden death. Therefore, patients should not receive treatment with both pimozide and Zoloft.
Through unknown mechanisms, Zoloft may increase the blood thinning action of warfarin (Coumadin, Jantoven). The effect of warfarin should be monitored when Zoloft is started or stopped.
Paxil
All SSRIs, including Paxil, should not be taken with any of the monoamine oxidase inhibitor (MAOI) class of antidepressants -- for example, isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), selegiline (Eldepryl, Carbex), and procarbazine (Matulane) -- or other drugs that inhibit monoamine oxidase such as linezolid (Zyvox) and intravenous methylene blue.
Such combinations may lead to confusion, high blood pressure, tremor, hyperactivity, coma, and death. (A period of 14 days without treatment should lapse when switching between Paxil and MAOIs.) Similar reactions occur when Paxil is combined with other drugs -- for example, tryptophan, St. John's wort, meperidine (Demerol), tramadol (Ultram) -- that increase serotonin in the brain.
Paxil may increase the effect of the blood thinner, warfarin (Coumadin), leading to excessive bleeding. Therefore, warfarin therapy should be monitored more frequently in patients who are also taking Paxil. Combining SSRIs such as Paxil with aspirin, nonsteroidal anti-inflammatory drugs or other drugs that affect bleeding may increase the likelihood of upper gastrointestinal bleeding. Phenytoin (Dilantin) and phenobarbital may decrease the amount of Paxil in the body and possibly reduce its effectiveness.
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Are Zoloft and Paxil safe to use while pregant or breastfeeding?
Zoloft
- Use of Zoloft during the third trimester of pregnancy may lead to adverse effects in the newborn.
- Use of Zoloft by nursing mothers has not been adequately evaluated.
Paxil
- Use of Paxil during pregnancy may result in congenital heart defects. Paxil should not be administered to pregnant women unless the need justifies the risk.
- Paxil is secreted in breast milk. Mothers who are taking Paxil should consider not breastfeeding.
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Summary
Zoloft (sertraline) and Paxil (paroxetine) are selective serotonin reuptake inhibitor (SSRI) type antidepressants used to treat depression, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder (PMDD).
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Related Disease Conditions
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Anxiety
Anxiety is a feeling of apprehension and fear characterized by symptoms such as trouble concentrating, headaches, sleep problems, and irritability. Anxiety disorders are serious medical illnesses that affect approximately 19 million American adults. Treatment for anxiety may incorporate medications and psychotherapy.
-
Panic Attacks
Panic attacks are sudden feelings of terror that strike without warning. These episodes can occur at any time, even during sleep. A person experiencing a panic attack may believe that he or she is having a heart attack or that death is imminent. The fear and terror that a person experiences during a panic attack are not in proportion to the true situation and may be unrelated to what is happening around them. Most people with panic attacks experience several of the following symptoms: racing heartbeat, faintness, dizziness, numbness or tingling in the hands and fingers, chills, chest pains, difficulty breathing, and a feeling of loss or control. There are several treatments for panic attacks.
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Depression
Depression is an illness that involves the body, mood, and thoughts and affects the way a person eats and sleeps, the way one feels about oneself, and the way one thinks about things. The principal types of depression are major depression, dysthymia, and bipolar disease (also called manic-depressive disease).
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Premenstrual Dysphoric Disorder (PMDD)
Premenstrual dysphoric disorder (PMDD) is considered a severe form of premenstrual syndrome (PMS). PMDD has also been referred to as late luteal phase dysphoric disorder. The cause of PMDD is unknown. Some of the common symptoms of PMDD (not an inclusive list) include mood swings, bloating, fatigue, headache, irritability, headache, breast tenderness, acne, and hot flashes. Treatment for PMDD is with medication to treat the symptoms of PMDD.
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Obsessive Compulsive Disorder (OCD)
Obsessive-compulsive disorder (OCD) is an anxiety disorder that causes a person to suffer repeated obsessions and compulsions. Symptoms include irresistible impulses despite a person's realization that the thoughts are irrational, excessive hand washing, skin picking, lock checking, or repeatedly rearranging items. People with OCD are more likely to develop trichotillomania, muscle or vocal tics, or an eating disorder. Treatment for OCD includes psychotherapy, behavioral therapy, and medication.
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Post-traumatic Stress Disorder
Post-traumatic stress disorder (PTSD), a psychiatric condition, can develop after any catastrophic life event. Symptoms include nightmares, flashbacks, sweating, rapid heart rate, detachment, amnesia, sleep problems, irritability, and exaggerated startle response. Treatment may involve psychotherapy, group support, and medication.
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