Side Effects of Paxil (paroxetine)

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.

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

• confusion,
• high blood pressure,
• tremor,
• hyperactivity,
• coma, and
• death.

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

• tryptophan,
• St. John's wort,
• meperidine, and
• tramadol.

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 common side effects of Paxil?

Common side effects of Paxil include

• nausea,
• headaches,
• anxiety,
• insomnia,
• drowsiness,
• constipation,
• weakness,
• dry mouth,
• sweating,
• diarrhea, and
• loss of appetite.

What are the serious side effects of Paxil?

Serious side effects of Paxil include

• increased blood pressure,
• seizures,
• sexual dysfunction, and
• increased risk of suicidal thinking and behavior (suicidality) in children and adolescents with depression and other psychiatric disorders.

Some patients may experience withdrawal reactions such as

• anxiety,
• nausea,
• nervousness, and
• insomnia upon stopping Paxil. 

Clinically Significant Drug Interactions

Table 6: Clinically Significant Drug Interactions with Paxil CR

• Patients should not abruptly discontinue Paxil and should discuss any tapering regimen with their healthcare provider.
• Adverse reactions can occur when Paxil is discontinued.

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

• Hypersensitivity reactions to paroxetine
• Suicidal Thoughts and Behaviors
• Serotonin Syndrome
• Embryofetal and Neonatal Toxicity
• Increased Risk of Bleeding
• Activation of Mania/Hypomania
• Discontinuation Syndrome
• Seizures
• Angle-closure Glaucoma
• Hyponatremia
• Bone Fracture

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

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: 

• allergic reaction,
• tachycardia,
• vasodilatation,
• hypertension,
• migraine,
• vomiting,
• weight loss,
• weight gain,
• hypertonia,
• paresthesia,
• agitation,
• confusion,
• myoclonus,
• concentration impaired,
• depression,
• rhinitis,
• cough increased,
• bronchitis,
• photosensitivity,
• eczema,
• taste perversion,
• UTI,
• menstrual disorder,
• urinary frequency,
• urination impaired, and
• vaginitis.

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 10^a,b,c

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

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).