Medications to treat OCD?​

Here's a comprehensive list of medications used to treat Obsessive-Compulsive Disorder (OCD), including typical dosages, onset of action, common side effects, and mechanisms of action:

First-Line Medications: SSRIs (Selective Serotonin Reuptake Inhibitors)
1. Fluoxetine (Prozac)

• Dosage: 20–80 mg/day
• Onset: 4–6 weeks (can take up to 12 weeks for full effect)
• Common Side Effects: Nausea, insomnia, anxiety, sexual dysfunction, headache
• Mechanism: Inhibits the reuptake of serotonin (5-HT) into presynaptic neurons, increasing extracellular serotonin in the synaptic cleft.
• Neurobiology: Enhances serotonergic tone in the cortico-striatal-thalamo-cortical (CSTC) circuit, reducing intrusive thoughts and compulsions.

2. Fluvoxamine (Luvox)

• Dosage: 100–300 mg/day (start at 50 mg)
• Onset: 4–6 weeks
• Common Side Effects: Sedation, nausea, sexual dysfunction, dry mouth
• Mechanism: Potent SSRI; may also affect sigma-1 receptors, which modulate mood and cognition.

3. Sertraline (Zoloft)

• Dosage: 50–200 mg/day
• Onset: 4–6 weeks
• Common Side Effects: Diarrhea, insomnia, sexual dysfunction, agitation
• Mechanism: Inhibits reuptake of serotonin; weak dopamine transporter inhibition in higher doses may benefit comorbid anhedonia or fatigue.

4. Paroxetine (Paxil)

• Dosage: 20–60 mg/day
• Onset: 4–6 weeks
• Common Side Effects: Weight gain, sedation, sexual dysfunction, anticholinergic effects
• Mechanism: Strong serotonin reuptake inhibition with mild norepinephrine reuptake inhibition; has anticholinergic properties.

5. Escitalopram (Lexapro)

• Dosage: 10–30 mg/day (higher than depression dose)
• Onset: 4–6 weeks
• Common Side Effects: Insomnia, nausea, sexual dysfunction
• Mechanism: Highly selective SSRI with fewer drug interactions and a cleaner receptor profile.

Second-Line: Clomipramine (TCA)
​6. Clomipramine (Anafranil)

• Dosage: 25–250 mg/day
• Onset: 2–6 weeks
• Common Side Effects: Sedation, dry mouth, constipation, weight gain, sexual dysfunction, orthostatic hypotension
• Mechanism: TCA with potent serotonin reuptake inhibition and weak norepinephrine reuptake inhibition.
• Neurobiology: Strong serotonergic effect in CSTC circuit; generally considered more effective than SSRIs but with more side effects.

Augmentation Strategies
7. Risperidone (Risperdal)

• Dosage: 0.25–2 mg/day (low dose)
• Onset: 1–2 weeks for augmentation
• Common Side Effects: Weight gain, extrapyramidal symptoms, sedation, prolactin elevation
• Mechanism: D2 receptor antagonist and 5-HT2A antagonist; may help with intrusive thoughts by reducing dopamine hyperactivity in subcortical regions.

8. Aripiprazole (Abilify)

• Dosage: 2–15 mg/day
• Onset: 1–2 weeks for augmentation
• Common Side Effects: Akathisia, insomnia, agitation
• Mechanism: Partial dopamine D2 and serotonin 5-HT1A agonist; antagonist at 5-HT2A. Modulates dopamine and serotonin transmission.

9. Quetiapine (Seroquel)

• Dosage: 50–300 mg/day (off-label use)
• Onset: 1–2 weeks for augmentation
• Common Side Effects: Sedation, weight gain, orthostatic hypotension
• Mechanism: Antagonist at D2 and 5-HT2A receptors; impacts multiple neurotransmitter systems, used in treatment-resistant cases.

Emerging or Off-label Agents
10. Venlafaxine XR (Effexor XR)

• Dosage: 75–225 mg/day
• Onset: 4–6 weeks
• Common Side Effects: Hypertension at higher doses, nausea, insomnia
• Mechanism: Serotonin and norepinephrine reuptake inhibition; less effective than SSRIs but used in SSRI-refractory OCD.

11. Mirtazapine (Remeron)

• Dosage: 15–45 mg/day
• Mechanism: Alpha-2 antagonist, increases serotonin and norepinephrine, 5-HT2 and 5-HT3 antagonist (anti-anxiety and anti-nausea)
• Note: Not a first-line agent for OCD, but sometimes used in patients with comorbid anxiety or insomnia.

Neurobiology of OCD and Medication Effects

• Core circuitry: Hyperactivity in the CSTC loop (cortico-striato-thalamo-cortical), especially between the orbitofrontal cortex, caudate nucleus, and thalamus.
• Serotonin (5-HT): Dysregulation leads to poor inhibition of intrusive thoughts.
• Dopamine: Modulates motor and reward behaviors; may contribute to compulsions.
• Glutamate: Elevated glutamate levels found in some patients; ongoing research into glutamate-modulating agents.

​ Notes on Treatment

• High doses of SSRIs are typically required for OCD compared to depression.
• Duration: May require 10–12 weeks before determining effectiveness.
• Maintenance: Continue treatment for at least 1–2 years, sometimes longer.
• Therapy: CBT with Exposure and Response Prevention (ERP) is the gold standard and often more effective when combined with medication.

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