Selective serotonin reuptake inhibitor (SSRI) add-on therapy for the negative symptoms of schizophrenia: a meta-analysis.

BACKGROUND: Negative symptoms are among the most chronic symptoms of schizophrenia. Even with the advent of atypical antipsychotic drugs, negative symptoms remain mostly refractory to treatment. It has been proposed that selective serotonin reuptake inhibitor (SSRI) augmentation therapy in schizophrenia could provide a greater relief of these symptoms. Published studies, however promising, have produced conflicting results. OBJECTIVE: To overcome this discrepancy in results, we performed a meta-analysis of studies assessing SSRI add-on therapy for the negative symptoms of schizophrenia. DATA SOURCES AND STUDY SELECTION: A search was performed using the computerized search engines PsycINFO, PubMed (MEDLINE), and Current Contents. Keywords used were schizophrenia and (for SSRI) sertraline, citalopram, paroxetine, fluoxetine, and fluvoxamine. Hand search of published review articles as well as cross-referencing were carried out, too. Pharmaceutical companies were also contacted. Studies were retained if (1) SSRI add-on therapy was compared with antipsychotic monotherapy among schizophrenia-spectrum disorder patients; (2) the clinical trial was randomized, double-blind, placebo-controlled with parallel-arm design; (3) negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms or the Positive and Negative Syndrome Scale-negative subscale. DATA EXTRACTION: With a consensus, authors (A.A.S. and S.P.) extracted and checked the data independently on the basis of predetermined exclusion and inclusion criteria. Effect size estimates were calculated using Comprehensive Meta-Analysis software. DATA SYNTHESIS: Eleven studies responded to our inclusion criteria. Within a random-effects model, a nonsignificant composite effect size estimate for (end point) negative symptoms was obtained (N = 393; adjusted Hedges' g = 0.178; p = .191). However, when studies were divided according to severity of illness, a moderate and significant effect size emerged for the studies involving so-called "chronic patients" (N = 274; adjusted Hedges' g = 0.386; p = .014). CONCLUSION: The current meta-analysis provides no global support for an improvement in negative symptoms with SSRI augmentation therapy in schizophrenia.

Quetiapine augmentation of treatment-resistant depression: a comparison with lithium.

OBJECTIVE: The prevalence of and morbidity associated with treatment-resistant depression has motivated the exploration of treatment alternatives. In this study, quetiapine was compared with lithium in the augmentation of treatment-resistant depression. RESEARCH DESIGN AND METHODS: Open-label, comparative study in 20 patients with major depression who had failed to respond after 4 weeks of treatment with an antidepressant at the maximal recommended dose. Patients were randomised to either lithium or quetiapine in addition to the maximally dosed antidepressant and any other concurrent medications. Lithium was initiated at 600 mg/day; quetiapine was titrated to 400 mg by day 7. RESULTS: Depression, measured by the Hamilton Depression Rating Scale (HAM-D), significantly improved from baseline in both quetiapine (F(1,90) = 25.11, p < 0.0001) and lithium (F(1,90) = 34.54, p < 0.0001). The difference in improvement between the two groups began at day 14 and was seen at all timepoints thereafter (p < 0.05), with the quetiapine group showing greater improvement than the lithium group. In the Montgomery-Asberg Depression Rating Scale (MADRS) analysis, the difference between the quetiapine and lithium group was significant from day 28 onwards (p < 0.05), with subjects improving more in the quetiapine group than the lithium group. The treatment by week interaction showed a significant difference overall between the two groups (p < 0.0001). The severity of psychomotor retardation showed a significant decrease in the Widlocher Psychomotor Retardation Scale scores in the quetiapine (p < 0.0001) and lithium (p < 0.0001) groups. CONCLUSIONS: In this pilot study, quetiapine was an effective augmenting agent in treatment-resistant depression.

Quetiapine in patients with comorbid schizophrenia-spectrum and substance use disorders: an open-label trial.

BACKGROUND: Preliminary evidence suggests that clozapine relieves the craving for psychoactive substances in schizophrenia patients. Quetiapine shares crucial pharmacological properties with clozapine. Promising results have been described with quetiapine therapy in patients with psychosis and substance use disorder. METHODS: Based on Diagnostic and Statistical Manual of Mental Disorders - fourth edition (DSM-IV) criteria, patients were diagnosed with comorbid schizophrenia-spectrum and substance use disorders. Patients were switched to quetiapine for a 12-week open-label trial. Craving, quantities used, days of consumption, and severity of substance abuse were assessed every 3 weeks. Alcohol and Drug Use Scales were administered on baseline and end-point. Psychiatric symptoms, depressive symptoms, extrapyramidal symptoms, and cognition were also assessed at baseline, week 6 and week 12. RESULTS: Twenty-four schizophrenia-spectrum patients were included in the last observation carried forward (LOCF) analyses, responding to one or more of the following substance use disorders: cannabis (15 patients), alcohol (10 patients), and other psychoactive substances (nine patients). Overall, severity of substance abuse improved during the study. Less weekly days were spent on drugs of abuse. A decrease in the weekly Canadian dollars spent on psychoactive substances was also observed. Cognition, psychiatric, depressive, and extrapyramidal symptoms also significantly improved (p < 0.05). CONCLUSIONS: In this open-label, uncontrolled trial, significant improvements were noted in substance abuse, psychiatric symptoms, extrapyramidal symptoms, and cognition during quetiapine therapy. The study suffered from three main limitations: (1) the open-label design of the study; (2) the patients' poor compliance; and (3) the small sample size involved. Controlled studies on the use of quetiapine in dual diagnosis schizophrenia are warranted to confirm that the effects are drug-related.

Impact of a unilateral brain lesion on cortisol secretion and emotional state: anterior/posterior dissociation in humans.

The main goal of this study was to evaluate whether a unilateral brain lesion in a human population is associated with a modification of the circadian cortisol secretion profile, and/or patient's emotional state. The second goal of this study was to assess whether there would be differences in both the pattern of cortisol secretion and emotional state in brain-damaged patients as a function of side of lesion, and localization (anterior vs posterior) of lesion. Eight patients with a left cortical lesion, six patients with a right cortical lesion, four patients with basal ganglia lesions (2 left and 2 right) and ten healthy volunteers were evaluated daily on measures of salivary cortisol levels and subjective feelings of joy and sadness at 0700, 1200, 1600 and 1900 hours over a 15-day period. Patients with cortical brain lesions presented higher cortisol levels and higher scores of sadness at the time of the morning peak (7:00 am), when compared to healthy volunteers and patients with basal ganglia lesions. Laterality of the lesion was not related to cortisol secretion, but frontal damage (anterior lesion) was associated with higher cortisol levels at the time of the morning peak (7:00 am) when compared to more posterior damage. There was no significant correlation between basal circulating levels of cortisol and emotional states in patients and healthy subjects. The results of this study suggest that hypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with unilateral injury particularly in frontal areas. These results, obtained in a human population, go along with recent animal studies reporting an implication of frontal regions in HPA activity.

Strategies of collaboration between general practitioners and psychiatrists: a survey of practitioners' opinions and characteristics.

BACKGROUND: The description of collaboration models and the key underlying principles provide important information for designing services. However, to apply this broad corpus of information to clinical services and policymaking, we need to know which key principles (or strategies) of collaboration are the most accepted by local physicians. METHOD: In this context, we designed a survey that included 2 objectives: 1) to collect the opinions of practising general practitioners (GPs) and psychiatrists in Montreal with respect to strategies for improving collaboration between these 2 groups and 2) to identify demographic and practice characteristics of those physicians associated with the acceptance of such strategies. We designed a questionnaire to specifically elicit physicians' opinions about strategies involving communication, continuing medical education (CME) for GPs in psychiatry, and access to consulting psychiatrists, as well as to identify the profiles of the respondent physicians. We mailed the questionnaire to 203 GPs and 203 psychiatrists who were randomly selected. RESULTS: The response rate was 86% for GPs and 87% for psychiatrists. Physicians expressed favourable opinions about most strategies involving 1) the improvement of communication and 2) the organization of CME activities concerning GP practices in the field of psychiatry. On the other hand, they did not indicate acceptance of the strategies involving on-site collaboration between GPs and psychiatrists. Physician age, sex, place of practice, type of practice (such as seeing patients with or without appointments), and responsibility for administrative duties associated significantly with the degree of acceptance of the proposed strategies. CONCLUSION: Communication and CME strategies for GPs in psychiatry can be an option to improve collaboration between GPs and psychiatrists. However, strategies of access to consulting psychiatrists require significant alterations to established clinical routines and professional roles.