Which neurotransmitter is primarily implicated in the pathophysiology of Obsessive-Compulsive Disorder (OCD)?

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From the Guidelines

Serotonin is the primary neurotransmitter implicated in the pathophysiology of Obsessive-Compulsive Disorder (OCD). This understanding forms the basis for the first-line pharmacological treatment of OCD, which involves selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, sertraline, paroxetine, fluvoxamine, and escitalopram 1. These medications are typically prescribed at higher doses than those used for depression and require longer treatment durations (10-12 weeks) to assess efficacy. The serotonergic hypothesis is supported by the clinical response to SSRIs and neuroimaging studies showing abnormalities in serotonin receptor binding and transporter function in OCD patients 1. Additionally, the cortico-striatal-thalamo-cortical circuit, which is heavily modulated by serotonin, shows hyperactivity in OCD.

While other neurotransmitters like dopamine and glutamate may play secondary roles in OCD pathophysiology, particularly in treatment-resistant cases where augmentation strategies might target these systems, serotonin dysregulation remains the central neurochemical abnormality associated with OCD symptoms 1. The involvement of the dopaminergic system and glutamatergic system in OCD is also noted, with some studies suggesting alterations in these systems in OCD patients 1. However, the primary focus of treatment remains on the serotonergic system, with SSRIs being the first-line treatment option.

The treatment algorithm for OCD typically involves a stepped approach, starting with SSRIs or cognitive-behavioral therapy (CBT), and progressing to augmentation with other treatment modalities, such as atypical antipsychotics or glutamate modulators, in cases of inadequate response 1. Neurosurgery, including deep brain stimulation, may be considered in highly refractory and severe cases 1. Overall, the evidence suggests that serotonin dysregulation is the primary neurochemical abnormality associated with OCD symptoms, and that SSRIs remain the first-line treatment option for this condition.

From the Research

Neurotransmitters Implicated in OCD

  • The primary neurotransmitter implicated in the pathophysiology of OCD is serotonin [@\1@, @\2@, @\3@, @\4@, @\5@]
  • Dopamine also appears to be crucially involved in OCD neuropathology due to its implication in systems relating to goal-directed behaviour and maladaptive habits [@\1@]
  • Other neurotransmitters such as norepinephrine and second-messenger systems may also play a role in treatment [@\4@]

Treatment Options

  • Selective serotonin reuptake inhibitors (SSRIs) are the most common choice for the pharmacological treatment of OCD [@\2@, @\3@, @\4@, @\5@]
  • Antipsychotics, such as risperidone, aripiprazole, and haloperidol, may be useful in treatment-resistant cases [@\1@]
  • Cognitive behavioral therapy (CBT) and exposure and response prevention (ERP) are also effective treatments for OCD [@\3@, @\5@]

Neurotransmitter Involvement

  • Serotonin reuptake inhibitors (SRIs) have been shown to be effective in reducing symptoms of OCD [@\2@, @\3@, @\4@, @\5@]
  • The involvement of dopamine in OCD neuropathology suggests that antipsychotics may be a useful treatment option [@\1@]

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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