Adjunctive estrogen treatment in women with chronic schizophrenia: a double-blind, randomized, and placebo-controlled trial

Akhondzadeh, Shahin; Nejatisafa, Ali‐Akbar; Amini, Homayoun; Mohammadi, Mohammad Reza; Larijani, Bagher; Kashani, Ladan; Raisi, Firoozeh; Kamalipour, Abbas

doi:10.1016/s0278-5846(03)00161-1

Cited by 131 publications

(72 citation statements)

References 20 publications

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“…As detailed in the Introduction, it has been suggested that exogenous estrogen may have antipsychotic properties or increase response to APDs in women with schizophrenia. Although the latter has been supported in several studies (Agius et al, 2009;Akhondzadeh et al, 2003;Cyr et al, 2002;Korhonen et al, 1995;Kulkarni, 2009;Kulkarni et al, 1996Kulkarni et al, , 2001Kulkarni et al, , 2008aLindamer et al, 2001;Mortimer, 2007;Rao and Kolsch, 2003), other studies reported that estrogen treatment failed to improve or even worsened symptoms (Bergemann et al, 2005;Chua et al, 2005;Gattaz et al, 1994;Lindamer et al, 2001; for review see Mortimer, 2007). We previously provided support for antipsychotic capacity of 17b-estradiol by showing a synergistic effect of ineffective doses of 17b-estradiol and APDs in reversing OVX-induced disrupted LI , and have replicated such a synergistic effect here for amphetamine-induced disrupted LI.…”

Section: Discussionmentioning

confidence: 81%

Contrasting Effects of Increased and Decreased Dopamine Transmission on Latent Inhibition in Ovariectomized Rats and Their Modulation by 17β-Estradiol: An Animal Model of Menopausal Psychosis?

Arad

Weiner

2010

Neuropsychopharmacol

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Women with schizophrenia have later onset and better response to antipsychotic drugs (APDs) than men during reproductive years, but the menopausal period is associated with increased symptom severity and reduced treatment response. Estrogen replacement therapy has been suggested as beneficial but clinical data are inconsistent. Latent inhibition (LI), the capacity to ignore irrelevant stimuli, is a measure of selective attention that is disrupted in acute schizophrenia patients and in rats and humans treated with the psychosisinducing drug amphetamine and can be reversed by typical and atypical APDs. Here we used amphetamine (1 mg/kg)-induced disrupted LI in ovariectomized rats to model low levels of estrogen along with hyperfunction of the dopaminergic system that may be occurring in menopausal psychosis, and tested the efficacy of APDs and estrogen in reversing disrupted LI. 17b-Estradiol (50, 150 mg/kg), clozapine (atypical APD; 5, 10 mg/kg), and haloperidol (typical APD; 0.1, 0.3 mg/kg) effectively reversed amphetamine-induced LI disruption in sham rats, but were much less effective in ovariectomized rats; 17b-estradiol and clozapine were effective only at high doses (150 mg/kg and 10 mg/kg, respectively), whereas haloperidol failed at both doses. Haloperidol and clozapine regained efficacy if coadministered with 17b-estradiol (50 mg/kg, an ineffective dose). Reduced sensitivity to dopamine (DA) blockade coupled with spared/potentiated sensitivity to DA stimulation after ovariectomy may provide a novel model recapitulating the combination of increased vulnerability to psychosis with reduced response to APD treatment in female patients during menopause. In addition, our data show that 17b-estradiol exerts antipsychotic activity.

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Section: Discussionmentioning

confidence: 81%

Contrasting Effects of Increased and Decreased Dopamine Transmission on Latent Inhibition in Ovariectomized Rats and Their Modulation by 17β-Estradiol: An Animal Model of Menopausal Psychosis?

Arad

Weiner

2010

Neuropsychopharmacol

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“…In 2003, Akhondzadeh et al [46] published a randomized study of 32 women of childbearing age with chronic schizophrenia. They administered ethinyl estradiol as an adjunct to haloperidol over 8 weeks while the control group received haloperidol only.…”

Section: Intervention Studiesmentioning

confidence: 99%

Estrogens and Gonadal Function in Schizophrenia and Related Psychoses

Riecher-Rössler¹,

Kulkarni

2010

Biological Basis of Sex Differences in Psychopharmacology

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“…Possible reasons could include genetic factors (2,53), difference in brain structure (54,55), higher rates of marriage among women (56,57), lower rates of substance abuse (57), greater social expectations and pressure concerning vocational expectations for men, and differences in social support systems. Hormonal differences may also play a role (58)(59)(60)(61)(62).…”

Section: Sex Differences In Patients With Psychotic Disorders Other Tmentioning

confidence: 99%

“…Seeman has proposed that estrogen serves as a "natural" antipsychotic agent by inhibiting postsynaptic dopamine transmission (58)(59). Psychopathology has been shown to improve when estradiol levels rise, and vice-versa (60)(61)(62). If the estrogen hypothesis is correct, and estrogen truly exerts a natural antipsychotic property, it would follow that during child-bearing years, women with schizophrenia would show reduced psychotic activity compared to men over time, at least until menopause.…”

Section: Psychosis and The Estrogen Hypothesismentioning

confidence: 99%

Sex differences in schizophrenia and other psychotic disorders: a 20-year longitudinal study of psychosis and recovery

Grossman

Harrow

Rosen

et al. 2008

Comprehensive Psychiatry

142

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This longitudinal study was designed to provide data on sex differences in the course of illness in schizophrenia and other psychotic disorders. Ninety-seven participants (43 women and 54 men) were assessed during index hospitalization when they were in the acute phase of illness, and then reassessed prospectively at 6 consecutive followups over a 20 year period. Patients were evaluated by a series of standardized measures on many aspects of illness including the presence of psychosis, global outcome, and rate of recovery. When women were compared to men in this sample, the data demonstrated a lower percentage of psychotic activity for women over the course of illness (significant at the 7.5 and 20 year followups), and a significant improvement in psychotic activity over 20 years for women (p<.05), but not for men. Additionally, women showed significantly better global functioning (p<.05) at 3 of the 6 followups (the 2, 7.5, and 10-year followups). Significantly higher percentages (p<.05) of women were in recovery at 2 of the 6 followup years (the 2 and 10-year followups). Cumulatively, 61% of the women with schizophrenia showed a period of recovery at some point during the 20 year period, compared to 41% of the men. The sex difference patterns were similar for patients with schizophrenia and for those with other types of psychotic disorders. Sex differences in this sample were specifically not attributable to differences in age of onset or premorbid developmental achievements.

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Adjunctive estrogen treatment in women with chronic schizophrenia: a double-blind, randomized, and placebo-controlled trial

Cited by 131 publications

References 20 publications

Contrasting Effects of Increased and Decreased Dopamine Transmission on Latent Inhibition in Ovariectomized Rats and Their Modulation by 17β-Estradiol: An Animal Model of Menopausal Psychosis?

Contrasting Effects of Increased and Decreased Dopamine Transmission on Latent Inhibition in Ovariectomized Rats and Their Modulation by 17β-Estradiol: An Animal Model of Menopausal Psychosis?

Estrogens and Gonadal Function in Schizophrenia and Related Psychoses

Sex differences in schizophrenia and other psychotic disorders: a 20-year longitudinal study of psychosis and recovery

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