Can antipsychotics worsen Tourette's Syndrome?

Antipsychotics Can Worsen Tourette's Syndrome Through Paradoxical Induction of Tics

Yes, antipsychotics can paradoxically worsen Tourette's syndrome by inducing or exacerbating tics in some patients, despite being commonly used to treat the condition.

Mechanism and Evidence

Antipsychotics are actually among the primary treatments for Tourette's syndrome, with three medications having FDA approval for this indication: pimozide, haloperidol (both typical antipsychotics), and aripiprazole (atypical antipsychotic) 1. However, systematic review evidence has identified numerous cases where these medications paradoxically worsen symptoms:

• A comprehensive systematic review identified 60 cases of antipsychotic-associated tics, occurring either during treatment (44 cases) or following discontinuation (16 cases) 2
• First-generation antipsychotics were associated with a significantly higher occurrence of vocal tics compared to second-generation antipsychotics (p<0.0001) 2
• Specific vocal tics like barking and coprolalia were more common with first-generation antipsychotics 2

Risk Factors and Clinical Presentation

The paradoxical worsening can manifest as:

• New onset of tics in patients without prior history
• Exacerbation of existing tics
• Development of tics after discontinuation of antipsychotics

Risk factors that may increase the likelihood of this adverse effect include:

• Use of high-potency antipsychotics
• Higher doses
• First-generation (typical) antipsychotics carry higher risk than second-generation (atypical) agents 2

Management Recommendations

When antipsychotics are needed for Tourette's syndrome:

1. First-line approach: Consider alpha-2 adrenergic receptor agonists (clonidine, guanfacine) before antipsychotics, as they have better safety profiles with moderate evidence of efficacy 3

2. If antipsychotics are necessary:

   • Start with low doses and titrate slowly
   • Monitor closely for emergence or worsening of tics
   • Consider atypical antipsychotics over typical ones, as they have lower risk of inducing tics 2
   • Aripiprazole may be preferred as it has FDA approval for Tourette's and potentially lower risk of adverse effects 1

3. If tics worsen on antipsychotics:

   • Reduce the dose
   • Consider switching to a different antipsychotic class
   • Discontinue the offending agent if necessary
   • Consider non-pharmacological approaches like habit reversal training (HRT) or comprehensive behavioral intervention for tics (CBIT), which have moderate evidence of efficacy 3

Important Caveats

• Symptoms may not be fully reversible after discontinuation of the offending antipsychotic 2
• Tic disorders naturally wax and wane, making causality assessment challenging
• The risk-benefit profile must be carefully considered, as antipsychotics remain an important treatment option for severe Tourette's despite this paradoxical risk

Alternative Treatments

For patients who experience worsening of tics with antipsychotics, consider:

• Behavioral interventions: HRT/CBIT have demonstrated efficacy (SMD = -0.64; 95% CI -0.99, -0.29) 3
• Alpha-2 adrenergic receptor agonists (clonidine, guanfacine) have moderate evidence of efficacy (SMD = -0.71; 95% CI -1.03, -0.40) 3
• Other pharmacological options with some evidence include baclofen, topiramate, and tetrabenazine 4

Clinicians should maintain vigilance when initiating or modifying antipsychotic regimens in patients with Tourette's syndrome, as the paradoxical worsening of tics represents a significant clinical challenge that can impact treatment adherence and outcomes.