1. Paroxetine
Flavio Guzmán, MD

2. Paroxetine - Overview
Many clinicians see it as suitable for anxious depression
Sexual dysfunction
Discontinuation syndrome
Weight gain

3. Pharmacology and MOA

4. Paroxetine Pharmacodynamics
At high doses: NET inhibition
Muscarinic blockade: anticholinergic properties.
Potentially problematic in the elderly
Inhibits SERT
Bourin, M., Chue, P., & Guillon, Y. (2001). Paroxetine: a review. CNS drug reviews, 7(1),

5. Clinical Uses

6. FDA-approved indications for paroxetine
Immediate Release
Controlled Release
Major depressive disorder X
Anxiety Disorders
Panic disorder
Social anxiety disorder
Generalized anxiety disorder
Post-traumatic stress disorder
Obsessive compulsive disorder
Premenstrual dysphoric disorder
Paxil CR (Paroxetine CR) [Prescribing Information]. Research Triangle Park, NC : GlaxoSmithKline, 2014.
Paxil (Paroxetine CR) [Prescribing Information]. Research Triangle Park, NC : GlaxoSmithKline, 2014.

7. Pharmacokinetics

8. Paroxetine is a CYP2D6 inhibitor
CYP2D6 inhibitor and substrate.
Nonlinear pharmacokinetics
Potential increases of TCA, phenothiazines, type 1C antiarrythmics.
Gibiino, S., & Serretti, A. (2012). Paroxetine for the treatment of depression: a critical update. Expert opinion on pharmacotherapy, 13(3),

9. Adverse Effects

10. Common side effects
Nausea
Headache
Somnolence
Dry mouth
Sweating

11. SSRI-induced sexual dysfunction
Sexual dysfunction more problematic with paroxetine than with other SSRIs
Dose dependent side effect

12. Weight gain
Weight gain needs to be considered when choosing paroxetine
One of the antidepressants with highest risk of weight gain
Dent, Robert, et al. “Changes in body weight and psychotropic drugs: a systematic synthesis of the literature.” PloS one 7.6 (2012): e36889.

13. Discontinuation syndrome
Discontinuation syndrome with paroxetine
1/3 of patients after abrupt cessation
Short half life
No active metabolites
Schatzberg, Alan F., and Charles B. Nemeroff, eds. The American psychiatric publishing textbook of psychopharmacology. American Psychiatric Pub, 2009.

14. Prescribing information

15. Dosage range Immediate release Controlled Release (CR) Depression
20-50 mg/day
mg/day
Paxil CR (Paroxetine CR) [Prescribing Information]. Research Triangle Park, NC : GlaxoSmithKline, 2014.
Paxil (Paroxetine CR) [Prescribing Information]. Research Triangle Park, NC : GlaxoSmithKline, 2014.

16. Prescribing information
Immediate release
Controlled release (CR)
Formulations
Tablets:
10 mg scored
20 mg scored
30 mg
40 mg
12.5 mg
25 mg
37.5 mg
Due to incomplete dissolution from the wax matrix, the dose of the CR formulation is higher.
Also available: liquid formulation
Paxil CR (Paroxetine CR) [Prescribing Information]. Research Triangle Park, NC : GlaxoSmithKline, 2014.
Paxil (Paroxetine CR) [Prescribing Information]. Research Triangle Park, NC : GlaxoSmithKline, 2014.

17. Prescribing information
Immediate release
Controlled release (CR)
Why was CR developed?
Dropout rate 16%
Nausea main side effect
Dropout rate 10%
Polymeric matrix: delays drug release 4 to 5 hours.
Tips
Scored tablets available
Chewing or cutting in half can alter CR properties
Single daily dose
Pregnancy Risk category D
Paxil CR (Paroxetine CR) [Prescribing Information]. Research Triangle Park, NC : GlaxoSmithKline. Accessed April 2014.
Paxil (Paroxetine CR) [Prescribing Information]. Research Triangle Park, NC : GlaxoSmithKline. Accessed April 2014.