Effects of pioglitazone on metabolic abnormalities, psychopathology, and cognitive function in schizophrenic patients treated with antipsychotic medication: A randomized double-blind study

Robert C. Smith, Hua Jin, Chunbo Li, Nigel Bark, Anantha Shekhar, Sauburah Dwivedi, Catherine Mortiere, James Lohr, Qiaoyan Hu, John M. Davis

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Schizophrenic patients treated with antipsychotic drugs (AP) have an increased frequency of glucose-lipid metabolic abnormalities and diabetes. Pioglitazone has been shown to be effective in the treatment of glucose and lipid abnormalities in diabetes and decreasing longer-term conversion of impaired glucose tolerance to frank diabetes. Some studies also suggest possible pro-cognitive and antidepressant effects of pioglitazone. We studied the effects of pioglitazone on potential metabolic, symptomatic and cognitive benefits in schizophrenic patients treated with AP. Methods: 54 schizophrenic patients with at least both a)impaired glucose and b) triglycerides ≥ 120. mg/dL and/or low HDL levels, participated in a double-blind placebo controlled study of 3. month treatment with Pioglitazone (30-45. mg/day) or matched placebo, at 5 sites (4 U.S., 1 China). Fasting glucose and lipid parameters, and psychopathology (PANSS scale) were assessed monthly, and patients had a glucose tolerance test and cognitive testing (RBANS and CPT) at baseline and at the end of study. Statistical analysis used mixed model repeated measures analysis, supplemented by completer and LOCF analysis. Results: In the total sample there was an overall effect (P's < .05 to < .01) of pioglitazone on preventing deterioration in fasting glucose and improving HDL and PANSS depression scores; in the pioglitazone group comparison of baseline vs 3. month values also showed significant (P < .05) decreases in fasting insulin, 2. h glucose in GTT and insulin resistance (HOMA-IR). However there were marked differences between the responses of patients in the U.S. sites vs the China site. In the U.S. sample, patients treated with pioglitazone, when compared to placebo treated patents, had significantly lower fasting glucose (F = 3.99, P = 0.02), improved insulin sensitivity (lower H0MA-IR, F = 6.24, P = .002), lower triglycerides (F = 2.68, P = .06) and increased HDL (F = 6.50, P = .001). By the end of the study 52% of the pioglitazone treated patients compared to 15% of the placebo patients had fasting glucose in the normal range (Fisher's exact test P = .02). Pioglitazone also significantly improved PANSS depression factor scores (F = 2.82, P = 0.05). It did not improve cognitive performance on the RBANS or CPT tasks. Pioglitazone did not increase weight or produce any other significant side-effects. In the small mainland China site sample, pioglitazone treatment, as compared to placebo, did not show greater improvement in metabolic parameters or psychopathology ratings. Conclusions: In the sample of patients from the U.S., pioglitazone was an efficacious and safe treatment for glucose and lipid metabolic abnormalities in schizophrenic patients treated with AP, and it may also have beneficial effects on depressive symptoms. It may be particularly useful in patients whose weight gain effects from antipsychotics have plateaued and where weight loss is not the primary goal. The risk vs. benefits of longer term treatment with pioglitazone has to be carefully evaluated for individual patients.

Original languageEnglish (US)
Pages (from-to)18-24
Number of pages7
JournalSchizophrenia Research
Volume143
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

pioglitazone
Psychopathology
Double-Blind Method
Cognition
Antipsychotic Agents
Glucose
Fasting
Placebos
Lipids
China
Depression
Insulin Resistance
Triglycerides

Keywords

  • Cognition
  • Depression
  • Diabetes
  • Glucose metabolism
  • Pioglitazone
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Effects of pioglitazone on metabolic abnormalities, psychopathology, and cognitive function in schizophrenic patients treated with antipsychotic medication : A randomized double-blind study. / Smith, Robert C.; Jin, Hua; Li, Chunbo; Bark, Nigel; Shekhar, Anantha; Dwivedi, Sauburah; Mortiere, Catherine; Lohr, James; Hu, Qiaoyan; Davis, John M.

In: Schizophrenia Research, Vol. 143, No. 1, 01.01.2013, p. 18-24.

Research output: Contribution to journalArticle

Smith, Robert C. ; Jin, Hua ; Li, Chunbo ; Bark, Nigel ; Shekhar, Anantha ; Dwivedi, Sauburah ; Mortiere, Catherine ; Lohr, James ; Hu, Qiaoyan ; Davis, John M. / Effects of pioglitazone on metabolic abnormalities, psychopathology, and cognitive function in schizophrenic patients treated with antipsychotic medication : A randomized double-blind study. In: Schizophrenia Research. 2013 ; Vol. 143, No. 1. pp. 18-24.
@article{511ef72e6acf4594a41838059e9ca398,
title = "Effects of pioglitazone on metabolic abnormalities, psychopathology, and cognitive function in schizophrenic patients treated with antipsychotic medication: A randomized double-blind study",
abstract = "Background: Schizophrenic patients treated with antipsychotic drugs (AP) have an increased frequency of glucose-lipid metabolic abnormalities and diabetes. Pioglitazone has been shown to be effective in the treatment of glucose and lipid abnormalities in diabetes and decreasing longer-term conversion of impaired glucose tolerance to frank diabetes. Some studies also suggest possible pro-cognitive and antidepressant effects of pioglitazone. We studied the effects of pioglitazone on potential metabolic, symptomatic and cognitive benefits in schizophrenic patients treated with AP. Methods: 54 schizophrenic patients with at least both a)impaired glucose and b) triglycerides ≥ 120. mg/dL and/or low HDL levels, participated in a double-blind placebo controlled study of 3. month treatment with Pioglitazone (30-45. mg/day) or matched placebo, at 5 sites (4 U.S., 1 China). Fasting glucose and lipid parameters, and psychopathology (PANSS scale) were assessed monthly, and patients had a glucose tolerance test and cognitive testing (RBANS and CPT) at baseline and at the end of study. Statistical analysis used mixed model repeated measures analysis, supplemented by completer and LOCF analysis. Results: In the total sample there was an overall effect (P's < .05 to < .01) of pioglitazone on preventing deterioration in fasting glucose and improving HDL and PANSS depression scores; in the pioglitazone group comparison of baseline vs 3. month values also showed significant (P < .05) decreases in fasting insulin, 2. h glucose in GTT and insulin resistance (HOMA-IR). However there were marked differences between the responses of patients in the U.S. sites vs the China site. In the U.S. sample, patients treated with pioglitazone, when compared to placebo treated patents, had significantly lower fasting glucose (F = 3.99, P = 0.02), improved insulin sensitivity (lower H0MA-IR, F = 6.24, P = .002), lower triglycerides (F = 2.68, P = .06) and increased HDL (F = 6.50, P = .001). By the end of the study 52{\%} of the pioglitazone treated patients compared to 15{\%} of the placebo patients had fasting glucose in the normal range (Fisher's exact test P = .02). Pioglitazone also significantly improved PANSS depression factor scores (F = 2.82, P = 0.05). It did not improve cognitive performance on the RBANS or CPT tasks. Pioglitazone did not increase weight or produce any other significant side-effects. In the small mainland China site sample, pioglitazone treatment, as compared to placebo, did not show greater improvement in metabolic parameters or psychopathology ratings. Conclusions: In the sample of patients from the U.S., pioglitazone was an efficacious and safe treatment for glucose and lipid metabolic abnormalities in schizophrenic patients treated with AP, and it may also have beneficial effects on depressive symptoms. It may be particularly useful in patients whose weight gain effects from antipsychotics have plateaued and where weight loss is not the primary goal. The risk vs. benefits of longer term treatment with pioglitazone has to be carefully evaluated for individual patients.",
keywords = "Cognition, Depression, Diabetes, Glucose metabolism, Pioglitazone, Schizophrenia",
author = "Smith, {Robert C.} and Hua Jin and Chunbo Li and Nigel Bark and Anantha Shekhar and Sauburah Dwivedi and Catherine Mortiere and James Lohr and Qiaoyan Hu and Davis, {John M.}",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.schres.2012.10.023",
language = "English (US)",
volume = "143",
pages = "18--24",
journal = "Schizophrenia Research",
issn = "0920-9964",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Effects of pioglitazone on metabolic abnormalities, psychopathology, and cognitive function in schizophrenic patients treated with antipsychotic medication

T2 - A randomized double-blind study

AU - Smith, Robert C.

AU - Jin, Hua

AU - Li, Chunbo

AU - Bark, Nigel

AU - Shekhar, Anantha

AU - Dwivedi, Sauburah

AU - Mortiere, Catherine

AU - Lohr, James

AU - Hu, Qiaoyan

AU - Davis, John M.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Background: Schizophrenic patients treated with antipsychotic drugs (AP) have an increased frequency of glucose-lipid metabolic abnormalities and diabetes. Pioglitazone has been shown to be effective in the treatment of glucose and lipid abnormalities in diabetes and decreasing longer-term conversion of impaired glucose tolerance to frank diabetes. Some studies also suggest possible pro-cognitive and antidepressant effects of pioglitazone. We studied the effects of pioglitazone on potential metabolic, symptomatic and cognitive benefits in schizophrenic patients treated with AP. Methods: 54 schizophrenic patients with at least both a)impaired glucose and b) triglycerides ≥ 120. mg/dL and/or low HDL levels, participated in a double-blind placebo controlled study of 3. month treatment with Pioglitazone (30-45. mg/day) or matched placebo, at 5 sites (4 U.S., 1 China). Fasting glucose and lipid parameters, and psychopathology (PANSS scale) were assessed monthly, and patients had a glucose tolerance test and cognitive testing (RBANS and CPT) at baseline and at the end of study. Statistical analysis used mixed model repeated measures analysis, supplemented by completer and LOCF analysis. Results: In the total sample there was an overall effect (P's < .05 to < .01) of pioglitazone on preventing deterioration in fasting glucose and improving HDL and PANSS depression scores; in the pioglitazone group comparison of baseline vs 3. month values also showed significant (P < .05) decreases in fasting insulin, 2. h glucose in GTT and insulin resistance (HOMA-IR). However there were marked differences between the responses of patients in the U.S. sites vs the China site. In the U.S. sample, patients treated with pioglitazone, when compared to placebo treated patents, had significantly lower fasting glucose (F = 3.99, P = 0.02), improved insulin sensitivity (lower H0MA-IR, F = 6.24, P = .002), lower triglycerides (F = 2.68, P = .06) and increased HDL (F = 6.50, P = .001). By the end of the study 52% of the pioglitazone treated patients compared to 15% of the placebo patients had fasting glucose in the normal range (Fisher's exact test P = .02). Pioglitazone also significantly improved PANSS depression factor scores (F = 2.82, P = 0.05). It did not improve cognitive performance on the RBANS or CPT tasks. Pioglitazone did not increase weight or produce any other significant side-effects. In the small mainland China site sample, pioglitazone treatment, as compared to placebo, did not show greater improvement in metabolic parameters or psychopathology ratings. Conclusions: In the sample of patients from the U.S., pioglitazone was an efficacious and safe treatment for glucose and lipid metabolic abnormalities in schizophrenic patients treated with AP, and it may also have beneficial effects on depressive symptoms. It may be particularly useful in patients whose weight gain effects from antipsychotics have plateaued and where weight loss is not the primary goal. The risk vs. benefits of longer term treatment with pioglitazone has to be carefully evaluated for individual patients.

AB - Background: Schizophrenic patients treated with antipsychotic drugs (AP) have an increased frequency of glucose-lipid metabolic abnormalities and diabetes. Pioglitazone has been shown to be effective in the treatment of glucose and lipid abnormalities in diabetes and decreasing longer-term conversion of impaired glucose tolerance to frank diabetes. Some studies also suggest possible pro-cognitive and antidepressant effects of pioglitazone. We studied the effects of pioglitazone on potential metabolic, symptomatic and cognitive benefits in schizophrenic patients treated with AP. Methods: 54 schizophrenic patients with at least both a)impaired glucose and b) triglycerides ≥ 120. mg/dL and/or low HDL levels, participated in a double-blind placebo controlled study of 3. month treatment with Pioglitazone (30-45. mg/day) or matched placebo, at 5 sites (4 U.S., 1 China). Fasting glucose and lipid parameters, and psychopathology (PANSS scale) were assessed monthly, and patients had a glucose tolerance test and cognitive testing (RBANS and CPT) at baseline and at the end of study. Statistical analysis used mixed model repeated measures analysis, supplemented by completer and LOCF analysis. Results: In the total sample there was an overall effect (P's < .05 to < .01) of pioglitazone on preventing deterioration in fasting glucose and improving HDL and PANSS depression scores; in the pioglitazone group comparison of baseline vs 3. month values also showed significant (P < .05) decreases in fasting insulin, 2. h glucose in GTT and insulin resistance (HOMA-IR). However there were marked differences between the responses of patients in the U.S. sites vs the China site. In the U.S. sample, patients treated with pioglitazone, when compared to placebo treated patents, had significantly lower fasting glucose (F = 3.99, P = 0.02), improved insulin sensitivity (lower H0MA-IR, F = 6.24, P = .002), lower triglycerides (F = 2.68, P = .06) and increased HDL (F = 6.50, P = .001). By the end of the study 52% of the pioglitazone treated patients compared to 15% of the placebo patients had fasting glucose in the normal range (Fisher's exact test P = .02). Pioglitazone also significantly improved PANSS depression factor scores (F = 2.82, P = 0.05). It did not improve cognitive performance on the RBANS or CPT tasks. Pioglitazone did not increase weight or produce any other significant side-effects. In the small mainland China site sample, pioglitazone treatment, as compared to placebo, did not show greater improvement in metabolic parameters or psychopathology ratings. Conclusions: In the sample of patients from the U.S., pioglitazone was an efficacious and safe treatment for glucose and lipid metabolic abnormalities in schizophrenic patients treated with AP, and it may also have beneficial effects on depressive symptoms. It may be particularly useful in patients whose weight gain effects from antipsychotics have plateaued and where weight loss is not the primary goal. The risk vs. benefits of longer term treatment with pioglitazone has to be carefully evaluated for individual patients.

KW - Cognition

KW - Depression

KW - Diabetes

KW - Glucose metabolism

KW - Pioglitazone

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=84871934676&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871934676&partnerID=8YFLogxK

U2 - 10.1016/j.schres.2012.10.023

DO - 10.1016/j.schres.2012.10.023

M3 - Article

C2 - 23200554

AN - SCOPUS:84871934676

VL - 143

SP - 18

EP - 24

JO - Schizophrenia Research

JF - Schizophrenia Research

SN - 0920-9964

IS - 1

ER -