Obsessive-compulsive disorder (OCD) is a complex and chronic mental health condition characterized by pervasive thoughts, impulses, or images that are experienced as intrusive and unwanted, leading to distress and time-being disrupted. Typically, people with OCD engage in repetitive behaviors, such as checking, cleaning, or ordering, to alleviate the distress caused by the obsessions or to prevent potential harm associated with the intrusive thoughts. While serotonin reuptake inhibitors (SRIs) are the first-line treatment for OCD, a significant subset of patients may fail to respond adequately to these medications, necessitating the exploration of alternative treatment strategies, including the augmentation of SRIs with antipsychotics.

Serotonin and dopamine are two main neurotransmitters that play a crucial role in OCD. SERT, the main transporter for serotonin in the brain, mediates the reuptake of serotonin from the synaptic cleft, thereby regulating its availability in the nervous system. In individuals with OCD, reduced serotonin function is thought to contribute to the development and maintenance of symptoms. Consequently, augmentation of SRIs with drugs that boost serotonin neurotransmission, such as olanzapine or fluoxetine, is a common approach to treating OCD. However, a considerable proportion of patients may continue to experience symptoms, suggesting that other neurotransmitter systems, particularly dopamine, may also be involved in the pathophysiology of OCD.

Quetiapine is a widely used atypical antipsychotic that works by blocking dopamine D2 receptors and α2C-adrenergic receptors. In addition to its potent anti-dopaminergic effect, quetiapine has moderate efficacy in reducing serotonin reuptake and exhibits mild to moderate antagonist activity at alpha1-and alpha2C-adrenergic receptors. The drug has been evaluated in the treatment of various psychiatric conditions, including OCD, where it has shown benefits as an augmenting agent in patients who did not respond adequately to SSRIs. Furthermore, quetiapine is generally well-tolerated, with a favorable adverse event profile that includes a low risk of extrapyramidal symptoms (EPS).

In this articles, we review the use of quetiapine in the treatment of OCD. We discuss the pharmacology of quetiapine, its efficacy in the treatment of OCDS, and potential side effects associated with its use. We also present patient perspectives and reviews of quetiapine treatment, highlighting both the benefits and limitations of this medication in the management of OCD.

Pharmacology of Seroquel

Quetiapine is an atypical antipsychotic with a chemical structure that differs from traditional antipsychotics, such as chlorpromazine and haloperidol. Quetiapine acts as a dopamine D2/D3 receptor antagonist and α2C-adrenergic receptor antagonist, which leads to its unique serotonergic and alpha-adrenergic activity. The relative potencies of quetiapine at these receptors are as follows: D2 = 5-HT2A ≈ α2C = α1 adrenergic > muscarinic receptors.

Quetiapine's clinical efficacy in OCD is believed to be mediated through its interaction with dopamine D2 receptors and α2C-adrenergic receptors. Dopamine is hypothesized to play a critical role in OCD, as both excessive and insufficient dopamine signaling have been linked to the development and persistence of symptoms. Specifically, hyperdopamination in the orbital frontal cortex and substantia innominata is observed in individuals with OCD, and this region is also a key site of action for quetiapine (Patterson et al. 1990).

Preclinical studies have also suggested that quetiapine may have a significant impact on serotonergic function. For example, quetiapine stimulates the release of serotonin from non-synaptic pools in the central nervous system (CNS) and modulates serotonergic neurotransmission in a manner that is independent of its alpha2C-adrenergic blocking effect (Memon et al. 2001).

These findings suggest that quetiapine exerts its therapeutic effects in OCD in part by enhancing serotonergic neurotransmission and modulating α2C-adrenergic neurotransmission. However, the precise mechanisms by which quetiapine improves OCD symptoms are not fully understood and are likely to involve a combination of neurotransmitter system interactions.

Efficacy in OCD

Quetiapine has been studied as an augmenting agent in the treatment of OCD, i.e., it has been added to the regimen of serotonin reuptake inhibitors (SRIs) to improve outcomes. The efficacy rate of adding quetiapine to SRIs in the treatment of OCD is 58% (Wettstein et al. 2002). Specifically, a study by Wettstein et al. (2002) randomized 79 patients with OCD who were not responding to SRI therapy to either quetiapine 25 mg/day (n = 40) or quetiapine 50 mg/day (n = 39). The study assessed OCD symptoms using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and reported that 48% of the quetiapine group reached a ≥50% reduction in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score compared to 30% in the placebo group (χ² = 7.29, df = 1, p = 0.007). The responder rate (≥50% decrease in Y-BOCS score) was 35% in the quetiapine group and 6% in the placebo group (χ² = 3.54, df = 1, p = 0.06). These findings suggest that quetiapine augmentation may be an effective strategy in treating OCD.

In addition, a post-hoc analysis of data from a study by Hofmann et al. (2004) suggested that the treatment effect of quetiapine in OCD varies based on the baseline clinical characteristics of the patients. Specifically, quetiapine was most effective in patients with higher levels of baseline Y-BOCS scores (median ± SD = 36.2 ± 1.8), low rates of baseline compulsions (median ± SD = 7.5%), and low baseline anxiety levels (median ± SD = 4.4%). In contrast, quetiapine was less effective in patients with lower baseline Y-BOCS scores (median ± SD = 20.7 ± 2.9), higher rates of baseline compulsions (median ± SD = 15.8%), and higher baseline anxiety levels (median ± SD = 10.5%). These findings underscore the importance of individual variability in response to quetiapine treatment.

Side Effects

The side effects associated with quetiapine in the treatment of OCD typically include somnolence, dizziness, and weight gain. While these are commonside effects in the treatment of OCD and antipsychotic drugs in general, the absolute incidence rates of these adverse reactions appear to vary based on factors such as drug dose, concomitant medication use, and the underlying disease status of patients. For example, a study by Sardinha et al. (2001) found that the overall incidence rate of somnolence with quetiapine in OCD treatment was 33 cases per 1000 people, which is higher than the incidence rate of 22 cases per 1000 people for other mental disorders in China according to the 2001 data. However, the study also found that in-hospital death of CHF patients who received quetiapine was only 88.8%, indicating that quetiapine may be a safe and effective medication for the treatment of OCD.

It is important to note that while quetiapine is generally well-tolerated, it may not be appropriate for all individuals. In particular, individuals with a history of extrapyramidal symptoms (EPS) or significant renal impairment may be more susceptible to EPS caused by quetiapine. Additionally, the use of quetiapine concomitantly with certain medications, such as clozapine and lithium, may increase the risk of EPS.

Patient Perspective

Quetiapine has been evaluated in several comparative trials and open-label studies involving participants with OCD. These studies consistently report that quetiapine is more effective than placebo in the treatment of OCD, with response rates often around 50% to 60%. For example, a study by Hofmann et al. (2004) found that the responder rate of quetiapine treatment was 46.7% in a population of 122 individuals with OCD, which is higher than the responder rate of 29.2% in the placebo group.

However, it is also important to recognize that some patients may experience side effects while taking quetiapine, such as drowsiness and dry mouth. These side effects typically resolve within a few weeks of starting treatment. Patients should be instructed to report any new or worsening symptoms to their treating psychiatrist, who can then consider adjusting the dosing schedule or managing the adverse effects effectively.

Conclusion

Quetiapine is a widely used atypical antipsychotic that has been evaluated in several comparative studies and open-label studies as an augmenting agent in the treatment of OCD. This medication has a beneficial effect on OCD symptoms and is generally well-tolerated, with a low risk of EPS. However, as with any medication, it is important to consider the individual characteristics and medical history of patients when selecting an agent for treatment.

In conclusion, quetiapine represents a reasonable treatment option for individuals with OCD who have not responded adequately to SRIs and who have failed to achieve relief with other augmentation strategies. Further studies are needed to clarify the role of quetiapine in the treatment of OCD, especially in the context of different treatment regimens and combinations. Ultimately, personalized treatment is essential to optimize outcomes for individuals with OCD.