Brain Motor Region Diffusion Tensor Imaging in Patients with Catatonic Schizophrenia: A Case-Control Study.

BACKGROUND: Only a small proportion of schizophrenia patients present with catatonic symptoms. Imaging studies suggest that brain motor circuits are involved in the underlying pathology of catatonia. However, data about diffusivity dysregulation of these circuits in catatonic schizophrenia are scarce. OBJECTIVES: To assess the involvement of brain motor circuits in schizophrenia patients with catatonia. METHODS: Diffusion tensor imaging (DTI) was used to measure white matter signals in selected brain regions linked to motor circuits. Relevant DTI data of seven catatonic schizophrenia patients were compared to those of seven non-catatonic schizophrenia patients, matched for sex, age, and education level. RESULTS: Significantly elevated fractional anisotropy values were found in the splenium of the corpus callosum, the right peduncle of the cerebellum, and the right internal capsule of the schizophrenia patients with catatonia compared to those without catatonia. This finding showed altered diffusivity in selected motor-related brain areas. CONCLUSIONS: Catatonic schizophrenia is associated with dysregulation of the connectivity in specific motoric brain regions and corresponding circuits. Future DTI studies are needed to address the neural correlates of motor abnormalities in schizophrenia-related catatonia during the acute and remitted state of the illness to identify the specific pathophysiology of this disorder.

[THERE IS ROOM FOR IMPROVEMENT: THE RATE OF CLOZAPINE USE AMONG PATIENTS WITH SCHIZOPHRENIA IN ISRAEL].

BACKGROUND: About a third of schizophrenia patients would not have sufficient clinical response to antipsychotic treatment. The only drug approved for this population is clozapine, yet worldwide reports suggest underuse of clozapine and significant delay in initiating treatment. OBJECTIVES: To assess, for the first time in Israel, the rate of clozapine use in patients with schizophrenia. METHODS: A retrospective cohort study of "Clalit Health Services" electronic records was conducted. People diagnosed with schizophrenia (F.20 ICD 10 code) who had at least one prescription filled for clozapine were followed up between 2012 and 2014. RESULTS: Of 28,983 people diagnosed with schizophrenia, clozapine was prescribed and purchased by 1817 (6.5%) patients during the study period. In addition, 60% of patients with clozapine had polytherapy with other antipsychotic compound or lithium. Polytherapy was associated with HR of 2.1 for morality during the follow-up period. CONCLUSIONS: Clozapine is underutilized in Israel, similar to reports from other countries. Moreover, the data suggests that when treatment is given it is not optimized, as reflected by high rates of polytherapy associated with increased mortality. Using therapeutic drug monitoring, now available in Israel, for clozapine might increase clozapine dosage optimization.

Association between bipolar episodes and fluid and electrolyte homeostasis: a retrospective longitudinal study.

OBJECTIVES: Imbalance of fluid and electrolyte homeostasis has been suggested to be associated with the neuropathological processes underlying bipolar disorder. However, longitudinal data regarding the association of bipolar episodes with fluid balance are still lacking. We hypothesized that mania may be associated with a relative fluid retention and hemodilution, and depression with a relative hemoconcentration. METHODS: Patients with bipolar disorder (n = 43) admitted to a mental health center, both with depressive and manic episodes, were retrospectively followed between 2005 and 2013. Fluid balance and electrolyte serum indices were compared between their manic and depressive episodes. We adjusted for physical and psychiatric comorbidities and for psychotropic treatment, using two-way analysis of variance with repeated measures. RESULTS: There was a significant reduction in serum fluid balance indices during mania compared to depression: mean hemoglobin concentration 13.9 ± 1.4 g/dL versus 14.5 ± 1.4 g/dL, paired t = -4.2, p < 0.0005; mean hematocrit 41.1 ± 4.1% versus 42.3 ± 3.7%, paired t = -3.0, p < 0.005; mean albumin concentration 4.2 ± 0.3 g/dL versus 4.5 ± 0.3 g/dL, paired t = -4.5, p < 0.0001; and mean sodium concentration 140.3 ± 2.0 mEq/L versus 141.0 ± 2.0 mEq/L, paired t = -2.1, p = 0.04, respectively. Controlling for physical and psychiatric comorbidities and psychotropic treatment did not alter these associations. CONCLUSIONS: Our results support the notion of an imbalance of fluid and electrolyte homeostasis among bipolar episodes, which is suggestive for relative hemoconcentration during depressive episodes and relative hemodilution during manic episodes. These findings may eventually lead to novel therapeutic targets.

Aggression-impulsivity, mental pain, and communication difficulties in medically serious and medically non-serious suicide attempters.

BACKGROUND: Unbearable mental pain, depression, and hopelessness have been associated with suicidal behavior in general, while difficulties with social communication and loneliness have been associated with highly lethal suicide attempts in particular. The literature also links aggression and impulsivity with suicidal behavior but raises questions about their influence on the lethality and outcome of the suicide attempt. OBJECTIVES: To evaluate the relative effects of aggression and impulsivity on the lethality of suicide attempts we hypothesized that impulsivity and aggression differentiate between suicide attempters and non-attempters and between medically serious and medically non-serious suicide attempters. METHOD: The study group included 196 participants divided into four groups: 43 medically serious suicide attempters; 49 medically non-serious suicide attempters, 47 psychiatric patients who had never attempted suicide; and 57 healthy control subjects. Data on sociodemographic parameters, clinical history, and details of the suicide attempts were collected. Participants completed a battery of instruments for assessment of aggression-impulsivity, mental pain, and communication difficulties. RESULTS: The medically serious and medically non-serious suicide attempters scored significantly higher than both control groups on mental pain, depression, and hopelessness (p<.001 for all) and on anger-in, anger-out, violence, and impulsivity (p<.05 for all), with no significant difference between the two suicide attempter groups. Medically serious suicide attempters had significantly lower self-disclosure (p<.05) and more schizoid tendencies (p<.001) than the other three groups and significantly more feelings of loneliness than the medically non-serious suicide attempters and nonsuicidal psychiatric patients (p<.05). Analysis of aggression-impulsivity, mental pain, and communication variables with suicide lethality yielded significant correlations for self-disclosure, schizoid tendency, and loneliness. The interaction between mental pain and schizoid traits explained some of the variance in suicide lethality, over and above the contribution of each component alone. CONCLUSIONS: Aggression-impulsivity and mental pain are risk factors for suicide attempts. However, only difficulties in communication differentiate medically serious from medically non-serious suicide attempters. The combination of unbearable mental pain and difficulties in communication has a magnifying effect on the risk of lethal suicidal behavior.

[Neurocognitive disturbances and psychiatric disorders among patients living with HIV-1 positive in Israel].

INTRODUCTION: Neurocognitive dysfunction and psychiatric disorders are common among people living with HIV. A large number of the patients are asymptomatic, but in neurocognitive assessment and specific questionnaires subclinical disturbances can be diagnosed. The aim of this research was to study the rate of neurocognitive disturbances, as well as psychiatric disorders (depression and anxiety) among Israeli people living with HIV, and to find predictors for these disturbances. METHODS: VaLidated neurocognitive tests and psychiatric assessment questionnaires (PHQ-9 and STAI) were conducted among 57 asymptomatic HIV-1 positive patients. Sociodemographic and clinical characteristics were collected from the patients' files. RESULTS: The rate of disturbances in the neurocognitive test was dependent on the test used. Whereas in Trail making A and B (TMA, TMB) high rates of disturbances were found, almost no patients with disturbances were found when the digit symbol substitution test (DSST) was used. In immediate and delayed memory testing (IMT and DMT) 47.7% and 49% memorized less than 75% of the numbers, respectively, while 18% of the patients had anxiety and 24% suffered from depression. The median quality of life measured by the analog scale was 7. In multivariate analysis we could not find predictive variables for neurocognitive or psychiatric disorders. DISCUSSION: Neurocognitive disturbances and psychiatric disorders are common among asymptomatic people living with HIV, irrelevant of the time of being positive, immunoLogical status, viral load or treatment received.

Outcomes of compulsorily admitted schizophrenia patients who agreed or disagreed to prolong their hospitalization.

BACKGROUND: Compulsory admission is practiced around the world with legislative variations. The legal status during compulsory hospitalization might be changed to consent or the patient might be discharged against medical advice (AMA), if he no longer poses a risk. OBJECTIVE: In the present study, we investigated the outcome of compulsory admitted patients who left the hospital after commitment period despite request by the treating psychiatrist to remain in the hospital (AMA) vs those who agreed to prolong their hospitalization. RESULTS: Of 320 patients with schizophrenia admitted involuntarily, 157 (49%) were discharged without converting to consent, and 163 (51%) agreed to stay in the hospital. There was no difference in baseline clinical and demographic characteristics and outcome measures (rate of readmission, legal status of next admission, and length of stay in the next admission) between the 2 groups. CONCLUSIONS: Prolongation of length of stay in compulsorily psychiatrist-ordered schizophrenia patients did not affect their rate of rehospitalizations or the length of next admission compared with those who left the hospital immediately after the change in their legal status AMA.

[The cognitive deficit in schizophrenia].

Schizophrenia is a chronic debilitating disorder with a wide spectrum of clinical phenomenology, of which the positive signs, delusions and haLLucinations are best known. The cognitive deficit in schizophrenia patients is one of the prominent dimensions of the disorder The deficit starts early in the course of the disease even before the other signs manifest, it is profound and pervasive and involves several skills including the working memory, attention, learning and social functioning. The current pharmacotherapy for schizophrenia does not affect the cognitive status. Moreover, it appears that the severity of the deficit is the best predictor for social functioning in the community. In recent years, the cognitive deficit is the focus of research. As a result, a battery of cognitive tests was established and validated as a consensus measure for assessing the deficit and evaluating the effectiveness of novel compounds geared to enhance cognitive function in schizophrenia.

Premorbid functioning and treatment response in recent-onset schizophrenia: prospective study with risperidone long-acting injectable.

Premorbid functioning may be associated with treatment response, but this is confounded by a lack of prospective longitudinal data and controls for medication compliance. This study tested the hypothesis that good premorbid functioning will be associated with better antipsychotic treatment response after controlling for drug adherence by using a long-acting injectable antipsychotic. This was a 6-month, open label, multicenter, phase IV trial in recent-onset schizophrenia treated with flexible doses of risperidone long-acting injectable (25-50 mg every 14 days). Premorbid functioning was assessed with the Premorbid Adjustment Scale (PAS)-Structured Interview; efficacy was evaluated with clinician-rated Positive and Negative Syndrome Scale, Clinical Global Impression scale of Severity of Illness, Clinical Global Impression scale of Change, Global Assessment of Functioning Scale, and trial participant completed SF-36. Analyses controlled for baseline scores and demographics. With the use of a priori PAS scoring criteria, the participants' premorbid functioning was categorized as stable-good (n = 142), stable-poor (n = 116), and deteriorating (n = 36). At baseline, the stable-good group had the best functioning on most efficacy measures. All groups showed significant improvement on efficacy measures with treatment. Improvement was significantly higher for the stable-good group. The PAS global assessment of highest level of functioning scale (excellent, n = 75; good, n = 117; fair, n = 78; and poor, n = 31) showed a strong association with baseline functioning and improvement and had a significant linear association with meeting Remission in Schizophrenia Working Group symptom criteria at baseline (P = 0.003) and attained and sustained remission for 3 months during study (47.7%, 49.3%, 29.6%, and 22.2%; P = 0.006). Good premorbid functioning corresponds with better treatment response in recent-onset psychosis as captured on both clinician and patient-reported measures.

Stability of schizoaffective disorder in correlation with duration of follow-up: retrospective analysis.

BACKGROUND/AIMS: Previous studies have indicated that the validity and reliability of schizoaffective disorder (SAD) diagnosis according to the DSM-IV criteria are insufficient, and that the stability of the diagnosis is poor. However, no study has examined exclusively the diagnostic stability of SAD. The aims of this study were to examine the longitudinal stability of the diagnosis of SAD and SAD subtypes among a large sample of patients, and to examine demographic and clinical variables as predictors of diagnostic stability. METHODS: A retrospective chart review of 123 inpatients who were admitted to Geha Mental Health Center between the years 2000 and 2005, and who had been diagnosed with SAD at some stage of their illness. We compared the group of patients whose diagnosis of SAD had remained stable and the group of patients whose diagnosis had changed. RESULTS: The diagnostic stability for SAD was 73.1%. Diagnostic transitions were mainly from and towards schizophrenia. We found an association between the SAD bipolar subtype and higher rates of diagnostic stability. The time that had elapsed since SAD diagnosis was made was significantly shorter in the group of patients with stable diagnosis than in the group of patients whose diagnosis had changed (p = 0.037). CONCLUSIONS: The diagnostic stability of SAD might be higher than previously reported. Patients who are diagnosed with SAD manic subtype have a higher tendency to retain their diagnosis than patients with other SAD subtypes. The diagnostic changes are derived from manifestations of new symptoms in the course of the disease. Clarification of the current diagnostic criteria in order to enable a more precise utilization of the SAD subtype diagnoses is warranted. STUDY LIMITATIONS: (a) The study design was retrospective and further prospective studies are needed to establish our findings; (b) there is a misusage of the SAD subtype definitions, thus conclusions regarding polarity of SAD and stability of diagnosis are limited, and (c) the population studied was comprised of inpatients, therefore generalization to the outpatient population should be done with caution.

Reducing Stigma Toward Psychiatry Among Medical Students: A Multicenter Controlled Trial.

OBJECTIVE: To examine the effect of a novel antistigma intervention curriculum (ASIC) in reducing stigma toward psychiatry among medical students. METHODS: Medical students from 8 hospitals in central Israel were divided into intervention (n = 57) and control (n = 163) arms. The students completed the 30-item Attitudes Toward Psychiatry (ATP-30) and the Attitudes Toward Mental Illness (AMI) scales at psychiatry rotation onset and conclusion. The ASIC was designed to target prejudices and stigma through direct informal encounters with people with serious mental illness (SMI) during periods of remission and recovery. Supervised small-group discussions followed those encounters to facilitate processing of thoughts and emotions that ensued and to discuss salient topics in psychiatry. The study was conducted between November 2017 and July 2018. RESULTS: Significant between-group differences were found at endpoint for attitudes toward psychiatry and psychiatric patients (P < .001). Although changing attitudes toward psychiatry as a career choice was not part of the ASIC, a significant between-group difference emerged by endpoint (P < .001). CONCLUSIONS: Implementation of an ASIC that includes contact with individuals with lived SMI experience followed by supervised small-group discussions is effective in reducing stigma in medical students' perceptions of people with mental illness and psychiatry. Further evaluation is warranted with regard to the long-term destigmatizing effects of an ASIC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03907696.

The possible involvement of metabotropic glutamate receptors in schizophrenia.

Glutamate disruption is thought to have a major role in schizophrenia brain processes, possibly involving NMDA hypofunction. The metabotropic glutamate receptors are distributed in brain regions related to schizophrenia and seem to affect glutamate release in a moderate way. Compounds modulating these receptors are being investigated in animal models of schizophrenia, in an attempt to discover new antipsychotics. This article reviews the current research data regarding the role of these receptors in schizophrenia animal models. It was found that more research was done on Group I and II metabotropic receptors while investigation of group III receptors is still trailing behind. Accumulating evidence shows that mGluR5 antagonists by themselves do not necessarily disrupt pre-pulse inhibition (PPI), but can exacerbate disruption of PPI caused by MK-801 and PCP, while positive modulation of this receptor has beneficial effects on these models of psychosis. Group II agonists are also showing beneficial effects in animal models. It seems that metabotropic glutamate receptor modulators could be developed into a novel treatment of schizophrenia by altering glutamate release, thus overcoming the putative NMDA hypofunction. Although the implications from these pre-clinical studies to human schizophrenia patients are premature, the data obtained with some compounds point to promising results for drug development. More studies, with agents active at other mGluRs in animal models and schizophrenia patients as well as with human subjects are needed in order to clarify the role of the metabotropic glutamate receptors in the pathophysiology and pharmacotherapy of schizophrenia.

Addition of memantine to antipsychotic treatment in schizophrenia inpatients with residual symptoms: A preliminary study.

BACKGROUND: Schizophrenia is comprised of several debilitating symptoms. Antipsychotics offer an effective treatment for positive symptoms, while the negative signs and cognitive deficits are usually treatment-resistant. It was suggested that glutamate dysregulation may be involved in the neuropathology of schizophrenia, mainly through NMDA dysfunction. We hypothesized that addition of memantine, a weak non-selective NMDA receptor antagonist approved for dementia, to antipsychotics would improve the clinical status of un-remitted schizophrenia patients, notably the negative signs and cognitive deficits. METHODS: Seven schizophrenia patients, were included in a six-week open-label study, with weekly increasing dosage (5, 10, 15, 20 mg) of memantine added to their on-going antipsychotic treatment. RESULTS: We found a significant improvement of the PANSS score (baseline 116.28+/-21.9 vs. 97.86+/-24.48 after six weeks, t=5.98, p<0.001) with the most prominent improvement (21%) in negative signs sub-scale (baseline 40+/-6.38 vs. 31.71+/-7.76 after six weeks, t=5.87, p<0.001). Cognitive status, measured with the Neurobehavioral Cognitive Examination (NCSE) and Clock Drawing Test (CDT) showed no improvement. CONCLUSION: Memantine addition to antipsychotic treatment, in schizophrenia patients might improve their clinical status, primarily the negative signs, but not their cognitive deficits. Further research is needed to replicate these observations.

Predictive value of psychological characteristics and suicide history on medical lethality of suicide attempts: A follow-up study of hospitalized patients.

BACKGROUND: This study examined the role of mental pain, communication difficulties, and suicide history in predicting the medical severity of follow-up suicide attempts. METHODS: The cohort included 153 consecutive psychiatric in-patients who participated in earlier studies 1-9 years previously. Fifty-three had a history of a medically serious suicide attempt (MSSA), 64 had a history of a medically non-serious suicide attempt (MNSSA), and 36 had no history of suicide. A MSSA was defined as a suicide attempt that warranted hospitalization for at least 24h and extensive medical treatment. Participants completed a battery of instruments measuring mental pain and communication difficulties. Findings were analyzed in relation to follow-up suicide attempts and their severity. RESULTS: Fifty-three patients (35.5%) had attempted suicide: 15 (9.9%) a MSSA (including 5 fatalities) and 38 (25%) a MNSSA. The medical severity of the index attempt and level of hopelessness at the index attempt were significantly correlated with medical severity of the follow-up attempt. In younger patients, high levels of depression and self-disclosure predicted the medical severity of the follow-up attempt. In patients with relatively low hopelessness, the medical severity of the attempt increased with the level of self-disclosure. LIMITATIONS: (i) Possibly incomplete patient information, as some of the patients who participated in the index studies could not be located. (ii) Relatively small group of patients with an index MSSA. CONCLUSIONS: Patients who have made a suicide attempt should be assessed for medical severity of the attempt, hopelessness, and communication difficulties, which are important factors in follow-up attempts.

Family-based association study of 5-HT(2A) receptor T102C polymorphism and suicidal behavior in Ashkenazi inpatient adolescents.

UNLABELLED: Suicidal behavior runs in families and is partially genetically determined. Since greater serotonin 5-HT(2A) receptor binding has been reported in postmortem brain and platelets of suicide victims, the 5-HT(2A) receptor gene polymorphism T102C became one of the candidate sites in the study of suicide and impulsive-aggressive traits. However, studies that examined the association of this polymorphism with suicidality have contradictory results. This study used a family-based method and one homogenous ethnic group to overcome ethnic stratification in order to test this association. METHODS: Thirty families of inpatient adolescents from Jewish Ashkenazi origin, with a recent suicide attempt, were genotyped. All subjects were interviewed for clinical diagnosis, depressive and impulsive-aggressive traits and demographic data. Allele frequencies were assessed using the Haplotype Relative Risk method for trios. RESULTS: No difference was found in allelic distribution between transmitted and non-transmitted alleles. There was no significant association of genotype with any of the clinical traits CONCLUSIONS: These preliminary results suggest that the 5-HT(2A) T102C polymorphism is unlikely to be associated with suicidal behavior and related traits in adolescent suicide attempters.

Attention patterns in children with attention deficit disorder with or without hyperactivity.

The objective of this study was to differentiate the attention patterns associated with attention deficit disorder with or without hyperactivity using continuous performance test (CPT). The diagnoses were based on the DSM-III, III-R, and IV criteria and of the 39 children who participated in the study, 14 had attention deficit disorder with hyperactivity (ADDH) and 11 had attention deficit disorder without hyperactivity (ADDWO), while 14 normal children served as a control group. Attention patterns were examined according to the performance of subjects on the CPT and parental scores on the ADHD Rating Scale, the Child Attention Profile, and the Conners Rating Scale. CPT performances were assessed before and after administration of 10 mg methylphenidate. We found as hypothesized that the CPT differentiated between the ADDH and ADDWO groups. However, contrary to our expectations, the ADDH children made more omission errors than the ADDWO children; they also showed more hyperactivity and impulsivity. The performance of both groups improved to an equal degree after the administration of methylphenidate. It is concluded that different subtypes of the attention deficit disorders are characterized by different attention profiles and that methylphenidate improves scores on test of continuous performance.

Mental pain, communication difficulties, and medically serious suicide attempts: a case-control study.

Medical severe suicide attempts (MSSA) are epidemiologically very similar to individuals who complete suicide. Thus the investigation of individuals who have made MSSAs may add to our understanding of the risk factors for completed suicide. The aim of this study was to assess the role of mental pain and communication difficulties in MSSA. A total of 336 subjects were divided into 4 groups: 78 meeting criteria for MSSA compared with116 subjects who made a medically non-serious suicide attempt (MNSSA), 47 psychiatric controls with no history of suicidal behavior, and 95 healthy controls. Mental pain variants (e.g., hopelessness), facets of communication difficulties (e.g., self-disclosure), as well as socio-demographic and clinical characteristics were assessed. The MSSA had significantly higher communication difficulties than the other 3 groups. Moreover, the interaction between mental pain and communication difficulties explained some of the variance in suicide lethality, above and beyond the contribution of each component alone. This report underlines the importance of mental pain for suicide attempts in general while difficulties in communication abilities play a critical role in differentiating MSSA from MNSSA. The co-existence of unbearable mental pain with difficulties in communication significantly enhances the risk for more lethal forms of suicidal behavior.

Acute manic episode is associated with an increased risk of lower limb edema.

OBJECTIVE: Lower limb edema (LLE) was suggested to be associated with the use of psychotropic drugs among patients suffering from severe mental illnesses; however no direct mechanism was found. Therefore, we examined the association between the occurrence of LLE and acute untreated episode leading to hospitalization. METHODS: A retrospective cross-sectional study was conducted using medical charts of 2529 patients admitted to Geha Mental Health Center between 2002 and 2012. Incident cases of LLE, demographic and clinical data were retrieved. Admission clinical status was modeled as three non-overlapping groups of patients: (i) Patients with a non-affective psychosis (NAP) episode (n = 1563), (ii) patients with a manic episode (n = 366), and (iii) patients with a depressive episode (n = 600). We performed a logistic regression analysis with LLE as the dependent variable controlling for the demographic and clinical variables that may be associated with LLE. RESULTS: LLE was diagnosed in 3.8% (n = 95) of the study population. The rate of LLE was 3-fold higher (χ(2) = 51.9, df = 2, p<0.001) in patients admitted with a manic episode (n = 38; 10.4%) compared to patients admitted with a NAP episode (n = 41; 2.6%) and patients admitted with a depressive episode (n = 16; 2.7%). Manic episode was associated with an increased risk for LLE compared to depressive episode (OR 8.72, 95% CI: 3.53-21.52, p<0.001) or NAP episode (OR 3.96, 95% CI: 2.16-7.26, p<0.001) after controlling for relevant confounders. CONCLUSION: Acute manic episode, leading to hospitalization, is associated with an increased risk of LLE, compared to NAP or depressive episode, suggesting causal relationship between mood and fluid imbalance. Yet, future prospective studies are needed to rule out the contribution of physical agitation and lithium treatment.

Predictors of clozapine discontinuation in patients with schizophrenia.

Clozapine has superior efficacy for treating patients with schizophrenia. Its discontinuation could have detrimental consequences. We attempted to identify the clinical parameters that could predict clozapine discontinuation in patients diagnosed as having schizophrenia by conducting a retrospective analysis of all of those who started on clozapine treatment during their hospitalization in our institution between 2002 and 2008 (n=100). Demographic and clinical parameters were analyzed and compared between the 58 patients who continued and the 42 who discontinued clozapine treatment during a follow-up period of 8.1 years. Twenty of the latter patients (47.6%) discontinued clozapine because of nonadherence and 11 (26.2%) because of side effects. Thirty-three of them (78.6%) stopped taking clozapine during the first year of treatment. The duration of clozapine use correlated significantly with the time to readmission (P<0.001). The decrease in number of suicide attempts was higher in those who continued clozapine treatment compared with those who discontinued it (P=0.02). Predictors for drug discontinuation were old age at clozapine initiation and comorbid substance abuse. These findings indicate that patients with schizophrenia with those risk factors need special incentives to be compliant during the first year of clozapine treatment to minimize the negative sequelae of clozapine discontinuation.