Can Amisulpride (antipsychotic medication) worsen Obsessive-Compulsive Disorder (OCD) symptoms?

Can Amisulpride Worsen OCD?

No, amisulpride does not worsen OCD symptoms—in fact, it is used as an augmentation agent to improve treatment-resistant OCD, though it carries a notable risk of acute akathisia in SSRI-treated OCD patients.

Evidence for Amisulpride as OCD Augmentation

Amisulpride is specifically used to improve OCD symptoms when SSRIs alone are insufficient:

• In treatment-resistant OCD, amisulpride augmentation (200-600 mg/day added to ongoing SSRI therapy) significantly reduced Yale-Brown Obsessive-Compulsive Scale scores from 26.7 to 12.5 over 12 weeks, with 70% of patients showing meaningful improvement 1.

• A separate case series demonstrated that amisulpride 200 mg/day as add-on therapy reduced Y-BOCS scores from 25.3 to 12.2 after 6 weeks, with 7 of 10 patients achieving significant or partial improvement 2.

• Guidelines recommend antipsychotic augmentation (including second-generation antipsychotics) for patients with inadequate response to SSRIs after adequate trials 3, 4.

Critical Caveat: Akathisia Risk in OCD Patients

The major concern with amisulpride in OCD is not symptom worsening, but rather a high incidence of acute akathisia, particularly in SSRI-treated patients with less severe OCD symptoms:

• Nearly 50% of OCD patients experienced acute akathisia following a single dose of amisulpride in an experimental study, with higher rates in those with less severe obsessive-compulsive symptoms 5.

• This suggests dysfunctional dopamine-serotonin interactions in certain OCD patients, which may explain why some patients don't respond adequately to SSRI monotherapy 5.

• One patient in a case series required dose reduction from 200 mg to 100 mg due to acute extrapyramidal adverse effects 2.

Common Side Effects (Not OCD Worsening)

When amisulpride is used in OCD, the typical adverse effects include:

• Weight gain (70% of patients) 1
• Mild sedation (65% of patients) 1
• Asthenia/fatigue (35% of patients) 1
• Extrapyramidal symptoms including akathisia 2, 5

Clinical Algorithm for Amisulpride Use in OCD

Start with 100-200 mg/day and titrate cautiously:

• Begin at 100-200 mg/day added to ongoing SSRI therapy 2, 1
• Monitor closely for akathisia at each visit, especially in the first 2 weeks 5
• If tolerated, can increase to 200-600 mg/day in flexible dosing based on response 1
• Assess efficacy at 6-12 weeks using Y-BOCS scores 2, 1
• If acute akathisia develops, reduce dose immediately or discontinue 2

When to Consider Amisulpride

Use amisulpride augmentation when:

• Patient has failed adequate trials of at least 2 SSRIs at maximum tolerated doses for 8-12 weeks each 3, 4
• Residual Y-BOCS scores remain elevated despite SSRI therapy 2, 1
• Patient does not have bipolar disorder (where mood stabilization takes priority) 4