Does Paxil (paroxetine) cause side effects?

Paxil (paroxetine) is a selective serotonin reuptake inhibitor (SSRI) antidepressant used to treat depression.

Paxil affects neurotransmitters, the chemicals that nerves within the brain use to communicate with each other. Neurotransmitters are manufactured and released by nerves and then travel and attach to other nearby nerves.

Experts believe an imbalance among neurotransmitters is the cause of depression. Paxil works by preventing the reuptake of one neurotransmitter, 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.

Common side effects of Paxil include

Serious side effects of Paxil include

Some patients may experience withdrawal reactions such as

Drug interactions of Paxil include monoamine oxidase inhibitors (MAOIs) or other drugs that inhibit monoamine oxidase such as linezolid and intravenous methylene blue because it may lead to

Similar reactions occur when Paxil is combined with other drugs that increase serotonin in the brain such as

Paxil may increase the effect of the blood thinner, warfarin, leading to excessive bleeding.

Combining SSRIs such as Paxil with aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or other drugs that affect bleeding may increase the likelihood of upper gastrointestinal bleeding.

Phenytoin and phenobarbital may decrease the amount of Paxil in the body and possibly reduce its effectiveness.

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.

What are the important side effects of Paxil (paroxetine)?

Common side effects of paroxetine are:

Other important side effects include:

  • increased blood pressure
  • seizures
  • sexual dysfunction

Some patients may experience withdrawal reactions upon stopping paroxetine. Symptoms of withdrawal include:

  • anxiety,
  • nausea,
  • nervousness, and
  • insomnia.

The dose of paroxetine should be gradually reduced when therapy is discontinued.

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 paroxetine 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.

Paxil (paroxetine) side effects list for healthcare professionals

The following adverse reactions are included in more detail in other sections of the prescribing information:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Safety data for Paxil CR is from 11 short-term, placebo-controlled clinical trials including 3 studies in patients with major depressive disorder (MDD) (Studies 1, 2, and 3), 3 studies in patients with panic disorder (PD) (Studies 4, 5, and 6), 1 study in patients with social anxiety disorder (SAD) (Study 7), and 4 studies in female patients with premenstrual dysphoric disorder (PMDD) (Studies 8, 9, 10, and 11). These 11 trials included 1627 patients treated with Paxil CR.

  • Studies 1 and 2 were 12-week studies that enrolled patients 18 to 65 years old who received Paxil CR at doses ranging from 25 mg to 62.5 mg once daily. Study 3 was a 12-week study in patients 60 to 88 years old who received Paxil CR at doses ranging from 12.5 mg to 50 mg once daily.
  • Studies 4, 5, and 6 were 10-week studies in patients 19 to 72 years old who received Paxil CR at doses ranging from 12.5 mg to 75 mg once daily.
  • Study 7 was a 12-week study that enrolled adult patients who received Paxil CR at doses ranging from 12.5 mg to 37.5 mg once daily.
  • Studies 8, 9, and 10 were 12-week, placebo-controlled trials in female patients 18 to 46 years old who received Paxil CR at doses of 12.5 mg or 25 mg once daily. Study 11 was a 12-week placebo-controlled trial in patients 18 to 46 years old who received Paxil CR 2 weeks prior to the onset of menses (luteal phase dosing) at doses of 12.5 mg or 25 mg once daily.

Adverse Reactions Leading To Discontinuation In Patients With MDD, PD, SAD, And PMDD

In pooled studies in patients with MDD, PD and SAD, the most common adverse reactions leading to study withdrawal were:

  • nausea (up to 4% of patients),
  • asthenia,
  • headache,
  • depression,
  • insomnia, and
  • abnormal liver function tests (each occurring in up to 2% of patients), and
  • dizziness, somnolence, and diarrhea (each occurring in up to 1% of patients).

In pooled studies for PMDD, the most common adverse reactions leading to study withdrawal were:

  • nausea (occurring in up to 6% of patients),
  • asthenia (occurring in up to 5% of patients),
  • somnolence (occurring in up to 4% of patients),
  • insomnia (occurring in approximately 2% of patients); and
  • impaired concentration, dry mouth, dizziness, decreased appetite, sweating, tremor, yawn and diarrhea (occurring in less than or equal to 2% of patients).

Adverse Reactions In MDD, PD, And SAD

Table 3 presents the most common adverse reactions in Paxil CR-treated patients (incidence ≥5% and greater than placebo within at least 1 of the indications) in controlled trials in patients with MDD, PD, and SAD.

Table 3: Adverse Reactions (≥5% of Patients Treated with Paxil CR and Greater than Placebo) in 10 to 12 Week Studies of MDD, PD, and SAD

Body System/ Adverse ReactionMDD18 to 65 year oldsMDD≥60 years oldPanic DisorderSocial Anxiety Disorder
Paxil CR
(N=212) %
Placebo
(N=211) %
Paxil CR
(N=104) %
Placebo
(N=109 %
Paxil CR
(N=444) %
Placebo
(N=445) %
Paxil CR
(N=186) %
Placebo
(N=184) %
Body as a Whole
Headache27201713NANA2317
Asthenia14915141510187
Abdominal Pain74--6454
Back Pain53--NANA41
Digestive System
Nausea2210--2317226
Diarrhea18715912998
Dry Mouth15818713932
Constipation1041359652
Flatulence64--NANANANA
Decreased Appetite2125861<1
DyspepsiaNANA1310NANA2<1
Musculoskel etal System
MyalgiaNANA--53NANA
Nervous System
Somnolence228211220994
Insomnia179108201194
Dizziness14495NANA74
Libido Decreased738<1941
NervousnessNANA--87NANA
Tremor71708242
AnxietyNANA--5421
Respiratory System
SinusitisNANA--85NANA
Yawn0--3020
Skin and Appendages
Sweating6210<172143
Special Senses
Abnormal Visiona51--3<120
Urogenital System
Abnormal Ejaculationb,c261173273151
Female Genital Disorderb,d10<17130
Impotenceb539310190
Hyphen = the reaction listed occurred in <5% of patients treated with Paxil CR
NA = the adverse reaction listed did not occur in this group of patients
a Mostly blurred vision
b Based on the number of males or females
c Mostly anorgasmia or delayed ejaculation
d Mostly anorgasmia or delayed orgasm

Other Adverse Reactions Observed During The Premarketing Evaluation Of Paxil CR

Adverse reactions from studies in MDD (not including Study 3 in elderly patients), PD, and SAD that occurred between 1% and 5% of patients treated with Paxil CR and at a rate greater than in placebo-treated patients include: 

Adverse Reactions In Patients With PMDD

Table 4 displays adverse reactions that occurred (incidence of 5% or more and greater than placebo within at least 1 of the studies) in patients treated with Paxil CR in Studies 8, 9, 10, and 11.

Table 4: Adverse Reactions (≥5% of Patients Treated with Paxil CR and Greater than Placebo) in Pooled Studies PMDD (Studies 8, 9, 11), and in Study 10a,b,c

Body 40%
System/Adverse Reaction
% Reporting Atverse Reaction
Continuous Dosing Studies 8, 9, and 10Luteal Phase Dosing Study 11
Paxil CR
(n = 681) %
Placebo
(n = 349) %
Paxil CR
(n = 246) %
Placebo
(n = 120) %
Body as a Whole
Asthenia176154
Headache1512NANA
Infection64NANA
Digestive System
Nausea177182
Diarrhea6260
Constipation512<1
Nervous System
Libido Decreased12596
Somnolence923<1
Insomnia8273
Dizziness7363
Tremor4<150
Skin and Appendages
Sweating7<16<1
Urogenital System
Female Genital Disordersc8120
NA= the adverse reaction information is not available in this population.
a <1% means greater than zero and less than 1%.
b The luteal phase and continuous dosing PMDD trials were not designed for making direct comparisons between the 2 dosing regimens.
c Mostly anorgasmia or difficulty achieving orgasm.

Dose Dependent Adverse Reactions

Comparison of the incidence of adverse reactions (placebo vs. 12.5 mg Paxil CR vs. 25 mg Paxil CR) from studies 8, 9, 10 showed the following adverse reactions to be dose-related:

  • Nausea,
  • somnolence,
  • sweating,
  • dry mouth,
  • dizziness,
  • decreased appetite,
  • tremor,
  • impaired concentration,
  • yawn,
  • paresthesia,
  • hyperkinesia, and
  • vaginitis.

Male And Female Sexual Dysfunction

Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment.

However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, in part because patients and healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence.

The percentage of patients reporting symptoms of sexual dysfunction in the Studies 1 and 2 (nonelderly patients with MDD), 4, 5, 6, 7, 8, 9, 10, and 11 are presented in Table 5:

Table 5: Adverse Reactions Related To Sexual Dysfunction In Patients Treated With Paxil CR in Pooled 10-12 Week Studies of MDD, PD, SAD, and PMDD

Studies 1 and 2 %Studies 4, 5, and 6 %Study 7 %Studies 8, 9, and 11 (Continuous Dosing) %Study 10 (Luteal Phase Dosing) %
Paxil CRPlaceboPaxil CRPlaceboPAXI L CRPlaceboPaxil CRPlaceboPAXI L CRPlacebo
n (males)78781621948897NANANANA
Decreased Libido10596131NANANANA
Abnormal ejaculation261273151NANANANA
Impotence53101%90NANANANA
n (females)1341332822519887681349246120
Decreased Libido42824112596
Orgasmic Disturbance10<171308120
NA = the adverse reaction listed did not occur in this group of patients.

Paroxetine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae.

Less Common Adverse Reactions

The following adverse reactions occurred during the clinical studies of Paxil CR and are not included elsewhere in the labeling.

Reactions are categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse reactions are those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients; rare reactions are those occurring in fewer than 1/1,000 patients.

Cardiovascular System: Infrequent was postural hypotension.

Hemic and Lymphatic System: Rare was thrombocytopenia.

Metabolic and Nutritional Disorders: Infrequent were generalized edema and hypercholesteremia.

Nervous System: Infrequent were convulsion, akathisia, and manic reaction.

Psychiatric: Infrequent were hallucinations.

Skin and Appendages: Frequent was rash; infrequent was urticaria; rare was angioedema and erythema multiforme.

Urogenital System: Infrequent was urinary retention; rare was urinary incontinence.

Postmarketing Experience

The following reactions have been identified during post approval use of paroxetine. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Acute pancreatitis, elevated liver function tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction), Guillain-Barré syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, priapism, syndrome of inappropriate ADH secretion (SIADH), prolactinemia and galactorrhea; extrapyramidal symptoms which have included akathisia, bradykinesia, cogwheel rigidity, dystonia, hypertonia, trismus; status epilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anaphylaxis, eclampsia, laryngismus, optic neuritis, porphyria, restless legs syndrome (RLS), ventricular fibrillation, ventricular tachycardia (including torsade de pointes), hemolytic anemia, events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis), and vasculitic syndromes (such as Henoch-Schönlein purpura).

What drugs interact with Paxil (paroxetine)?

Clinically Significant Drug Interactions

Table 6: Clinically Significant Drug Interactions with Paxil CR

Monoamine Oxidase Inhibitors (MAOIs)
Clinical Impact The concomitant use of SSRIs, including Paxil CR, and MAOIs increases the risk of serotonin syndrome.
Intervention Paxil CR is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue.
Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue
Pimozide and Thioridazine
Clinical Impact Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias.
Intervention Paxil CR is contraindicated in patients taking pimozide or thioridazine.
Other Serotonergic Drugs
Clinical Impact The concomitant use of serotonergic drugs with Paxil CR increases the risk of serotonin syndrome.
Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of Paxil CR and/or concomitant serotonergic drugs.
Examples other SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort
Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants)
Clinical Impact The concurrent use of an antiplatelet agent or anticoagulant with Paxil CR may potentiate the risk of bleeding.
Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of Paxil CR and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio.
Examples aspirin, clopidogrel, heparin, warfarin
Drugs Highly Bound to Plasma Protein
Clinical Impact Paxil CR is highly bound to plasma protein. The concomitant use of Paxil CR with another drug that is highly bound to plasma protein may increase free concentrations of Paxil CR or other tightly-bound drugs in plasma.
Intervention Monitor for adverse reactions and reduce dosage of Paxil CR or other protein-bound drugs as warranted.
Examples warfarin
Drugs Metabolized by CYP2D6
Clinical Impact Paxil CR is a CYP2D6 inhibitor. The concomitant use of Paxil CR with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate.
Intervention Decrease the dosage of a CYP2D6 substrate if needed with concomitant Paxil CR use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if Paxil CR is discontinued.
Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone.
Tamoxifen
Clinical Impact Concomitant use of tamoxifen with Paxil CR may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen
Intervention Consider use of an alternative antidepressant little or no CYP2D6 inhibition.
Fosamprenavir/Ritonavir
Clinical Impact Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine.
Intervention Any dose adjustment should be guided by clinical effect (tolerability and efficacy).

Summary

Paxil (paroxetine) is a selective serotonin reuptake inhibitor (SSRI) antidepressant used to treat depression. Common side effects of Paxil include nausea, headaches, anxiety, insomnia, drowsiness, constipation, weakness, dry mouth, sweating, diarrhea, and loss of appetite. 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.

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Medically Reviewed on 7/27/2020
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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