Paroxetine is indicated for the treatment of:

• Major Depressive Disorder
• Obsessive Compulsive Disorder (OCD)
• Panic Disorder
• Social Anxiety Disorder
• Generalized Anxiety Disorder
• Post-Traumatic Stress Disorder (PTSD)

The therapeutic effect of Paroxetine is believed to be associated with enhancement of serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin (5-hydroxytryptamine, 5-HT). At clinically relevant doses, Paroxetine has been shown to block serotonin uptake into human platelets. Animal and in vitro studies indicate that Paroxetine is a potent and selective inhibitor of serotonin reuptake with minimal effects on norepinephrine and dopamine reuptake. Receptor binding studies show that Paroxetine has little affinity for muscarinic, alpha1, alpha2, beta-adrenergic, dopamine (D2), 5-HT1, 5-HT2, and histamine (H1) receptors. Therefore, it is less likely to produce anticholinergic, sedative, or cardiovascular side effects commonly associated with other psychotropic drugs. Its major metabolites have very low activity (less than 1/50 of the parent compound) and are considered clinically inactive.

Major Depressive Disorder:

• Usual Initial Dosage: Paroxetine (Paroxetine hydrochloride) should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dose is 20 mg/day. Some patients not responding to a 20 mg dose may benefit from dose increases, in 10 mg/day increments, up to a maximum of 50 mg/day. Dose changes should occur at intervals of at least 1 week.
• Maintenance Therapy: Systematic evaluation of the efficacy of Paroxetine hydrochloride has shown that efficacy is maintained for periods of up to 1 year with doses that averaged about 30 mg.

Obsessive Compulsive Disorder (OCD):

• Usual Initial Dosage: Paroxetine (Paroxetine hydrochloride) should be administered as a single daily dose with or without food, usually in the morning. The recommended dose of Paroxetine in the treatment of OCD is 40 mg daily. Patients should be started on 20 mg/day and the dose can be increased in 10 mg/day increments. Dose changes should occur at intervals of at least 1 week.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Panic Disorder:

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The target dose of Paroxetine in the treatment of panic disorder is 40 mg/day. Patients should be started on 10 mg/day. Dose changes should occur in 10 mg/day increments and at intervals of at least 1 week. The maximum dosage should not exceed 60 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Social Anxiety Disorder (SAD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dosage is 20 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Generalized Anxiety Disorder (GAD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended starting dosage and the established effective dosage is 20 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Posttraumatic Stress Disorder (PTSD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended starting dosage and the established effective dosage is 20 mg/day. Dose changes, if indicated, should occur in 10 mg/day increments and at intervals of at least 1 week.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Food/antacids: The absorption and pharmacokinetics of Paroxetine are not affected by food or antacids.

Tryptophan: As with other serotonin (5-HT) reuptake inhibitors, animal studies suggest that Paroxetine may interact with Tryptophan, potentially leading to serotonin syndrome characterized by agitation, restlessness, and gastrointestinal symptoms such as diarrhea.

Drug metabolizing enzyme inducers/inhibitors: The metabolism and pharmacokinetics of Paroxetine may be influenced by drugs that induce or inhibit hepatic enzymes. When used with enzyme inhibitors, lower doses of Paroxetine may be considered. No initial dose adjustment is required with enzyme inducers, but further dosing should be guided by clinical response (tolerability and efficacy).

Alcohol: Paroxetine does not significantly enhance alcohol-induced impairment of mental or motor function; however, concurrent use with alcohol is not recommended in patients with depression.

Haloperidol/amylobarbitone/oxazepam: Limited studies in healthy subjects show that Paroxetine does not increase sedation or drowsiness when used with these medications.

MAOIs: As with other serotonergic drugs, interactions with monoamine oxidase inhibitors (MAOIs) may occur and can be serious.

Lithium: Due to limited clinical experience and reported interactions with other serotonergic agents, co-administration should be done with caution. Lithium levels should be monitored.

Phenytoin/anticonvulsants: Co-administration may reduce Paroxetine plasma levels and increase adverse effects. Other anticonvulsants may also increase the risk of side effects.

Warfarin: Preliminary data suggest a pharmacodynamic interaction that may increase bleeding risk without affecting prothrombin time. Caution is required in patients receiving oral anticoagulants.

Concomitant use with monoamine oxidase inhibitors (MAOIs) or thioridazine is contraindicated. Paroxetine is also contraindicated in patients with known hypersensitivity to the drug.

Major depressive disorder: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders.

Obsessive compulsive disorder: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence, and abnormal ejaculation.

Panic disorder: Asthenia, sweating, decreased appetite, decreased libido, tremor, abnormal ejaculation, female genital disorders, and impotence.

Social anxiety disorder: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, decreased libido, yawning, abnormal ejaculation, female genital disorders, and impotence.

Generalized anxiety disorder: Asthenia, infections, constipation, decreased appetite, dry mouth, nausea, decreased libido, somnolence, tremor, sweating, and abnormal ejaculation.

Post-traumatic stress disorder: Asthenia, sweating, nausea, dry mouth, diarrhea, decreased appetite, somnolence, decreased libido, abnormal ejaculation, female genital disorders, and impotence.

This drug should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.

Labor and delivery: The effect of Paroxetine on labor and delivery in humans is unknown.

Nursing mothers: Paroxetine is excreted in human breast milk. Caution should be exercised when administering it to breastfeeding women.

Cardiac conditions: Paroxetine does not cause clinically significant changes in blood pressure, heart rate, or ECG. However, as with all psychoactive drugs, caution is advised in patients with cardiac disease.

Epilepsy: As with other antidepressants, Paroxetine should be used with caution in patients with epilepsy.

Seizures: The overall incidence of seizures in patients treated with Paroxetine is less than 0.1%. Paroxetine should be discontinued if a patient develops seizures.

ECT: There is limited clinical experience with the concurrent use of Paroxetine and electroconvulsive therapy (ECT).

Ability to drive/use machines: Clinical studies show that Paroxetine is not associated with impairment of cognitive or psychomotor function. However, patients should still be cautioned regarding driving or operating machinery, as with all psychoactive medications.

Discontinuation of treatment: Clinical trials generally used a gradual dose reduction rather than abrupt discontinuation. In GAD and PTSD studies, the dose was reduced by 10 mg per day at weekly intervals until 20 mg/day was reached, then continued for one week before stopping.

Elderly, debilitated patients, and patients with severe renal or hepatic impairment: The recommended starting dose is 10 mg/day. Dose may be increased if necessary, but should not exceed 40 mg/day.

Selective Serotonin Reuptake Inhibitors (SSRIs) & related antidepressant drugs

Keep out of reach of children. Store in a cool, dry place. Protect from light and moisture.