Gender Differences in Pharmacokinetics and Side Effects of Second Generation Antipsychotic Drugs

Aichhorn, Wolfgang; Gasser, M.; Weiss, Elisabeth M.; Adlassnig, Christine; Marksteiner, Josef

doi:10.2174/1570159052773440

Cited by 15 publications

(14 citation statements)

References 103 publications

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“…Antipsychotics are lipophilic drugs likely to be metabolized differently among women compared to men due to differences in body composition, with a resulting higher volume distribution and higher serum levels at similar doses to men; [32] [33] female users of antipsychotics have also been found to have greater incidence of adverse events compared to males. [34] However, SSRIs are also lipophilic and the same gender difference in prevalent LUTS was not observed. It is also possible that women in our study using antipsychotics may differentially report symptoms compared to women taking only SSRIs, but the fact that we did not observe the same for men using antipsychotics suggests otherwise.…”

Section: Discussionmentioning

confidence: 99%

1726 Are Commonly-Used Psychoactive Medications Associated With Lower Urinary Tract Symptoms?

et al. 2012

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Purpose-Lower urinary tract symptoms (LUTS) such as urinary frequency and urgency are bothersome and associated with reduced quality-of-life. Atypical antipsychotics (AAPs) have been implicated in increasing the risk of urinary incontinence. In a large community-based sample of men and women, we examined the associations of AAP use and selective serotonin reuptake inhibitor (SSRIs) use with LUTS.Methods-Data were collected (2002)(2003)(2004)(2005)) from a generalizable sample of Boston, MA, USA residents aged 30-79 (N=5503). LUTS were assessed using the American Urologic Association Symptom Index (AUA-SI). The prevalence of clinically-significant LUTS was estimated using a cutoff AUA-SI score of 8+ to indicate moderate-to-severe symptoms. Confounder-adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated from multivariate logistic regression to estimate the associations for psychoactive drugs used in the previous month (SSRIs, AAPs, both) and LUTS.Results-Among women, AAP users had a higher prevalence of LUTS (46.2%) compared to SSRI users (23.5%) and those with depressive symptoms not using SSRIs or AAPs (26.3%). Corresponding prevalence estimates among men were 32.7%, 29.8%, and 33.3%. In multivariate models, AAP use was significantly associated with LUTS among women when used either with SSRIs (OR=2.72, or without SSRIs (OR=3.05,) but SSRI use without AAP use was not associated with LUTS, compared to non-users without depressive symptoms. No associations were observed among men.Conclusions-In our study, AAPs but not SSRIs were associated with increased prevalence of LUTS among women only. Further prospective research is needed to determine time sequence and cause-and-effect.

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Section: Discussionmentioning

confidence: 99%

1726 Are Commonly-Used Psychoactive Medications Associated With Lower Urinary Tract Symptoms?

et al. 2012

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“…Antipsychotics are lipophilic drugs likely to be metabolized differently among women compared to men due to differences in body composition, with a resulting higher volume distribution and higher serum levels at similar doses to men;[32] [33] female users of antipsychotics have also been found to have greater incidence of adverse events compared to males. [34] However, SSRIs are also lipophilic and the same gender difference in prevalent LUTS was not observed. It is also possible that women in our study using antipsychotics may differentially report symptoms compared to women taking only SSRIs, but the fact that we did not observe the same for men using antipsychotics suggests otherwise.…”

Section: Discussionmentioning

confidence: 99%

Are commonly used psychoactive medications associated with lower urinary tract symptoms?

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Maserejian

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et al. 2011

Eur J Clin Pharmacol

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Purpose Lower urinary tract symptoms (LUTS) such as urinary frequency and urgency are bothersome and associated with reduced quality-of-life. Atypical antipsychotics (AAPs) have been implicated in increasing the risk of urinary incontinence. In a large community-based sample of men and women, we examined the associations of AAP use and selective serotonin reuptake inhibitor (SSRIs) use with LUTS. Methods Data were collected (2002–2005) from a generalizable sample of Boston, MA, USA residents aged 30–79 (N=5503). LUTS were assessed using the American Urologic Association Symptom Index (AUA-SI). The prevalence of clinically-significant LUTS was estimated using a cutoff AUA-SI score of 8+ to indicate moderate-to-severe symptoms. Confounder-adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated from multivariate logistic regression to estimate the associations for psychoactive drugs used in the previous month (SSRIs, AAPs, both) and LUTS. Results Among women, AAP users had a higher prevalence of LUTS (46.2%) compared to SSRI users (23.5%) and those with depressive symptoms not using SSRIs or AAPs (26.3%). Corresponding prevalence estimates among men were 32.7%, 29.8%, and 33.3%. In multivariate models, AAP use was significantly associated with LUTS among women when used either with SSRIs (OR=2.72, 95%CI:1.45–5.10), or without SSRIs (OR=3.05, 95%CI:1.30–7.16) but SSRI use without AAP use was not associated with LUTS, compared to non-users without depressive symptoms. No associations were observed among men. Conclusions In our study, AAPs but not SSRIs were associated with increased prevalence of LUTS among women only. Further prospective research is needed to determine time sequence and cause-and-effect.

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“…Unlike olanzapine, risperidone might induce an increase in prolactin (Volavka, et al, 2004;Aichhorn, et al, 2005). Although we may hypothesise that it might cause steroid hormone disregulations (Aichhorn, et al, 2005), this relationship is still to be determined.…”

Section: Associations Of Metabolic Abnormalities and Sga Treatmentmentioning

confidence: 95%

“…Although we may hypothesise that it might cause steroid hormone disregulations (Aichhorn, et al, 2005), this relationship is still to be determined. However, as is known that oral contraceptives might induce Very Low-Density Lipoprotein (VLDL) formation and subsequent triglyceride increase, and a similar mechanism might occur during SGA application (Harrison, et al, 1997).…”

Section: Associations Of Metabolic Abnormalities and Sga Treatmentmentioning

confidence: 96%

“…Third, all the study subjects were women, which set a limitation to generalising the findings to male subjects with schizophrenia. However, at the same time, this contributes to the homogeneity of the study sample because sex differences in the course of metabolic abnormalities during the course of illness and treatment have been described (Aichhorn, et al, 2005). However, as the strong point of the study would be that all analyses were performed on subjects who received no antipsychotic medication prior to our study, which is a major confounding factor in most studies evaluating effects of SGA on metabolic parameters.…”

Section: Limitations Of the Studymentioning

confidence: 99%

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Metabolic syndrome in female patients with schizophrenia treated with second generation antipsychotics: a 3-month follow-up

et al. 2008

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The objective of this study was to determine the occurrence of metabolic abnormalities among previously unmedicated female patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia spectrum disorders and their associations with olanzapine and risperidone treatment. We analysed 94 female patients who were treated with olanzapine or risperidone in the period of 3 months. Analysed variables included fasting glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoproteins and triglycerides in blood, blood pressure (BP), waist and hip circumferences and body mass index (BMI). At baseline, 14 patients (15%) fulfilled criteria for metabolic syndrome. After 3 months of treatment, 25 patients (27%) fulfilled criteria for metabolic syndrome, and their baseline BMI was the only predictor for its development. Treatment with both antipsychotics was associated with significant increase in waist circumference. Positive family history of diabetes mellitus contributed to a significant greater increase in abdominal obesity, significant higher baseline levels and a borderline significant increase in fasting glucose among olanzapine-treated patients. Olanzapine admission was associated with a significant increase in LDL and risperidone with a significant increase in triglycerides. Metabolic abnormalities seem to be more prevalent in unmedicated female patients with schizophrenia spectrum disorders than expected based on results in general population (adjusted for age and sex). Olanzapine treatment might induce significant alterations in metabolic profiles, especially among patients with positive family history of diabetes, mostly by inducing abdominal obesity. The association of risperidone application and increase in triglyceride level still needs to be determined.

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Gender Differences in Pharmacokinetics and Side Effects of Second Generation Antipsychotic Drugs

Cited by 15 publications

References 103 publications

1726 Are Commonly-Used Psychoactive Medications Associated With Lower Urinary Tract Symptoms?

1726 Are Commonly-Used Psychoactive Medications Associated With Lower Urinary Tract Symptoms?

Are commonly used psychoactive medications associated with lower urinary tract symptoms?

Metabolic syndrome in female patients with schizophrenia treated with second generation antipsychotics: a 3-month follow-up

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