Paroxetine Adverse Reactions
- abdominal pain
- agitation
- akathisia
- amnesia
- angioedema
- anorexia
- anxiety
- appetite stimulation
- asthenia
- back pain
- bleeding
- blurred vision
- chest pain (unspecified)
- chills
- confusion
- constipation
- cough
- depression
- diaphoresis
- diarrhea
- dizziness
- drowsiness
- dysgeusia
- dysmenorrhea
- dyspepsia
- dysuria
- ecchymosis
- ejaculation dysfunction
- elevated hepatic enzymes
- emotional lability
- fever
- flatulence
- flushing
- headache
- hostility
- hypertension
- hyponatremia
- hypotension
- impaired cognition
- impotence
- increased urinary frequency
- insomnia
- irritability
- libido decrease
- maculopapular rash
- malaise
- mania
- myalgia
- myasthenia
- myoclonia
- myopathy
- nausea/vomiting
- neonatal abstinence syndrome
- orgasm dysfunction
- orthostatic hypotension
- palpitations
- paresthesias
- pharyngitis
- platelet dysfunction
- priapism
- pruritus
- purpura
- rash (unspecified)
- rhinitis
- serotonin syndrome
- SIADH
- sinus tachycardia
- sinusitis
- suicidal ideation
- syncope
- tremor
- urticaria
- vertigo
- visual impairment
- weight gain
- weight loss
- withdrawal
- xerostomia
- yawning
Paroxetine Adverse Reactions
The following adverse events (ADR), unless otherwise specified, represent treatment-emergent adverse effects with paroxetine in manufacturer-based placebo-controlled trials for all approved indications. Of paroxetine-treated patients in worldwide clinical trials, roughly 9 - 20% discontinued treatment due to an adverse event. Clinicians should note that incidences of ADRs reported may differ depending on the patient population or disease state studied. In some trials, ADRs occurred at a rate higher than that of placebo, while in other studies the same ADR may have appeared at an equal or lower than that of the placebo group. Incidences of side effects occurring with immediate-release formulations of paroxetine are similar to those occurring with controlled-release formulations, although exact percentages quoted may differ slightly.
Nausea/vomiting occur in 25%/0 - 2% of patients; nausea is the most common adverse reaction reported with paroxetine and the most frequent (3.2%) cause of drug discontinuation. With continued treatment over several weeks, adaptation to some GI adverse events (e.g., nausea) may occur, but other effects (e.g., dry mouth) may continue. Xerostomia occurs in roughly 18% of patients, constipation or diarrhea in 5 - 16%; these effects cause drug discontinuation in roughly 1% of patients. Anorexia (as decreased appetite) has been reported in approximately 6 - 9% of patients. Most GI effects appear to be dose-related and may respond well to dosage reduction. Other gastrointestinal adverse effects include abdominal pain (4%), appetite stimulation (2 - 4%), dyspepsia (2%), and flatulence (4%) and a manufacturer-described ‘oropharynx disorder’ which includes a feeling of ‘lump’ or’tightness’ in the throat (2%). Significant weight loss may be an undesirable result of treatment for some patients, but on average, patients in controlled trials had minimal (roughly 0.45 kg) weight loss vs. smaller changes on placebo or active control. Weight gain may also occur infrequently. In controlled clinical trials, patients treated with paroxetine exhibited abnormal liver function tests at no greater rate than that seen in placebo-treated patients.
Common adverse CNS effects due to paroxetine (incidence vs. placebo as listed) include anxiety or nervousness (5 - 9% vs 3 - 8%), dizziness (13 - 24% vs 6 - 16%), drowsiness (19 - 24% vs 5 - 11%), insomnia (13% vs 6%) and tremor (8 - 11% vs 1 - 2%). With continued treatment over 4 - 6 weeks, there was evidence of adaptation to some adverse events with continued therapy (e.g., dizziness). Approximately 2.3% of all patients require discontinuation due to somnolence; tremor leads to drug discontinuation in roughly 1% of patients. Other less common CNS effects of paroxetine (incidence vs. placebo as listed) may include abnormal dreams (4% vs. 1%), agitation (3 - 5% vs 1 - 4%), amnesia (2% vs 1%), confusion (1% vs 0%), depersonalization (3% vs 0%), impaired cognition or concentration (3 - 4% vs 0 - 2%), myoclonia (3% vs 1 - 2%), paresthesias (4% vs 2%), and a nonspecific drugged feeling (2% vs 1%). Yawning is a unique side effect and has been reported with other SSRIs; increased yawning was reported in 4 - 5% of paroxetine-treated patients vs. 1% of those receiving placebo. Some CNS effects, including anorexia, dizziness, drowsiness, impaired cognition, tremor, xerostomia and yawning may respond to dosage reduction. Note that dependent on the disease state studied, some CNS events occurred in rates similar to placebo in controlled clinical trials.
All effective antidepressants can precipitate mania in predisposed individuals suffering from depression. During controlled trials, hypomania or mania occurred in approximately 1% of paroxetine-treated unipolar patients compared to 1.1% of active-control and 0.3% of placebo-treated unipolar patients. In a subset of patients classified as bipolar, the rate of manic episodes was 2.2% for paroxetine and 11.6% for the combined active-control groups. If mania occurs, the antidepressant should be held and appropriate therapy to treat the manic symptoms initiated.
Suicidal ideation has been reported in antidepressant clinical trials. The symptoms of aggressiveness, akathisia (psychomotor restlessness), agitation, anxiety, insomnia, irritability, hostility, mania, hypomania, impulsivity, and panic attacks have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidal ideation. A change or discontinuation of the therapeutic regimen should especially be considered if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Many of these adverse symptoms have been reported in clinical trials and have not always been associated with suicidality. Rapid discontinuation of SSRIs may also result in many of these adverse CNS events.
Palpitations (3%), and vasodilation/flushing (3%) are reported cardiovascular effects of paroxetine in controlled trials. No significant changes in vital signs ( including systolic and diastolic blood pressure, pulse, temperature) or ECG patterns were observed in patients treated with paroxetine versus placebo in controlled clinical trials. Orthostatic hypotension occurred at a rate equal to or less than placebo.
For the body as a whole, asthenia is reported in 15% of patients on paroxetine vs. 6% of those taking placebo. Fever, back pain, chest pain (unspecified) and trauma are each reported in 1 - 2% of patients receiving paroxetine, the frequency of these complaints is generally no higher for paroxetine than for placebo. Headache is reported in 18% of patients, with an incidence similar to placebo (17%).
Musculoskeletal system disorders reported with paroxetine include myopathy (2%), myalgia (2 - 4%), and myasthenia (1%) vs. a 0 - 1% incidence of these effects in those receiving placebo.
Taste perversion (dysgeusia) is reported in 2% of paroxetine-treated patients. Visual impairment or blurred vision is reported in 4% of patients receiving paroxetine.
Rhinitis and pharyngitis are reported at rates similar to placebo-treated patients in many trials. Diaphoresis (increased sweating) is reported in 6 - 14% of patients, and appears to be dose-related. Hypersensitivity or skin rashes appear infrequent. Rash (unspecified) occurs in 2% of paroxetine-treated patients and in 1% of those on placebo; pruritus has been reported in <= 1%. Maculopapular rash or urticaria is reported infrequently. Rarely angioedema or serious skin reactions may occur, but causality has not been determined.
Increased urinary frequency and dysuria, which includes difficulty with micturation, urinary hesitancy, and urinary tract infection, occur in roughly 2 - 3% of paroxetine-treated patients. Dysmenorrhea is reported in 4 - 5% of females, a rate similar to placebo. Sexual dysfunction seen with paroxetine includes libido decrease (6 - 14% of males and 1 - 9% of females), orgasm dysfunction (anorgasmia and difficulty reaching orgasm, occurring in up to 10% each of males or females), impotence (2 - 8%), and ejaculation dysfunction in males (primarily delayed ejaculation, 13 - 28%). Priapism, a medical emergency, has been reported rarely with all of the SSRIs; in those cases with a known outcome, the male patients recovered without sequelae after drug discontinuation and appropriate treatment. Although the initial frequency of urogenital side-effects was reported to be relatively low, post-marketing experience has suggested that the frequency of sexual adverse events is actually much higher than previously recognized. Many physicians report an incidence of up to 90% based on their clinical experience. A higher frequency of drug-induced sexual adverse events may be noted in clinical practice.
There have been several reports of abnormal bleeding (mostly ecchymosis and purpura) associated with paroxetine treatment, including a report of impaired platelet aggregation. While a causal relationship to paroxetine has not been established, platelet dysfunction may result from platelet serotonin depletion and may contribute to abnormal bleeding.
Several cases of hyponatremia have been reported with the use of paroxetine and other SSRIs. While the cases were complex, some instances may have been due to the syndrome of inappropriate antidiuretic hormone (SIADH). Like with all SSRIs, the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) presents as hyposmolarity of serum and urine, and hyponatremia. The hyponatremia appeared to be reversible when paroxetine was discontinued. The majority of cases have been seen in patients that are elderly, taking diuretics, or volume depleted. In a prospective cohort study, 9 of 75 (12%) patients age 63 - 90 years taking paroxetine developed hyponatremia (plasma sodium < 135 mEq/L). The median time to development of hyponatremia after initiation of paroxetine was 9 days (range 1 - 14 days). Predictors for development of hyponatremia included lower baseline plasma sodium (< 138 mEq/L) and lower body mass index. The authors recommend monitoring plasma sodium and blood urea nitrogen at baseline and within 2 weeks of initiating treatment. Hyponatremia does not appear to be associated with plasma concentrations of paroxetine.
Withdrawal symptoms have been reported with abrupt or rapid discontinuation of short-acting SSRIs such as paroxetine. The most commonly reported withdrawal symptoms include fatigue, abdominal pain or nausea, dizziness/light-headedness, tremor, chills, diaphoresis, and incoordination. Other reported symptoms include impaired memory, insomnia, shock sensations, headaches, and agitation or aggression. Withdrawal symptoms usually begin 1 - 3 days after abrupt discontinuation of the SSRI and remit within 1 - 2 weeks. Gradual tapering is recommended during discontinuation of any SSRI to decrease or prevent the occurrence of withdrawal symptoms.
Serotonin syndrome has been reported when SSRIs are administered concomitantly with other medications known to increase CNS or peripheral serotonin levels or during SSRI overdose. Signs and symptoms of serotonin syndrome or overdose with paroxetine include nausea, vomiting, excessive sedation, dizziness, diaphoresis (sweating), facial flush, mental status changes (e.g., coma), myoclonus, restlessness, shivering, tachycardia, and tremor. It should be noted that a withdrawal syndrome resembling serotonin syndrome has been reported in newborns immediately following birth from mothers who used SSRIs while pregnant. Other notable signs and symptoms observed with overdoses involving paroxetine (alone or with other substances) include mydriasis, convulsions (including status epilepticus), ventricular dysrhythmias (including torsade de pointes), hypertension, aggressive reactions, syncope, hypotension, stupor, bradycardia, dystonia, rhabdomyolysis, symptoms of hepatic dysfunction (including hepatic failure, hepatic necrosis, jaundice, hepatitis, and hepatic steatosis), serotonin syndrome, manic reactions, acute renal failure, and urinary retention. Limited data indicate that paroxetine increases seizure length in patients undergoing electroconvulsive therapy (ECT). A fatal outcome of overdose has been reported rarely.
A neonatal abstinence syndrome has been reported in infants exposed to paroxetine in utero. After birth, symptoms consistent with withdrawal (i.e., poor feeding, hypoglycemia, hypothermia, lethargy or irritability, vomiting, etc.) were noted. Such complications can arise immediately upon delivery. Other symptoms have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, and constant crying. Serum concentrations of paroxetine were measurable in the infants affected. Several other symptoms (bloody stools, necrotizing enterocolitis) may have been attributable to rebound platelet activation on withdrawal of the exposure to the SSRI. Neonatal symptoms generally improved over several days. Additionally, a cohort study of 55 women revealed that 22% (12/55) of neonates exposed to paroxetine in the third trimester had complications requiring treatment or extended hospitalization compared with 6% in comparison groups. Complications included respiratory distress (n=9), hypoglycemia (n=2) and jaundice (n=1). The incidence of prematurity in the third trimester paroxetine group was significant at 20% vs. 3.7% of controls. These features are consistent with either a direct toxic effect of serotonergic agents, or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with the serotonin syndrome. When treating a pregnant woman with an SSRI or other serotonergic agent during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, and taking the half-life into consideration, tapering of the serotonergic agent prior to delivery may be considered as an alternative.
Elevated hepatic enzymes (1.9% paroxetine CR vs. 0% placebo) have been infrequently reported in short-term trials evaluating controlled-release paroxetine for depressive disorders. Associated laboratory changes in AST or ALT have not been reported.
Spontaneously reported adverse events were monitored in studies of both continuous and intermittent dosing of controlled-release paroxetine in the treatment of PMDD. Generally there were few differences in the adverse event profiles of the 2 dosing regimens. Thirteen percent (88/681) of patients treated with controlled-release paroxetine in PMDD studies of continuous dosing discontinued treatment due to an adverse event. The most common events resulting in discontinuation of treatment in PMDD studies utilizing the 25 mg PO dose included nausea (15 vs. 6.3% placebo), asthenia (6 vs. 0.9%), drowsiness (4.3 vs. 0.3%), insomnia (2.3 vs. 0%), impaired concentration (2 vs. 0.3%) and dry mouth (2 vs. 0.3%). Reduction in the dose to 12.5 mg PO may lessen the incidence of some adverse events.
The following adverse events have also been reported to occur in 1% of paroxetine-treated patients for all indications, except those already listed. These events come from data in all trials, including open-label and uncontrolled studies. It is important to emphasize that although the events reported occurred during treatment with paroxetine, they were not necessarily caused by it. Some events occurred at rates similar to placebo in controlled clinical trials. The following events are listed by body system. Body as a whole: chills, malaise. Cardiovascular system: hypertension, syncope, sinus tachycardia. Note that in controlled trials clinically significant changes in vital signs were not noted versus placebo, including blood pressure and heart rate. Central nervous system: amnesia, CNS stimulation, impaired concentration, depression, emotional lability, and vertigo. Respiratory system: cough increased, sinusitis. NOTE: additional reported infrequent side effects (0.1 - 1% of patients) and rare events (<= 0.1% of patients) in which a causal relationship to paroxetine has not been established are listed in the manufacturer’s prescribing information.
[ Last revised: 11/10/2005 1:32:00 PM ]
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