Quetiapine in patients with comorbid schizophrenia-spectrum and substance use disorders: an open-label trial (original) (raw)
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Frontiers in Psychiatry, 2011
Neurological and psychiatric symptoms are consequences of substance abuse in schizophrenia and non-schizophrenia patients. The present case-control study examined changes in substance abuse/dependence, and neurological and psychiatric symptoms in substance abusers with [dual diagnosis (DD) group, n = 26] and without schizophrenia [substance use disorder (SUD) group, n = 24] and in non-abusing schizophrenia patients (SCZ group, n = 23) undergoing 12-week treatment with the atypical antipsychotic, quetiapine. Neurological and psychiatric symptoms were evaluated with the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, the Extrapyramidal Symptoms Rating Scale, and the Barnes Akathisia Rating Scale. At endpoint, DD and SCZ patients were receiving significantly higher doses of quetiapine (mean = 554 and 478 mg/day, respectively), relative to SUD patients (mean = 150 mg/day). We found that SUD patients showed greater improvement in weekly dollars spent on alcohol and drugs and SUD severity, compared to DD patients. At endpoint, there was no significant difference in dollars spent, but DD patients still had a higher mean SUD severity. Interestingly, DD patients had significantly higher parkinsonism and depression than SCZ patients at baseline and endpoint. On the other hand, we found that SUD patients had significantly more akathisia at baseline, improved more than SCZ patients, and this was related to cannabis abuse/dependence. Finally, SUD patients improved more in Positive and Negative Syndrome Scale positive scores than DD and SCZ patients. Taken together, our results provide evidence for increased vulnerability to the adverse effects of alcohol and drugs in schizophrenia patients. They also suggest that substance abuse/withdrawal may mimic some symptoms of schizophrenia. Future studies will need to determine the role quetiapine played in these improvements.
Journal of Psychopharmacology, 2012
Substance abuse and psychotic disorders have a high rate of comorbidity. Both disorders are associated with changes in the dopaminergic transmission in the mesocorticolimbic pathways of the brain. Since antipsychotic medications interact with the dopamine receptors in these pathways, these medications could affect craving for substances. In the current study, the effect of clozapine (n ¼ 27, mean dosage 350 mg), risperidone (n ¼ 54, mean dosage 3.46 mg) and olanzapine (n ¼ 60, mean dosage 13.78 mg) on subjective craving for cannabis was compared in 123 patients with cannabis dependence and psychotic disorder. Patients treated with risperidone reported significantly more craving compared with patients treated with clozapine (Z ¼ À3.19, p ¼ .001) or olanzapine (Z ¼ À2.24, p ¼ .025). No significant differences in craving between clozapine and olanzapine were found. These results are in concordance with findings in the literature on this subject and could be explained by differences in three dopamine mediated mechanisms of these compounds: 1) occupancy rate of dopamine D 2 receptors, 2) dissociation rate of dopamine D 2 receptors, 3) D 1 /D 2 occupancy ratio. Risperidone and clozapine show a maximal difference in D 2 receptor occupancy rate, dissociation rate and D 1 /D 2 ratio. Olanzapine is intermediate between risperidone and clozapine in these characteristics.
Quetiapine: efficacy and tolerability in schizophrenia
European Neuropsychopharmacology, 2001
Quetiapine, in common with clozapine, has a greater affinity for 5-HT receptors than D receptors and preclinical studies have 2 2 consistently predicted efficacy against schizophrenia, with a low potential for causing extrapyramidal symptoms (EPS). In clinical trials, the efficacy of quetiapine was consistently superior to placebo and it was effective against both positive and negative symptoms.
Quetiapine in the treatment of schizophrenia and related disorders
Neuropsychiatric Disease and Treatment, 2007
Quetiapine was developed in 1985 by scientists at AstraZeneca (formerly Zeneca) Pharmaceuticals. It received offi cial US Food and Drug Administration approval in September 1997 and approval in Germany in 2000. Since then, quetiapine has been used in the treatment of severe mental illness in approximately 70 countries including Canada, most Western European countries, and Japan. Quetiapine is a dibenzothiazepine derivative with a relatively broad receptor binding profi le. It has major affi nity to cerebral serotonergic (5HT 2A ), histaminergic (H1), and dopaminergic D 1 and D 2 receptors, moderate affi nity to α 1 -und α 2 -adrenergic receptors, and minor affi nity to muscarinergic M1 receptors; it demonstrates a substantial selectivity for the limbic system. This receptor occupancy profi le with relatively higher affi nity for the 5HT 2A receptor compared with the D 2 receptor is in part responsible for the antipsychotic characteristics and low incidence of extrapyramidal side-effects of quetiapine. The effi cacy of quetiapine in reducing positive and negative symptoms of schizophrenia has been proven in several clinical trials with placebo-controlled comparators. Quetiapine has also demonstrated robust effi cacy for treatment of cognitive, anxious-depressive, and aggressive symptoms in schizophrenia. Long-term trials show sustained tolerability for a broad spectrum of symptoms. Quetiapine has also proven effi cacy and tolerability in the treatment of moderate to severe manic episodes, and in the treatment of juveniles with oppositional-defi ant or conduct disorders, and in the geriatric dementia population. Recent data indicate that quetiapine may also be effective in the treatment of bipolar depressive symptoms without increasing the risk of triggering manic episodes, and in borderline personality disorder. In comparison with other antipsychotics, quetiapine has a favorable side-effect profi le. In clinical trials only small insignifi cant prolongations of the QT interval were observed. Weight-gain liabilities and new-onset metabolic side-effects occupy a middle-ground among newer antipsychotics. As a result of its good effi cacy and tolerability profi le quetiapine has become well established in the treatment of schizophrenia and manic episodes.
International Clinical Psychopharmacology, 2003
Although life prevalence of substance use disorders among patients with schizophrenia is close to 50%, few studies have been carried out to date to identify an integrated pharmacological treatment for this comorbidity. So far, the most promising results, that we report here, have been obtained with clozapine. To a lesser extent, quetiapine and olanzapine, both clozapine analogues, have also shown promising results. Further to these observations, the present paper critically reviews the advantages associated with clozapine, quetiapine and olanzapine, and their relevance to the treatment of addiction among schizophrenic patients. Six characteristics seem to distinguish clozapine, quetiapine and olanzapine from the firstgeneration antipsychotics: (1) acting preferentially on the reward system, these second-generation antipsychotics (mainly clozapine and quetiapine) induce almost no extrapyramidal symptoms; (2) quickly dissociating from D 2 , theses drugs (mainly clozapine and quetiapine) seem not to induce dysphoria, unlike conventional antipsychotics like haloperidol;(3) these drugs (mainly clozapine) seem more effective in the treatment of negative symptoms than conventional antipsychotics; (4) because of a diversified activity on several serotoninergic and noradrenergic receptors, these drugs positively alter mood, which does not seem to be the case with conventional antipsychotics, except for flupenthixol; (5) these drugs have a positive impact on cognition, which is not the case with the firstgeneration antipsychotics; (6) unlike conventional antipsychotics, these drugs seem to have a moderate affinity for 5-HT 3 , the receptor on which ondansetron, an anti-craving medication, acts. Int Clin Psychopharmacol 18:121-132
Quetiapine for the Treatment of Cocaine Dependence
Journal of Clinical Psychopharmacology, 2008
The monaminergic properties of second generation antipsychotics are prompting research on their use to treat cocaine dependence, with inconclusive results to date. In preliminary reports, the atypical antipsychotic quetiapine has shown promise for the treatment of substance abuse disorders. The primary objective of the current study was to assess the efficacy of quetiapine in reducing cocaine cravings and use in nonpsychotic subjects with cocaine dependence over 6 weeks of open-label treatment. Twenty-two cocaine-dependent, nonpsychotic men were initiated to open-label treatment with quetiapine (300-600 mg/d). The primary outcome measure was weekly self-report of cocaine cravings as assessed with the Brief Substance Craving Scale. Cocaine use was captured with a self-report Timeline Follow-back calendar, administered every 2 weeks. Side effect monitoring was conducted weekly, and movement disorders were assessed every 2 weeks. Intent-to-treat regression analyses (n = 22) indicated that the Brief Substance Craving Scale total score decreased significantly overtime (P < 0.001). Self-reports also suggested decreased cocaine use. There was no treatment-related increase in movement disorders, and most side effects were mild. However, all subjects did experience sedation, and several subjects dropped out because of it. What is more, weight increased significantly over time (P < 0.001). Open-label quetiapine treatment reduced cravings and improved some aspects of cocaine dependence in nonpsychotic individuals. Additional research is needed to confirm the current findings and to further delineate the role quetiapine may play in the treatment of cocaine use disorders.
Schizophrenia Research, 2008
Objective: This double-blind study compared a second generation (atypical) antipsychotic drugs compared to a representative older agent for patients with schizophrenia who use or avoid illicit substances. Methods: Schizophrenic subjects were recruited at 57 U.S. sites and randomly assigned to olanzapine, perphenazine, quetiapine, risperidone or ziprasidone for up to 18 months. The primary aim of this analysis was to delineate differences between the overall effectiveness of these five treatments among patients who used or did not use illicit substances. Results: There were no significant differences between treatment groups in time to all-cause treatment discontinuation among patients who use illicit drugs (median 3.3 to 6.8 months). Among non-users time to treatment discontinuation was significantly longer for patients treated with olanzapine (median 13.0 months) than perphenazine ( 5.9 months), risperidone (5.6 months), or quetiapine (5.0 months); time to discontinuation for ziprasidone (4.3 months) was even shorter, although the latter difference was not significant. The difference between risperidone and quetiapine, although small, was significant. All remaining differences were non-significant. Similar results were found for discontinuation due to inefficacy. There were no differences between illicit users and non-users in symptom reduction and global improvement, after adjustment for differential duration of treatment. Differences in discontinuation results were attenuated by non-compliance, but the trends persisted after controlling for treatment compliance. Conclusions: Among patients with chronic schizophrenia who avoid use of illicit drugs, olanzapine was more effective than other antipsychotics as reflected by longer time to all-cause discontinuation, but illicit substance abuse attenuated this advantage, reinforcing the need for concurrent substance abuse treatment.
A Case Series of Quetiapine Addiction / Dependence
2013
Quetiapine is a second-generation antipsychotic, which is commonly used in clinical practice for treatment of schizophrenia, acute mania and depressive episodes as well as maintenance therapy in bipolar disorders. It is also used for other psychotic disorders and popularly for non-psychotic symptoms such as anxiety and insomnia. Quetiapine is not a controlled substance and not considered to be an addictive substance. However, contrary to this there have been few case reports world wide of its abuse. Here we are reporting a case-series of quetiapine addiction noted among patients attending the outpatient department of a tertiary care psychiatry hospital (German J Psychiatry 2013; 16(4): 152-155).
Pharmacotherapy of Co-Occurring Schizophrenia and Substance Use Disorders
Current Addiction Reports, 2014
Substance use disorders, common in patients with schizophrenia, can lead to poor outcomes. Here we review the literature on the use of antipsychotics in patients with cooccurring schizophrenia and substance use disorder as well as evidence for the use of adjunctive pharmacological treatments targeting substance use in these patients. We also discuss a neurobiological formulation suggesting that the cooccurrence of these disorders may be related to a dysfunction in the dopamine mediated brain reward circuitry. Typical antipsychotics do not appear to decrease substance use in this population. Randomized, controlled trials provide some support for use of the atypical antipsychotic clozapine for cooccurring cannabis use disorder, naltrexone and disulfiram for alcohol use disorder, and also nicotine replacement therapy, sustained-release bupropion and varenicline for tobacco use disorder. Nonetheless, data regarding treatment in patients with these co-occurring disorders are still limited, and many studies reported to date have been either underpowered or did not include a control condition. Further research is needed to evaluate optimal pharmacotherapeutic strategies for this population.
Quetiapine at high doses for the treatment of refractory schizophrenia
Schizophrenia Research, 2008
Selecting the appropriate dose of antipsychotic medication is essential for successful long-term treatment in people with schizophrenia. However, there is much debate in the literature about the correct dosing of antipsychotics. This is especially true for quetiapine, a second-generation antipsychotic which experts have advocated using doses above the maximum recommended by the FDA of 800 mg/day.(Kane et al., 2003) In this letter we report on a 12-week open label trial of high dose quetiapine for subjects with documented treatment refractory schizophrenia. All subjects were titrated to the target dose of 1,200 ± 200 mg/day over a three-week period. Subjects were evaluated weekly with the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Scale (CGI). Response was defined as ≥ 20% decrease in total BPRS score from baseline. Other weekly measurements included vital signs, the Simpson Angus Scale (SAS), Barnes Akathisia Scale (BAS), and the Assessment of Involuntary Movements Scale (AIMS). Laboratory assessments and electrocardiogram monitoring were done at baseline and end of study. Statistical analysis was conducted using the Cochran-Mantel-Haenszel method for monotonic correlations between scores and time, using a summary χ 2 statistic for evidence of time by visit correlations, stratifying the analysis with subject.(Arndt et al., 1993) Within-subject Spearman correlation coefficients between symptom scores and time were calculated, and the mean of these correlations calculated. Dichotomous variables were evaluated with Fisher's exact test. All analysis was done using SAS® 9.1 (SAS Institute Inc., Cary, NC) using two-tailed tests at α = 0.05. Twelve subjects were recruited into this study. Eight were enrolled after not responding to treatment in a pervious double-blind placebo controlled study(Conley et al., 2005); the remaining 4 meet the same inclusion criteria for this open label study as those in the doubleblind study. Mean age for subjects was 50.3 ± 8.3 years old. One subject was female and 66% were African American. Previous antipsychotic therapy for subjects included: 4(33%) risperidone, 3(25%) fluphenazine, 2(17%) quetiapine, 1(8.3%) olanzapine, 1(8.3%) ziprasidone, and 1(8.3%) risperidone with fluphenazine. Subject's baseline symptom characteristics are listed in Table 1.