thiothixene

General Information

Thiothixene is a high-potency FGA (thioxanthene) used for schizophrenia. It is an oral-only medication with no LAI formulation (label/clinical).

Compared with low-potency phenothiazines, thiothixene is generally less sedating and less anticholinergic, but movement-disorder risk (EPS and tardive dyskinesia) is often more prominent and can be the limiting factor (label/clinical).

Many clinicians consider it mainly for cost-sensitive maintenance in stable patients who have previously tolerated FGAs; it is less commonly chosen for first-episode care due to tolerability and adherence considerations (AHRQ/clinical).

Early follow-up often focuses on akathisia (inner restlessness) because it can be mistaken for anxiety or agitation and can drive nonadherence if not recognized (clinical).

The thiothixene compare view, evidence feed, and print page help compare EPS, sedation, and metabolic trade-offs.

Thiothixene is an older, inexpensive oral antipsychotic. Its role is often constrained by movement-disorder risk and lack of a depot formulation, especially when adherence concerns are prominent (AHRQ/clinical).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Dopamine D2 receptor antagonism is the primary antipsychotic mechanism.

Relative “high potency” is associated with higher EPS risk at clinical doses.

• D2 receptor antagonism (antipsychotic effect).

Metabolism and Pharmacokinetics

• Thiothixene is hepatically metabolized; patient-to-patient tolerability and response variability are managed clinically via titration (label/clinical).
• Therapeutic drug monitoring is not routine for thiothixene; dose adjustment is typically guided by symptom response and movement symptoms rather than serum levels (AGNP/clinical).

Dosing and Administration

• The label recommends individualizing dose based on chronicity and severity, starting low and titrating gradually to the optimal effective level (label).
• Label examples: in milder conditions, an initial dose of 2 mg three times daily; in more severe conditions, an initial dose of 5 mg twice daily (label).
• The label describes an “usual optimal” total daily dose of 20–30 mg, with increases up to 60 mg/day sometimes used; doses above 60 mg/day rarely increase benefit (label).
• Once-a-day dosing is described as possible for some patients after stabilization, depending on response and adverse effects (label).
• The label states use in children under 12 years is not recommended because safe conditions for its use have not been established (label).

Monitoring & Labs

• Movement symptoms (akathisia, rigidity, tremor; tardive dyskinesia screening).
• Hyperprolactinemia symptoms (amenorrhea, galactorrhea, sexual dysfunction).
• Sedation and functional impairment (falls risk).
• Weight and cardiometabolic risk factors over time (pragmatic baseline/periodic monitoring).
• Akathisia check-in after dose changes (restlessness can mimic anxiety or agitation).

Adverse Effects

Interactions

• Additive CNS depression with alcohol, opioids, benzodiazepines, and other sedatives (clinical).
• Antipsychotic polypharmacy increases cumulative adverse effects; when used, teams typically document rationale and monitoring (clinical).
• QT-prolonging combinations and electrolyte abnormalities can increase arrhythmia risk; ECG monitoring is commonly considered when risk factors accumulate (clinical).
• Additive anticholinergic burden (e.g., tricyclic antidepressants and first-generation antihistamines) can increase constipation, urinary retention, and delirium risk (clinical).

Other Useful Information

• For schizophrenia, modern workflows often compare oral FGAs vs SGAs and consider LAI options early when adherence is uncertain (APA).
• Because thiothixene has no depot formulation, transitioning to an LAI alternative is often evaluated when relapse risk is driven by missed oral doses (APA/clinical).

References

1. Thiothixene capsules prescribing information — DailyMed (2025)
2. First Generation Versus Second Generation Antipsychotics IN Adults: Comparative Effectiveness — Agency for Healthcare Research and Quality (NCBI Bookshelf) (2012)
3. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)
4. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)