Marie-France Demers

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

ABSTRACT 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.

Longitudinal comparative study of risperidone and conventional neuroleptics for treating patients with schizophrenia. The Quebec Schizophrenia Study Group.

This study compared the long-term (12 months) effectiveness of risperidone (RP) with that of conventional neuroleptics (CNs) in a population with chronic schizophrenia who had shown suboptimal response to CNs. A randomized, open, parallel, multicenter design was used. One hundred eighty-four subjects meeting DSM-IV criteria for schizophrenia were randomly assigned to receive either RP or a CN, and 165 of them completed the follow-up. Outcome measures were taken at 3, 6, and 12 months and included the Positive and Negative Syndrome Scale (PANSS) and the Extrapyramidal Symptom Rating Scale. Within this 12-month follow-up, RP was found to be superior to CNs in terms of both the average change in score from baseline on the PANSS (p = 0.006) and the proportion of good responders (as defined by a 20% decrease in total PANSS scores;p = 0.03). For positive symptoms, the effectiveness of the RP treatment tended to increase over time. At 12 months, the percentage of good responders in the RP group was twice as large as that in the CN group (30% vs. 15%;p = 0.03). The superiority of RP over CNs was constant over the three dose categories. In both the RP and the CN groups, the maximum decrease in psychopathology was achieved with the lowest dose range. A worsening of akathisia was less frequent in subjects receiving RP than in those receiving CNs (p = 0.02). In conclusion, this study showed that, compared with CNs, RP is beneficial in the treatment of patients with chronic schizophrenia and that some of these benefits may appear only after longer-term treatment.

Endogenous cannabinoids in patients with schizophrenia and substance use disorder during quetiapine therapy

Disturbances in the endogenous cannabinoid (ECB) system in schizophrenia may contribute to their enhanced sensitivity to psychoactive substances, and the beneficial effects of second-generation antipsychotics for substance abuse in schizophrenia may involve modulatory effects on ECB. To verify these two assumptions, 29 patients (24 completers) with schizophrenia and substance use disorders (SUD) were treated with quetiapine for 12 weeks, and peripheral ECB levels were measured, using high-performance liquid chromatography/mass spectrometry, in patients (weeks 0, 6 and 12) and 17 healthy volunteers. Baseline anandamide levels were significantly higher in patients, relative to controls. This result is consistent with studies describing ECB dysfunctions in schizophrenia. SUD parameters improved during treatment, but no changes in ECB occurred over time. Improvements in substance abuse were probably not mediated by modulatory effects of quetiapine on ECB. Lastly, baseline anandamide predicted endpoint SUD scores (alcohol/ cannabis). Anandamide is a potential target for medications aimed at relieving SUD in schizophrenia.

Comparative effectiveness and safety of antipsychotic drugs in schizophrenia treatment: a real-world observational study

The objective was to compare, in a real‐world setting, the risk of mental and physical health events associated with different antipsychotic drugs (clozapine, olanzapine, risperidone, quetiapine and first‐generation antipsychotics) in patients with SZ.

Anhedonia and social adaptation predict substance abuse evolution in dual diagnosis schizophrenia.

The current study sought to identify the variables, derived from the self-medication hypothesis, which predicted substance abuse evolution during a homogeneous 3-month antipsychotic treatment. Twenty-four patients were diagnosed with schizophrenia and substance abuse (mainly cannabis and alcohol). Substance abuse, psychiatric symptoms, anhedonia, and social adjustment were assessed at baseline and study endpoint. Linear regression analyses were performed. Better social adaptation and worse anhedonia predicted substance abuse improvements. Conversely, greater psychoactive substance (PAS) use predicted endpoint positive and depressive symptoms. These results suggest that: (i) substance abuse interferes with psychiatric prognosis in schizophrenia; and (ii) dual diagnosis treatments leading patients to engage in alternative social activities may render substance abuse less appealing. Further studies are warranted to dissociate the causes and consequences of substance abuse in schizophrenia.