Pharmacokinetics of serotonergic drugs: focus on OCD

ABSTRACT

Introduction: Although the treatment of obsessive-compulsive disorder (OCD), a common, chronic, and disabling psychiatric condition, has significantly improved in the last decades, with the demonstration of the specific effectiveness of serotonin reuptake inhibitors (SRIs), a large proportion of patients still show high relapse rates. In addition, pharmacological treatments should be maintained for years, so that the clinicians should take into account the pharmacokinetic changes in the long-term, which may be responsible for dangerous side effects or interactions.

Areas covered: The aim of this paper was to review the literature on the pharmacokinetics of SSRIs and clomipramine, and on their pharmacokinetic parameters in OCD patients.

Expert opinion: Although the literature on the pharmacokinetics of both clomipramine and SSRIs is consistent, data on pharmacokinetic parameters in OCD patients are very few. Given the impact of OCD, its chronicity requiring long-term treatments, together with the need to increase the clinical response rate, more studies in this field are urgently required.

KEYWORDS:

• Obsessive-compulsive disorder
• pharmacological treatment
• serotonin reuptake inhibitors
• selective serotonin reuptake inhibitors
• pharmacokinetics
• cytochromes

Article highlights

• Obsessive-compulsive disorder is a common and disabling condition requiring long-term pharmacological treatments. SSRIs represent the goal standard treatments in OCD.

• With long-term or maintenance treatments, the pharmacokinetic changes responsible for unwanted side effects and dangerous interactions should be considered.

• The pharmacokinetics of SSRIs and clomipramine has been deeply investigated, each compound showing some peculiarities.

• Fluoxetine, paroxetine, and sertraline, although the latter only to a small extent, inhibit the CYP2D6 isoenzyme of cytochrome P450 that metabolizes tricyclics (TCAs), beta-blockers and antiarrhythmic agents. Fluvoxamine inhibits both CYP1A2 and CYP3A4 which eliminate warfarin, TCAs, benzodiazepines and some anti-arrhythmic. Citalopram and escitalopram have no significant metabolic liver interactions. Clomipramine undergoes an extensive first-pass metabolism in the liver, where it is converted in its main metabolites including the principal desmethyl-CMI.

• The studies carried out on pharmacokinetics of SRIs in OCD patients, although desirable, are just a few and, as such, of limited impact on the clinical practice.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One peer reviewer has received honoraria from Janssen Cilag, Pfizer, and Lundbeck. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.