What are the common oral medications for managing behavioral tics?

Oral Medications for Behavioral Tics

For moderate to severe tics requiring pharmacological treatment, alpha-2 agonists (clonidine or guanfacine) are the recommended first-line oral medications, with risperidone as the preferred second-line agent when alpha-2 agonists are ineffective or poorly tolerated. 1

First-Line Medications: Alpha-2 Agonists

Clonidine and guanfacine have the best safety profile and should be initiated first for tics of moderate severity. 2, 1

Clonidine Dosing

• Start with 0.05 mg at bedtime 2
• Increase by 0.05 mg every 4-7 days as needed and tolerated 2
• Maximum dosage: 0.3-0.4 mg/day divided 3-4 times daily 2
• Preferably administer in the evening due to somnolence/fatigue as a common adverse effect 3

Guanfacine Dosing

• Start with 0.5 mg at bedtime 2
• Increase by 0.5 mg weekly as needed and tolerated 2
• Maximum dosage: 3-4 mg/day divided twice daily 2
• Evening administration is generally preferable due to sedation 3

Evidence Supporting Alpha-2 Agonists

• Moderate-quality evidence from 4 trials (N=164) shows significant benefit with standardized mean difference of -0.71 (95% CI -1.03 to -0.40) 1
• These agents have a reasonable safety profile and are considered first-line for moderate tics 2
• Clinical trials found that tics did not worsen under treatment with these medications, contrary to historical concerns 3

Second-Line Medications: Atypical Antipsychotics

When alpha-2 agonists are ineffective or poorly tolerated, risperidone is the preferred atypical antipsychotic due to the strongest evidence base. 4, 1

Risperidone Dosing

• Start with 0.01 mg/kg/dose once daily 2
• Increase by 0.02 mg/kg/day at weekly intervals 2
• Maximum: 0.06 mg/kg/dose once daily 2
• For adults, initial dosage is 0.25 mg/day at bedtime, with maximum of 2-3 mg/day usually divided twice daily 5
• Extrapyramidal symptoms may occur at doses ≥2 mg/day, requiring careful monitoring 6, 5

Evidence Supporting Risperidone

• Best evidence level among atypical antipsychotics for tic treatment 4
• May have additional efficacy for behavioral problems that often accompany tics 2
• Low-quality evidence from 4 antipsychotic trials (N=76) shows benefit with standardized mean difference of -0.74 (95% CI -1.08 to -0.40), but carries risk of harm 1

Alternative Atypical Antipsychotics

• Aripiprazole: Second choice with limited but promising data and low risk for adverse reactions 4
  • Target dose 10 mg/day in adolescents, starting at 2 mg and titrating up 7
• Ziprasidone and olanzapine: Reasonable alternatives to risperidone 2

Third-Line Medications: Typical Antipsychotics

Typical antipsychotics (haloperidol, pimozide, fluphenazine) are the most potent medications for severe tics but should be reserved for cases where atypical antipsychotics fail due to higher risk of bothersome side effects. 2, 1

• Pimozide has the best evidence among typical antipsychotics 4
• Efficacy is proportionate to affinity for dopamine D2 receptors 2
• These agents commonly cause extrapyramidal symptoms and carry risk of tardive dyskinesia 2

Alternative Agent: Tiapride

Tiapride has the largest clinical experience in Europe with a low rate of adverse reactions and can be considered as first-line treatment alongside risperidone. 4

Special Considerations for Comorbid ADHD

When tics coexist with ADHD, optimize alpha-2 agonist dosing first, as undertreated ADHD can manifest as increased irritability and oppositional behavior. 6

• Consider atomoxetine, stimulants, or clonidine for ADHD symptoms 4
• Atomoxetine is particularly useful in tic disorder with comorbid ADHD, as clinical trials found tics did not worsen under treatment 3
• If tics are severe with ADHD, combine stimulants with risperidone 4

Treatment Algorithm

1. Mild/occasional tics: Education and reassurance only; no medication needed 2
2. Moderate tics: Start clonidine or guanfacine as first-line 2, 1
3. Inadequate response or intolerance to alpha-2 agonists: Switch to risperidone 4, 1
4. Severe tics unresponsive to risperidone: Consider aripiprazole or other atypical antipsychotics 4
5. Refractory severe tics: Consider typical antipsychotics (pimozide, haloperidol) with careful monitoring 2, 1

Important Caveats

• Antipsychotics carry risk of extrapyramidal symptoms, weight gain, metabolic changes, and tardive dyskinesia—reserve for when benefits clearly outweigh risks 5, 1
• The balance of clinical benefits to harm favors alpha-2 agonists as first-line agents when medication is appropriate 1
• Behavioral interventions (Comprehensive Behavioral Intervention for Tics/CBIT) have moderate-quality evidence and should be considered as first-line treatment when available, either alone or combined with medication 1, 8
• Treatment should target the most troubling symptom, as comorbid conditions (ADHD, OCD, anxiety) occur in >50% of patients and may be more bothersome than tics themselves 2