Antipsychotic Response Worsens With Postmenopausal Duration in Women With Schizophrenia.
BACKGROUND
The loss of estrogens in the menopause may lead to increased vulnerability for psychotic relapse, poor clinical outcome, and a need for increased antipsychotic dose. However, confounders such as cumulative estrogen exposure and time since menopause have been inadequately studied. Our aim was to investigate potential variables capable of influencing antipsychotic response in a sample of postmenopausal women with schizophrenia.


METHODS
Sixty-four postmenopausal schizophrenic women were followed in a 12-week prospective treatment-by-clinical requirement study. Duration of reproductive years was considered an indirect measure of lifetime cumulative estrogens exposure. Psychopathological assessment included the following: Positive and Negative Syndrome Scale, Personal and Social Performance, and Clinical Global Impression-Schizophrenia Scale. Response was defined as a reduction of 30% or more of Positive and Negative Syndrome Scale total scores. Antipsychotic adherence was assessed by plasma level monitoring at 4 weeks. Regression analyses were performed to investigate the association between potential confounding factors and antipsychotic response.


RESULTS
Forty-two participants (66%) were found to be antipsychotic responders. Time since menopause was significantly and negatively associated with overall antipsychotic response, explaining almost 42% of the variance of the model used. Smoking and cumulative estrogen exposures were associated with improvement in negative symptoms. Smoking and time since menopause were associated with improvement in excitement symptoms, and smoking was positively associated with improvement in depressive and cognitive symptoms.


CONCLUSIONS
Time since menopause was significantly negatively associated with antipsychotic response in postmenopausal schizophrenic women, suggesting a decline in antipsychotic response after menopause. The neurobiological basis for antipsychotic response may include a role for estrogen and nicotine receptors.
From the *Barcelona Clinic Schizophrenia Unit, Neurosciences Institute, Hospital Clinic of Barcelona, Department of Psychiatry and Clinical Psychobiology, University of Barcelona, CIBERSAM, IDIBAPS; †Neurosciences Institute, ‡Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, Barcelona, Spain; and §Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Alexandre
A
González-Rodríguez
Rosa
R
Catalán
Rafael
R
Penadés
Victoria
V
Ruiz Cortés
Mercè
M
Torra
Mary V
MV
Seeman
Miquel
M
Bernardo
D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D017698:Postmenopause; D011446:Prospective Studies; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012907:Smoking; D013997:Time Factors
D014150:Antipsychotic Agents