Applies to paroxetine: oral capsule, oral suspension, oral tablet, oral tablet extended release
A study of 26,005 antidepressant users has reported 3.6 times more upper GI bleeding episodes with the use of SSRIs relative to the population who did not receive antidepressant medications. Upper gastrointestinal tract bleeding was observed up to 3.2 times more frequently in patients receiving paroxetine (the active ingredient contained in Paxil)
Gastrointestinal side effects have frequently included nausea (15% to 36%), dry mouth (4% to 36%), constipation (5% to 16%), diarrhea (6% to 19%), increased appetite (3%), decreased appetite (2% to 12%), flatulence (4% to 8%), vomiting (2% to 3%), oropharynx disorder (2%), taste perversion (2%), gingivitis (1%), and dyspepsia (2% to 13%). Bruxism, upper GI bleeding, colitis, dysphagia, eructation, gastritis, gastroenteritis, glossitis, increased salivation, rectal hemorrhage, ulcerative stomatitis, aphthous stomatitis, bloody diarrhea, bulimia, cholelithiasis, duodenitis, enteritis, esophagitis, fecal impaction, fecal incontinence, gum hemorrhage, hematemesis, ileitis, ileus, intestinal obstruction, melena, mouth ulceration, peptic ulcer, peritonitis , salivary gland enlargement, sialadenitis, stomach ulcer, stomatitis, tongue discoloration, tongue edema, loss of taste, and tooth caries have also been reported.
Chorea has been reported in 13 patients. One incidence of chorea occurred after a single dose of paroxetine (the active ingredient contained in Paxil)
Severe psychomotor retardation and stupor have been reported in one patient.
According to the manufacturer, one study reported that seizures occurred in 0.26% of patients treated with other commonly used antidepressants.
In one study, paroxetine was found to decrease rapid eye movement (REM) sleep, increase REM latency, increase awakenings, and reduce actual sleep time. Another study found a decreased amount of REM sleep without a detrimental effect on subjective sleep quality.
Nearly all selective serotonin reuptake inhibitors, mixed serotonin/norepinephrine reuptake inhibitors, and tricyclic antidepressants cause sleep abnormalities to some extent. These antidepressants have marked dose-dependent effects on rapid eye movement (REM) sleep, causing reductions in the overall amount of REM sleep over the night and delays the first entry into REM sleep (increased REM sleep onset latency (ROL)), both in healthy subjects and depressed patients. The antidepressants that increase serotonin function appear to have the greatest effect on REM sleep. The reduction in REM sleep is greatest early in treatment, but gradually returns towards baseline during long-term therapy; however, ROL remains long. Following discontinuation of therapy the amount of REM sleep tends to rebound. Some of these drugs (i.e., bupropion, mirtazapine, nefazodone, trazodone, trimipramine) appear to have a modest or minimal effect on REM sleep.
Nervous system side effects have frequently included somnolence (9% to 24%), dizziness (7% to 14%), insomnia (8% to 24%), tremor (4% to 11%), nervousness (2% to 9%), paresthesia (1% to 4%), decreased libido in both male and female patients (3% to 15%), 'drugged' feeling (2%), confusion (1%), sleep abnormalities, abnormal dreams (1% to 4%), impaired concentration (2% to 4%), myoclonus (1% to 3%), amnesia (1% to 2%), tremor (4% to 8%), hypertonia (2% to 3%), and vertigo (2%). Abnormal thinking, alcohol abuse, ataxia, dystonia, dyskinesia, hypesthesia, hypokinesia, incoordination, paralysis, abnormal gait, akinesia, antisocial reaction, aphasia, choreoathetosis, circumoral paresthesias, convulsion, delirium, delusions, dysarthria, extrapyramidal syndrome, fasciculations, grand mal convulsions, hyperalgesia, meningitis, myelitis, neuralgia, neuropathy, nystagmus, peripheral neuritis, decreased reflexes, increased reflexes, stupor, torticollis, trismus, tardive dyskinesia, seizures, status epilepticus, serotonin syndrome, extrapyramidal symptoms (including akathisia, bradykinesia, cogwheel rigidity, dystonia, and hypertonia), changes in rapid eye movement (REM) sleep, chorea, psychomotor retardation, and stupor have also been reported.
Other commonly used antidepressants induced mania in 11% of patients in one study.
Pooled results from clinical trials report hallucinations in 22 of 9089 patients who received paroxetine (the active ingredient contained in Paxil) and 4 of 3187 patients who received placebo.
Psychiatric side effects have frequently included anxiety (2% to 5%), agitation (2% to 5%), depersonalization (3%), depression (2%), lack of emotion (2%), and emotional lability. Euphoria, hallucinations, hostility, increased libido, neurosis, paranoid reaction, antisocial reaction, delusions, drug dependence, hysteria, manic-depressive reaction, psychotic depression, and psychosis. Mania has been reported in up to 2% of bipolar patients.
Seven cases of alopecia have been reported. In all cases, hair loss was eventually reversible.
A case of cutaneous leukocytoclastic vasculitis has been reported following treatment with paroxetine (the active ingredient contained in Paxil) The patient originally developed the lesions after treatment with escitalopram. The lesions disappeared one week following discontinuation of escitalopram and reappeared upon rechallenge. When the patient was switched to paroxetine a similar reaction occurred.
Dermatologic side effects have frequently included sweating (5% to 34%), rash (2% to 3%), photosensitivity (2%), eczema (1%), and pruritus. Acne, alopecia, contact dermatitis, dry skin, ecchymosis, herpes simplex, urticaria, erythema nodosus, erythema multiforme, exfoliative dermatitis, fungal dermatitis, furunculosis, herpes zoster, hirsutism, maculopapular rash, seborrhea, skin discoloration, skin hypertrophy, skin ulcer, decreased sweating, vesiculobullous rash, and toxic epidermal necrolysis have also been reported. Two cases of cutaneous vasculitis have also been reported. Dermatologic side effects reported postmarketing have included Stevens-Johnson syndrome.
There are no controlled clinical data regarding sexual dysfunction with paroxetine (the active ingredient contained in Paxil) use.
There are several reports of priapism associated with paroxetine use. In cases in which outcome was reported, all patients fully recovered.
Genitourinary side effects reported in males have included ejaculatory disturbance (13% to 28%), impotence (2% to 9%), and priapism. Genitourinary side effects reported in females have included anorgasmia, orgasmic disturbance, dysmenorrhea, eclampsia, menstrual disorder (2%), vaginitis (2%), amenorrhea, menorrhagia, abortion, endometrial disorder, female lactation, leukorrhea, mastitis, salpingitis, uterine spasm, vaginal hemorrhage, metrorrhagia, and vaginal moniliasis. Urinary tract infection (3%), sexual dysfunction, urinary frequency, urinary disorder, difficulty with micturition, urinary hesitancy, breast pain, breast atrophy, breast enlargement, fibrocystic breast, cystitis, dysuria, hematuria, nocturia, polyuria, pyuria, urinary incontinence, urinary retention, urinary urgency, epididymitis, kidney calculus, kidney pain, nephritis, oliguria, urethritis, urinary casts, and urolith have also been reported.
The effects on blood pressure have been reported to be inconsistent.
Cardiovascular side effects have frequently included palpitation (2% to 3%), vasodilation (2% to 4%), hypertension (2%), and tachycardia (including torsade de pointes). Bradycardia, hematoma, hypotension, postural hypotension, syncope, angioedema, angina pectoris, nodal arrhythmia, atrial fibrillation, bundle branch block, cerebral ischemia, cerebrovascular accident, congestive heart failure, heart block, low cardiac output, myocardial infarct, myocardial ischemia, phlebitis, supraventricular extrasystoles, thrombophlebitis, thrombosis, varicose vein, supraventricular tachycardia, vascular headache, vasculitic syndromes (including Henoch-Schonlein purpura), ventricular extrasystoles, and ventricular fibrillation have also been reported.
Paroxetine- induced hyponatremia may be more common in elderly female patients and those who are volume depleted or are receiving concomitant diuretic therapy.
Endocrine side effects have included diabetes mellitus, goiter, hyperthyroidism, hypothyroidism, and thyroiditis. Hyperprolactinemia, hyponatremia, and the syndrome of inappropriate antidiuretic hormone (SIADH) are increasingly being associated with selective serotonin reuptake inhibitors including paroxetine. A case of severe life-threatening hyponatremia in a patient receiving paroxetine has been reported.
The mechanism of paroxetine- induced bleeding may be related to drug-induced platelet dysfunction.
Hematologic side effects have included anemia, leukopenia, lymphadenopathy, purpura, abnormal erythrocytes, basophilia, increased bleeding time, eosinophilia, hypochromic anemia, iron deficiency anemia, leukocytosis, lymphedema, abnormal lymphocytes, lymphocytosis, microcytic anemia, monocytosis, normocytic anemia, thrombocythemia, thrombocytopenia, hemolytic anemia, and events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis). Several cases have also been reported suggesting that paroxetine may cause bleeding in patients with normal bleeding times, platelet counts, prothrombin times, and partial thromboplastin times.
A withdrawal syndrome, similar to that seen in other selective serotonin reuptake inhibitors, has been reported. Recent clinical trials by the manufacturer reported withdrawal events to be serious in 0.3% of patients who discontinued therapy with controlled-release paroxetine (the active ingredient contained in Paxil) tablets. Patients discontinuing paroxetine have complained of vertigo, lightheadedness, gait instability, malaise, myalgia, middle insomnia, nausea, emesis, diarrhea, and/or visual phenomena (similar to that associated with migraine) during withdrawal. Two cases of behavioral syndromes including severe aggressive and suicidal impulsivity following paroxetine withdrawal have been reported. One case of withdrawal hypomania has been reported. One case of unilateral facial numbness with blurred peripheral vision has also been reported upon withdrawal.
In one retrospective chart review of 352 patients who were supervised during tapering and discontinuation from serotonin reuptake inhibitor therapy, dizziness, lethargy, paresthesia, nausea, vivid dreams, irritability, and lowered mood were the most common symptoms reported. Patients with at least one qualitatively new symptom were defined in the paroxetine group at a rate of 17.2%.
Patients should be monitored for symptoms when discontinuing treatment. A gradual reduction in dosage rather than abrupt discontinuation of therapy is recommended when possible. If intolerable symptoms occur following discontinuation of therapy, then resumption of the previous dose may be considered. Subsequently, discontinuation of therapy may be retried at a more gradual rate.
Other side effects have frequently included headache (15% to 27%), asthenia (14% to 22%), infection (6% to 8%), abdominal pain (4% to 7%), chest pain (3%), back pain (3% to 5%), chills (2%), migraine (1%), and trauma (3% to 8%). Face edema, withdrawal syndrome, malaise, neck pain, adrenergic syndrome, cellulitis, moniliasis, neck rigidity, pelvic pain, sepsis, ulcer, ear pain, tinnitus, otitis media, deafness, pallor, hyperacusis, otitis externa, parosmia, Guillain-Barre syndrome, and neuroleptic malignant syndrome- like reaction.
Renal side effects have included acute renal failure.
Respiratory side effects have frequently included respiratory disorder (7%), sinusitis (4% to 8%), yawn (2% to 5%), rhinitis (3% to 4%), increased cough (1% to 2%), bronchitis (1% to 2%), and pharyngitis (4%). Asthma, dyspnea, epistaxis, hyperventilation, pneumonia, respiratory flu, emphysema, hemoptysis, hiccups, lung fibrosis, pulmonary edema, pulmonary embolus, increased sputum, stridor, porphyria, laryngismus, and alteration in voice have also been reported.
Hypersensitivity side effects have included allergic reactions in up to 2% of patients including allergic alveolitis and anaphylaxis.
Hepatic side effects have included a single case of severe hepatotoxicity with jaundice. Hepatitis and abnormal liver function tests have been reported rarely.
The manufacturer states that in placebo-controlled clinical trials patients receiving paroxetine experienced abnormal values on liver function tests at a rate equal to or less than that reported in patients receiving placebo. However, there have been postmarketing reports of patients developing elevated serum transaminases resulting in severe liver dysfunction, as well as, a few cases of elevated liver function tests resulting in death secondary to liver necrosis.
Ocular side effects have frequently included blurred vision (4%), abnormality of accommodation (2%), and abnormal vision (2% to 5%). Conjunctivitis, eye pain, keratoconjunctivitis, mydriasis, amblyopia, anisocoria, blepharitis, cataract, conjunctival edema, corneal ulcer, diplopia, exophthalmos, eye hemorrhage, glaucoma, night blindness, photophobia, ptosis, retinal hemorrhage, optic neuritis, and visual field effect have also been reported.
Musculoskeletal side effects have frequently included myopathy (2%), myalgia (2% to 5%), myasthenia (1%), and arthralgia (2%). Arthritis, arthrosis, bursitis, myositis, osteoporosis, generalized spasm, tenosynovitis, and tetany have also been reported. A single case of bruxism has been reported. Postmarketing reports have included restless legs syndrome.
In one study using the healthcare data from the providence of Ontario, Canada reviewing 8239 patients treated for hip fractures, the adjusted odds ratio for hip fracture was 2.4 for exposure to selective serotonin reuptake inhibitors (including fluoxetine, fluvoxamine, paroxetine, and sertraline), compared to participants who had no exposure to antidepressants.
Controlled studies reported an average weight loss of approximately 1 pound per patient versus smaller changes reported with placebo.
The results of one study appear to indicate that treatment with selective serotonin reuptake inhibitors (i.e., paroxetine (the active ingredient contained in Paxil) sertraline, citalopram) may cause an increase in serum total cholesterol, HDL cholesterol, and/or LDL cholesterol. However, additional studies are necessary to confirm these findings.
Numerous cases of hyponatremia have been reported following treatment with a selective serotonin reuptake inhibitor (SSRI). Risk factors for the development of SSRI- associated hyponatremia including advanced age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium levels have been identified. Hyponatremia tends to develop within the first few weeks of treatment (range 3 to 120 days) and typically resolves within 2 weeks (range 48 hours to 6 weeks) after therapy has been discontinued with some patients requiring treatment. The proposed mechanism for the development of hyponatremia involves the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) via release of antidiuretic hormone.
Metabolic side effects have frequently included weight gain (3%) and weight loss (1%). Edema, peripheral edema, thirst, bilirubinemia, dehydration, gout, hypercalcemia, hypercholesteremia, hyperglycemia, hyperkalemia, hyperphosphatemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, porphyria, and ketosis have also been reported. In addition, increased levels of SGOT, SGPT, alkaline phosphatase, BUN, creatinine phosphokinase, gamma globulins, lactic dehydrogenase, and non- protein nitrogen (NPN) have been reported. An increase in serum cholesterol has been reported following use of paroxetine.
General side effects including abnormal bleeding have been reported.