Paroxetine

Indications

Paroxetine is used for: Depression, Anxiety, Panic disorder, Obsessive-compulsive disorder, Posttraumatic stress disorder, Social anxiety disorder, Premenstrual dysmorphic disorder

Adult Dose

Oral Depression, Anxiety, Posttraumatic stress disorder Adult: 20 mg daily, increase gradually, if necessary, by 10-mg increments wkly; max: 50 mg/day. Obsessive compulsive disorder, Social anxiety disorder Adult: Initially, 20 mg daily, increase wkly in 10-mg increments. Maintenance: 40-60 mg daily. Panic disorder with or without agoraphobia Adult: Initially, 10 mg daily, increase wkly in 10-mg increments according to clinical response. Maintenance: 40-60 mg daily. Elderly: Initially, 10 mg daily, increase if needed by 10 mg/day at 1 wk intervals; max: 40 mg daily. Hepatic impairment: Severe: 10 mg daily, increase to a max of 40 mg daily as necessary.

Child Dose

Safety and efficacy not established

Renal Dose

Renal impairment: Severe: 10 mg daily, increase to a max of 40 mg daily as necessary.

Administration

May be taken with or without food. May be taken w/ meals to minimise GI upset.

Contra Indications

Use with or within 14 days of MAOIs; concurrent use with thioridazine or pimozide.

Precautions

Epilepsy, glaucoma, history of mania, cardiac disease, DM, history of bleeding disorders, on drugs with increased risk of bleeding; renal and hepatic impairment; patients receiving electroconvulsive therapy; achlorhydria or high gastric pH (reduced absorption of oral suspension). Pregnancy and lactation. The risk of suicidal behaviour may be higher in young adults, closely monitor. May impair ability to drive or perform tasks. Avoid abrupt withdrawal. Lactation Excreted in breast milk; use caution (AAP states effect on nursing infants is unknown but may be of concern)

Pregnancy-Lactation

Interactions

Levels/effects inhibited by cyproheptadine, phenytoin. Levels/effects increased by carbamazepine, cimetidine, CYP2D6 inhibitors (e.g. chlorpromazine, delavirdine, fluoxetine, miconazole, pergolide, quinidine, quinine, ritonavir, ropinirole). Increases levels/effects of atomoxetine, carvedilol, clozapine, CYP2B6 substrates (e.g. bupropion, promethazine, propofol, selegiline, sertraline), CYP2D6 substrates (e.g. amphetamines, selected beta-blockers, dextromethorphan, fluoxetine, lidocaine, mirtazapine, nefazodone, risperidone, ritonavir, thioridazine, TCAs, venlafaxine), duloxetine, galantamine, mexilitine, pimozide, procyclidine, propafenone. Decreases levels/effects of CYP2D6 prodrug substrates (e.g. codeine, hydrocodone, oxycodone, tramadol). Inhibits the metabolism of dextromethorphan, haloperidol, thioridazine. Enhances bradycardic effect of beta-blockers. Enhances toxic effects of other CNS depressants. Increased risk of serotonin syndrome with amphetamines, SSRIs, meperidine, nefazodone, trazodone, serotonin agonists, sibutramine, sympathomimetics, tramadol, venlafaxine. Increases risk of bleeding with NSAIDs, aspirin, warfarin, or other drugs affecting coagulation. Increases sensitivity to amphetamines. Neurotoxicity with lithium. Additive hyponatraemia with loop diuretics. Mania or hypertension with selegiline. Potentially Fatal: Fatal reactions with nonselective MAOI.

Adverse Effects

Side effects of Paroxetine : >10% (Based on 40 mg Dose) Nausea (15-24%),Insomnia (11-24%),Dry mouth (9-18%),Headache (17%),Asthenia (10-15%),Constipation (10-15%),Diarrhea (9-12%),Dizziness (6-14%),Ejaculation disorder (10-15%),Tremor (4-11%), 1-10% (Based on 40 mg Dose) Anxiety (5-10%),Blurred vision (5-10%),Decreased appetite (5-10%),Impotence (2-9%),Nervousness (2-5%),Paresthesia (2-5%),Hypomania (0.3 to 2.2%) Frequency Not Defined (Based on 40 mg Dose) Hypertension,Tachycardia,Emotional lability,Pruritus,Weight gain,Arthralgia,Tinnitus.Vertigo.Angle clossure glaucoma Serious Depression exacerbation,Mania (rare),Serotonin syndrome,Suicidal thoughts (rare),Suicide (rare),Seizure (rare),Toxic epidermal necrolysis,Hyponatremia (rare),Bleeding, abnormal (rare).Acute hepatitis (rare).Stevens-Johnson Syndrome

Mechanism of Action

Paroxetine selectively inhibits the reuptake of serotonin. It has limited direct action at other neurotransmitter sites including muscarinic receptors.