scholarly journals Examining side effect variation of antipsychotic treatment in schizophrenia spectrum disorders

2020 ◽  
Author(s):  
Maria S. Neumeier ◽  
Stephanie Homan ◽  
Stefan Vetter ◽  
Erich Seifritz ◽  
John M. Kane ◽  
...  
Keyword(s):  
Weight Gain ◽  
Side Effects ◽  
Precision Medicine ◽  
Side Effect ◽  
Antipsychotic Drugs ◽  
Schizophrenia Spectrum Disorders ◽  
Schizophrenia Spectrum ◽  
Second Generation Antipsychotics ◽  
Spectrum Disorders ◽  
The Right

Background: Side effects of antipsychotic drugs play a key role in non-adherence and discontinuation of treatment in schizophrenia spectrum disorders (SSD). Precision medicine aims to minimize such side effects by selecting the right treatment for the right patient. However, to determine the extent of precision medicine that is required, we need to (1) show that there is indeed variation in side effects and (2) estimate the amount of variation in those side effects between patients. While clinical observations suggest that such variation may be considerable, a statistical comparison of side effect variation between active and control treatments is required to confirm this. Here, we hypothesized to find larger side effect variation in treatment compared with control in patients treated with first and second generation antipsychotics. Methods: We included double-blind, placebo-controlled, randomized controlled trials (RCTs) of adults with a diagnosis of SSD and prescription for licensed antipsychotic drugs. Standard deviations of the pre-post treatment differences of weight gain, prolactin levels,and corrected QT (QTc) times were extracted. Data quality and validity were ensured by following the PRISMA guidelines. The outcome measure was the overall variability ratio of treatment to control across RCTs. Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model. Results: We included N = 16578 patients for weight gain, N = 16633 patients for prolactin levels, and N = 10384 patients for QTc time. Variability ratios (VR) were significantly increased for weight gain (VR = 1.08; 95% CI: 1.02 - 1.14; P = 0.004) and prolactin levels (VR = 1.38; 95% CI: 1.17 - 1.62; P < 0.001) but did not reach significance for QTc time (VR = 1.05; 95% CI: 0.98 - 1.12; P = 0.135). Conclusion: We found increased variability in major side effects in patients with SSD under treatment with second generation antipsychotics, suggesting that subgroups of patients or even individual patients may benefit from improved treatment allocation through stratified or personalized medicine, respectively.

scholarly journals T216. VARIATION IN SIDE EFFECTS TO ANTIPSYCHOTIC TREATMENT ACROSS SCHIZOPHRENIA SPECTRUM DISORDERS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S314-S315
Author(s):  
Maria Susanne Neumeier ◽  
Stephanie Winkelbeiner ◽  
John Kane ◽  
Erich Seifritz ◽  
Maximilian Huhn ◽  
...  
Keyword(s):  
Weight Gain ◽  
Side Effects ◽  
Adverse Effects ◽  
Precision Medicine ◽  
Antipsychotic Treatment ◽  
Schizophrenia Spectrum Disorders ◽  
Schizophrenia Spectrum ◽  
Second Generation Antipsychotics ◽  
Spectrum Disorders ◽  
The Right

Abstract Background Adverse effects of antipsychotic drugs play a key role in non-compliance and discontinuation of treatment in Schizophrenia Spectrum Disorders (SSD). Precision medicine aims to minimize such adverse effects by selecting the right treatment for the right patients. To determine the need for precision medicine we need to estimate the amount of variation in adverse effects between patients. While clinical experience suggests that such variation is considerable, analyzing how variation differs between treated and untreated patients can answer this question. Here, we hypothesized to find larger variation in treatment compared to control groups of patients treated with second generation antipsychotics. Methods We included double-blind, placebo-controlled, randomized trials of adults with a diagnosis of schizophrenia spectrum disorders and prescription for licensed antipsychotic drugs. Means and variances of the pretreatment and posttreatment outcome differences of weight gain, prolactine levels, and corrected QTC times were extracted. Data quality and validity were ensured by following the PRISMA guidelines. The outcome measure was the overall variability ratio of treatment to control across RCTs. Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model. Results We included N = 13 282 patients for weight gain, N = 11 767 for prolactine levels, and N = 7 203 for QTC time. For all the measured adverse effects, variances were greater in treatment compared to control. Specifically, variance ratios were increased for weight gain (VR = 1.13, 95% CI: 1.06, 1.20), prolactine levels (VR = 1.38, 95% CI: 1.13, 1.68) and QTc time (VR = 1.06, 95% CI: 1.01, 1.12). Discussion We found increased variability in the major side effects that patients with SSD had under treatment with second generation antipsychotics. Indeed, some patients were more susceptible than others to weight gain, prolactine level increase, and QTC time increase, suggesting that precision medicine in antipsychotic treatment should be informed by individual differences in side effects rather than treatment effects. Future studies should aim at finding biological predictors of such individual differences in side effects.

scholarly journals S201. HIPPOCAMPAL SUBFIELD VOLUMES AND CHANGE IN BODY MASS OVER 12 MONTHS OF TREATMENT IN FIRST-EPISODE SCHIZOPHRENIA SPECTRUM DISORDERS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S114-S115
Author(s):  
Stéfan Du Plessis ◽  
Hilmar Luckhoff ◽  
Sanja Kilian ◽  
Laila Asmal ◽  
Frederika Scheffler ◽  
...  
Keyword(s):  
Substance Use ◽  
Weight Gain ◽  
Body Mass ◽  
Interactive Effect ◽  
First Episode ◽  
Schizophrenia Spectrum Disorders ◽  
Hippocampal Subfields ◽  
Schizophrenia Spectrum ◽  
Spectrum Disorders ◽  
First Episode Schizophrenia

Abstract Background In this study, we explored the relationship between hippocampal subfield volumes and change in body mass over 12 months of treatment in 90 first-episode schizophrenia spectrum disorder patients (66 males, 24 females; mean age= 24.7±6.8 years). Methods Body mass index was assessed in patients at baseline, and at months 3, 6, 9 and 12. Hippocampal subfields of interest were assessed using a segmentation algorithm included in the FreeSurfer 6.0 software program. Results Linear regression analysis showed a significant interactive effect between sex and anterior hippocampus size as a predictor of change in body mass over 12 months, adjusting for age, substance use, treatment duration, and posterior hippocampal volumes. In an exploratory sub-analysis, partial correlations revealed a significant association between weight gain and smaller CA1, CA3 and subiculum volumes in females, but not males, adjusting for age and substance use, with similar trends evident for the CA4 and presubiculum subfields. Discussion In conclusion, our findings suggest that smaller anterior hippocampal subfields are associated with the development of weight gain over the course of treatment in first-episode schizophrenia spectrum disorders in a sex-specific fashion, and may partly explain the more severe and ongoing increase in body mass evident for female patients.

Schizotypy and Hemisphericity

2011 ◽  
Vol 109 (2) ◽  
pp. 533-552 ◽  
Author(s):  
Michael P. Kelley
Keyword(s):  
Right Hemisphere ◽  
Schizophrenia Spectrum Disorders ◽  
Normal Range ◽  
Schizophrenia Spectrum ◽  
Hemispheric Activation ◽  
Spectrum Disorders ◽  
Cognitive Mode ◽  
Related Characteristic ◽  
The Right ◽  
And Behavior

There is considerable evidence that schizophrenia spectrum disorders are associated with a variety of abnormal asymmetries of brain structure, function, and behavior. Schizotypy is a personality trait dimension extending into the normal range, which at its extreme, is associated with a vulnerability to schizophrenia spectrum disorders. Schizotypy in the normal range is also associated with a variety of neurobiological characteristics associated with schizophrenia spectrum disorders, including abnormal brain and behavioral asymmetries. Previous studies have suggested that normal schizotypy (as well as belief in the paranormal) is associated with an increased reliance on the right hemisphere in a variety of tasks. Hemisphericity is a trait-related characteristic preference for the cognitive mode of one or the other cerebral hemispheres, putatively related to hemispheric activation asymmetry. A sample of 256 undergraduates was administered five schizotypy scales, as well as three hemisphericity measures. Higher schizotypy scores were associated with an increase in right hemisphericity and a decrease in integrated hemisphericity. Although the construct of hemisphericity has been criticized, there is evidence to suggest that questionnaire and eye movement measures of hemisphericity may yet have construct validity, and further research on hemisphericity may be warranted.

scholarly journals Cognitive effectiveness of olanzapine and risperidone in first-episode psychosis

2009 ◽  
Vol 194 (5) ◽  
pp. 439-445 ◽  
Author(s):  
Manuel J. Cuesta ◽  
Elena García de Jalón ◽  
M. Soledad Campos ◽  
Victor Peralta
Keyword(s):  
Neuropsychological Tests ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Reliable Change Index ◽  
First Episode ◽  
Schizophrenia Spectrum Disorders ◽  
Cognitive Improvement ◽  
Schizophrenia Spectrum ◽  
Second Generation Antipsychotic ◽  
Spectrum Disorders

BackgroundCognitive impairment in schizophrenia-spectrum disorders is highly prevalent and notably influences functional outcomes.AimsTo characterise the cognitive effectiveness of second-generation antipsychotic drugs.MethodOne hundred consecutive and previously unmedicated patients with first-episode schizophrenia-spectrum disorders were admitted. Seventy-seven completed baseline, 1-month and 6-month psychopathological and neuropsychological assessments. Patients were randomised to risperidone or olanzapine treatment. Four final treatment allocation groups were defined since patients continued treatment in their normal setting: risperidone, olanzapine, mixed and no-antipsychotic groups.ResultsThere were no differences in cognitive effectiveness between the four treatment groups. Reliable change index methods demonstrated that nearly a half of patients showed an improvement in Global Cognitive Score at the 6-month assessment. Improvement on the neuropsychological tests ranged from 17 to 54%.A strong predictor of cognitive response was poor performance on baseline neuropsychological tests; response was moderately influenced by a low premorbid scholastic performance and IQ.ConclusionsCognitive improvement related to second-generation antipsychotic drugs appeared within the first 4 weeks of treatment and persisted at 6 months irrespective of treatment group. Greater cognitive dysfunction at baseline and lower premorbid cognitive background predicted cognitive improvement in our sample.

scholarly journals Antipsychotic medication for women with schizophrenia spectrum disorders

2021 ◽  
pp. 1-15
Author(s):  
Bodyl A. Brand ◽  
Yudith R. A. Haveman ◽  
Franciska de Beer ◽  
Janna N. de Boer ◽  
Paola Dazzan ◽  
...  
Keyword(s):  
Side Effects ◽  
Treatment Guidelines ◽  
Premenopausal Women ◽  
Receptor Occupancy ◽  
Serum Levels ◽  
Protective Effects ◽  
Schizophrenia Spectrum Disorders ◽  
Comprehensive Overview ◽  
Schizophrenia Spectrum ◽  
Spectrum Disorders

Abstract There are significant differences between men and women in the efficacy and tolerability of antipsychotic drugs. Here, we provide a comprehensive overview of what is currently known about the pharmacokinetics and pharmacodynamics of antipsychotics in women with schizophrenia spectrum disorders (SSDs) and translate these insights into considerations for clinical practice. Slower drug absorption, metabolism and excretion in women all lead to higher plasma levels, which increase the risk for side-effects. Moreover, women reach higher dopamine receptor occupancy compared to men at similar serum levels, since oestrogens increase dopamine sensitivity. As current treatment guidelines are based on studies predominantly conducted in men, women are likely to be overmedicated by default. The risk of overmedicating generally increases when sex hormone levels are high (e.g. during ovulation and gestation), whereas higher doses may be required during low-hormonal phases (e.g. during menstruation and menopause). For premenopausal women, with the exceptions of quetiapine and lurasidone, doses of antipsychotics should be lower with largest adjustments required for olanzapine. Clinicians should be wary of side-effects that are particularly harmful in women, such as hyperprolactinaemia which can cause oestrogen deficiency and metabolic symptoms that may cause cardiovascular diseases. Given the protective effects of oestrogens on the course of SSD, oestrogen replacement therapy should be considered for postmenopausal patients, who are more vulnerable to side-effects and yet require higher dosages of most antipsychotics to reach similar efficacy. In conclusion, there is a need for tailored, female-specific prescription guidelines, which take into account adjustments required across different phases of life.

scholarly journals Increased Heschl’s Gyrus Duplication in Schizophrenia Spectrum Disorders: A Cross-Sectional MRI Study

2021 ◽  
Vol 11 (1) ◽  
pp. 40
Author(s):  
Tsutomu Takahashi ◽  
Daiki Sasabayashi ◽  
Yoichiro Takayanagi ◽  
Atsushi Furuichi ◽  
Mikio Kido ◽  
...  
Keyword(s):  
Imaging Study ◽  
Schizophrenia Spectrum Disorders ◽  
Cross Sectional ◽  
Heschl’S Gyrus ◽  
Schizophrenia Spectrum ◽  
Significant Difference ◽  
Spectrum Disorders ◽  
Heschl's Gyrus ◽  
The Right ◽  
Schizotypal Disorder

Duplicated Heschl’s gyrus (HG) is prevalent in patients with schizophrenia and may reflect early neurodevelopmental anomalies. However, it currently remains unclear whether patients with schizotypal disorder, a prototypic disorder within the schizophrenia spectrum, exhibit a similar HG gyrification pattern. In this magnetic resonance imaging study, HG gyrification patterns were examined in 47 patients with schizotypal disorder, 111 with schizophrenia, and 88 age- and sex-matched healthy subjects. HG gyrification patterns were classified as single, common stem duplication (CSD), or complete posterior duplication (CPD). The prevalence of the duplicated HG patterns (CSD or CPD) bilaterally was higher in the schizophrenia and schizotypal groups than in healthy controls, whereas no significant difference was observed between the schizophrenia and schizotypal groups. Schizophrenia patients with the right CPD pattern had less severe positive symptoms, whereas the right single HG pattern was associated with higher doses of antipsychotic medication in schizotypal patients. The present study demonstrated shared HG gyrification patterns in schizophrenia spectrum disorders, which may reflect a common biological vulnerability factor. HG patterns may also be associated with susceptibility to psychopathology.

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