Paroxetine Hydrochloride

Approved Indications:

• Major Depressive Disorder (MDD): Treatment of moderate to severe unipolar depression in adults.
• Generalized Anxiety Disorder (GAD): Approved for long-term management of excessive anxiety and worry.
• Panic Disorder (with or without agoraphobia): Effective in reducing panic attack frequency and severity.
• Social Anxiety Disorder (Social Phobia): Approved for treating persistent fear and avoidance in social situations.
• Obsessive-Compulsive Disorder (OCD): Reduces the frequency and severity of obsessions and compulsions.
• Post-Traumatic Stress Disorder (PTSD): Used for the management of intrusive symptoms and hyperarousal.
• Premenstrual Dysphoric Disorder (PMDD): Alleviates irritability, tension, and mood disturbances.

Clinically Accepted Off-label Uses:

• Vasomotor Symptoms in Menopause (Hot Flashes): Used in women who cannot take hormone therapy.
• Premature Ejaculation: Low-dose paroxetine is used to prolong ejaculatory latency.
• Chronic Pain Syndromes (e.g., fibromyalgia): Occasionally used as an adjunct in treatment.

Route of Administration: Oral
Dosage Forms: Immediate-release tablets, controlled-release tablets, oral suspension

Adults:

• Major Depressive Disorder:
  Initial: 20 mg once daily (morning)
  Maintenance: 20–50 mg/day
  Maximum: 50 mg/day
• Panic Disorder:
  Initial: 10 mg once daily
  Increase by 10 mg/week
  Usual: 20–40 mg/day
  Maximum: 60 mg/day
• OCD, PTSD, GAD, Social Anxiety Disorder:
  Initial: 20 mg once daily
  Maintenance: 20–50 mg/day
  Maximum: 60 mg/day
• PMDD (Controlled-Release):
  Continuous Dosing: Start at 12.5 mg/day
  Titration: Up to 25 mg/day
  Luteal Phase Dosing: 12.5–25 mg/day from day 14 to start of menses
• Premature Ejaculation (off-label):
  10–20 mg taken daily or 3–6 hours before intercourse

Geriatric Patients:

• Initial: 10 mg/day
• Maximum: 40 mg/day
• Titrate slowly due to increased sensitivity to side effects

Pediatric Use:

• Not FDA-approved; safety and efficacy not established for depression

Renal or Hepatic Impairment:

• Initial: 10 mg/day
• Maximum: 40 mg/day
• Caution advised due to reduced drug clearance

Administration Advice:

• Administer with or without food
• Controlled-release tablets must be swallowed whole
• Taper gradually when discontinuing to avoid withdrawal symptoms

Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI). It blocks the serotonin transporter (SERT) in presynaptic neurons, preventing the reuptake of serotonin (5-HT) and increasing its concentration in the synaptic cleft. This enhanced serotonergic activity contributes to improved mood, reduced anxiety, and suppression of obsessive-compulsive behaviors. Unlike tricyclic antidepressants, paroxetine has minimal action on noradrenaline or dopamine reuptake and negligible affinity for muscarinic, histaminergic, or adrenergic receptors, minimizing anticholinergic and sedative side effects.

• Absorption: Rapid and well absorbed; oral bioavailability ~50% due to first-pass hepatic metabolism
• Peak Plasma Time: 5–8 hours (immediate-release); 8–10 hours (controlled-release)
• Distribution: Volume of distribution ~3–28 L/kg; protein binding ~95%
• Metabolism: Extensively metabolized in the liver primarily by CYP2D6
• Active Metabolites: None of clinical relevance
• Elimination: 64% in urine, 36% in feces (mainly as metabolites)
• Half-life: Approximately 21–24 hours; may be prolonged in elderly or hepatic dysfunction

• Pregnancy:
  Former FDA Category D – Use in the first trimester is associated with increased risk of congenital heart defects and persistent pulmonary hypertension of the newborn (PPHN). Use only if clearly needed.
  Paroxetine should be avoided especially during the first trimester unless no safer alternative is available.
• Lactation:
  Paroxetine is excreted into breast milk in low concentrations. It is generally considered acceptable for breastfeeding, but infants should be monitored for irritability, poor feeding, or sedation. Prefer alternatives if risk outweighs benefit.

• Primary Class: Antidepressant
• Subclass: Selective Serotonin Reuptake Inhibitor (SSRI)
• Generation: Second-generation antidepressant

• Known hypersensitivity to paroxetine or any formulation component
• Concurrent use or recent use (within 14 days) of MAO inhibitors
• Use with thioridazine or pimozide due to QT prolongation risk
• Severe hepatic or renal impairment without dosage adjustment
• Use in children and adolescents for depression (due to suicidality risk)

• Suicidality: Higher risk in adolescents and young adults (boxed warning)
• Serotonin Syndrome: Especially with concurrent serotonergic agents (e.g., triptans, SSRIs, MAOIs)
• Discontinuation Syndrome: Taper gradually; abrupt withdrawal may cause dizziness, irritability, nausea
• Hyponatremia: More common in elderly and those on diuretics
• Bleeding Risk: Caution with NSAIDs, aspirin, or anticoagulants
• Mania/Hypomania: Use cautiously in bipolar disorder
• Seizures: Risk increases in seizure-prone individuals
• Angle-Closure Glaucoma: May precipitate acute attacks in susceptible patients

Common Side Effects:

• Central Nervous System: Dizziness, somnolence, insomnia, headache, tremor
• Gastrointestinal: Nausea, dry mouth, constipation, diarrhea, decreased appetite
• Sexual: Erectile dysfunction, delayed ejaculation, decreased libido, anorgasmia
• Other: Sweating, weight gain or loss, fatigue

Serious Side Effects:

• Suicidal ideation or behavior
• Serotonin syndrome
• Seizures
• Hyponatremia (confusion, seizures)
• QT prolongation (rare)
• Abnormal bleeding (especially with concurrent anticoagulants)

• MAOIs, Linezolid, Methylene Blue: Risk of life-threatening serotonin syndrome
• CYP2D6 Substrates (e.g., Tamoxifen): Paroxetine is a strong CYP2D6 inhibitor—may reduce efficacy of co-administered drugs
• NSAIDs, Aspirin, Warfarin: Increased risk of bleeding
• Tramadol, Triptans, Lithium: Serotonergic interaction risk
• Alcohol: May enhance CNS depression
• Thioridazine, Pimozide: QT prolongation risk

• FDA Advisory (Ongoing): Paroxetine carries a boxed warning regarding suicidality risk in individuals aged <24 years
• Pregnancy Use Warnings Enhanced: Strong caution advised during first trimester due to teratogenic risk
• EMA and NICE Guidelines: Recommend alternative SSRIs with fewer withdrawal concerns in certain patient groups
• Tapering Recommendations Reinforced: Slow tapering over weeks to prevent withdrawal symptoms

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C
• Humidity: Protect from moisture
• Light: Store in a light-resistant, tightly closed container
• Handling Precautions: Do not crush or chew controlled-release tablets
• Oral Suspension: Shake well before administration