Remission Of Negative Symptoms Research Articles

Influence of time to clozapine prescription on the clinical outcome

BackgroundThis study investigates whether early clozapine use is associated with improved responses in different clinical domains, including positive and negative symptoms, functioning, and well-being. MethodsData from 254 clozapine-treated patients at Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) were analysed. Among them, 231 (90.9 %) had a diagnosis of schizophrenia, 21 (8.3 %) schizoaffective disorder, and 2 (0.8 %) had other diagnoses. The International Classification of Diseases-Mortality and Morbidity Statistics criteria (ICD-10) were employed (World Health Organization, 1992). The cohort was assessed using the positive and negative syndrome scale (PANSS), the Brief Negative Symptom Scale (BNSS), Global Assessment of Functioning Scale (GAF), and the short version of Warwick-Edinburgh Mental Well-being Scale (SWEMWBS). Logistic regression models (for positive and negative symptom remission) and linear regression (for functioning and well-being) were utilized to assess the influence of time to clozapine initiation (TCI), age at the first episode of psychosis (AFE), duration of clozapine treatment (DCT), and gender. ResultsEarly clozapine treatment (within the first three years after the first episode of psychosis) was associated with increased negative symptom remission (exp (B) = 0.38; p = 0.02) and higher functioning scores (β = −0.12, p = 0.046). However, no effect of time to clozapine initiation was found on positive symptom remission rates or well-being scores. ConclusionsInitiating clozapine treatment within the first 3 years of the first episode of psychosis may lead to reduced severity of negative symptoms and improved functioning in clozapine-treated patients. The time to clozapine initiation did not influence its effect on positive symptom remission rates.

Subjective quality of life among first-episode psychosis patients in Chennai, India and Montreal, Canada.

Differences in subjective quality of life among persons receiving early intervention for psychosis in varying geo-sociocultural contexts have rarely been examined. Our prospective longitudinal study compared the quality of life of persons with first-episode psychosis receiving two years of similar early intervention in Chennai, India and Montreal, Canada. We hypothesized that general life satisfaction would be higher in Chennai compared to Montreal, and that social relations (a specific quality of life component) would also be higher in Chennai and positively contribute to general life satisfaction. Participants completed the general satisfaction and social relations domains of the Wisconsin Quality of Life Index at baseline, months 12 and 24. Baseline weighted mean general satisfaction and social relations scores were in the low to moderate range. Generalized estimating equation analyses showed that general satisfaction scores increased with time [Wald χ2 (1)=125.28, p<0.001] and were higher in Chennai than in Montreal [Wald χ2 (1)=7.50, p=0.006]. Social relations scores showed the highest association with general satisfaction scores (B=0.52), followed by positive symptom remission (B=0.24) and gender (B=0.18) with Chennai males having the highest general satisfaction scores. Social relations weighted mean scores increased with time [Wald χ2 (1)=87.30, p<0.001] and were positively associated with years of education [Wald χ2 (1)=4.76, p=0.029] and early negative symptom remission [Wald χ2 (1)=7.38, p=0.007]. Our results suggest that subjective quality of life may improve following early intervention for psychosis across contexts. Our findings advance knowledge about the role of sociocultural (e.g., gender) and clinical factors in influencing subjective outcomes in psychosis, and point to social support networks and symptom remission as avenues to boost quality of life.

Negative symptoms and associated factors in older people with schizophrenia

IntroductionThe evolution of schizophrenia with age remains poorly studied. The prevalence of negative symptoms in elderly people with schizophrenia is even less described in the literature.Objectivesto evaluate the prevalence of remission of negative symptoms in the elderly and to study the sociodemographic and clinical variables associated with this remission.MethodsThe sample consisted of 83 subjects aged 55 years and over, followed at the psychiatry department "G" of the Razi hospital in Tunis and suffering from schizophrenia according to the DSM5 criteria. Global remission was defined as a score below 4 on the seven negative symptom items of the PANSS. A questionnaire was administered to each patient to collect epidemiological and anamnestic data.Results59% of the sample showed remission of global negative symptoms. 84% and 60% were in remission on the emotional and cognitive subscales, respectively. The existence of remission was correlated with lower PANSS global score, more preserved cognitive functioning, later age of onset, more family and social support, and the absence of a concomitant somatic illness.ConclusionsThis study showed that measures to optimize treatment of positive symptoms and cognitive functioning may have an impact on negative symptoms. Similarly, quality of social network in later life impacts the level of negative symptoms.Disclosure of InterestNone Declared

Lurasidone use in Cannabis-Induced Psychosis: A Novel Therapeutic Strategy and Clinical Considerations in Four Cases Report

Lurasidone is an atypical antipsychotic approved for the acute and maintenance treatment of schizophrenia. Recently, lurasidone was also extended FDA approval for adults with major depressive episodes associated with bipolar I disorder (bipolar depression), as either a monotherapy or as adjunctive therapy with lithium or valproate. The use of low doses of atypical antipsychotics is an essential component of early intervention in psychosis, but little has yet been studied on first episode cannabis-induced psychosis. For its particular performance and tolerability, lurasidone is becoming an important option for the treatment of first-episode psychosis in youth. Case presentation four patients experiencing first cannabis-induced psychotic episode were treated with lurasidone. In all patients, there was an improvement in the clinical picture of psychosis. The recovery was positive, not only with the remission of positive and negative symptoms, but also regarding disruptive behaviour, with the return of functioning. All the patients were treated with lurasidone, with a target dose of 74-128 mg/day. No significant side effects were reported. There are non-controlled studies for the use of lurasidone in first episode psychosis cannabis induced. These findings suggest that lurasidone is an atypical antipsychotic beneficial in this clinical picture. Treatment with medium-high doses of lurasidone could be effective and tolerable in this phase of the disorder. Randomized control trials with longer follow-up are recommended to confirm these positive results.

Clozapine and urinary incontinence

IntroductionClozapine is an atypical antipsychotic, which has been shown to have superior efficacy in the remission of positive and negative symptoms in patients with treatment-resistant schizophrenia, compared to other antipsychotics. However, its benefits have been limited by the lethal adverse effects that this drug can cause, the most common, agranulocytosis. Other less serious and more common adverse effects are sedation, hypersalivation, hypo and hypertension, weight gain and urinary incontinence. It is estimated that approximately 1% of patients treated with Clozapine suffer from urinary incontinence. Data that varies from 0.3% to 42% in the articles reviewed, being undervalued in some of these for many reasons; it is stigmatizing and the patient is ashamed to express it.ObjectivesThe objective of this study is to assess the percentage of urinary incontinence in patients in treatment with clozapine, taking into account the presence or absence of this side effect as the main variable, and the diagnosis, gender and dose of clozapine as secondary variables.MethodsA retrospective observational study was carried out in which 40 patients belonging to the Adult Mental Health area of the Nuestra Señora del Prado Hospital, were collected, all of them diagnosed with some type of psychotic disorder and undergoing treatment with Clozapine.ResultsOf the total of patients studied, 25% presented urinary incontinence as an adverse effect, and of these, 60% were with doses equal to or greater than 400 mg of Clozapine.ConclusionsWe must be careful and bear this side effect in mind in all patients taking Clozapine.DisclosureNo significant relationships.

The Efficacy of Animal-Assisted Therapy in Patients with Dual Diagnosis: Schizophrenia and Addiction.

The objective of the study was to evaluate the efficacy of an animal-assisted-therapy (AAT) program in patients diagnosed with schizophrenia-spectrum disorders and substance-use disorders in residential treatment in order to intervene in the remission of negative and positive symptoms and improve quality of life and adherence to treatment, favouring the clinical stabilization of patients who participate in the AAT program, within the context of a mental-illness-treatment device. This was a quasi-experimental prospective study with intersubject and intrasubject factors. The sample comprised 36 patients (21 in the experimental group and 15 in the control group) who were evaluated at three time points (in the 3rd, 6th, and 10th sessions). The program lasted 3 months and consisted of 10 sessions that were implemented once a week, with a maximum participation of 10 patients per group. The participants were evaluated with the Positive and Negative Syndrome Scale (PANSS) for schizophrenia and the Life Skills Profile-20 (LSP-20) questionnaire. We observed a decrease in the positive symptoms of psychosis (F: 27.80, p = 0.001) and an improvement in functionality (F: 26.70, p < 0.001) as the sessions progressed. On the basis of these results, we concluded that AAT seems to be valid as a coadjuvant therapy as part of the rehabilitation processes of patients diagnosed with schizophrenia and addiction-spectrum disorders (dual diagnosis).

Remission of Persistent Negative Symptoms and Psychosocial Consequences by Combined Clozapine and Cariprazine Treatment in a Patient With Long-Standing Treatment-Resistant Schizoaffective Disorder.

This patient case report describes a 45-year old white unmarried man with disability pension due to schizoaffective disorder, diagnosed at the age of 24. He lives in an apartment and has housing support. Retrospectively, the patient displayed prodromal markers of a disorder within the schizophrenia spectrum many years before the onset of frank psychosis, indeed since childhood. Over the years several symptoms and signs across schizophrenia domains have been manifest: positive, negative, cognitive, and affective, among which the negative and affective symptoms and signs were the earliest to appear. While the positive, disorganized, and catatonic symptoms responded to treatment – when duly tested and complied with – the negative and affective symptoms have been notoriously difficult to handle. We now report on the successful introduction of cariprazine (CAR) to his ongoing clozapine (CLZ) medication, the result of which has been a near-complete remission of his persistent negative and psychosocial issues. We interpret this remarkable alleviation of the patient's disease – and concomitant improvement of his quality of life – in terms of neuroreceptor target complementarity between CLZ and CAR, with particular emphasis on the contributions from the D3 and D2 receptor partial agonist components of the latter agent.

An observational study of antipsychotic medication discontinuation in first-episode psychosis: clinical and functional outcomes.

To study the impact of supervised antipsychotic medication discontinuation on clinical and functional outcomes in first-episode psychosis (FEP) in two different cultural environments. FEP patients(N = 253), treated in two early intervention services (Montreal, Canada and Chennai, India) for 2 years, were assessed for medication use, positive and negative symptom remission and social-occupational functioning at regular intervals. Between months 4 and 24 of treatment, 107 patients discontinued medication ('Off'group) as compared to 146 who stayed on medication ('On'group). Medication discontinuation was higher in Chennai as compared to Montreal (n = 80, 49.07% vs n = 27, 16.87%; χ2 37.80, p < 0.001), with no difference in time to discontinuation [Means(SDs) = 10.64(6.82) and 10.04(5.43), respectively, p = 0.71). At month 24 (N = 235), there were no differences in the rate of positive symptom remission between the on and Off groups (81.5 vs 88.0%, respectively) at both sites. The rate of negative symptom remission was lower among patients in the On compared to the Off group (63.2 vs 87.9%, respectively, χ2 = 17.91, p < 0.001), but only in Montreal (55.4% vs 80.0%, respectively, χ2 = 4.12, p < 0.05). Social and Occupational Functioning Assessment Scale scores were equally high in both Off and On medication groups in Chennai [Means (SDs) = 79.43(12.95) and 73.59(17.63), respectively] but higher in the Off compared to the On group in Montreal Means (SDs) = 77.47(14.97) and 64.94(19.02), respectively; Time × site interaction F = 3.96(1,217), p < 0.05]. Medication status (On-Off) had no impact on the outcomes, independent of other variables known to influence outcomes. Certain cultural environments and patient characteristics may facilitate supervised discontinuation of antipsychotic medication following treatment of an FEP without negative consequences.

Impact of childhood trauma on positive and negative symptom remission in first episode psychosis

ObjectiveEarly life adversity is suspected to play an important role for onset and course of psychosis, but its relationship with longer-term clinical outcome is not entirely clear. In this longitudinal study, we investigated the impact of childhood trauma (CT) on positive and negative symptom remission in first episode psychosis (FEP) patients over two years. MethodsA total of 210 FEP patients were assessed with the Childhood Trauma Questionnaire. Patients reporting moderate to severe trauma (CT; N = 114; 54.3%) were compared to those without trauma (N-CT; N = 96; 45.7%). Positive (PSR) and negative symptom remission (NSR) were determined monthly over 24 months following established criteria using the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms. Global Functioning was evaluated at baseline and 24 months of follow-up. ResultsCompared to N-CT patients, CT patients had achieved significantly lower rates of PSR at 12 months and significantly lower rates of NSR at 24 months. A dose-response relationship was observed between the number of trauma categories fulfilled and the number of patients not achieving PSR and NSR at these time points. Higher trauma scores were significantly associated with poor functioning and higher positive and negative symptom severity at 24 months, but not at baseline and 12 months of follow-up. ConclusionDifferential effects of CT on clinical outcome may not be apparent at psychosis onset, but only become evident through poor symptomatic remission and general functioning over time. Targeted diagnostic and therapeutic efforts after illness onset might limit these detrimental consequences.

Comparison of clinical outcomes following 2 years of treatment of first-episode psychosis in urban early intervention services in Canada and India.

Purported superior outcomes for treatment of psychosis in low- and middle-income (LMICs) compared with high-income (HICs) countries have not been examined in the context of early intervention services (EIS). To compare 2-year clinical outcomes in first-episode psychosis (FEP) treated in EIS in Chennai (LMIC) and Montreal (HIC) using a similar EIS treatment protocol and to identify factors associated with any outcome differences. Patients with FEP treated in EIS in Chennai (n = 168) and Montreal (n = 165) were compared on change in level of symptoms and rate and duration of positive and negative symptom remission over a 2-year period. Repeated-measures analysis of variance, and logistic and linear regression analyses were conducted. Four patients died in Chennai compared with none in Montreal. Family support was higher for Chennai patients (F = 14.05, d.f. = 1, P < 0.001, ƞp2 = 0.061) and increased over time at both sites (F = 7.0, d.f. = 1.915, P < 0.001, ƞp2 = 0.03). Negative symptom outcomes were significantly better in Chennai for level of symptoms (time × site interaction F = 7.36, d.f. = 1.49, P = 0.002, ƞp2 = 0.03), duration of remission (mean 16.1 v. 9.78 months, t = -7.35, d.f. = 331, P < 0.001, Cohen's d = 0.80) and the proportion of patients in remission (81.5% v. 60.3%, χ2 = 16.12, d.f. = 1, P < 0.001). The site differences in outcome remained robust after adjusting for inter-site differences in other characteristics. Early remission and family support facilitated better outcome on negative symptoms. No significant differences were observed in positive symptom outcomes. Patients with FEP treated in EIS in LMIC contexts are likely to show better outcome on negative symptoms compared with those in HIC contexts. Early remission and family support may benefit patients across both contexts.

T214. ANTIPSYCHOTIC TREATMENT PATTERNS AND EFFECTS DURING THE EARLY YEARS AMONG 316 NEWLY DIAGNOSED PATIENTS WITH SCHIZOPHRENIA FROM THE OPUS TRIAL

BackgroundIn studies investigating the relapse rate of psychotic symptoms in patients diagnosed with schizophrenia there is a discrepancy between discontinuation studies finding a relapse rate up to 90% after discontinuation of antipsychotic medication and long-term follow-up studies finding approx. 30% of patients living without antipsychotic medication and psychotic symptoms. Long-term follow-up studies often have multiple follow-up assessments, but little is known about the use of medication in the intervals between the follow-up points. While register studies can follow large cohorts of patients, they are unable to investigate psychopathology and level of functioning in patients who discontinue their medication. In this study we use data from a clinical cohort with information on participants symptoms and functioning and combine them with register data on the individual participants prescriptions and hospitalizations.MethodsThe present study represents a combination of a clinical study from early intervention settings and register-based information on antipsychotic drug use and hospital contacts. For the present study, patients were included 18 months into their 24 months early intervention treatment and followed up 3 ½ year later. At baseline and follow-up we performed clinical assessments with all patients and via the Danish National Hospital Register and the Danish National Prescription Register, we had complete nationwide information for all patients identifying all redeemed prescriptions for antipsychotic drugs from 6 to 42 months after inclusion into the study. Based on medication information from the Danish National Prescription Register, we divided participants in the following four groups: 1) Non-users, 2) compliant on medication, 3) stopped but resumed later with medication, and 4) stopped with medication.ResultsOf the 316 participants included in this study 94.3% had I diagnosis of schizophrenia. In the 3 years preceding the 5 years follow-up 28.2% did not redeem any prescriptions for antipsychotics drugs while 21.2% discontinued their treatment during the follow-up, 20.9% discontinued their treatment but resumed later and 29.7% remained in stable treatment. At the 5 years follow-up the 30.3% of the Never-users where in competitive employment, the mean psychotic symptom score were 1.4 SD (1.4) and negative symptoms 1.1 SD (0.9). Whiles these results were worse for patients Compliant on medication (17%, 1.9 SD (1.3), 1.8 SD (1.0)), Stopped but resumed medication (10.6%, 22.4 SD (1.4), 1.5 SD (1.0)) and Stopped medication (17%, 1.6 SD (1.3), 1.3 SD (1.0)), respectively. Of the Never-user 23.6% were in remission of both positive and negative symptoms, while this was only the case for 12.8% of those compliant on medication.DiscussionThis study is a naturalistic cohort study and we are unable to draw any conclusion regarding the causality between symptoms remission and use of antipsychotic medication. The study shows that a substantial proportion of patients, for several years, can discontinue their medical treatment without being re-hospitalized and with lower symptoms burden then patients who continue their medical treatment. Some patients discontinue their treatment but resume it later. These patients have approximately the same functional level and psychotypological scores as those who are compliant with their medical treatment and are treated with equivalent doses of antipsychotic at the time of the follow-up.

The effect of minocycline on amelioration of cognitive deficits and pro-inflammatory cytokines levels in patients with schizophrenia

BackgroundCognitive deficits of schizophrenia are predictors of poor function, but antipsychotic medication has limited efficacy for cognitive deficits. These deficits in learning and memory may result from activity of pro-inflammatory cytokines, which microglia produce. The microglia inhibitor minocycline might arrest this cytokine damage to the hippocampus and reverse the cognitive deficits of schizophrenia. MethodsA double-blind, placebo-controlled study involved 75 patients with schizophrenia who randomly received low dose (100 mg/day) or high dose minocycline (200 mg/day) or placebo added to risperidone. MATRICS Consensus Cognitive Battery (MCCB) was used to assess the cognitive functioning, and serum levels of Interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor–α (TNF-α) were assessed. ResultsMinocyclinehigh dose group was significantly superior to minocyclinelow dose or placebo group not only for the improvements in cognitive tests' scores as well (P < 0.05), but for IL-1β and IL-6 serum levels reduction (P < 0.01). The amelioration of cognitive deficits with minocycline correlated not only with the remission of negative symptoms, but also with the reduction in serum levels of IL-1β and IL-6. ConclusionsMinocycline adjunctive treatment was effective in improving cognitive deficits of patients with schizophrenia. The beneficial effect of minocycline may be related to reducing pro-inflammatory cytokines through microglia inhibition.

Sex Differences in Clinical and Functional Outcomes among Patients Treated in an Early Intervention Service for Psychotic Disorders: An Observational Study.

It has been shown that men with a longstanding psychotic disorder have worse clinical and functional outcomes than women. Our objectives were to examine whether these sex differences are also present among patients treated in an early intervention service (EIS) for psychosis and to determine if these differences are related to risk factors other than sex. Patients (N = 569) were assessed for demographic/clinical characteristics at entry and for symptoms/functioning over 2 years of treatment. Clinical outcomes included remission of positive, negative, and total symptoms. Functional outcomes included good functioning and functional remission. Logistic regression models examined the relationship between sex and outcomes after 1 and 2 years of treatment while controlling for the influence of other risk factors. Men reported to be less educated and have a longer duration of untreated psychosis, poorer childhood and early adolescent premorbid functioning, higher rates of substance abuse/dependence disorders, greater severity of baseline negative symptoms, and poorer baseline social/occupational functioning than women. Women were more likely to achieve symptom remission than men after 2 years of treatment (negative odds ratio [OR], 1.69; 95% confidence interval [CI], 1.02 to 2.78; total OR, 1.79; 95% CI, 1.08 to 2.98). Women were also more likely than men to exhibit good functioning (OR, 1.61; 95% CI, 1.04 to 2.49) after 1 but not after 2 years of treatment. These results did not persist after controlling for other risk factors that could confound these associations (i.e., childhood premorbid functioning and age at onset of psychosis). Sex differences seen in outcomes among patients treated in an EIS for psychosis may be largely influenced by the disparity of other risk factors that exist between the 2 sexes.

Short duration of untreated psychosis enhances negative symptom remission in extended early intervention service for psychosis.

To test whether duration of untreated psychosis (DUP)<3months, recommended by the World Health Organization/International Early Psychosis Association, enhances the effects of an extended early intervention service (EEIS) on symptom remission. We examined data from a randomized controlled trial in which patients who received 2years of treatment in EIS for psychosis were subsequently randomized to either 3years of EEIS or 3years of regular care (RC). Using a DUP cut-off≤12weeks (approximately<3months), patients were split into two groups. Length of positive, negative and total symptom remission were the outcomes. Patients (N=217) were mostly male (68%) with schizophrenia spectrum disorder (65%); 108 (50%) received EEIS (58 had DUP ≤12weeks; 50 had DUP >12weeks). Interaction between treatment condition (EEIS vs. RC) and DUP cut-off≤12weeks was only significant in multiple linear regression model examining length of negative symptom remission as the outcome (adjusted β=36.88 [SE=15.88], t=2.32, P=0.02). EEIS patients with DUP ≤12weeks achieved 25 more weeks of negative symptom remission than EEIS patients with DUP >12weeks. Having a short DUP may be critical in deriving long-term benefits from EIS for psychosis, including EEIS settings. This work empirically supports policy recommendations of reducing DUP <3months.

Progressive Grey Matter Volume Changes in Patients with Schizophrenia over 6 Weeks of Antipsychotic Treatment and Their Relationship to Clinical Improvement

Cross-sectional and longitudinal studies have identified widespread and progressive grey matter volume (GMV) reductions in schizophrenia, especially in the frontal lobe. In this study, we found a progressive GMV decrease in the rostral medial frontal cortex (rMFC, including the anterior cingulate cortex) in the patient group during a 6-week follow-up of 40 patients with schizophrenia and 31 healthy controls well-matched for age, gender, and education. The higher baseline GMV in the rMFC predicted better improvement in the positive score on the Positive and Negative Syndrome Scale (PANSS), and this might be related to the improved reality-monitoring. Besides, a higher baseline GMV in the posterior rMFC predicted better remission of general symptoms, and a lesser GMV reduction in this region was correlated with better remission of negative symptoms, probably associated with ameliorated self-referential processing and social cognition. Besides, a shorter disease course and higher educational level contributed to better improvement in the general psychopathological PANSS score, and a family history was negatively associated with improvement of the negative and total PANSS scores. These phenomena might be important for understanding the neuropathological mechanisms underlying the symptoms of schizophrenia and for making clinical decisions.

S69. A CASE STUDY OF CLOZAPINE AND COGNITION: FRIEND OR FOE?

BackgroundCognitive dysfunction is as a hallmark feature of schizophrenia. Antipsychotic medication is effective for treating the positive symptoms of psychosis, but their potential for therapeutic effects on cognition continues to divide researchers.Improvements in clinical symptoms can occur independently of cognitive functioning, whereby typical antipsychotics improve different clinical domains, but have little or no efficacy for improving primary cognitive functions. However, it has been suggested that the second-generation antipsychotic clozapine can improve cognition in schizophrenia. Unusual cases, such as remitted patients who decide to stop taking clozapine, thus represent a unique opportunity to understand the effect of antipsychotic medication on cognition, as described in the case study below.MethodsA 38-year old man suffered severe psychotic episodes at age 19, leading to a diagnosis of treatment-resistant schizophrenia. Clozapine was initiated at age 21, with excellent treatment response and complete remission of positive, negative and depressive symptoms. For the following 16 years, he had a full-time paid job, lived independently and had an ample social circle. For the last five years, he was stable and compliant taking 175 mg of clozapine, with clozapine levels in sub-therapeutic range (between 0.17 and 0.26 mg/L). He had no metabolic syndrome and no oversedation, but complained of hypersalivation and persistent memory problems. He decided, against advice, that medication was no longer needed and requested support for waning off clozapine.A five-month program was subsequently implemented, with 25 mg reductions of clozapine every six weeks. Four enhanced assessments were scheduled after two weeks on stable doses of 125, 75, 25 and 0 mg, respectively, which included the Brief Assessment of Cognition in Schizophrenia (BACS) and the Clinical Global Impression-Schizophrenia scale (CGI-SCH).ResultsAt each level of clozapine dose, the patient continued to be stable. However, the patient showed impaired cognitive performance at the highest dose of clozapine titration (see T-scores from Table and figure), with improvements then shown at each level of dose reduction (75 and 25 mg). The final assessment was done after 6 weeks of not taking medication. At this time, he was admitted to hospital for psychotic relapse. Unfortunately, the patient refused to re-initiate clozapine and has remained floridly psychotic for 18 months.Our case suggests that cognitive impairment is dose-dependent with clozapine. As presented, the t-score of the patient at 125 mg was worse than normative data reported for healthy controls (z-score=0.50) and patients with schizophrenia treated with other first-or second generation antipsychotics (z-score=-1.42). However, cognitive performance of the patient was most notably impaired when medication-free.DiscussionThe longterm effects of high-dose antipsychotic medication on cognition in patients with schizophrenia are largely unknown. It is also possible that changes in cognitive states are either domain-specific with clozapine. Nonetheless, daily antipsychotic dose and polypharmacy have been shown to predict poor cognitive functioning.The present case is also a reminder that the appropriate long-term maintenance dose of clozapine is poorly understood. As this case suggests, the current recommended therapeutic levels of clozapine (0.35 to 0.50 mg/L) might be unnecessarily high for patients in full remission. Controlled studies are therefore needed to evaluate the potential for cognitive improvements in schizophrenia as a function of reduced clozapine dose, to ensure the optimal delivery needed not just for good clinical but also good cognitive outcome.

Pathways to functional outcomes following a first episode of psychosis: The roles of premorbid adjustment, verbal memory and symptom remission.

Most studies have investigated either the singular or relative contributions of premorbid adjustment, verbal memory and symptom remission to functional outcomes in first-episode psychosis. Fewer studies have examined the pathways of these factors in impacting functioning. Our study addresses this gap. The objective was to determine whether the relationship between premorbid adjustment and functional outcomes was mediated by verbal memory and symptom remission. A total of 334 first-episode psychosis participants (aged 14-35 years) were assessed on premorbid adjustment, verbal memory upon entry, and positive and negative symptom remission and functioning at multiple time points over a 2-year follow-up. Mediation analyses showed that over the first year, the relationship between premorbid adjustment and functioning was mediated by verbal memory and positive symptom remission (β = -0.18; 95% confidence interval = [-0.51, -0.04]), as well as by verbal memory and negative symptom remission (β = -0.41; 95% confidence interval = [-1.11, -1.03]). Over 2 years, the relationship between premorbid adjustment and functioning was mediated by verbal memory and only negative symptom remission (β = -0.38; 95% confidence interval = [-1.46, -0.02]). Comparatively less malleable factors (premorbid adjustment and verbal memory) may contribute to functional outcomes through more malleable factors (symptoms). Promoting remission may be an important parsimonious means to achieving better functional outcomes.

Comparing three-year extension of early intervention service to regular care following two years of early intervention service in first-episode psychosis: a randomized single blind clinical trial.

This study aimed to determine if, following two years of early intervention service for first-episode psychosis, three-year extension of that service was superior to three years of regular care. We conducted a randomized single blind clinical trial using an urn randomization balanced for gender and substance abuse. Participants were recruited from early intervention service clinics in Montreal. Patients (N=220), 18-35 years old, were randomized to an extension of early intervention service (EEIS; N=110) or to regular care (N=110). EEIS included case management, family intervention, cognitive behaviour therapy and crisis intervention, while regular care involved transfer to primary (community health and social services and family physicians) or secondary care (psychiatric outpatient clinics). Cumulative length of positive and negative symptom remission was the primary outcome measure. EEIS patients had a significantly longer mean length of remission of positive symptoms (92.5 vs. 63.6 weeks, t=4.47, p<0.001), negative symptoms (73.4 vs. 59.6 weeks, t=2.84, p=0.005) and both positive and negative symptoms (66.5 vs. 56.7 weeks, t=2.25, p=0.03) compared to regular care patients. EEIS patients stayed in treatment longer than regular care patients (mean 131.7 vs. 105.3 weeks, t=3.98, p<0.001 through contact with physicians; 134.8 ± 37.7 vs. 89.8 ± 55.2, t=6.45, p<0.0001 through contact with other health care providers) and received more units of treatment (mean 74.9 vs. 39.9, t=4.21, p<0.001 from physicians, and 57.3 vs. 28.2, t=4.08, p<0.001 from other health care professionals). Length of treatment had an independent effect on the length of remission of positive symptoms (t=2.62, p=0.009), while number of units of treatment by any health care provider had an effect on length of remission of negative symptoms (t=-2.70, p=0.008) as well as total symptoms (t=-2.40, p=0.02). Post-hoc analysis showed that patients randomized to primary care, based on their better clinical profile at randomization, maintained their better outcome, especially as to remission of negative symptoms, at the end of the study. These data suggest that extending early intervention service for three additional years has a positive impact on length of remission of positive and negative symptoms compared to regular care. This may have policy implications for extending early intervention services beyond the current two years.

Recovery in schizophrenia: related factors in a group of patients followed up for 5 years in a private practice

ABSTRACTOBJECTIVE: The aim of this study was to determine recovery rates and related factors in schizophrenia outpatients treated by the same physician in a private practice.METHODS: Seventy patients with schizophrenia and schizoaffective disorder who followed up for 5 years were examined retrospectively. Psychopathological status was evaluated by means of standardized symptomatic remission criteria, and the Clinical Global Impression-Severity. Functionality of the patients was evaluated using the Global Assessment of Functioning. Recovery required remission of positive and negative symptoms and adequate social/vocational functioning for at least 24 months.RESULTS: In a 5-year period, 35.7% of the patients achieved recovery criteria. There were no demographic and clinical differences between patients with schizophrenia and schizoaffective disorder. Recovery was predicted by the onset of illness (OR 1.14, 95% CI 1.01–1.30, p = .044) and type of illness – schizoaffective disorder (OR 6.84, 95% CI 1.54–30.34...

Adolescent vs. adult onset of a first episode psychosis: Impact on remission of positive and negative symptoms

ObjectiveAdolescent-onset psychosis has traditionally been characterized as a more severe form of psychosis with a poorer prognosis. However, it is still unclear if patients with an adolescent-onset have worse symptom remission outcomes. Symptom remission is the principal clinical outcome known to predict quality of life and social functioning in the long term. The goal of this study is to clarify the influence of age of onset of psychosis on symptom remission in a sample of first-episode psychosis patients. MethodA total of 246 first-episode psychosis patients were recruited from a specialized early intervention program serving a defined epidemiological catchment area. Age of onset of psychosis (adolescence vs. adulthood) was used as the main predictor, and duration of untreated psychosis (DUP), baseline symptoms, baseline functioning, substance abuse diagnosis, medication adherence and gender were used as covariates in hierarchical regression models predicting the following positive and negative symptom remission outcomes: maximum continuous months in remission and early remission (i.e., occurring in the first three months of follow-up). ResultsAfter controlling for other variables, onset of psychosis in adulthood and shorter DUP predicted early remission of positive symptoms. This effect was stronger in patients with a diagnosis of a schizophrenia-spectrum disorder. Remission of negative symptoms did not depend on age of onset, and was only predicted by baseline negative symptoms. ConclusionPatients with onset of psychosis during adulthood are more likely to achieve early positive symptom remission than those with adolescent onset. This effect might be stronger in patients with a diagnosis of a schizophrenia-spectrum disorder.