Benzodiazepine Medication Research Articles

Primary care hypnotic and anxiolytic prescription: Reviewing prescribing practice over 8 years.

Introduction:Over the last few years, hypnotic and anxiolytic medications have had their clinical efficacy questioned in the context of concerns regarding dependence, tolerance alongside other adverse effects. It remains unclear how these concerns have impacted clinical prescribing practice.Materials and Methods:This is a study reviewing community-dispensed prescribing data for patients on the East Practice Medical Center list in Arbroath, Scotland, in 2007, 2011 and 2015. Anxiolytic and hypnotic medications were defined in accordance with the British National Formulary chapter 4.1.1 and chapter 4.1.2. All patients receiving a drug within this class in any of the study years were collated and anonymized using primary care prescribing data. The patients’ age, gender, name of the prescribed drug(s), and total number of prescriptions in this class over the year were extracted.Results:The proportion of patients prescribed a benzodiazepine medication decreased between 2007 and 2015: 83.8% (n = 109) in 2007, 70.5% (n = 122) in 2011, and 51.7% (n = 138) in 2015 (P = 0.006). The proportion of these patients prescribed a nonbenzodiazepine drug increased between 2007 and 2015: 30% (n = 39) in 2007, 46.2% (n = 80) in 2011, and 52.4% (n = 140) in 2015 (P = 0.001). There was a significant increase in the number of patients prescribed melatonin (P = 0.020).Discussion:This study reports a reduction in benzodiazepine prescriptions in primary care alongside increases in nonbenzodiazepine and melatonin prescribing, with an increase in prescribing rates of this drug class overall.Conclusion:Changes in this prescribing practice may reflect the medicalization of insomnia, local changes in prescribing practice and alongside national recommendations.

Risk factors associated with benzodiazepine use among people who inject drugs in an urban Canadian setting

BackgroundThough known to have abuse potential, benzodiazepine medications remain widely prescribed. Furthermore, issues related to benzodiazepine use by people who inject drugs (PWID) remain to be fully characterized. We therefore sought to examine the prevalence of and risk factors associated with benzodiazepine use in a street-involved urban population. MethodsBetween May 1996 and November 2013, data were derived from two open prospective cohort studies in Vancouver, Canada, restricted to PWID. Multivariable logistic regression with generalized estimating equations (GEE) was used to determine factors independently associated with benzodiazepine use. ResultsOver the study period, 2806 individuals were recruited, including 949 (34%) women. Of these, 1080 (38.5%) participants reported benzodiazepine use at least once during the study period. In the multivariable analysis, Caucasian ethnicity, ≥ daily heroin injection, ≥ daily cocaine injection, non-fatal overdose, incarceration, syringe sharing, and unsafe sex were all independently associated with benzodiazepine use. Conversely, older age, homelessness, and ≥ daily crack smoking were negatively associated with benzodiazepine use. ConclusionsUse of benzodiazepines was common in this urban setting and was associated with several markers of addiction severity and significant health and social vulnerabilities including syringe sharing and unsafe sex. These findings underscore the need to promote treatment for benzodiazepine use, safer benzodiazepine prescribing, including greater recognition of the limited indications for evidence-based use of this medication class.

Sharp-wave EEG abnormalities and neural complexity in depressive patients: preliminary report

According to recent findings cognitive and emotional dysregulation in depression and psychiatric disorders may be related to deficits in inhibitory functions and temporo-limbic seizure-like activity due to specific changes in neural dynamics and complexity of neural networks. In order to evaluate the clinical utility of nonlinear analysis of EEG complexity (measured by Lyapunov exponents) and to assess underlying epileptiform changes, we studied a sample of 19 depressive patients including nine depressive patients with episodic sharp-wave EEG abnormalities and ten depressive patients without any abnormalities, and compared also subgroups of these patients who used benzodiazepine medication to assess its influence on EEG complexity. The results show that the depressive patients with episodic sharp-wave EEG abnormalities had significantly lower EEG complexity than the control groups of patients. The data also indicate that benzodiazepines significantly influence neural complexity and increase it in the subgroup of patients with sharp wave abnormalities, and on the other hand decrease the level of complexity in the control subgroup of depressive patients. In agreement with other findings results of this study suggest that sharp waves or other underlying epileptiform EEG abnormalities related to abnormal neural excitability and disturbances in brain inhibitory systems may be reflected in specific changes of EEG complexity. These specific changes in EEG complexity may be related to treatment resistance to usual medications in several depressive patients and might represent clinical indicators for anticonvulsant treatment.

Benzodiazepine use as an independent risk factor for HIV infection in a Canadian setting

BackgroundAlthough the harms of prescription drug diversion are of growing international concern, the potential impact of prescription drug use on HIV infection has not been well assessed. We evaluated whether benzodiazepine use was associated with HIV seroconversion among a cohort of persons who inject drugs (PWID) in a Canadian setting. MethodsBetween May, 1996 and November, 2013, data were derived through a prospective cohort study of PWID in Vancouver, Canada. A total of 1682 baseline HIV negative participants were followed for a median of 79.5 months (interquartile range: 32.1–119.1), among whom 501 (29.8%) reported benzodiazepine use at baseline, and 176 seroconverted during follow-up, equal to an incidence density of 1.5 (95% Confidence Interval [CI]: 1.3–1.7) cases per 100 person-years. Poisson regression with time-dependent variables was used to assess whether benzodiazepine use was associated with the time to HIV seroconversion. ResultsAfter adjustment for potential confounders, benzodiazepine use (Adjusted Rate Ratio: 1.50; 95% CI: 1.01–2.24) was independently associated with a higher rate of HIV seroconversion. ConclusionsBenzodiazepine use was an independent risk factor for HIV seroconversion among PWID in this setting. Greater recognition of the safety concerns related to benzodiazepine medications including diversion are needed.

Delirium transitions in the medical ICU: exploring the role of sleep quality and other factors.

Disrupted sleep is a common and potentially modifiable risk factor for delirium in the ICU. As part of a quality improvement project to promote sleep in the ICU, we examined the association of perceived sleep quality ratings and other patient and ICU risk factors with daily transition to delirium. Secondary analysis of prospective observational study. Medical ICU over a 201-day period. Two hundred twenty-three patients with greater than or equal to one night in the medical ICU in between two consecutive days of delirium assessment. None. Daily perceived sleep quality ratings were measured using the Richards-Campbell Sleep Questionnaire. Delirium was measured twice daily using the Confusion Assessment Method for the ICU. Other covariates evaluated included age, sex, race, ICU admission diagnosis, nighttime mechanical ventilation status, prior day's delirium status, and daily sedation using benzodiazepines and opioids, via both bolus and continuous infusion. Perceived sleep quality was similar in patients who were ever versus never delirious in the ICU (median [interquartile range] ratings, 58 [35-76] vs 57 [33-78], respectively; p = 0.71), and perceived sleep quality was unrelated to delirium transition (adjusted odds ratio, 1.00; 95% CI, 0.99-1.00). In mechanically ventilated patients, receipt of a continuous benzodiazepine and/or opioid infusion was associated with delirium transition (adjusted odds ratio, 4.02; 95% CI, 2.19-7.38; p < 0.001), and patients reporting use of pharmacological sleep aids at home were less likely to transition to delirium (adjusted odds ratio, 0.40; 95% CI, 0.20-0.80; p = 0.01). We found no association between daily perceived sleep quality ratings and transition to delirium. Infusion of benzodiazepine and/or opioid medications was strongly associated with transition to delirium in the ICU in mechanically ventilated patients and is an important, modifiable risk factor for delirium in critically ill patients.

Differences in prescribing patterns for anxiety and depression between General Internal Medicine and Family Medicine

IntroductionDepression and anxiety are routinely managed by physicians in Family Medicine (FM) or General Internal Medicine (GIM). Because FM requires more behavioral health training than GIM, we sought to determine if prescribing patterns for patients with anxiety, depression, or both differed between FM vs. GIM providers. MethodsIn a cross-sectional design, patient data and provider type were obtained from 2008 to 2013 electronic medical record patient data registry (n=27,225 (FM=10,994, GIM=16,231)) Prescription orders were modeled for specific benzodiazepines and antidepressants and by drug class. Covariates included gender, age, race, marital status and comorbidity index. Separate logistic regression models were computed, before and after adjusting for covariates, to estimate the odds of FM vs. GIM providers prescribing benzodiazepine or antidepressant medication to patients with anxiety, depression, and both disorders. ResultsAfter adjusting for covariates, patients with anxiety alone, depression alone, and both had significantly greater odds of receiving an antidepressant (OR=2.08;95%CI:1.46–2.96, OR=2.13;95%CI:1.48–3.06, and OR=2.26;95%CI:1.09–4.66, respectively) if treated by FM vs. GIM. Benzodiazepine prescription did not differ by physician type. LimitationsIt is not known if results will generalize to other regions of the United States. ConclusionsPatients with anxiety, depression, and both seen by FM providers, as compared to GIM providers, are more likely to receive antidepressant medications. Further investigation into the determinants of these differences is warranted. Under-treatment in GIM may result in less advantageous outcomes.

Seizure threshold and the half-age method in bilateral electroconvulsive therapy in Japanese patients.

Seizure threshold (ST) in electroconvulsive therapy (ECT) has not been reported previously in Japanese patients. We investigated ST in bilateral ECT in Japanese patients using the dose-titration method. The associations between demographic and clinical characteristics and ST were analyzed to identify the predictors of ST. Finally, the validity of the half-age method for the stimulus dose was evaluated. Fifty-four Japanese patients with mood disorder, schizophrenia, and other psychotic disorders received an acute course of bilateral ECT using a brief-pulse device. ST was determined at the first session using a fixed titration schedule. ST was correlated with age, sex, body mass index, history of previous ECT, and psychotropic drugs on multiple regression analysis. Furthermore, the rate of accomplished seizures was calculated using the half-age method. Mean ST was 136 mC. ST was influenced by age, sex, history of previous ECT, and medication with benzodiazepines. The accomplished seizure rate using the half-age method was 72%, which was significantly lower in men and subjects on benzodiazepines. ST in Japanese patients was equal to or slightly higher than that previously reported in other ethnic groups, which might be attributable, at least in part, to high prevalence of and large-dose benzodiazepine prescription. Higher age, male gender, no history of ECT, and benzodiazepines were related to higher ST. The half-age method was especially useful in female patients and subjects without benzodiazepine medication.

P-12 * THE STUDY OF TREATMENT RESPONSE IN DEPRESSIVE PATIENTS WITH ALCOHOL USE DISORDERS BY USING HAM-D

Introduction. It is known that high rate of comorbidity exists between mood disorders and alcohol use disorders. In this study, we assessed the change of the HAM-D 17-items from baseline to study endpoint to evaluate treatment-resistant depression symptoms in those patients with alcohol use disorders. Method. Fifty-eight participants with depression were divided into 2 groups: non-alcohol use disorder (NAUD) group (n = 36) and alcohol use disorder (AUD) group (n = 22) according to AUDIT score (NAUD: below 12, AUD: over 12). The effect of medication on depressive symptoms was monitored at 2, 4, 8, 12 weeks using the HAM-D. Results. The baseline score of HAM-D sleep item was higher in AUD than in NAUD. AUD showed significantly less improvement in the HAM-D sleep items from baseline to endpoint compared to NAUD. Benzodiazepine medications (equivalent to greater than 10mg of diazepam) resulted in significant baseline to endpoint improvement in insomnia early item of HAM-D in NAUD. On the other hand, there was no significant improvement in HAM-D sleep items after treatment in AUD. Conclusion. These results suggest that alcohol use disorder may negatively affect depression treatment outcomes not only in the overall response rate but also in the efficacy of benzodiazepines for sleep disturbance.

Pregnant women with posttraumatic stress disorder and risk of preterm birth.

Posttraumatic stress disorder (PTSD) occurs in about 8% of pregnant women. Stressful conditions, including PTSD, are inconsistently linked to preterm birth. Psychotropic treatment has been frequently associated with preterm birth. Identifying whether the psychiatric illness or its treatment is independently associated with preterm birth may help clinicians and patients when making management decisions. To determine whether a likely diagnosis of PTSD or antidepressant and benzodiazepine treatment during pregnancy is associated with risk of preterm birth. We hypothesized that pregnant women who likely had PTSD and women receiving antidepressant or anxiolytic treatment would be more likely to experience preterm birth. Longitudinal, prospective cohort study of 2654 women who were recruited before 17 completed weeks of pregnancy from 137 obstetrical practices in Connecticut and Western Massachusetts. Posttraumatic stress disorder, major depressive episode, and use of antidepressant and benzodiazepine medications. Preterm birth, operationalized as delivery prior to 37 completed weeks of pregnancy. Likely psychiatric diagnoses were generated through administration of the Composite International Diagnostic Interview and the Modified PTSD Symptom Scale. Data on medication use were gathered at each participant interview. Recursive partitioning analysis showed elevated rates of preterm birth among women with PTSD. A further split of the PTSD node showed high rates for women who met criteria for a major depressive episode, which suggests an interaction between these 2 exposures. Logistic regression analysis confirmed risk for women who likely had both conditions (odds ratio [OR], 4.08 [95% CI, 1.27-13.15]). For each point increase on the Modified PTSD Symptom Scale (range, 0-110), the risk of preterm birth increased by 1% to 2%. The odds of preterm birth are high for women who used a serotonin reuptake inhibitor (OR, 1.55 [95% CI, 1.02-2.36]) and women who used a benzodiazepine medication (OR, 1.99 [95% CI, 0.98-4.03]). Women with likely diagnoses of both PTSD and a major depressive episode are at a 4-fold increased risk of preterm birth; this risk is greater than, and independent of, antidepressant and benzodiazepine use and is not simply a function of mood or anxiety symptoms.

Current Treatments for Anxiety and Obsessive-Compulsive Disorders

Anxiety disorders are prevalent and represent an important focus of treatment within the field of psychiatry as well as within medicine more broadly. First-line pharmacotherapy treatment for anxiety disorders is serotonin selective reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). For patients who do not responsd to an initial first-line treatment, clinicians should ensure that there has been adequate exposure to the medication by assessing compliance and optimizing the prescribed dose. Non-response to a treatment trial should also prompt a re-evaluation of the diagnosis and a search for occult psychiatric, substance, or general medical disorders. Laboratory tests and other components of a diagnostic work-up should be considered if they have not already been completed. Following confirmation of the diagnosis, the clinician should consider a switch to an agent from a different class, for example a tricyclic antidepressant or monoamine oxidase inhibitor. Combination treatments with an antidepressant plus a benzodiazepine, second-generation antipsychotic, anticonvulsant, β-blocker, or other medication may be considered but data is limited. Psychotherapy is an important treatment component for anxiety disorders and should be implemented whenever feasible. Variants of cognitive behavioral therapy (CBT) in particular are effective in reducing anxiety symptoms, and data suggest that the combination for CBT plus medication may be particularly beneficial for patients. Obsessive-compulsive disorder (OCD), while sharing many clinical features with anxiety disorders, represents its own unique clinical challenge and has been removed from the category of anxiety disorders in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). SSRIs are first-line therapy for OCD and higher doses are often required compared with anxiety disorders or major depressive disorder. Exposure and response prevention may be a particularly helpful form of psychotherapy for this patient population. For severe, intractable OCD, deep brain stimulation may be an appropriate therapeutic option.

Datura stramonium intoxication in two children.

Datura stramonium is a toxic plant member of the Solanaceae family. Its consumption may result in severe anticholinergic toxicity. We report the intoxication of 5- and 4-year-old brothers with Datura stramonium, which presented in two different manners. The first child presented agitation, hallucination and mydriasis that improved rapidly with benzodiazepine medication. The second presented comatose, mydriasis and Babinski signs. Gastric lavage and activated charcoal administration were performed. The child was intubated and mechanically ventilated until consciousness improvement. Datura stramonium poisoning may be considered by physicians in case of acute onset of decreased consciousness or behaviour trouble associated with anticholinergic signs and symptoms.

Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial.

The American Board of Internal Medicine Foundation Choosing Wisely Campaign recommends against the use of benzodiazepine drugs for adults 65 years and older. The effect of direct patient education to catalyze collaborative care for reducing inappropriate prescriptions remains unknown. To compare the effect of a direct-to-consumer educational intervention against usual care on benzodiazepine therapy discontinuation in community-dwelling older adults. Cluster randomized trial (EMPOWER [Eliminating Medications Through Patient Ownership of End Results] study [2010-2012, 6-month follow-up]). Community pharmacies were randomly allocated to the intervention or control arm in nonstratified, blocked groups of 4. Participants (303 long-term users of benzodiazepine medication aged 65-95 years, recruited from 30 community pharmacies) were screened and enrolled prior to randomization: 15 pharmacies randomized to the educational intervention included 148 participants and 15 pharmacies randomized to the "wait list" control included 155 participants. Participants, physicians, pharmacists, and evaluators were blinded to outcome assessment. The active arm received a deprescribing patient empowerment intervention describing the risks of benzodiazepine use and a stepwise tapering protocol. The control arm received usual care. Benzodiazepine therapy discontinuation at 6 months after randomization, ascertained by pharmacy medication renewal profiles. A total of 261 participants (86%) completed the 6-month follow-up. Of the recipients in the intervention group, 62% initiated conversation about benzodiazepine therapy cessation with a physician and/or pharmacist. At 6 months, 27% of the intervention group had discontinued benzodiazepine use compared with 5% of the control group (risk difference, 23% [95% CI, 14%-32%]; intracluster correlation, 0.008; number needed to treat, 4). Dose reduction occurred in an additional 11% (95% CI, 6%-16%). In multivariate subanalyses, age greater than 80 years, sex, duration of use, indication for use, dose, previous attempt to taper, and concomitant polypharmacy (10 drugs or more per day) did not have a significant interaction effect with benzodiazepine therapy discontinuation. Direct-to-consumer education effectively elicits shared decision making around the overuse of medications that increase the risk of harm in older adults. clinicaltrials.gov Identifier: NCT01148186.

Predictors of serious fall injury in hospitalized patients.

The purpose of this study was to identify predictors of falls that result in serious injury in hospitalized patients. The study involved secondary data analysis of 1,438 patient falls in a community hospital system between 2008 and 2010. The analysis included demographics, severity of illness, diagnosis-related group (surgical vs. medical), event type (bathroom, bed, chair, transfer, ambulating), risk factors identified by the Hendrich II fall risk assessment prior to the fall (confusion, depression, altered elimination, dizziness, antiepileptic or benzodiazepine medications), and contributing factors identified through an online event reporting system post-fall (incontinence, confusion, history of falls, alteration in mobility, and medication-related). Logistic regression results indicated that the overall model was a good fit and two predictors, age greater than 64 and male gender, were statistically reliable in predicting which patient falls would result in serious injury.

Stress, Injury, and Healing

Introduction:Patient-centered medical care for chronic diseases increasingly requires physician support for self-management, such as blood glucose monitoring in diabetes. For patients with diseases caused or aggravated by excessive sympathetic nervous system activity, such as anxiety, hypertension, and benign arrhythmias, the current options are cognitive behavioral therapy, medication, or self-regulation. In this exploratory study, I employed personalized oneon-one patient education on the effects of stress on a medical diagnosis and an exercise designed to reduce sympathetic tone. Heart rate variability (HRV) was chosen as an outcome measure based on medical evidence1 that the lowest HRV tertile is associated with a 2.5 greater risk of early all-cause mortality and a six times greater risk of cardiac death.2 Self-measured results and trends were discussed during a routine office visit.Method:A series of 42 patients with whom I share a doctor-patient relationship gave informed consent to receive additional coaching in the physiology of their illness and were taught a deep inspiratory maneuver, visual imagery, and how to use a device that displays heart rate variability (EMwave PSR, manufactured by Quantum Intech Inc). Office sessions were displayed in a PC version of HeartMath software. The patients were pre-screened, and those with significant arrhythmias, pacemaker dependence, psychosis, active mania, and severe personality disorders were excluded. They were informed that the use of biofeedback in this setting is not medically validated for diagnosis nor approved for treatment. Patients were not charged for the use of the technology or my time. All patients were encouraged to continue current medications, diet, and exercise. All were asked to report any symptoms to my office and not to use the device for any acute condition. A detailed statistical analysis was not performed.Results:Of the 42 patients, 36 had an improvement in HRV amplitude and/or reduction in the very low frequency spectrum, consistent with decreased sympathetic autonomic activity. Most patients reported an increased “feeling of control”; three patients were nervous about the meaning of the waveforms and returned the device. Nine of 18 patients taking benzodiazepine medications were successfully weaned during the study period. There were no complications attributed to this intervention. Eleven of the patients have continued using this technique on their own.Conclusion:This exploratory study used HRV as a biofeedback tool for patients with autonomic sensitive disease states. It appears to be safe in the type of patients studied. This was not a controlled study and is no doubt heavily influenced by the fact that the author spent additional time and effort with this cohort. In addition, a strong patient-physician relationship is likely necessary due to the patient expectation that medical therapy requires “a pill.” This tool is not validated, but neither is the stethoscope, which has similar risks of use. The use of biofeedback tools including glucometers, blood pressure cuffs, accelerometers, oximetry, and now HRV may be key to empowering patients and motivating them for health behavior change.

Novel Developments in the Pharmacological Management of Insomnia

Advances in the basic science of sleep/wake neurophysiology are driving the exploration of new pharmacologic approaches with continued improvement in efficacy and safety.

The Multiple Anxieties of Getting Older: Tranquilizers and the Ambivalence of Effect

Most studies on benzodiazepines emphasize overconsumption and warn of addiction, especially by older adults. This article is about the avoidance of benzodiazepine medications by ‘aging’ women living in a Brazilian village. This case study helps to support our central concern: to call attention to the ambiguities that exist in discussing these medications, and to stress the importance of a multilayered understanding of effect. We argue that benzodiazepines, like other psychopharmaka, induce bodily sensations that, at least in part, correspond to and are shaped by the situated self-image of individuals in distress.

Benzodiazepine augmentation of antipsychotic drugs in schizophrenia: A meta-analysis and cochrane review of randomized controlled trials

Applying various psychopharmacological combination and augmentation strategies in schizophrenia is common clinical practice. This meta-analysis evaluated the efficacy of benzodiazepines added to antipsychotics. The Cochrane Schizophrenia Group trial register (until February 2011) and PubMed/Medline (until July 2012) were searched for randomized controlled trials (RCTs) with a minimum duration of one week that compared benzodiazepine augmentation of antipsychotics with a control group receiving antipsychotic monotherapy in schizophrenia and schizophrenia-like psychoses. Study selection and data extraction were conducted independently by at least two authors. The primary outcome was response to treatment. Secondary outcomes were positive and negative schizophrenic symptoms, anxiety symptoms, and dropouts due to any reason, inefficacy of treatment, and adverse events. Pooled risk ratios (RRs) with the 95% confidence intervals (CIs) were calculated using a random-effects model, with number-needed-to-treat/harm (NNT/H) calculations where appropriate. Overall, 16 relevant RCTs with 1045 participants were identified. Benzodiazepine augmentation was not associated with statistically significantly more responders (N=6; n=511; RR 0.97, 95% CI 0.77–1.22). Adjunctive benzodiazepines were well accepted and tolerated according to dropout-rates and adverse effects apart from dizziness (N=3; n=190; RR 2.58, 95% CI 1.08–6.15) and somnolence (N=2; n=118; RR 3.30, 95% CI 1.04–10.40). There is no evidence for antipsychotic efficacy of additional benzodiazepine medication in schizophrenia. Therefore, benzodiazepines should be considered primarily for desired ultra short-term sedation of acutely agitated patients but not for augmentation of antipsychotics in the medium- and long-term pharmacotherapy of schizophrenia and related disorders.

English

Results: Our clinical case focuses on a patient who was diagnosed with a mixed picture delirium after developing PUO. This case report notes that Mr A, a patient already prescribed donepezil hydrochloride, saw an improvement in his behavioral symptoms after an increase in his dose. This enabled the patient to avoid receiving neuroleptic or benzodiazepine medication, known to be particularly problematic in older patients.

Do drug treatment variables predict cognitive performance in multidrug-treated opioid-dependent patients? A regression analysis study

BackgroundCognitive deficits and multiple psychoactive drug regimens are both common in patients treated for opioid-dependence. Therefore, we examined whether the cognitive performance of patients in opioid-substitution treatment (OST) is associated with their drug treatment variables.MethodsOpioid-dependent patients (N = 104) who were treated either with buprenorphine or methadone (n = 52 in both groups) were given attention, working memory, verbal, and visual memory tests after they had been a minimum of six months in treatment. Group-wise results were analysed by analysis of variance. Predictors of cognitive performance were examined by hierarchical regression analysis.ResultsBuprenorphine-treated patients performed statistically significantly better in a simple reaction time test than methadone-treated ones. No other significant differences between groups in cognitive performance were found. In each OST drug group, approximately 10% of the attention performance could be predicted by drug treatment variables. Use of benzodiazepine medication predicted about 10% of performance variance in working memory. Treatment with more than one other psychoactive drug (than opioid or BZD) and frequent substance abuse during the past month predicted about 20% of verbal memory performance.ConclusionsAlthough this study does not prove a causal relationship between multiple prescription drug use and poor cognitive functioning, the results are relevant for psychosocial recovery, vocational rehabilitation, and psychological treatment of OST patients. Especially for patients with BZD treatment, other treatment options should be actively sought.

Poster #219 SEROTONIN 5-HT2A RECEPTORANTAGONISTSFORTREATMENTOF SCHIZOPHRENIA

Applying various psychopharmacological combination and augmentation strategies in schizophrenia is common clinical practice. This meta-analysis evaluated the efficacy of benzodiazepines added to antipsychotics. The Cochrane Schizophrenia Group trial register (until February 2011) and PubMed/Medline (until July 2012) were searched for randomized controlled trials (RCTs) with a minimum duration of one week that compared benzodiazepine augmentation of antipsychotics with a control group receiving antipsychotic monotherapy in schizophrenia and schizophrenia-like psychoses. Study selection and data extraction were conducted independently by at least two authors. The primary outcome was response to treatment. Secondary outcomes were positive and negative schizophrenic symptoms, anxiety symptoms, and dropouts due to any reason, inefficacy of treatment, and adverse events. Pooled risk ratios (RRs) with the 95% confidence intervals (CIs) were calculated using a random-effects model, with number-needed-to-treat/harm (NNT/H) calculations where appropriate. Overall, 16 relevant RCTs with 1045 participants were identified. Benzodiazepine augmentation was not associated with statistically significantly more responders (N=6; n=511; RR 0.97, 95% CI 0.77–1.22). Adjunctive benzodiazepines were well accepted and tolerated according to dropout-rates and adverse effects apart from dizziness (N=3; n=190; RR 2.58, 95% CI 1.08–6.15) and somnolence (N=2; n=118; RR 3.30, 95% CI 1.04–10.40). There is no evidence for antipsychotic efficacy of additional benzodiazepine medication in schizophrenia. Therefore, benzodiazepines should be considered primarily for desired ultra short-term sedation of acutely agitated patients but not for augmentation of antipsychotics in the medium- and long-term pharmacotherapy of schizophrenia and related disorders.