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<p class="ltrs-br-ltr-br-title"><span class="bold">Paroxetine: Into Oblivion?</span></p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold">To the Editor:</span> Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that is approved by the US Food and Drug Administration (FDA) for adult depression, obsessive-compulsive disorder, anxiety disorders, and vasomotor changes of menopause. Nonetheless, its clinical use has recently fallen into disfavor.<span class="htm-cite"><a href="#ref1">1</a></span> Moreover, the FDA advised against its use in the child and adolescent population.</p>
<p class="ltrs-br-ltr-br-body-text">This aversive attitude in practice might be ascribed to a multitude of reasons related to its pharmacologic properties. These properties might be broadly subdivided into anticholinergic actions, cytochrome P450 2D6 (CYP2D6) inhibitory properties, and a miscellaneous group.</p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold-ital">Anticholinergic actions.</span> Paroxetine is the most anticholinergic of the SSRIs on the market, which is especially problematic in the geriatric population due to its anticognitive properties. Paroxetine has been associated with highest weight gain among the SSRIs,<span class="htm-cite"><a href="#ref2">2</a></span> mainly during the first 12 months of treatment. Antimuscarinic and sedative properties of paroxetine might be contributory to weight gain. Also, paroxetine is infamous for sexual dysfunction (up to 75% of patients), and it is more likely to cause disorders of arousal and anorgasmia than other SSRIs.</p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold-ital">CYP2D6 inhibitory properties.</span> Paroxetine is a potent CYP2D6 inhibitor, so pharmacokinetic interactions with drugs that are substrate to CYP2D6 are commonplace (eg, risperidone). This pharmacological portfolio, especially in poor metabolizers, may translate into clinical toxicity. Furthermore, inhibiting CYP2D6 may render drugs like tamoxifen in breast cancer ineffective by blocking its conversion into endoxifen.</p>
<p class="ltrs-br-ltr-br-body-text">Paroxetine is notorious for its discontinuation syndrome, which may, in part, be due to its ability to inhibit its own metabolism<span class="htm-cite"><a href="#ref3">3</a></span>—as it is a substrate for CYP2D6—hence, the rapid decline of levels and discontinuation symptoms once it is rapidly stopped.</p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold-ital">Miscellaneous.</span> Paroxetine has been tied to activation of suicidal ideations most often in youth. The FDA downgraded paroxetine to pregnancy category D, as association with ventricular septal defects has been reported. Notably, in the child and adolescent population, 2 randomized controlled trials<span class="htm-cite"><a href="#ref4">4</a>,<a href="#ref5">5</a></span> of paroxetine for juvenile depression were negative. Last, but not least, paroxetine has been demonstrated to decrease the heart rate variability, which has been linked to increased cardiovascular mortality.<span class="htm-cite"><a href="#ref6">6</a></span></p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold-ital">Conclusion.</span> In all, I surmise that the problems and inherent risks associated with paroxetine use speak to the idea of a psychotropic “falling off the track” and render it a less appealing choice in clinical practice compared to far more efficacious and safer alternatives already available on market. It is then incumbent on clinicians to be vigilant and prudent when prescribing paroxetine, especially in child and adolescent, female, and geriatric populations.</p>
<p class="references_references-heading"><span class="smallcaps">References</span></p>
<p class="references-references-text-1-9"><a name="ref1"></a><span class="htm-ref"> 1.	</span>Nevels RM, Gontkovsky ST, Williams BE. Paroxetine: the antidepressant from hell? probably not, but caution required. <span class="italic">Psychopharmacol Bull</span>. 2016;46(1):77–104. <a href="
https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=27738376&dopt=Abstract"><span class="pubmed-crossref">PubMed</span></a></p>
<p class="references-references-text-1-9"><a name="ref2"></a><span class="htm-ref"> 2.	</span>Fava M, Judge R, Hoog SL, et al. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. <span class="italic">J Clin Psychiatry</span>. 2000;61(11):863–867. <a href="
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https://doi.org/10.4088/JCP.v61n1109"><span class="pubmed-crossref">CrossRef</span></a></p>
<p class="references-references-text-1-9"><a name="ref3"></a><span class="htm-ref"> 3.	</span>DeVane CL. Pharmacokinetics, drug interactions, and tolerability of paroxetine and paroxetine CR. <span class="italic">Psychopharmacol Bull</span>. 2003;37(suppl 1):29–41. <a href="
https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14566199&dopt=Abstract"><span class="pubmed-crossref">PubMed</span></a></p>
<p class="references-references-text-1-9"><a name="ref4"></a><span class="htm-ref"> 4.	</span>Emslie GJ, Wagner KD, Kutcher S, et al. Paroxetine treatment in children and adolescents with major depressive disorder: a randomized, multicenter, double-blind, placebo-controlled trial. <span class="italic">J Am Acad Child Adolesc Psychiatry</span>. 2006;45(6):709–719. <a href="
https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16721321&dopt=Abstract"><span class="pubmed-crossref">PubMed</span></a> <a href="
https://doi.org/10.1097/01.chi.0000214189.73240.63"><span class="pubmed-crossref">CrossRef</span></a></p>
<p class="references-references-text-1-9"><a name="ref5"></a><span class="htm-ref"> 5.	</span>Berard R, Fong R, Carpenter DJ, et al. An international, multi-centre, placebo-controlled trial of paroxetine in adolescents with major depressive disorder. <span class="italic">J Child Adolesc Psychopharmacol</span>. 2006;16(1–2):59–75. <a href="
https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16553529&dopt=Abstract"><span class="pubmed-crossref">PubMed</span></a> <a href="
https://doi.org/10.1089/cap.2006.16.59"><span class="pubmed-crossref">CrossRef</span></a></p>
<p class="references-references-text-1-9"><span class="htm-ref"> </span>6.	Yeh TC, Kao LC, Tzeng NS, et al. Heart rate variability in major depressive disorder and after antidepressant treatment with agomelatine and paroxetine: findings from the Taiwan Study of Depression and Anxiety (TAISDA). <span class="italic">Prog Neuropsychopharmacol Biol Psychiatry</span>. 2016;64:60–67. <a href="
https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=26216863&dopt=Abstract"><span class="pubmed-crossref">PubMed</span></a> <a href="
https://doi.org/10.1016/j.pnpbp.2015.07.007"><span class="pubmed-crossref">CrossRef</span></a> </p>
<p class="ltrs-br-ltr-br-author"><a id="_idTextAnchor000"></a><span class="bold">Ahmed Naguy, MBBch, MSc</span><span class="superscript">a</span></p>
<p class="ltrs-br-ltr-br-author"><a href="
mailto:ahmednagy@hotmail.co.uk">
ahmednagy@hotmail.co.uk</a></p>
<p class="end-matter"><span class="superscript">a</span>Child/Adolescent Psychiatry, Kuwait Center for Mental Health, Kuwait</p>
<p class="end-matter"><span class="bold-italic">Potential conflicts of interest: </span>None.</p>
<p class="end-matter"><span class="bold-italic">Funding/support: </span>None.</p>
<p class="end-matter"><span class="bold-italic">Published online:</span> January 11, 2018.</p>
<p class="end-matter"><span class="italic">Prim Care Companion CNS Disord 2018;20(1):17l02113</span></p>
<p class="end-matter"><span class="bold-italic">To cite: </span>Naguy A. Paroxetine: into oblivion? <span class="italic">Prim Care Companion CNS Disord.</span> 2018;20(1):17l02113.</p>
<p class="doi-line"><span class="bold-italic">To share: </span><a href="
https://doi.org/10.4088/PCC.17l02113">
https://doi.org/<span class="doi">10.4088/PCC.17l02113</span></a></p>
<p class="end-matter"><span class="italic">© Copyright 2018 Physicians Postgraduate Press, Inc.</span></p>
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