Barcelona snapshots

Prof. Pino Alonso

Pino Alonso Ortega psychiatrist Controversies Psiquiatry Barcelona
Universitat de Barcelona & Bellvitge Hospital, Spain
Talk Innovation in OCD
Date Thursday, April 10th, 2025
Time 18:15 - 19:00
Panel Innovation in Pharmacotherapy

BIOGRAPHY

Dr. Mª del Pino Alonso Ortega is a psychiatrist, Head of Department at the Psychiatry Service of Bellvitge Hospital in Barcelona and Head of the Obsessive-Compulsive Disorder (OCD) Unit of that center. She is also an associate professor at the Faculty of Medicine of the University of Barcelona and a researcher at CIBERSAM (Spanish Research Network in Mental Health) and IDIBELL. In the last twenty-five years, her healthcare and research work has focused on studying the causes and treatment of OCD, with special interest in the particularly severe forms of the disorders and in factors predicting the long-term prognosis of the disease. She is author or co-author of 132 international articles on OCD, focusing on clinical aspects of the disease, as well as on genetic and neuroimaging factors that predispose to OCD. She has supervised five doctoral theses on OCD and is currently directing three new theses on the subject. She is the author of several chapters in national and international books on OCD and principal investigator since 2007 of six projects funded by the Carlos III Health Institute and the La Marató Foundation to study Obsessive Compulsive Disorder. Dr. Alonso is a member of the main international OCD study groups and consortia, including the OCD working groups of the Psychiatric Genetics Consortium (PGC) and ENIGMA (International Study Group on Neuroimaging in Mental Disorders). Finally, Dr. Alonso is president of the TOC2.0 Association of Barcelona, of people affected with OCD and relatives, and actively collaborates in proposals and dissemination activities that help increase the visibility of OCD in society.

ABSTRACT

Obsessive-Compulsive Disorder is a mental illness that affects 2-3% of the population and usually begins in childhood, adolescence or early adulthood, a critical period for establishing stable affective relationships in the family environment and among peers, successfully integrating into school or accessing the labour market. Therefore, in severe forms of the disease, the affected persons may show a significant deterioration in all these vital areas and see their ability to adapt to their family, social, academic and/or work environment greatly reduced.

Cognitive-behavioral therapy (through exposure with response prevention) and selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment for OCD. However, only 50-60% of patients will respond to these approaches and often their response will be partial. The search for predictors of response, both clinical and biomarkers, is vital to individualize the therapeutic approach to OCD and increase response rates, but advances on this field have been very limited. Of all the factors analyzed, the one most clearly associated with a worse therapeutic response and a higher risk of chronicity is the prolonged duration of OCD before starting treatment, so it is essential to develop strategies that facilitate early diagnosis and therapeutic intervention.

In those patients resistant to first-line approaches, the use of combination strategies (simultaneous behavioral therapy with the use of SSRIs) or monotherapy with a second SSRI is proposed, and in the absence of improvement, the use of clomipramine (which due to its worse tolerance profile is reserved for this second line of treatment).

If these approaches fail, guidelines recommend strategies for boosting SSRIs or clomipramine with antipsychotics (APS). It should be noted that the only APS that have demonstrated antiobsessive efficacy as enhancers are especially aripiprazole (at doses of 10-15 mg/day) and, to a lesser extent, risperidone and haloperidol (the latter two, especially in patients with comorbid tic disorder). There is no scientific evidence to support the use in OCD of other APS such as olanzapine, quetiapine, paliperidone or other more recent APS (lurasidone, cariprazine or brexppiprazole).

Current lines of research on the pharmacological approach in patients with resistant OCD basically focus on the use of glutamatergic modulators as well as psychedelics. There is scientific evidence from neuroimaging, genetic, and animal model studies that support the existence of a glutamatergic dysfunction in OCD. It is postulated that patients with OCD have an increased cortical glutamatergic activity, specifically in the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC), two key areas of the dysfunctional cortical-striatum-thalamic-cortical circuit hypothesized as underlying OCD. This circuit would encompass two pathways, one direct and the other indirect, producing in OCD an imbalance between the two, with a predominance of the glutamatergic projections activating the direct pathway over the indirect pathway. Based on these findings, several glutamatergic modulators have been tested in patients with resistant forms of OCD, including NMDA receptor antagonists (memantine, ketamine, esketamine), AMPA/kainate receptor antagonists (lamotrigine, topiramate) and drugs with mixed actions on the glutamatergic system such as riluzole, troriluzole, pregabalin, minocycline and N-acetylcysteine. The studies published to date are limited, with very small samples and with high heterogeneity in design, but they point to promising results especially for memantine. In relation to psychedelics, the most analyzed is psilocybin, an agonist of the serotonergic receptors 5HT2a, 5HT2C and 5HT1A, which modulates the activity of the orbitofrontal cortex and the Default Mode Network (DMN) and normalizes the glutamatergic hyperactivity of the CSTC circuit. At present, several trials are underway on the use of both glutamatergic agents and psilocybin in patients with resistant OCD, so it is expected that in the coming years more scientific evidence will be available on their possible usefulness in the treatment of OCD.

In the presentation, we will analyze the available data on the use of some drugs that affect fear acquisition and extinction mechanisms as enhancers or facilitators of other OCD therapies, specifically behavioral therapy, or the possible facilitation of the action of deep brain stimulation through some psychotropic drugs. Finally, we will conclude by reviewing the available evidence to advance in the implementation of personalized approaches in patients with OCD.

REFERENCES