Seroxat/Seroxat CR Special Precautions

Seroxat: Treatment with paroxetine should be initiated cautiously two weeks after terminating treatment with an irreversible MAOI or 24 hours after terminating treatment with a reversible MAO inhibitor. Dosage of paroxetine should be increased gradually until an optimal response is reached (see Contraindications and Interactions).
Suicide/suicidal thoughts or clinical worsening: Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.
Other psychiatric conditions for which paroxetine is prescribed can be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with Major Depressive Disorder (MDD). The same precautions observed when treating patients with MDD should therefore be observed when treating patients with other psychiatric disorders.
Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at a greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old (see Pharmacology: Pharmacodynamics under Actions).
Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients, (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.
Akathisia/psychomotor restlessness: The use of paroxetine has been associated with the development of akathisia, which is characterised by an inner sense of restlessness and psychomotor agitation such as an inability to sit or stand still usually associated with subjective distress. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
Serotonin Syndrome/Neuroleptic Malignant Syndrome: On rare occasions development of a serotonin syndrome or neuroleptic malignant syndrome-like events may occur in association with treatment of paroxetine, particularly when given in combination with other serotonergic and/or neuroleptic drugs. As these syndromes may result in potentially life-threatening conditions, treatment with paroxetine should be discontinued if such events (characterised by clusters of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes including confusion, irritability, extreme agitation progressing to delirium and coma) occur and supportive symptomatic treatment should be initiated. Paroxetine should not be used in combination with serotonin-precursors (such as L-tryptophan, oxitriptan) due to the risk of serotonergic syndrome (see Contraindications and Interactions).
Mania: As with all antidepressants, paroxetine should be used with caution in patients with a history of mania. Paroxetine should be discontinued in any patient entering a manic phase.
Renal/hepatic impairment: Caution is recommended in patients with severe renal impairment or in those with hepatic impairment (see Dosage & Administration).
Diabetes: In patients with diabetes, treatment with an SSRI may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted. Additionally, there have been studies suggesting an increase in blood glucose levels may occur when paroxetine and pravastatin are co-administered (see Interactions).
Epilepsy: As with other antidepressants, paroxetine should be used with caution in patients with epilepsy.
Seizures: Overall the incidence of seizures is <0.1% in patients treated with paroxetine. The drug should be discontinued in any patient who develops seizures.
Electroconvulsive therapy (ECT): There is little clinical experience of the concurrent administration of paroxetine with ECT.
Glaucoma: As with other SSRIs, paroxetine can cause mydriasis and should be used with caution in patients with narrow angle glaucoma or history of glaucoma.
Cardiac Conditions: The usual precautions should be observed in patients with cardiac conditions.
Hyponatraemia: Hyponatraemia has been reported rarely, predominantly in the elderly. Caution should also be exercised in those patients at risk of hyponatraemia e.g. from concomitant medications and cirrhosis. The hyponatraemia generally reverses on discontinuation of paroxetine.
Haemorrhage: There have been reports of cutaneous bleeding abnormalities such as ecchymoses and purpura with SSRIs. Other haemorrhagic manifestations e.g. gastrointestinal and gynaecological haemorrhage have been reported. Elderly patients may be at an increased risk for non-menses related events of bleeding.
Caution is advised in patients taking SSRIs concomitantly with oral anticoagulants, drugs known to affect platelet function or other drugs that may increase risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazines, most TCAs, acetylsalicylic acid, NSAIDs, COX-2 inhibitors) as well as in patients with a history of bleeding disorders or conditions which may predispose to bleeding (see Adverse Reactions).
Interaction with tamoxifen: Paroxetine, a potent inhibitor of CYP2D6, may lead to reduced concentrations of endoxifen, one of the most important active metabolites of tamoxifen. Therefore, paroxetine should whenever possible be avoided during tamoxifen treatment (see Interactions).
Drugs affecting gastric pH: In patients receiving oral suspension, the paroxetine plasma concentration may be influenced by gastric pH. In vitro data have shown that an acidic environment is required for release of the active drug from the suspension, hence absorption may be reduced in patients with a high gastric pH or achlorhydria, such as after the use of certain drugs (antacid drugs, histamine H2-receptor antagonists, proton pump inhibitors), in certain disease states (e.g. atrophic gastritis, pernicious anemia, chronic Helicobacter pylori infection), and after surgery (vagotomy, gastrectomy). The pH dependency should be taken into account when changing paroxetine formulation (e.g. the plasma paroxetine concentration may decrease after changing from tablet to oral suspension in patients with a high gastric pH). Caution is therefore recommended in patients when initiating or ending treatment with drugs increasing gastric pH. Dose adjustments may be necessary in such situations.
Withdrawal symptoms seen on discontinuation of SEROXAT treatment: Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt (see Adverse Reactions). In clinical trials adverse events seen on treatment discontinuation occurred in 30% of patients treated with paroxetine compared to 20% of patients treated with placebo. The occurrence of withdrawal symptoms is not the same as the drug being addictive or dependence producing.
The risk of withdrawal symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction.
Dizziness, sensory disturbances (including paraesthesia, electric shock sensations and tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances have been reported. Generally these symptoms are mild to moderate; however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose. Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that paroxetine should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs (see Dosage & Administration).
Effects on ability to drive and use machines: Clinical experience has shown that therapy with paroxetine is not associated with impairment of cognitive or psychomotor function. However, as with all psychoactive drugs, patients should be cautioned about their ability to drive a car and operate machinery.
Although paroxetine does not increase the mental and motor skill impairments caused by alcohol, the concomitant use of paroxetine and alcohol is not advised.
Use in children: Paroxetine should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
Seroxat CR: General: Potential Association with Behavioural and Emotional Changes, including Self-Harm.
Rigorous clinical monitoring for suicidal ideation or other indicators of potential for suicidal behaviour is advised in patients of all ages. This includes monitoring for agitation-type emotional and behavioural changes.
An FDA meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients ages 18 to 24 years with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressant compared to placebo.
Discontinuation Symptoms: Patients currently taking SEROXAT CR should NOT be discontinued abruptly, due to risk of discontinuation symptoms. At the time that a medical decision is made to discontinue an SSRI or other newer antidepressant drug, a gradual reduction in the dose rather than an abrupt cessation is recommended.
Discontinuation of Treatment with SEROXAT CR: When discontinuing treatment, patients should be monitored for symptoms which may be associated with discontinuation (e.g. dizziness, sleep disturbances including abnormal dreams, sensory disturbances (including paresthesias, electric shock sensations and tinnitus), agitation, anxiety, headache, tremor, confusion, diarrhea, nausea, vomiting and sweating) or other symptoms which may be of clinical significance [see Adverse Reactions]. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should be managed on the basis of the patient's clinical response. (See Adverse Reactions and Dosage & Administration).
SEROXAT CR Treatment During Pregnancy Effects on Newborns: Epidemiological studies of pregnancy outcomes following maternal exposure to antidepressants in the first trimester have reported an increase in the risk of congenital malformations, particularly cardiovascular (e.g. ventricular and atrial septal defects), associated with the use of paroxetine. If a patient becomes pregnant while taking SEROXAT CR, consideration should be given to switching to other treatment options. Treatment with SEROXAT CR should only be continued for an individual pregnant patient, if the potential benefits outweigh the potential risks. Initiation of paroxetine, for women who intend to become pregnant, or are in their first trimester of pregnancy, should be considered only after other treatment options have been evaluated (see Precautions).
Post-marketing reports indicate that some neonates exposed to SEROXAT CR, SSRIs (Selective Serotonin Reuptake Inhibitors), or other newer antidepressants late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. When treating a pregnant woman with SEROXAT CR during the third trimester, the physician should carefully consider the potential risks and benefits of treatment (see Precautions and Dosage & Administration).
Potential for reduced efficacy of Tamoxifen with concomitant SSRI use, including SEROXAT CR: The antitumor agent tamoxifen is a pro-drug requiring metabolic activation by CYP2D6. Inhibition of CYP2D6 can lead to reduced plasma concentrations of a primary active metabolite (endoxifen). Chronic use of CYP2D6 inhibitors, including certain SSRIs, together with tamoxifen can lead to persistent reduction in levels of endoxifen (see Interactions). Some studies have shown that the efficacy of tamoxifen, as measured by the risk of breast cancer relapse/mortality, may be reduced when coprescribed with SEROXAT CR as a result of paroxetine's irreversible inhibition of CYP2D6. This risk may increase with longer duration of coadministration. When tamoxifen is used for the treatment of breast cancer, prescribers should consider using an alternative antidepressant with little or no CYP2D6 inhibition.
Psychomotor Impairment: Although paroxetine did not cause sedation or interfere with psychomotor performance in placebo-controlled studies in normal subjects, patients should be advised to avoid driving a car or operating hazardous machinery until they are reasonably certain that SEROXAT CR does not affect them adversely.
Bone fracture risk: Epidemiological studies show an increased risk of bone fracture following exposure to some antidepressants, including SSRIs. The risks appear to be greater at the initial stages of treatment, but significant increased risks were also observed at later stages of treatment. The possibility of fracture should be considered in the care of patients treated with SEROXAT CR. Elderly patients and patients with important risk factors for bone fractures should be advised of possible adverse events which increase the risk of falls, such as dizziness and orthostatic hypotension, especially at the early stages of treatment but also soon after withdrawal.
Preliminary data from observational studies show association of SSRIs and low bone mineral density in older men and women. Until further information becomes available, a possible effect on bone mineral density with long-term treatment with SSRIs, including SEROXAT CR, cannot be excluded, and may be a potential concern for patients with osteoporosis or major risk factors for bone fractures.
The following additional precautions are listed alphabetically.
Carcinogenesis and Mutagenesis: See Pharmacology: Toxicology: Preclinical safety data under Actions.
Cardiovascular: SEROXAT CR or immediate-release paroxetine have not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. The usual precautions should be observed in patients with cardiac conditions.
Concomitant Illnesses: Clinical experience with SEROXAT CR or immediate-release paroxetine in patients with certain concomitant systemic illnesses is limited. Caution is advisable in using SEROXAT CR in patients with diseases or conditions that could affect metabolism or hemodynamic responses.
Dependence Liability: SEROXAT CR or immediate-release paroxetine have not been systematically studied, in animals or humans, for its potential for abuse, tolerance, or physical dependence. Physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of SEROXAT CR.
Endocrine and Metabolism: Serum Cholesterol Elevation: Several public domain studies have shown increased LDL-cholesterol levels of ~10% in volunteers and patients taking paroxetine for 8 to 12 weeks, which generally normalized after paroxetine discontinuation. In addition, of the patients in placebo-controlled clinical trials for whom baseline and on-treatment measurements were taken, total serum levels of cholesterol showed a mean increase of ~ 1.5 mg/dL in paroxetine-treated patients (n = 653), compared to a mean decrease of ~ 5.0 mg/dL in placebo-treated patients (n = 379). Increases from baseline of 45 mg/dL or greater were recorded in 6.6% of paroxetine-treated patients compared to 2.6% of placebo-treated patients (see Monitoring and Laboratory Tests, Serum Cholesterol Elevation). These data should be taken into consideration when treating patients with underlying cardiac risk factors.
Hematologic: Abnormal Bleeding: SSRIs including SEROXAT CR may increase the risk of bleeding events by causing abnormal platelet aggregation. Concomitant use of acetylsalicylic acid (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin and other anticoagulants may add to the risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening haemorrhages. Gastrointestinal and gynaecological bleeding have also been reported following treatment with SEROXAT CR.
Patients should be cautioned about the risk of bleeding associated with the concomitant use of SEROXAT CR and NSAIDs, ASA, or other drugs that affect coagulation (see Interactions). Caution is advised in patients with a history of bleeding disorder or predisposing conditions (e.g. thrombocytopenia). (See Adverse Reactions.)
Hepatic/Biliary/Pancreatic: Hepatic Impairment: Pharmacokinetic studies of immediate-release paroxetine in subjects with clinically significant hepatic impairment suggest that prolongation of the elimination half-life and increased plasma levels can be expected in this patient group. SEROXAT CR should be used with caution and dosages restricted to the lower end of the range in patients with clinically significant hepatic impairment (see Dosage & Administration and Pharmacology under Actions).
Neurologic: Epilepsy: As with other antidepressants, SEROXAT CR should be used with caution in patients with epilepsy.
Seizures: During clinical trials, the overall incidence of seizures was 0.15% in patients treated with immediate-release paroxetine. However, patients with a history of convulsive disorders were excluded from these studies. Caution is recommended when the drug is administered to patients with a history of seizures. The drug should be discontinued in any patient who develops seizures.
Serotonin Syndrome/Neuroleptic Malignant Syndrome: On rare occasions serotonin syndrome or neuroleptic malignant syndrome-like events have occured in association with treatment of SEROXAT CR, particularly when given in combination with other serotonergic and/or neuroleptic/antipsychotic drugs. As these syndromes may result in potentially life-threatening conditions, treatment with SEROXAT CR should be discontinued if patients develop a combination of symptoms possibly including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes including confusion, irritability, extreme agitation progressing to delirium and coma, and supportive symptomatic treatment should be initiated. Due to the risk of serotonergic syndrome or neuroleptic malignant syndrome SEROXAT CR should not be used in combination with MAO inhibitors [including methylthioninium chloride (methylene blue)] or serotonin precursors (such as L-tryptophan, oxitriptan) and should be used with caution in patients receiving other serotonergic drugs (e.g., triptans, lithium, tramadol, St. John's Wort, most tricyclic antidepressants) or neuroleptics/antipsychotics (see Contraindications and Interactions).
Ophthalmologic: Angle-Closure Glaucoma: As with other antidepressants, SEROXAT CR can cause mydriasis which may trigger an angle-closure attack in a patient with anatomically narrow ocular angles. Caution should be used when paroxetine is prescribed for patients with untreated narrow angles. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients should be informed to seek immediate medical assistance if they experience eye pain, changes in vision or swelling or redness in or around the eye.
Psychiatric: Suicide: The possibility of a suicide attempt is inherent in depression and may persist until remission occurs. Patients with depression may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviours (suicidality) whether or not they are taking antidepressant medications. Notwithstanding, high risk patients should be closely supervised throughout therapy with appropriate consideration to the possible need for hospitalization. In order to minimize the opportunity for overdosage, prescriptions for SEROXAT CR should be written for the smallest quantity of drug consistent with good patient management.
Because of the well established comorbidity between depression and other psychiatric disorders, the same precautions observed when treating patients with depression should be observed when treating patients with other psychiatric disorders (see Precautions).
Activation of Mania/Hypomania: During clinical testing in a patient population comprised primarily of unipolar depressed patients, approximately 1% of patients treated with immediate-release paroxetine experienced manic reactions. When bipolar patients were considered as a sub-group the incidence of mania was 2%. As with all drugs effective in the treatment of depression, SEROXAT CR should be used with caution in patients with a history of mania. A major depressive episode may be the initial presentation of bipolar disorder. Patients with bipolar disorder may be at an increased risk of experiencing manic episodes when treated with antidepressants alone. Therefore, the decision to initiate symptomatic treatment of depression should only be made after patients have been adequately assessed to determine if they are at risk for bipolar disorder.
Electroconvulsive Therapy (ECT): The efficacy and safety of the concurrent use of SEROXAT CR and ECT have not been studied.
Renal: Hyponatremia: Several cases of hyponatremia have been reported. The hyponatremia appeared to be reversible when immediate-release paroxetine was discontinued. The majority of these occurrences have been in elderly individuals, some in patients taking diuretics or who were otherwise volume depleted.
Renal Impairment: Since SEROXAT CR is extensively metabolized by the liver; excretion of unchanged drug in urine is a minor route of elimination. However, single dose pharmacokinetic studies in subjects with clinically significant renal impairment suggest that plasma levels of paroxetine are elevated in such subjects. Paroxetine should therefore be used with caution and the dosage restricted to the lower end of the range in patients with clinically significant renal impairment (see Dosage & Administration and Pharmacology under Actions).
Sexual Function/Reproduction: Some clinical studies have shown that SSRIs (including paroxetine) may affect sperm quality. This effect appears to be reversible following discontinuation of treatment. Changes in sperm quality may affect fertility in some men (see also Pharmacology: Toxicology: Preclinical safety data under Actions).
Monitoring and Laboratory Tests Serum Cholesterol Elevation: Of the patients in placebo-controlled clinical trials for whom baseline and on-treatment measurements were taken, increases from baseline of 45 mg/dL or greater were recorded in 6.6% of paroxetine-treated patients compared to 2.6% of placebo-treated patients (see Adverse Reactions and Precautions). These data should be taken into consideration when treating patients with underlying cardiac risk factors.
Special Populations: Pregnant Women and Newborns: Risk of Cardiovascular Malformations following first trimester exposure to SSRIs: Epidemiological studies of pregnancy outcomes following maternal exposure to antidepressants in the first trimester have reported an increase in the risk of congenital malformations, particularly cardiovascular (e.g. ventricular and atrial septal defects), associated with the use of paroxetine. The data suggest that the risk of having an infant with a cardiovascular defect following maternal paroxetine exposure is approximately 1/50 (2%), compared with an expected rate for such defects of approximately 1/100 (1%) infants in the general population. In general, septal defects range from those that are symptomatic and may require surgery, to those that are asymptomatic and may resolve spontaneously. Information about the severity of the septal defects reported in the studies is not available.
While on SEROXAT CR: Pregnancy, or intent to become pregnant: If a patient becomes pregnant while taking SEROXAT CR, or intends to become pregnant, she should be informed of the current estimate of increased risk to the fetus with SEROXAT CR over other antidepressants. Examinations of additional databases, as well as updated analyses, may result in changes to the current risk estimates. Consideration should be given to switching to other treatment options, including another antidepressant or non-pharmaceutical treatment such as cognitive behavioural therapy. Treatment with SEROXAT CR should only be continued for an individual patient, if the potential benefits outweigh the potential risks. Due to the potential for discontinuation symptoms, if a decision is taken to discontinue SEROXAT CR treatment, a gradual reduction in the dose rather than an abrupt cessation is recommended (see Precautions, Adverse Reactions and Dosage & Administration).
Complications following late third trimester exposure to SSRIs: Post-marketing reports indicate that some neonates exposed to SEROXAT CR, SSRIs (Selective Serotonin Reuptake Inhibitors), or other newer antidepressants late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and other newer antidepressants, or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome (see Precautions). When treating a pregnant woman with SEROXAT CR during the third trimester, the physician should carefully consider the potential risks and benefits of treatment (see Dosage & Administration).
There have been post-marketing reports of premature birth in pregnant women exposed to paroxetine or other SSRIs. The causal relationship between SEROXAT CR and the emergence of these events has not been established.
Risk of PPHN and exposure to SSRIs (including paroxetine): Epidemiological studies on persistent pulmonary hypertension of the newborn (PPHN) have shown that the use of SSRIs (including SEROXAT CR) in pregnancy, particularly use in late pregnancy, was associated with an increased risk of PPHN. PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy (Odds Ratio 6.1, 95% CI 2.2-16.8). A study using data from the Swedish Medical Birth Register for 831,324 infants born in 1997-2005 found an increased risk of PPHN of approximately 2-fold associated with patient-reported maternal use of SSRIs in the first trimester of pregnancy (Risk Ratio 2.4, 95% CI 1.2-4.3), and an increased risk of PPHN of approximately 4-fold associated with a combination of patient-reported maternal use of SSRIs in the first trimester and an antenatal SSRI prescription in later pregnancy (Risk Ratio 3.6, 95% CI 1.2-8.3).
Nursing Women: The concentrations of paroxetine detected in the breast milk of lactating women are similar to those in the mother's plasma. Lactating women should not nurse their infants while receiving paroxetine unless in the opinion of the treating physician, breast feeding is necessary, in which case the infant should be closely monitored.
Pediatrics (< 18 years of age): SEROXAT CR is not indicated for use in patients below the age of 18 years (see Precautions, Indications and Dosage & Administration).
Controlled clinical studies in depression failed to demonstrate efficacy and do not support the use of paroxetine in the treatment of children under the age of 18 years with depression. Moreover, a higher incidence of adverse events related to behavioural and emotional changes, including self harm, was reported with paroxetine treatment compared to placebo during controlled clinical trials in depression, OCD and social anxiety disorder (see Adverse Reactions).
Geriatrics (≥ 65 years of age): Administration of SEROXAT CR to the elderly is associated with increased plasma levels and prolongation of the elimination half life relative to younger adults (see Pharmacology under Actions). Elderly patients should be initiated and maintained at the lowest daily dose of paroxetine which is associated with clinical efficacy (see Dosage & Administration).
Evaluation of approximately 800 elderly patients (≥ 65 years) treated with immediate-release paroxetine (10-40 mg daily) in worldwide premarketing clinical trials revealed no unusual pattern of adverse events relative to the clinical experience in younger patients.
In a controlled study focusing specifically on elderly patients with depression, SEROXAT CR (12.5-50 mg daily) was demonstrated to be safe and effective in the treatment of elderly patients (> 60 years of age) with depression (see Pharmacology: Pharmacodynamics: Clinical Trials under Actions and Adverse Reactions). However, it is not possible to rule out potential age-related differences in safety and effectiveness during chronic use, particularly in elderly patients who have concomitant systemic illnesses or who are receiving concomitant drugs.
Use in Children: Placebo-Controlled Clinical Trial Data: Recent analyses of placebo-controlled clinical trial safety databases from SSRIs and other newer antidepressants suggests that use of these drugs in patients under the age of 18 may be associated with behavioural and emotional changes, including an increased risk of suicidal ideation and behaviour over that of placebo.
The small denominators in the clinical trial database, as well as the variability in placebo rates, preclude reliable conclusions on the relative safety profiles among these drugs.
Adult and Pediatrics: Additional data: There are clinical trial and post-marketing reports with SSRIs and other newer antidepressants, in both pediatrics and adults, of severe agitation-type adverse events coupled with self-harm or harm to others. The agitation-type events include: akathisia, agitation, disinhibition, emotional lability, hostility, aggression, and depersonalization. In some cases, the events occurred within several weeks of starting treatment.