BRAND NAMES
 MECHANISM OF ACTION
Paroxetine is a selective serotonin reuptake inhibitor (SSRI). It blocks the reuptake of serotonin into the presynaptic cell, increasing its level within the synaptic cleft. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs
- Major depressive disorder; A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks; it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation
- Social anxiety disorder  (A marked and persistent fear of one or more social or performance situations in which the person is exposed to unfamiliar people or to possible scrutiny by others)
- Panic disorder  ( unexpected discrete period of intense fear or discomfort, symptoms can include palpitations, sweating, trembling, sensations of shortness of breath, chest pain or discomfort, nausea or abdominal distress, feeling dizzy and fear of dying)
- Obsessive compulsive disorder: Obsessive compulsive disorder is characterized by recurrent and persistent ideas, thoughts, impulses, or images (obsessions) that are ego-dystonic and/or repetitive, purposeful, and intentional behaviors (compulsions) that are recognized by the person as excessive or unreasonable.
- Premenstrual Dysphoric Disorder (depressed mood, anxiety or tension, affective lability, persistent anger or irritability, decreased interest in usual activities, difficulty concentrating, lack of energy and change in appetite or sleep)
- Posttraumatic stress disorder (PTSD)
- Premature ejaculation (PE)
- Major Depressive Disorder: 20 mg/day in the morning with or without food, is recommended as the initial dose. Recommended dosage range: 20-50 mg/day. The full therapeutic effect may be delayed until 5 weeks of treatment or longer. Acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy.
- Obsessive Compulsive Disorder: 20 mg/day in the morning with or without food, is recommended as the initial dose, to be titrated to 40 mg/day. Recommended dosage range: 20-60 mg/day. The full therapeutic effect may be delayed until 5 weeks of treatment or longer. It is reasonable to consider continuation of therapy for a responding patient.
- Social Anxiety Disorder: 20 mg/day in the morning with or without food, is the recommended dose
- Panic disorder and obsessive compulsive disorder: Patients should be started on 10 mg/day. Titrate to the target dose of 40 mg/day.
- Social Anxiety Disorder: 20 mg/day in the morning with or without food, is the starting and recommended dose
- Posttraumatic Stress Disorder: 20 mg/day in the morning with or without food, is the recommended dose.
- Premature ejaculation (Off label): 20 mg, 4-6 hours previous to intercourse. 
- Hypersensitivity to Paroxetine
- It's use within 14 days of stopping an MAOI because of an increased risk of serotonin syndrome
- Do not start Paroxetine in a patient who is being treated with linezolid or intravenous methylene blue
- Concomitant use with pimozide (Orap®) or Thioridazine (due to risk of drug interaction or QTc prolongation).
- Use with caution in those with history of seizures, mania, renal disease , cardiac disease, children, breast feeding, suicidal ideation.
- Caution while driving and operating machinery.
- Avoid alcohol
- FDA Black Box Warning for Paroxetine : Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Paroxetine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Paroxetine is not approved for use in pediatric patients.
- Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including Paroxetine, both when taken alone, but especially when co-administered with other serotonergic agents (including Triptans, Tricyclic antidepressants, Fentanyl, Lithium, Tramadol, Tryptophan, Buspirone and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOI, both those intended to treat psychiatric disorders and also others, such as Linezolid and intravenous Methylene blue). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).If such symptoms occur, discontinue Paroxetine and initiate supportive treatment. If concomitant use of Paroxetine with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
- Abnormal Bleeding: May increase the risk of bleeding. Use with NSAIDs, Aspirin, Warfarin, or drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding
- Hyponatremia: Hyponatremia has been reported with Paroxetine use, either alone or in combination with some diuretics (Hydrochlorothiazide, Furosemide). Hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Signs and symptoms include headache, new or increased seizure frequency, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to fall. Severe Hyponatremia may cause hallucination, syncope, seizure, coma, respiratory arrest, and death.
- Monoamine Oxidase Inhibitors (MAOIs): increased risk for serotonin syndrome (See contraindications)
- Pimozide: Risk of drug interaction or QTc prolongation (Contraindicated)
- Thioridazine: Risk of QTc interval prolongation or potential for elevated thioridazine plasma levels. (Contraindicated)
- Serotonergic agents (Triptans, Tricyclic antidepressants, Fentanyl, Lithium carbonate, Tramadol, Tryptophan, Buspirone and St. John’s Wort): increased risk for serotonin syndrome
- Paroxetine is a CYP1A2 and CYP2D6 substrate and is a potent inhibitor of these two cytochromes as well, that's why it increases effects of drugs also metabolised by these isoenzymes if given concomitantly. 
- Cyproheptadine decreases the effects of SSRI
- Risk of bleeding is associated with the concomitant use of Paroxetine with NSAIDs, aspirin, or other drugs that affect coagulation.
- Tamoxifen: Paroxetine is an irreversible inhibitor of CYP2D6. Tamoxifen indicated for palliative and adjuvant treatment of estrogen-receptor-positive breast cancer is a prodrug, and the formation of the active metabolite is mediated by the CYP2D6 enzyme. Concentrations of the tamoxifen active metabolites in patients concomitantly treated with CYP2D6 enzyme inhibitors including Paroxetine may be reduced. There have been an increased risk of death from breast cancer from 24% to 91%, depending on duration of coexposure. 
 PREGNANCY AND LACTATION
- Pregnancy Category D (US). Epidemiological studies have shown that infants exposed to paroxetine in the first trimester of pregnancy have an increased risk of congenital malformations, particularly cardiovascular malformations. If a patient becomes pregnant while taking paroxetine, she should be advised of the potential harm to the fetus. Unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant.
- Paroxetine is excreted in human breast milk. Caution should be exercised when Paroxetine is administered to a nursing woman
 SIDE EFFECTS
May cause Dizziness, drowsiness, headache, decreased appetite, dry mouth, insomnia, diarrhea, constipation, diaphoresis, postural hypotension, palpitations, Nausea, vasodilation, flatulence, dyspepsia, abdominal pain, back pain,, decreased libido, abnormal ejaculation, impotence, abnormal dreams, anxiety, yawning and photosensitivity.
 RELATED LINKS
|Tricyclic antidepressants||Amitriptyline (Elavil, Laroxyl) • Clomipramine (Anafranil) • Doxepin (Sinequan) • Imipramine (Tofranil) • Nortriptyline (Aventyl, Pamelor) • Trimipramine (Surmontil)|
|Selective serotonin reuptake inhibitors (SSRIs)||Citalopram (Celexa, Seropram) • Escitalopram (Cipralex, Lexapro) • Fluoxetine (Prozac) • Fluvoxamine (Luvox, Maveral) • Paroxetine (Paxil, Seroxat) • Sertraline (Zoloft)|
|Serotonin–norepinephrine reuptake inhibitors (SNRIs)||Desvenlafaxine (Pristiq) • Duloxetine (Cymbalta, Xeristar) • Venlafaxine (Efexor, Effexor)|
|Serotonin antagonists and reuptake inhibitors (SARIs)||Trazodone (Desyrel, Oleptro)|
|Norepinephrine reuptake inhibitors (NRIs)||Maprotiline (Ludiomil) • Reboxetine (Edronax)|
|Norepinephrine-dopamine reuptake inhibitors (NDRIs)||Bupropion (Wellbutrin)|
|Noradrenergic and specific serotonergic antidepressants (NaSSAs)||Mianserin (Lantanon) • Mirtazapine (Remeron)|
|Norepinephrine-dopamine disinhibitors (NDDIs)||Agomelatine (Valdoxan, Thymanax)|
|Monoamine oxidase inhibitors Nonselective||Tranylcypromine (Parnate)|
|Monoamine oxidase inhibitors B-Selective||Selegiline (Transdermal) (Emsam)|
|Others||5-Hydroxytryptophan • S-Adenosyl methionine • Hypericum (St John's wort)|