The Effects of adjuvant treatment with L-triiodothyronine (T3) on acute schizophrenia treatment with risperidone

Abstract

Introduction: Acute psychotic patients have differences in thyroid hormones concentrations in comparison to healthy controls [1].Better understanding of thyroid hormone effects in the brain could help us to find new targets for the treatment of mental disorders [2]. In acute schizophrenic patients T3 decisively enhanced the antipsychotic effects of chlorpromazine [3]. There are no studies of effects of T3 on schizophrenia treatment with second-generation antipsychotics. The aim: To evaluate efficacy and safety of adjuvant treatment with L-triiodothyronine (T3) on acute schizophrenia treatment with risperidone. Methods: 32 patients, hospitalized for acute psychotic episode treatment (17 men and 15 women, mean age (SD) 41(11) years), with diagnosis of schizophrenia (295.1–295.9) (DSM-IV-TR, using MINI-Plus), with no history of significant or unstable medical condition, physically healthy on the basis of physical examination, ECG, blood and urine tests, endocrinology consultation, TSH and TPOAb concentrations in reference range, were randomly assigned − 14 patients to receive oral Risperidone (RIS) and T3 25 mg; 18 patients to receive oral RIS and Placebo (PLB). RIS flexible dose 2−8 mg/da, T3/PLB-once a day in the morning. Concomitant lorazepam treatment of agitation, irritability, restlessness or hostility was administered to 31 patients; 14 patients − zolpidem for insomnia and 20 patients − trihexyphenidyl for movement disorders. Psychiatric state (using BPRS and CGI-S) were assessed and blood samples were drawn for free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), of sex hormone binding globulin (SHBG) concentrations (radioimmune assays) on two occasions: during randomization and at the end of the study visit; CGI-I − at the end of the study. Treatment period − up to maximally 6 weeks and ended, when patient met response to treatment criteria: CGI-S 3 and CGI-I 3. Results: The patients, who received adjuvant T3 treatment at randomization, had higher BPRS scores (F = 5.3 p = 0.028) but similar CGI-S scores compared to patients who received adjuvant PLB. Therefore, all treatment effects were statistically adjusted for randomization BPRS score. All 32 study patients during the end of the study visit met treatment response criteria and were considered as ‘mildly ill’ (CGI-S =3). Patients who received treatment with RIS+T3 required a significantly shorter duration of response to treatment period than did RIS+PLB group [32 (95% CI, 21−36) vs. 26 (95% CI, 22−29) treatment days; p = 0.022]. Patients on RIS+T3 during treatment showed close to a significant (p = 0.053) greater improvement according to BPRS score and a greater (p = 0.048) BPRS score decrease in percent from randomization than patients on RIS+PLB (treatment effect F = 13.1 p = 0.001). There were no significant differences between groups according to CGI-I scores. All 32 patients fully completed all treatment period: there were no drop outs and serious adverse events, with no significant differences in the frequency of adverse effects, and in frequency and magnitude of dose of concomitant medication in two treatment groups. Conclusions: The adjuvant administration of T3 compared to PLB is safe and effective in acute schizophrenia patients treated with RIS, accelerating and enhancing antipsychotic RIS effects. Due to small sample size these data need to be treated as preliminary.