Clinical predictors of response to clozapine in Tunisian patients with treatment resistant schizophrenia.

INTRODUCTION: Treatment resistant schizophrenia (TRS), affecting approximately one-third of patients with schizophrenia, is associated with a serious impairment in global psychosocial functioning. Clozapine is the only licensed drug for TRS. However its prescription remains limited by its side effects requiring mandatory monitoring. The need to identify clinical factors associated with good response to clozapine in TRS has been established. The presence of ethnic differences in these factors and the scarcity of data on the Tunisian or more generally the North-African population warrants the conduct of a clinical study on the subject. The aim of this study was to investigate demographic, clinical, and biochemical patient characteristics as potential predictors of response to clozapine. METHODS: This is a cross-sectional and retrospective study, at the "F and A psychiatry departments" of Razi Hospital in Manouba, Tunisia. All patients, with DSM 5 diagnosis of schizophrenia in its resistant form, on clozapine for at least 12 months and who consulted from June 1, 2018 to November 30, 2018 were included. We investigated premorbid functioning by the premorbid adjusment scale, demographic and clinical characteristics, and clozapine plasma level as potential clozapine response predictors. The response to clozapine was defined by a total BPRS score of 35 or less. RESULTS: Sixty-three patients were included in the study. The mean age at clozapine introduction was 30,84 ±9,25 years. The mean duration of clozapine treatment was 7,22 ± 4,02 years. There were 16 clozapine responders (25%) who had BPRS total scores below or equal to 35 and 47 non-responders (75%). A higher premorbid social functioning in childhood (p = 0,018) and early adolescence (p = 0,024) was associated with better response to clozapine. A delay clozapine initiation shorter than 7 years(p = 0,036), one atypical antipsychotic trial (p = 0,029) and schizophrenia paranoid subtype (p< 0.01) were found to be significantly predictive of good clozapine response. None of the demographic factors or biochemical characteristics were associated with clozapine response. CONCLUSIONS: Our work is consistent with previous studies suggesting the need for clinicians to be aware of the clinical predictors of a good response to clozapine to overcome their reluctance to prescribe it. It also highlighted the major prognostic role of premorbid adjustment in the clinical response to treatment. However, prospective studies including therapeutic drug monitoring would be very useful to better delineate the sub-group of patients to whom clozapine would benefit the most and to improve prescription modalities.

Prevalence of Mood Disorders and Associated Factors at the Time of the COVID-19 Pandemic: Potocol for a Community Survey in La Manouba Governorate, Tunisia.

Aims: The present survey aims to assess the overall mood disorder prevalence and identify associated socio-demographic and clinical factors in a Tunisian community sample, with special attention to the COVID-19 pandemic. Background: Mood disorders are one of the leading causes of all non-fatal burdens of disease, with depression being at the top of the list. The COVID-19 pandemic may have increased the prevalence of mood disorders, especially in Low and Middle-income countries (LMICs) and in vulnerable populations. Objective: 1/ Assess point and lifetime prevalence of depressive and bipolar disorders as well as subthreshold bipolarity in a representative population sample of La Manouba governorate and assess treatment patterns for these disorders; 2/Study socio-demographic and clinical correlates of mood disorders 3/ Assess the association between mood disorders and quality of life 4/ Study the impact of the COVID-pandemic on the prevalence of mood disorders 5/ Assess coping mechanisms to the COVID-pandemic and whether these mechanisms moderate the appearance of mood disorders or symptoms since the beginning of the pandemic. Methods: This is a household cross-sectional observational survey to be conducted in La Manouba Governorate in a sample of 4540 randomly selected individuals aged ≥ 15 years. Data collection will be carried out by trained interviewers with clinical experience, through face-to-face interviews and the use of the computer assisted personal interviewing approach (CAPI). The following assessment tools are administered. Results: Structured clinical Interview for DSM IV-TR (Mood disorder section and Screening questions on Anxiety), Mood Disorder Questionnaire (MDQ), Suicide Behaviors Questionnaire-Revised (SBQ), 12-item Short Form Survey (SF-12), the Brief-COPE, and a questionnaire about a headache. In addition, socio-demographic and clinical data will be collected. Conclusion: This will be one of the very few household surveys in a general population sample to assess mental health problems and COVID-19-related variables since the beginning of the pandemic. Through this research, we aim to obtain an epidemiological profile of mood disorders in Tunisia and an estimation of the impact of the COVID-19 pandemic on their prevalence. Results should contribute to improving mental health care in Tunisia.

La résistance à la sectorisation : exemple du gouvernorat de Nabeul en Tunisie.

Sectorisation was introduced in Tunisia in 1999. The objective of this study was to examine the difficulties and resistance to the sectorisation of psychiatric care in the state of Nabeul. A transversal study was conducted over a period of 5 months from 1 November 2014 to 31 March 2015 on 96 patients resident in the state of Nabeul and treated at Razi hospital. Patients were aged between 18 and 69 years old ( sex ratio equal to one), 55.2% were single and 46% had a low socioeconomic level (n=44). Chronic psychotic disorder was diagnosed in 64.3% , depression in 12.3%, bipolar disorder in 18.8% and mental retardation in 3% of cases. Most of them refused to continue psychiatric treatment in the second or the first line of care. Resistance to sectorisation was associated with a low socioeconomic level (P = 0.039), availability of a companion (P = 0.04), celibacy (P = 0.04), gender (P = 0.05) and negatively correlated to psychotic disorder diagnosis. It was concluded that the environment plays an important role in the choice of the place of care. Subjects treated for mental illness were found to have greater trust in the structures that treated the acute episode of their illness, and paradoxically felt less stigmatized in Razi hospital.

High prevalence of antineuronal antibodies in Tunisian psychiatric inpatients.

The authors aimed to determine the prevalence of antineuronal antibodies in 103 psychiatric inpatients and 41 control subjects with no history of malignancies or neurological disorders. All sera were tested by indirect immunofluorescence and positive sera by immunoblot. Using immunofluorescence, antineuronal nuclear autoantibodies were detected in 20 patients and none of the control subjects, and antibodies reacted with the cytoplasm of Purkinje cells in six patients and two control subjects. The immunoblot confirmed well-characterized antineuronal antibodies only in five patients: two had anti-Ri and three had anti-Yo antibodies. After a follow-up of 5 years, none of these patients developed neurological disorder or malignancy.

[The name in schizophrenia: a study of 60 patients]. / Le patronyme dans la schizophrénie: une etude à propos de 60 patients.

BACKGROUND: Clinical aspects in schizophrenia suggest a unique relationship with the proper name. aim: Discuss the validity of the hypothesis that the non-transmission of the surname may be a vulnerability factor in schizophrenia. METHODS: Descriptive cross-sectional study conducted among 60 patients with schizophrenia and their families. Data were collected using a semi-structured interview. results: Seven patients carried a different surname from their father (11.6% of participants). The disparity has only concerned the child with schizophrenia. Family characteristics (birth rank, desired character of pregnancy, family history of schizophrenia) and evolutif profile of the disease were comparable between patients with a family name according to the father and those with a different surname. CONCLUSIONS: It appears that patients with schizophrenia maintain a special relationship with the proper name, which could be involved in the genesis of schizophrenia. Our early hypothesis, supported by the psychoanalytic, transgenerational and behavioral theories, would be a plausible starting point for studies with a broader spectrum including witnesses of the general and psychiatric populations.

[Validity and reliability of the Tunisian version of section G of the Composite International Diagnostic Interview, relative to schizophrenia]. / Validation de la section G du Composite International Diagnostic Interview relative à la schizophrénie, traduite au dialecte tunisien.

BACKGROUND: Early diagnosis of schizophrenia can improve its outcome. Hence, screening policies should be held and suitable tools must be available for general practitioners. AIM: To translate the section G (about schizophrenia) of the Composite International Diagnostic Interview to the Tunisian dialect and to check its validity and reliability. METHODS: The Arabic version of section G of the Composite International Diagnostic Interview has been translated to the Tunisian dialect by psychiatrists speaking fluently both languages. Metric features of the instrument (sensitivity, specificity and predictive values) were assessed by checking its results against those of the gold standard i.e. the expert's opinion owing to the criteria of the Diagnostical and Statistical Manual of mental disorders 3rd revised edition. Reliability has been measured by the index of observer agreement. RESULTS: The instrument showed a low sensitivity of 45% [32% - 58%] and a high specificity of 96% [93% - 99%]. It looked as a diagnostical test that can avoid wrong diagnoses of such a serious and stigmatizing illness. These values are similar or even better than those of literature. The observer agreement index was 0.83 showing a very good reliability. The interviews mean duration was 20 minutes. The instrument showed no variability towards the sex, the age or the educational level of interviewees. CONCLUSION: Even though section G of the Composite International Diagnostic Interview failed to detect most cases with schizophrenia and showed a poor sensitivity, this instrument can be useful for screening strategies carried out by lay interviewers in the general population.

[Effects of tobacco on antipsychotic treatments and their symptoms in schizophrenia]. / Effets du tabac sur les neuroleptiques et leurs effets extrapyramidaux dans la schizophrénie.

BACKGROUND: The prevalence of cigarette smoking is significantly higher among patients with schizophrenia than in the general population. Several authors explained this excess of smoking by the self-medication hypothesis. It suggests that patients with schizophrenia smoke to reduce psychotic symptoms or antipsychotic side effects. AIM: In this study, we aimed to evaluate the prevalence of tobacco consumption in patients with schizophrenia and to test if smoking reduces psychotic and extra-pyramidal symptoms. METHODS: We included 115 patients with schizophrenia (DSM IV) treated with conventional antipsychotics. We assessed psychotic symptoms with the Positive and Negative Syndrome Scale (PANSS) and extrapyramidal symptoms with the Simpson-Angus scale. RESULTS: Prevalence of smoking was 60% (80% in men and 22.5% in women). The majority of them started their consumption before their illness. Smokers and non-smokers had similar rates of psychotic and extrapyramidal symptoms with comparable doses of antipsychotics and anticholinergic agents which were prescribed for similar durations. CONCLUSION: In this study, patients with schizophrenia smoke a lot for reasons other than reducing psychotic or extrapyramidal symptoms.

Hospitalizations in psychiatry during the month of Ramadan: A study at the Tunisian mental health hospital.

BACKGROUND: Muslims fast each year during the Holy Month of Ramadan. This rite has major socio-cultural consequences. The circadian rhythms, energy expenditure, body temperature and biological clock are also influenced by Ramadan fasting. The impact of fasting on patients with mental disorders has been little studied. The aim of this study was to assess the number of hospitalizations in psychiatry during Ramadan compared to the other months of the lunar year. METHOD: A cross-sectional and retrospective study was conducted at Razi hospital, the psychiatric hospital in Tunis. The following data over the five lunar years (1434-1438) was checked for: The monthly and the annual number of hospitalizations in the different departments of Razi mental health hospital in Tunis as well as the monthly and annual rates of different legal modalities of admissions. RESULTS: An important decrease in the number of hospitalizations during Ramadan was observed each year followed by a constant increase during the following month.Ramadan was the only lunar month to have had a consistently below-average number of admissions. There has been a significant increase in the mean number of hospitalizations per month over the years. A general trend towards an increase in the proportion of enforced hospitalizations has been noted. CONCLUSION: Ramadan stands out not only on a religious but also on a social level. Our results add support to the usefulness of research on mental health and Ramadan in the psychiatric community.

[Effectiveness of acupuncture in treating schizophrenia: a clinical randomized trial of 31 patients]. / Apport de l'acupuncture dans le traitement de la schizophrénie : etude randomisée en double-aveugle portant sur 31 patients

BACKGROUND: Acupuncture is one of the most popular types of complementary/alternative medicine in the world. It is sometimes used as a treatment for schizophrenia mainly in China. AIM: To assess the contribution of acupuncture in the treatment of patients treated for schizophrenia in Tunisian population. METHODS: Our study is a clinical randomized trial about 31 hospitalized patients with schizophrenia or schizo-affectif disorder (DSM IV). They were evaluated by the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) the first and 23nd day of the study. Manual acupuncture was used for 10 sessions at the rate of three sessions per week. All patients were under drug therapy. Among them, 15 were treated by acupuncture and 16 by sham acupuncture. RESULTS: Scores of the PANSS, SAPS and SANS were similar in the two groups at the end of the study. CONCLUSION: Our study did not provide any evidence for the effectiveness of acupuncture in treating schizophrenic symptoms.

Plasma homocysteine in schizophrenia: determinants and clinical correlations in Tunisian patients free from antipsychotics.

The existence of association between hyperhomocysteinaemia (HHC) and schizophrenia has been suggested by several recent studies. This study aimed to determine the prevalence of HHC and its main determinants, and sought a correlation with clinical features in Tunisian patients with schizophrenia. Plasma homocysteine (Hcy), folate, and vitamin B12, as well as the C677T methylene tetrahydrofolate reductase (MTHFR) polymorphism, were studied in 33 patients with schizophrenia, all free from antipsychotic treatment, and 35 age- and smoking-habit-matched healthy subjects as controls. Biochemical determinations and psychometric evaluations were carried out in patients before the administration of antipsychotics. The prevalence of HHC was higher and plasma B12 vitamin was significantly lower in patients. There was no significant difference in genotypic distribution and allelic frequency of the C677T MTHFR polymorphism between groups. Hcy was significantly correlated to the 'anhedonia-asociality' subscales of the Scale for the Assessment of Negative Symptoms (SANS). This study showed an association between HHC and schizophrenia, especially with the negative symptoms of the disease. In the Tunisian population, HHC in schizophrenia seems to be linked to vitamin B12 deficiency, likely caused by a lack of dietary animal proteins.