Treatment of the obsessive-compulsive and bipolar disorders comorbidity: pharmacodynamic and pharmacokinetic evaluation

ABSTRACT

Introduction: The comorbidity between obsessive-compulsive disorder (OCD) and bipolar disorders (BDs) is a frequent and severe condition characterized by a chronic course, high suicidal risk and tendency towards chronicity and treatment non-response. It represents a real challenge to psychiatrists, while requiring a careful and appropriate therapeutic management consisting in the combination of serotonergic antidepressants (ADs), such as serotonin reuptake inhibitors (SRIs), with mood stabilizers. This combination, like any other, raises the problems related to drug interactions that may lead to pharmacokinetic and pharmacodynamic changes, resulting in the modification of the pharmacologic effect and safety profile of a given compound.

Areas covered: The aim of the present paper was to review the literature on the pharmacokinetic and pharmacodynamic changes resulting from the interactions of the different drugs prescribed in the OCD-BD comorbidity.

Expert opinion: The literature data on pharmacokinetic and pharmacodynamic changes due to interactions of drugs commonly prescribed in the treatment of the OCD-BD comorbidity are extremely limited, and the information is inferred by findings gathered in psychiatric patients suffering from other disorders. This represents a gap in psychopharmacology that should be filled by specific studies on this important topic.

KEYWORDS:

• Obsessive-compulsive disorder
• bipolar disorders
• comorbidity
• pharmacological treatments
• drug interactions
• pharmacokinetics
• pharmacodynamics

Article highlights

• Obsessive-compulsive disorder (OCD) and bipolar disorders (BDs) are common and chronic conditions that are frequently comorbid: this comorbidity represents a real challenge to pharmacological treatment.

• The therapeutic management of the OCD-BD comorbidity includes combinations of selective serotonin reuptake inhibitors (SSRIs) or clomipramine with mood stabilizers (lithium, valproate, carbamazepine, oxcarbazepine, lamotrigine) and/or some first-generation (FGAs, haloperidol and pimozide) and second-generation antipsychotics (SGAs, risperidone, quetiapine, aripiprazole, olanzapine). Recently the combination of aripirazole with classical mood stabilizers (lithium or valproate) appears specifically effective in this comorbidity.

• The interactions of SRIs with mood stabilizers and antipsychotics may induce pharmacokinetic and pharmacokinetic changes that may alter significantly the expected pharmacological activity and the safety profile of the compounds, while leading also to toxic effects in some cases.

• Although the information is derived mainly by studies carried out in conditions other than the OCD-BD comorbidity, nevertheless the emerging findings suggest cautions when co-prescribing valproate, carbamazepine or oxcarbazepine with some SSRIs, except citalopram and escitalopram. By contrast, lithium seems safe in combinations with SSRIs and clomipramine. The data on haloperidol and pimozide would indicate a careful monitoring in the co-administration of SSRIs, while the combination of pimozide and clomipramine should be discouraged at all. The information on the combinations of SGAs plus SRIs or mood stabilizers is limited, but specific interactions requiring dosage adjustments should be considered in individual cases.

• There is a strong need of specific studies addressing the possible pharmacokinetic and pharmacodynamic changes occurring during the treatment of the OCD-BD comorbidity in order to achieve a significant clinical response, to prevent drug resistance, and also unwanted and severe toxic reactions.

This box summarizes key points contained in the article.

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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.