Triiodothyronine accelerates and enhances the antipsychotic effect of risperidone in acute schizophrenia

• Adjuvant triiodothyronine was effective in the treatment of acutely schizophrenic patients.
• Triiodothyronine accelerated and enhanced antipsychotic effect of risperidone.
• Triiodothyronine and risperidone was safe and well-tolerated treatment combination.

In acute psychotic schizophrenia patients we investigated if the combination of triiodothyronine (T3) plus risperidone was more effective when compared to risperidone monotherapy. Thirty-two in-patients meeting the DSM-IV-TR diagnostic criteria for schizophrenia and without thyroid disease received risperidone (flexibly adjusted dose for tolerability) and were randomized to additionally receive either T3 (25 μg daily; risperidone plus T3 group) or placebo (risperidone plus placebo group). Treatment lasted until meeting the response to treatment criteria defined as score of ≤3 on the Clinical Global Impression Severity and Improvement scales. Acute psychotic episode symptom severity was evaluated using the Brief Psychiatric Rating Scale (BPRS) at treatment initiation and at the final study assessment. Fourteen patients were randomized to receive risperidone plus T3 and eighteen to receive risperidone plus placebo. The time until treatment response was shorter in the risperidone plus T3 group relative to the risperidone plus placebo group (25.5 ± 4.4 days vs 32.2 ± 8.2 days, respectively; p = 0.001). Moreover, there was a greater reduction of BPRS-total score (p = 0.01) in the risperidone plus T3 group relative to the risperidone plus placebo group. Treatment with T3 was associated with shorter time to treatment response (β = −0.440, p = 0.022) and with greater improvement in BPRS score (β = 0.240, p = 0.053), independent of patients' gender, age, baseline BPRS score and mean risperidone dose. The study confirms that addition of T3 to risperidone was associated with accelerated and enhanced treatment response in acutely psychotic schizophrenic patients.