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Letter to the Editor

Paroxetine: Into Oblivion? Well, Guess Not

Ahmed Naguy, MBBch, MSc

Published: April 18, 2019

Paroxetine: Into Oblivion? Well, Guess Not

To the Editor: In a previous letter,1 I highlighted the reasons as to why paroxetine use in clinical practice has fallen into disfavor. To my surprise, this report caused an uproar in the psychiatric community.

Here, I would like to emphasize that paroxetine has double-blind evidence for efficacy in a wide array of depressive and anxiety disorders.2 This broad therapeutic potential might be ascribed to paroxetine’s ability to inhibit the norepinephrine transporter in vivo as a secondary pharmacodynamic property in addition to its designation as a selective serotonin reuptake inhibitor (SSRI). This mechanism has been demonstrated in an open-label, parallel-group, forced-titration study by Gilmor et al.3 Interestingly, paroxetine’s discontinuation syndrome might paradoxically foster compliance from a behaviorist viewpoint.

Paroxetine is also US Food and Drug Administration (FDA) approved for obsessive-compulsive disorder (OCD). And, since glutamate and γ-aminobutyric acid are highly expressed in neurocircuitry underlying OCD, paroxetine use might be advantageous over other SSRIs, at least theoretically, as it has been demonstrated to additionally normalize elevated caudate glutamate.4 Paroxetine also remains one of the preferred antidepressants for use during lactation, as shown in a systematic review.5 And, although the FDA advises against use of paroxetine in the child and adolescent psychiatric population, 2 randomized controlled trials showed positive efficacy signal in juvenile depression6 and OCD.7

Additionally, paroxetine-associated weight gain might prioritize its use in anorexia nervosa when an SSRI is indicated. Heiden et al8 reported on the successful use of paroxetine in a case of OCD, anorexia nervosa, and schizotypal personality disorder. Furthermore, paroxetine’s noted side effect of anorgasmia may be useful in the treatment of premature ejaculation. Rivera et al9 found paroxetine to be effective for this indication both on a daily basis and as needed.

So, where do we go from here? While paroxetine may have lost favor with some, it still has therapeutic potential in the treatment of various disorders. Thus, it behooves clinicians to be vigilant to navigate the pros and cons of using paroxetine in clinical practice.


1. Naguy A. Paroxetine: into oblivion? Prim Care Companion CNS Disord. 2018;20(1):17l02113. PubMed CrossRef

2. Bourin M, Chue P, Guillon Y. Paroxetine: a review. CNS Drug Rev. 2001;7(1):25-47. PubMed CrossRef

3. Gilmor ML, Owens MJ, Nemeroff CB. Inhibition of norepinephrine uptake in patients with major depression treated with paroxetine. Am J Psychiatry. 2002;159(10):1702-1710. PubMed CrossRef

4. Rosenberg DR, MacMaster FP, Keshavan MS, et al. Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry. 2000;39(9):1096-1103. PubMed CrossRef

5. Orsolini L, Bellantuono C. Serotonin reuptake inhibitors and breastfeeding: a systematic review. Hum Psychopharmacol. 2015;30(1):4-20. PubMed CrossRef

6. Keller MB, Ryan ND, Strober M, et al. Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry. 2001;40(7):762-772. PubMed CrossRef

7. Geller DA, Wagner KD, Emslie G, et al. Paroxetine treatment in children and adolescents with obsessive-compulsive disorder: a randomized, multicenter, double-blind, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2004;43(11):1387-1396. PubMed CrossRef

8. Heiden A, de Zwaan M, Frey R, et al. Paroxetine in a patient with obsessive-compulsive disorder, anorexia nervosa and schizotypal personality disorder. J Psychiatry Neurosci. 1998;23(3):179-180. PubMed

9. Rivera P, González R, González F, et al. Use of paroxetine on-demand in premature ejaculation. Actas Urol Esp. 2005;29(4):387-391. PubMed CrossRef

Ahmed Naguy, MBBch, MSca

aAl-Manara Centre, Kuwait Centre for Mental Health, Shuwaikh, Sulibikhat, Kuwait

Potential conflicts of interest: None.

Funding/support: None.

Published online: April 18, 2019.

Prim Care Companion CNS Disord 2019;21(2):18l02369

To cite: Naguy A. Paroxetine: into oblivion? well, guess not. Prim Care Companion CNS Disord. 2019;21(2):18l02369.

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