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. 2024 Apr 4;54(2):15–27. doi: 10.64719/pb.4486

Efficacy of Rivastigmine Augmentation on Positive and Negative Symptoms, General Psychopathology, and Quality of Life in Patients with Chronic Schizophrenia: A Randomized Controlled Trial

Sepideh Herizchi 1, Ali Reza Shafiee-Kandjani 2, Mostafa Farahbakhsh 3, Zahra Jahangiri 4, Shahriyar Ghanbarzadeh Javid 5, Hosein Azizi 6
PMCID: PMC11003261  PMID: 38601834

Abstract

The study aimed to assess Rivastigmine augmentation on positive and negative symptoms (PNSs), general psychopathology, and quality of life in patients with chronic Schizophrenia. A double-blind, parallel-design, randomized, placebo-controlled trial of 60 schizophrenia patients was conducted. Intervention group received rivastigmine 3 mg/day + Treatment as Usual (TAU) and the control group: TAU + placebo. Negative and positive symptoms, general psychopathology; and quality of life were measured using Positive and Negative Symptom Scale (PANSS) and Manchester Short Assessment of Quality of Life (MANSA). T-test, ANOVA, and the general univariate linear model tests were used for the analyses. Out of 60 participants, 52 (86.6%) were male. At baseline, no significant relationship was found for demographic and clinical characteristics between intervention and control groups. Between-group analysis indicated that all outcome measures PNSs, general psychopathology symptoms, and QoL score in rivastigmine group was significantly improved (p = 0.001). According to within-group analysis, a significant association was found between Rivastigmine and placebo groups in PNSs (p < 0.05). Rivastigmine augmentation improved PNSs and psychopathology in schizophrenia patients. However, no significant association found for improving the life quality after 8 weeks treatment.

Keywords: schizophrenia, rivastigmine, psychopathology, randomized controlled trial, quality of life

Introduction

Schizophrenia is a severe mental illness that is characterized by significant changes in behavior, emotion, personality and insight.1 The prevalence (median) of schizophrenia was reported 4.0 per 1000 for lifetime.2 Schizophrenia patients’ often suffer from memory problems, attentional shortages, and executive dysfunction. Despite a variety of bio-psychological treatments, only a low percentage of patients with schizophrenia fully recover, and most of them remain with chronic symptoms and problems for lifelong.3

Signs and symptoms of schizophrenia vary, however in general schizophrenia patients have signs of hallucinations or disorganized speech, delusions, and reflect an impaired ability to function.4 Among chronic schizophrenia patients, a large proportion of the acute symptoms resolved with or without treatment, and longitudinal studies show average improvement in function over the years.5 Investigations showed that positive symptoms often continue or recur in chronic patients, but a number of schizophrenia patients have negative symptoms in the acute phase or in the first episode.6,7

Despite the fact that dopamine has been considered the significant neurotransmitter participated in the pathogenesis of schizophrenic symptoms, several findings demonstrated cholinergic neurons roles in the disease process.8 Evidence suggests that rivastigmine, donepezil, and galantamine can delay cognitive features of Alzheimer’s patients,9 clozapine,10 and also adjuvant therapy11 alleviated cognitive, negative and positive symptoms (NPSs) of schizophrenia patients.12 Nevertheless, some evidence demonstrated that donepezil treatment was related to uncertain modify in the symptoms.13

The severity of cognitive impairments in antemortem among schizophrenia patients was reported to have a relationship with the reduction in brain choline acetyltransferase levels during postmortem assessment.14 Therefore, it is an effective option treatment with a cholinesterase inhibitor for motivating the activity of the nicotinic and muscarinic receptors.

A study found that treatment with rivastigmine improved cerebellar activity and impressed attentional processes.15 Case report studies indicated that rivastigmine treatment can improve refractory visual hallucinations in schizophrenia patient.16,17 However, some findings cannot find significant associations between rivastigmine augmentations on antipsychotics for decreasing cognitive impairments.18 A study indicated that Memantine add-on to risperidone therapy was not correlated with NPSs in schizophrenia patients.19,20

However, Randomized Controlled Trials (RCTs) reported that rivastigmine treatment improved cognitive impairments, but it cannot alleviate negative and positive symptoms of schizophrenia.6 Because of poor facilities of communities and families for maintaining and caring for schizophrenia cases, and many impairment features of the disease, the quality of life of patients has decreased.21–23 Moreover, the impact of rivastigmine augmentation on the quality of life (QoL) of schizophrenia patients is poorly understood.8

As a result of the existing contradictions, as well as the limited investigations on schizophrenia patients’ quality of life, conducting double-blinded RCTs can clarify the role of rivastigmine augmentation on schizophrenia patients’ clinical symptoms and their life quality. A double-blind, parallel design RCT is conducted to evaluate the role of rivastigmine augmentation on PNSs, psychopathology symptoms and QoL in schizophrenia patients.

Methods

Study Design

A double-blind and randomized placebo-controlled trial was conducted at Razi Psychiatric Hospital, Tabriz in 2020–21. The study population was chronic Schizophrenia patients of any sex. A total of 60 chronic Schizophrenia patients (30 patients in each group) who had medical records and were Hospitalized at Razi Psychiatric Hospital were randomized into two groups.

The sample size was determined by considering α = 0.05, Power (1–β) = 80%, and 20% clinically significant difference based on previous studies.12 The current study examines the efficacy and clinical outcomes of Rivastigmine augmentation on PNSs and QoL in patients with chronic schizophrenia.

Study Groups and Intervention

After a comprehensive explanation of the study process and written informed consent, eligible participants were randomized into two groups of intervention and control. The control group was given TAU + placebo and the intervention group was given Rivastigmine 3 mg per day (1.5 mg twice per day) + TAU. TAU was the current antipsychotic drugs including one of the routine antipsychotics such as Risperidone, chlorpromazine, and Olanzapine. Study groups were followed up and treated for 8 weeks. Outcomes were evaluated 3 times: baseline (before), 4 weeks, and 8 weeks (after).

Eligibility Criteria

Inclusion criteria were chronic schizophrenia patients diagnosed at least two years previously, patients treated with routine antipsychotics, and having at least one negative symptom. Schizophrenia diagnosis is measured using the DSM-5.24 Exclusion criteria were mental disabilities (IQ less than 70), substance use disorder, comorbidity of any psychiatric disorders, and/or neurological or medical disease, use of long-acting injectable antipsychotics, and Electroconvulsive Therapy (ECT) in the last two weeks.

Randomization and Masking

Schizophrenia patients were randomly allocated in 1:1 ratio arms (intervention and control). The randomization schedule was developed by an independent person (statistician). Patients, psychiatrists (investigators), and the Hospital staffs and nurses were blinded for the study groups and the recommended medications. Medications in each group were filled into similar sizes, colors, and capsules. A unique treatment number to identify each carton and contained capsules of the investigational medicinal products were used. The cartons of intervention and placebo groups were undistinguishable in appearance. No patients or investigators could guess or report that they could distinguish between intervention and placebo groups. Figure 1 shows the randomizations and study group assignments.

Figure 1.

Figure 1

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Consort Flow Chart

An investigational medicinal carton is allocated based on sequential treatment number order, after the randomization. Compliance with investigational medication was assessed by monitoring investigational medicinal consumption and daily audit by staffs.

Outcomes

Primary outcome was alternation in PNSs; and the general psychopathology symptoms of PANSS. The secondary outcome is alternation in the quality of life of the participants. Outcomes are evaluated three times at baseline (before), 4 weeks, and 8 weeks (after). There were no adverse reactions or morbidity and mortality outcomes to stop trial.

Measurements

We evaluated PNSs, and general psychopathology using Positive and Negative Symptom Scale (PANSS).25 PANSS comprises 30 questions and three subscales including 7 questions positive symptoms, 7 questions negative symptoms, and 16 questions general psychopathology. PANSS instrument uses a 7-point Likert-type scale (absent, minimal, mild, moderate, moderate severe, severe, and extreme). Among Iranian population, PANSS was validated by Ghamari-Givi et al26 and Abolghasemi27 using Cronbach’s Alpha test (α = 0.80). Manchester Short Assessment of Quality of life (MANSA) was used to assess the quality of life.28 MANSA instrument have been validated and used among Iranian population and in Tabriz (the study area).29

Statistical Analyses

We analyzed using SPSS software with version 22.0, Chicago, IL, USA. Chi-square (χ2) test is calculated for comparing binary variables. Exact Fisher test was used, when at least one cell of 2 × 2 table have less than 5 frequencies.

Student T-test were performed to display distribution of positive, negative, and psychopathology symptoms scores between. Repeated measure test was used for intra-groups analyses of outcome scores before, median (4 weeks), and after (8 weeks). P-value less than 5% was considered significant. Person correlation coefficient was performed for comparing baseline and after (endpoint) changes in the study outcome.

Results

The baseline characteristics of participants by intervention and control groups were tabulated in Table 1. A total of 60 chronic schizophrenia patients were participated. Two individuals in the intervention and three individuals in the control groups drop out of the study due to loss to follow-up (Figure 1). Out of 60 schizophrenia patients, 52 (86.6%) were males. In both intervention and placebo groups, the same number of males and females had been participated (p = 0.999). The mean age of participants in rivastigmine and placebo groups was 36.5 ± 6.96 and 37.13 ± 6.06 (p = 0.709), respectively. No significant relationship was found between groups at baseline.

Table 1. Baseline (Week = 0) Characteristics of the Participants.

Variables Intervention (Rivastigmine + TAU) n = 30 Control (TAU + Placebo) n = 30 P-value
Age Mead ± SD 36.5 ± 6.96 37.13 ± 6.06 0.709
Sex Female 4 4 0.999
Male 26 26
Marital Status Married 6 9 0.822
Single 21 19
Widow and Divorced 3 2
Occupation Unemployment 19 24 0.121
Worker or free 13 6
Educational level Primary school 22 26 0.646
Secondary school 4 3
Academic 4 1
No 0 0
Number of admissions ⩾ 3 18 23 0.267
< 3 12 7
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Table 2 displays the comparison of outcome measure scores among group analyses. A significant correlation was found between Rivastigmine and placebo groups in positive symptoms (at 4 and 8 weeks) and negative symptoms at three stages in baseline, week 4, and week 8 (P < 0.05).

Table 2. Comparison of Outcome Measures Score Based on Between Group’s Analyses.

Variables Intervention (Rivastigmine + TAU) n = 28 Control (TAU + Placebo) n = 27 t/z P-value
PANSS-positive score Baseline 8.5 ± 1.43 8.9 ± 0.944 Z = −1.61 0.110
Week 4 8.17 ± 1.12 8.88 ± 0.96 −2.25 0.029
Week 8 7.85 ± 0.84 8.70 ± 0.91 −3.56 0.001
PANSS-negative score Baseline 35.53 ± 5.09 30.83 ± 4.30 3.85 0.001
Week 4 34.42 ± 9.14 30.18 ± 3.99 2.21 0.031
Week 8 32.46 ± 4.00 30.07 ± 3.67 2.30 0.025
PANSS-general psychopathology score Baseline 28.93 ± 3.62 27.00 ± 2.22 Z = −1.88 0.060
Week 4 26.53 ± 2.60 26.62 ± 1.94 −0.151 0.880
Week 8 25.35 ± 3.04 26.11 ± 1.64 Z =−1.57 0.116
MANSA-Quality of life score Baseline 55.93 ± 4.00 56.00 ± 3.30 −0.141 0.889
Week 4 56.6 ± 3.78 56.62 ± 3.09 −0.024 0.981
Week 8 57.64 ± 3.78 57.14 ± 3.00 0.535 0.595
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Table 3 demonstrates the within-group analyses by repeated measure ANOVA test. The results show that all outcome measures PANSS-positive symptoms (p = 0.005; F = 3.57), PANSS-negative symptoms (p = 0.001; F=13.30), general psychopathology symptoms (p = 0.001; F = 14.02) and QoL score (p = 0.001; F = 8.84) in rivastigmine group is significantly improved. In the placebo group (routine antipsychotics), intra-group analyses revealed a noteworthy progress in the general psychopathology symptoms (p = 0.012; F = 5.32), and QoL (p = 0.023; F = 4.41) after 8 weeks treatment period. However, a significant association between PANSS-PNSs was not found.

Table 3. Comparison of Outcome Measures Score Based on Intra-Group Analyses (Repeated Measures ANOVA).

Variables Intervention (Rivastigmine + TAU) n = 28 F P-value Control (TAU + Placebo) n = 27 F P-value
PANSS-positive score Baseline 8.5 ± 1.43 3.57 0.005 8.9 ± 0.944 2.14 0.138
Week 4 8.17 ± 1.12 8.81 ± 0.96
Week 8 7.80 ± 0.84 8.70 ± 0.91
PANSS-negative score Baseline 35.53 ± 5.09 13.30 0.001 30.83 ± 4.30 2.95 0.071
Week 4 34.42 ± 9.14 30.18 ± 3.90
Week 8 32.46 ± 4.00 30.07 ± 3.67
PANSS-general psychopathology score Baseline 28.93 ± 3.62 14.02 0.001 27.00 ± 2.22 5.32 0.012
Week 4 26.53 ± 2.60 26.62 ± 1.94
Week 8 25.35 ± 3.04 26.11 ± 1.64
MANSA-Quality of life score Baseline 55.93 ± 4.00 8.48 0.001 56.00 ± 3.30 4.41 0.023
Week 4 56.60 ± 3.72 56.62 ± 3.09
Week 8 57.64 ± 3.78 57.14 ± 3.00
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Figures 2 and 3 demonstrates changes in PANSS PNSs based on the study assessment times. Treatment with rivastigmine reduced positive and negative scores in comparison with the placebo group and improved symptoms. Regarding the quality of life, no significant changes between baseline and week 4 were observed, however, after 8 weeks, QoL score was increased in rivastigmine group (Figure 4).

Figure 2.

Figure 2

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Comparison of Changes in Positive Symptoms Between Groups at Baseline, Week 4, and Week 8 (p = 0.005)

Figure 3.

Figure 3

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Comparison of Changes in Negative Symptoms Between Groups at Baseline, Week 4, and Week 8

Figure 4.

Figure 4

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Comparison of Changes in Quality of Life Score (MANSA) Between Groups at Baseline, Week 4, and Week 8

Discussion

The double-blinded RCT of rivastigmine for; 3 mg per day; augmentation of antipsychotics demonstrated a significant progress in PANSS scores and QoL in patients with chronic schizophrenia. Findings recommended that rivastigmine augmentation improves the cognitive functions among schizophrenia patients.12,30 Nevertheless, some studies were unable to find a significant progress in PANSS negative and positive symptoms.18,30

In this study rivastigmine augmentation treatment (3 mg per day for 8 weeks) improved PANSS positive and negative symptoms. Lenzi et al.8 in Italy, reported cognitive enhancement after treatment with rivastigmine in schizophrenia patients (12 mg per day for 12 months). Attention and memory improvement and problem-solving by improving social and professional functions were found in Hussain et al.31 study. Functional magnetic resonance imaging revealed that rivastigmine improved cerebellar activity and inclined attentional processes in patients with schizophrenia.15

Sachin et al. found positive effects from Acetylcholinesterase inhibitors for the treatment of visual hallucinations among schizophrenia cases in accordance with the present trial.17 It is a significant result that needs further high-sample-size studies. Likewise, Singh et al. found that Acetylcholinesterase inhibitors were favorable antipsychotics, which revealed a positive effect over antipsychotics and placebo in the general psychopathology and negative symptoms and cognitive function in PANSS.

Regarding QoL, the effect of rivastigmine augmentation on the QoL was poorly understood. In this trial, at the end of 8 weeks, MANSA score for QoL had modified in both rivastigmine and placebo groups. However, the score of QoL was higher in rivastigmine group than in the placebo group.

Currently, QoL is an important outcome for schizophrenia patients. However, the treatment options and effective factors that affect the life quality of patients who agonize from this severe mental disorder is not fully understood.

The correlation between mental disorders and psychological symptoms, and quality of life among schizophrenia patients have been investigated more extensively.32 Nevertheless, studies have yet to clarify how important Acetylcholinesterase inhibitors (treatment) especially rivastigmine are in regard to life quality, and which treatment holds the strongest relation to the quality of life.

This trial is one of the rarest double-blinded trials to evaluate the efficacy rivastigmine augmentation on antipsychotics in PNSs; and general psychopathology symptoms in schizophrenia patients. The findings of the intra-group analysis reveal that rivastigmine augmentation has a significant, positive association with QoL in schizophrenia, by promoting general psychopathology reliably evolving as the robust contributor to enhancing the QoL.

Furthermore, it deserves to investigatethe relationship between PNSs with QoL in schizophrenia patients. Some findings demonstrated that PNSs are not connected with the life quality of all groups of schizophrenia patients equally.32,33 However, such symptoms may be principally detrimental to the QoL in research on patients getting treatment in the field, and positive symptoms are only poorly associated with the quality of life in investigations of cases in the early stages of the disease. Such results can grasp several significant values for dealing progress and future QoL studies among schizophrenia patients.

According to the studies in the literature, general psychopathology has the robust link with the QoL,33,34 this recommends that nonpsychotic symptoms and signs are central goals for treatments pointing to advance QoL for schizophrenia patients.

The findings suggest that there is a strong link between psychopathology values and QoL, which may be the result of subjective ratings being unduly affected by mood.33,34 The effects of these signs and symptoms on QoL measurement are unclear, and it is uncertain whether they should be considered genuine targets for quality-of-life treatments. This study supports the latter because both objective and subjective measurements of life quality are highly correlated with general psychopathology.

Limitations

The present study had some limitations. There were several antipsychotics used in Treatment as Usual for schizophrenia patients. To diminish this confounder, most of the participating patients have received Risperidone in the current study. Another concern was given negative symptoms rating scales are close to being quality of life measures (overlap), and usually improve when positive symptoms improve. Therefore, to attribute the impact of the current treatment is a treatment for both may problematic. Although the QoL score (secondary endpoint) was improved after 8 weeks of treatment with rivastigmine however, the effect size was minor and we found no significant association for QoL in comparison with the control group. As the findings have shown, the symptoms of schizophrenia improve over time. On the other hand, the use of routine treatment in the control group also helps this recovery. Besides, it may find impartments in the QoL by rivastigmine augmentation in the long term (more than 8 weeks), and this can be a departure point for future investigations.1,35

Conclusion

This double-blinded RCT supports the rivastigmine (3 mg/day) augmentation of TAU antipsychotics as a strategy to improve PNSs and cognitive function in patients with schizophrenia. However, no significant association found for improving the QoL after 8 weeks of treatment.

Footnotes

Declarations

Ethics Approval and Consent to Participate

The trial was registered in the Iranian RCT website to number [IRCT20190530043769N1], date [26/01/2021], registration number [1399.53], and electronic address: https://fa.irct.ir/trial/39935. Ethics committee of Tabriz University of Medical Sciences was approved the protocol to number of IR.TBZMED.REC. 1399.923. Informed consent was obtained before the study.

Conflicts of Interests

There is no competing interests.

Funding

This study was funded by Tabriz University of Medical Sciences.

Author’s Contributions

All authors were involved in the conception, development, or review of the manuscript, or they played a significant role in the acquisition, analysis, and interpretation of the data, or both. All authors took part in manuscript development and gave substantial revision suggestions, and they all approved the final submitted version.

Acknowledgments

The authors gratefully acknowledge the Clinical Research Development Unit of Al-Zahra Research and Treatment Center for its research consulting services.

Contributor Information

Sepideh Herizchi, Herizchi, Associate Professor of Psychiatry, Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Science, Tabriz, Iran, ORCID: 0000-0002-0299-1122..

Ali Reza Shafiee-Kandjani, Shafiee-Kandjani, Professor of Psychiatry, Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Science, Tabriz, Iran..

Mostafa Farahbakhsh, Farahbakhsh, Assistant Professor of Psychiatry, Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Science, Tabriz, Iran..

Zahra Jahangiri, Jahangiri, MD, Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Science, Tabriz, Iran..

Shahriyar Ghanbarzadeh Javid, Ghanbarzadeh Javid, MD, Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran..

Hosein Azizi, Azizi, Assistant Professor of Epidemiology, Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran..

References

  • 1.Schmitt A, Maurus I, Falkai P. Treatment of negative symptoms in schizophrenia: A challenge for clinical research. 2023:1–2. doi: 10.1007/s00406-023-01595-w. In.: Springer. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Bhugra D. The global prevalence of schizophrenia. PLoS Medicine . 2005;2(5):e151. doi: 10.1371/journal.pmed.0020151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Gaebel W, WoĻlwer W, Toeller V. 4th European conference on schizophrenia research: Together for better treatment and care. Eur Arch Psychiatry Clin Neurosci . 2013;263(Suppl 1):1–4. doi: 10.1007/s00406-013-0435-y. [DOI] [PubMed] [Google Scholar]
  • 4.Yi Y, Huang Y, Jiang R, Chen Q, Yang M, Li H, Feng Y, Feng S, Zhou S, Zhang L. The percentage and clinical correlates of alexithymia in stable patients with schizophrenia. European Archives of Psychiatry and Clinical Neuroscience . 2023;273(3):679–686. doi: 10.1007/s00406-022-01492-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Green MF, Kern RS, Heaton RK. Longitudinal studies of cognition and functional outcome in schizophrenia: Implications for MATRICS. Schizophrenia Research . 2004;72(1):41–51. doi: 10.1016/j.schres.2004.09.009. [DOI] [PubMed] [Google Scholar]
  • 6.Shoja Shafti S, Jafarabad MS, Azizi R. Amelioration of deficit syndrome of schizophrenia by norepinephrine reuptake inhibitor. Therapeutic Advances in Psychopharmacology . 2015;5(5):263–270. doi: 10.1177/2045125315591953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Dupuy M, Abdallah M, Swendsen J, N’kaoua B, Chanraud S, Schweitzer P, Fatseas M, Serre F, Barse E, Auriacombe M. Real-time cognitive performance and positive symptom expression in schizophrenia. European Archives of Psychiatry and Clinical Neuroscience . 2022;272:415–425. doi: 10.1007/s00406-021-01296-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Lenzi A, Maltinti E, Poggi E, Fabrizio L, Coli E. Effects of rivastigmine on cognitive function and quality of life in patients with schizophrenia. Clinical Neuropharmacology . 2003;26(6):317–321. doi: 10.1097/00002826-200311000-00011. [DOI] [PubMed] [Google Scholar]
  • 9.Takeda A, Loveman E, Clegg A, Kirby J, Picot J, Payne E, Green C. A systematic review of the clinical effectiveness of donepezil, rivastigmine and galantamine on cognition, quality of life and adverse events in Alzheimer’s disease. International Journal of Geriatric Psychiatry: A Journal of the Psychiatry of Late Life and Allied Sciences . 2006;21(1):17–28. doi: 10.1002/gps.1402. [DOI] [PubMed] [Google Scholar]
  • 10.Moulier V, Krir MW, Dalmont M, Guillin O, Rothärmel M. A prospective multicenter assessor-blinded randomized controlled study to compare the efficacy of short versus long protocols of electroconvulsive therapy as an augmentation strategy to clozapine in patients with ultra-resistant schizophrenia (SURECT study) Trials . 2021;22(1):1–15. doi: 10.1186/s13063-021-05227-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Laan W, Selten J-P, Kahn RS, Huisman A-M, Heijnen CJ, Grobbee DE, Burger H. Acetylsalicylic acid as an adjuvant therapy for schizophrenia. Trials . 2006;7(1):1–6. doi: 10.1186/1745-6215-7-31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Shoja Shafti S, Azizi Khoei A. Effectiveness of rivastigmine on positive, negative, and cognitive symptoms of schizophrenia: A double-blind clinical trial. Therapeutic Advances in Psychopharmacology . 2016;6(5):308–316. doi: 10.1177/2045125316656334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Erickson SK, Schwarzkopf SB, Palumbo D, Badgley-Fleeman J, Smirnow AM, Light GA. Efficacy and tolerability of low-dose donepezil in schizophrenia. Clinical Neuropharmacology . 2005;28(4):179–184. doi: 10.1097/01.wnf.0000173714.61744.e6. [DOI] [PubMed] [Google Scholar]
  • 14.Karson CN, Mrak RE, Husain MM, Griffin WST. Decreased mesopontine choline acetyltransferase levels in schizophrenia. Molecular and Chemical Neuropathology . 1996;29(2):181–191. doi: 10.1007/BF02815001. [DOI] [PubMed] [Google Scholar]
  • 15.Aasen I, Kumari V, Sharma T. Effects of rivastigmine on sustained attention in schizophrenia: An FMRI study. Journal of Clinical Psychopharmacology . 2005;25(4):311–317. doi: 10.1097/01.jcp.0000169267.36797.76. [DOI] [PubMed] [Google Scholar]
  • 16.Abad NH, Doulatabad NS, Mohammadi A, Srazi HRG. Treatment of visual hallucinations in schizophrenia by acetylcholinesterase inhibitors: A case report. Iranian Journal of Psychiatry . 2011;6(4):161. [PMC free article] [PubMed] [Google Scholar]
  • 17.Patel SS, Attard A, Jacobsen P, Shergill S. Acetylcholinesterase Inhibitors (AChEI’s) for the treatment of visual hallucinations in schizophrenia: A case report. BMC Psychiatry . 2010;10(1):1–3. doi: 10.1186/1471-244X-10-68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Chouinard S, Stip E, Poulin J, Melun J-P, Godbout R, Guillem F, Cohen H. Rivastigmine treatment as an add-on to antipsychotics in patients with schizophrenia and cognitive deficits. Current Medical Research and Opinion . 2007;23(3):575–583. doi: 10.1185/030079906X167372. [DOI] [PubMed] [Google Scholar]
  • 19.de Lucena D, Fernandes BS, Berk M, Dodd S, Medeiros DW, Pedrini M, Kunz M, Gomes FA, Giglio LF, Lobato MI. Improvement of negative and positive symptoms in treatment-refractory schizophrenia: A double-blind, randomized, placebo-controlled trial with memantine as add-on therapy to clozapine. The Journal of Clinical Psychiatry . 2009;70(10):8775. doi: 10.4088/JCP.08m04935gry. [DOI] [PubMed] [Google Scholar]
  • 20.Di Iorio G, Baroni G, Lorusso M, Montemitro C, Spano MC, di Giannantonio M. Efficacy of memantine in schizophrenic patients: A systematic review. Journal of Amino Acids . 2017;2017:7021071. doi: 10.1155/2017/7021071. doi: Epub 2017 Jan 24. PMID: 28243470; PMCID: PMC5294374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Rössler W, Salize HJ, Van Os J, Riecher-Rössler A. Size of burden of schizophrenia and psychotic disorders. European Neuropsychopharmacology . 2005;15(4):399–409. doi: 10.1016/j.euroneuro.2005.04.009. [DOI] [PubMed] [Google Scholar]
  • 22.Torres-González F, Ibanez-Casas I, Saldivia S, Ballester D, Grandón P, Moreno-Küstner B, Xavier M, Gómez-Beneyto M. Unmet needs in the management of schizophrenia. Neuropsychiatric Disease and Treatment . 2014;10:97–110. doi: 10.2147/NDT.S41063. doi: PMID: 24476630; PMCID: PMC3897352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Dyck DG, Short RA, Hendryx MS, Norell D, Myers M, Patterson T, McDonell MG, Voss WD, McFarlane WR. Management of negative symptoms among patients with schizophrenia attending multiple-family groups. Psychiatric Services . 2000;51(4):513–519. doi: 10.1176/appi.ps.51.4.513. [DOI] [PubMed] [Google Scholar]
  • 24.American Psychiatric Association D, Association AP. Diagnostic and statistical manual of mental disorders: DSM-5. 2013;5 vol. American Psychiatric Association Washington, DC. [Google Scholar]
  • 25.Kay SR, Opler LA, Lindenmayer J-P. Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Research . 1988;23(1):99–110. doi: 10.1016/0165-1781(88)90038-8. [DOI] [PubMed] [Google Scholar]
  • 26.Heshmati R. Exploration of the factor structure of positive and negative syndrome scale in schizophrenia spectrum disorders. J Clin Psychol . 2010;2(2):1–10. [Google Scholar]
  • 27.Abolghasemi A. The relationship of meta-cognitive beliefs with positive and negative symptomes in the schizophrenia patients. Clinical Psychology and Personality . 2007;5(2):1–10. [Google Scholar]
  • 28.Björkman T, Svensson B. Quality of life in people with severe mental illness Reliability and validity of the Manchester Short Assessment of Quality of Life (MANSA) Nordic Journal of Psychiatry . 2005;59(4):302–306. doi: 10.1080/08039480500213733. [DOI] [PubMed] [Google Scholar]
  • 29.Farhang S, Ghaemmaghami M, Noorazar G, Veling W, Malek A, Shafiee-Kandjani AR, Alizadeh BZ, Bruggeman R. T152. Azeri recent onset acute phase psychosis survey (Aras Cohort): Preliminary reports from an observational cohort of first episode psychosis in Iran. Schizophrenia Bulletin . 2020;46(Suppl 1):S288. [Google Scholar]
  • 30.Kumar PNS, Mohemmedali SP, Anish P, Andrade C. Cognitive effects with rivastigmine augmentation of risperidone: A 12-month, randomized, double-blind, placebo-controlled study in schizophrenia. Indian Journal of Psychiatry . 2017;59(2):219. doi: 10.4103/psychiatry.IndianJPsychiatry_133_16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Hussain M, Chaudry A, Hussain S. Rivastigmine tartrate in treatment of neurocognitive deficits in clozapine treated schizophrenics. In: Poster presented at the 51st Annual Meeting of the Canadian Psychiatric Association, Montreal, Canada, 15–19 November 2001 [Google Scholar]
  • 32.Eack SM, Newhill CE. Psychiatric symptoms and quality of life in schizophrenia: A meta-analysis. Schizophrenia Bulletin . 2007;33(5):1225–1237. doi: 10.1093/schbul/sbl071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Schwarz N, Clore GL. Mood, misattribution, and judgments of well-being: Informative and directive functions of affective states. Journal of Personality and Social Psychology . 1983;45(3):513. [Google Scholar]
  • 34.Atkinson M, Zibin S, Chuang H. Characterizing quality of life among patients with chronic mental illness: A critical examination of the self-report methodology. American Journal of Psychiatry . 1997;154(1):99–105. doi: 10.1176/ajp.154.1.99. [DOI] [PubMed] [Google Scholar]
  • 35.Gaebel W, Wölwer W, Toeller V. 7th European conference on schizophrenia research-schizophrenia and other psychotic disorders: Time for precision medicine. 2019 doi: 10.1007/s00406-019-01045-6. Springer. [DOI] [PubMed] [Google Scholar]

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