Is There a Potential of Misuse for Quetiapine?: Literature Review and Analysis of the European Medicines Agency/European Medicines Agency Adverse Drug Reactions' Database
PURPOSE/BACKGROUND: A recent years' increase in both prescribing and availability of second-generation antipsychotics (SGAs) has been observed. According to the literature, typically made up by case studies/series, quetiapine seems to be the most commonly misused SGA, with both intranasal and intravenous intake modalities having been described. Another SGA that has been anecdotally reported to be misused is olanzapine. For these molecules, both a previous history of drug misuse and being an inmate have been described as factors associated with misuse. Hence, while providing here an updated literature review of the topic, we aimed at assessing all cases of quetiapine misuse/abuse/dependence/withdrawal as reported to the European Medicines Agency's EudraVigilance (EV) database; this was carried out in comparison with the reference drug olanzapine. METHODS: All spontaneous, European Medicines Agency database reports relating to both quetiapine (2005-2016) and olanzapine (2004-2016) misuse/abuse/dependence/withdrawal issues were retrieved, and a descriptive analysis was performed. RESULTS: From the EV database, 18,112 (8.64% of 209,571) and 4178 (7.58% of 55,100) adverse drug reaction reports of misuse/abuse/dependence/withdrawal were associated with quetiapine and olanzapine, respectively. The resulting proportional reporting ratio values suggested that the misuse/abuse-, dependence-, and withdrawal-related adverse drug reactions were more frequently reported for quetiapine (1.07, 1.01, and 5.25, respectively) in comparison with olanzapine. CONCLUSIONS: Despite data collection limitations, present EV data may suggest that, at least in comparison with olanzapine, quetiapine misuse may be a cause for concern.
Is There a Potential of Misuse for Quetiapine?
Quetiapine Fumarate Market 2022: Market Size, Top Countries Data - WICZ
Impact of FDA Black Box Advisory on Antipsychotic Medication Use
Background In April 2005, the US Food and Drug Administration (FDA) issued an advisory and subsequent black box warning regarding the risks of atypical anti-psychotic use among elderly patients with dementia. The impact of these warnings on atypical drug use is unknown. Methods We used quasi-experimental, interrupted time-series analyses to examine nationally representative data from IMS Health’s National Disease and Therapeutic Index from January 2003 through December 2008. The primary measurement from this audit of office-based physicians was the use of an atypical antipsychotic agent. We quantified the impact of the advisory on atypical anti-psychotic use among all individuals and those 65 years or older with dementia. Results From January 2003 to March 2005, mentions of total atypical antipsychotic drugs increased at an annual rate of 34%, and among patients with dementia, 16%. In the year prior to the FDA advisory, there were approximately 13.6 million atypical drug mentions, including 0.8 million among those with dementia. In the year following the advisory, atypical drug mentions fell 2% overall and 19% among those with dementia. In 2004, 19% (0.8 of 4.1 million) of drug mentions for dementia were for an atypical agent. By 2008, this proportion decreased to 9% (0.4 of 4.3 million). Atypical drug use slowed for both FDA-approved and off-label indications and declined through 2008 for all populations examined. Conclusion The FDA advisory was associated with decreases in the use of atypical antipsychotics, especially among elderly patients with dementia.
How common is off-label prescription of quetiapine? - PubMed
Evaluation of the use of low-dose quetiapine and the risk of metabolic consequences: A retrospective review
Introduction: Quetiapine fumarate is an atypical antipsychotic approved for the treatment of schizophrenia, major depressive disorder, and bipolar disorder. Due to the sedative effects observed at low doses, prescribers use quetiapine to aid patients with sleep disturbances. Current evidence has established that quetiapine can cause negative changes in metabolic parameters, but it is unknown if these consequences also occur at low doses. Due to the use of quetiapine for sleep, the purpose of this study is to identify if metabolic effects are also a risk with the use of low-dose quetiapine. Methods: Eligible subjects were identified through the Veterans Affairs electronic medical records as having an active prescription for quetiapine from June 30, 2012, through September 1, 2013. Subjects were then evaluated using inclusion and exclusion criteria for determination of study entrance. Descriptive statistics and t tests were utilized to identify clinical and statistical differences in outcomes. Results: A total of 403 subjects were included in the final analysis. The average dose of quetiapine was 116.8 mg and average duration of therapy was 44 months. Increases were observed in systolic blood pressure (+1.95 mmHg; P = .036), diastolic blood pressure (+1.97 mmHg; P = .001), body mass index (+0.52; P = .001), weight (+1.88 kg; P = .002), and fasting blood glucose (+6.71 mg/dL; P = .002). Conversely, a decrease in total cholesterol (−10.06 mg/dL; P < .001) was recognized. Discussion: As a result of the findings, there may be negative metabolic consequences with the use of low-dose quetiapine. Routine prescribing of low doses for sleep as a first-line medication should be avoided.
Evaluation of the use of low-dose quetiapine and the risk of metabolic consequences
Concerns about quetiapine - Australian Prescriber
Quetiapine for primary insomnia: Consider the risks | Cleveland Clinic Journal of Medicine
Quetiapine for primary insomnia: Consider the risks
The second-generation antipsychotic drug quetiapine (Seroquel) is increasingly being used off-label for treating insomnia in the general population, possibly to avoid standard medications with known addictive qualities and adverse side effects. However, evidence to support using it in this way is scant, and quetiapine is associated with weight gain and other metabolic effects. It must be used cautiously and with appropriate monitoring for adverse effects and abuse.
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Publisher: Cleveland Clinic Journal of Medicine Section: Review PMID: 33941603
Efficacy of quetiapine for delirium prevention in hospitalized older medical patients: a randomized double-blind controlled trial
BACKGROUND: Delirium is a common disorder among hospitalized older patients and results in increased morbidity and mortality. The prevention of delirium is still challenging in older patient care. The role of antipsychotics in delirium prevention has been limited. Therefore, we conducted a trial to investigate the efficacy of quetiapine use to prevent delirium in hospitalized older medical patients. METHODS: This study was a randomized double-blind controlled trial conducted at Ramathibodi Hospital, Bangkok, Thailand. Patients aged ≥65 years hospitalized in the internal medicine service were randomized to quetiapine 12.5 mg or placebo once daily at bedtime for a maximum 7-day duration. The primary end point was delirium incidence. Secondary end points were delirium duration, length of hospital stay, ICU admission, rehospitalization and mortality within 30 and 90 days. RESULTS: A total of 122 patients were enrolled in the study. Eight (6.6%) left the trial before receiving the first dose of the intervention, whereas 114 (93.4%) were included in an intention-to-treat analysis allocated to the quetiapine or placebo group (n = 57 each). The delirium incidence rates in the quetiapine and placebo groups were 14.0 and 8.8% (OR = 1.698, 95% CI 0.520-5.545, P = 0.381), respectively. Other endpoints in the quetiapine and placebo groups were the median length of hospital stay, 6 (4-8) days versus 5 (4-8) days (P = 0.133), respectively; delirium duration, 4 (2.3-6.5) versus 3 (1.5-4.0) days (P = 0.557), respectively; ICU admission, 3 (5.3%) patients from both groups (P = 1.000); and mortality in the quetiapine and placebo groups, 1 (1.8%) versus 2 (3.5%) at 30 days (P = 0.566) and 7 (12.3%) versus 9 (15.8%) days at 90 days (P = 0.591). There were no significant differences in other outcomes. None of the participants reported adverse events. CONCLUSIONS: Quetiapine prophylaxis did not reduce delirium incidence in hospitalized older medical patients. The use of quetiapine to prevent delirium in this population group should not be recommended. TRIAL REGISTRATION: This trial was retrospectively registered with the Thai clinical trials registry (TCTR) at clinicaltrials.in.th (TCTR20190927001) on September 26, 2019.
Efficacy of quetiapine for delirium prevention in hospitalized older medical patients
Quetiapine withdrawal: A systematic review
OBJECTIVE: Withdrawal from psychoactive medication such as quetiapine is a well-documented phenomenon. Despite the extensive use of quetiapine, there have been few studies into the presence of discontinuation symptoms. We therefore performed a systematic review of published literature for evidence of quetiapine withdrawal or symptoms associated with discontinuation. METHODS: We searched PubMed, Embase, CINAHL, Medline, Web of Science, PsycINFO for articles containing the terms 'Quetiapine' AND 'withdraw$' OR 'discontinue$'. We included all study types that reported on somatic withdrawal symptoms and had no language restrictions. We excluded studies where there was withdrawal from multiple medications or any other psychoactive substance, or where the only symptoms were psychological such as rebound psychosis or craving. RESULTS: We included 13 papers, all of which were individual case reports. The quality of the individual case reports was sub-optimal, as assessed by the CARE Case Report Guidelines. There was an association between rapid cessation of quetiapine and onset of somatic symptoms such as nausea, vomiting, agitation, restlessness, diaphoresis, irritability, anxiety, dysphoria, sleep disturbance, insomnia, tachycardia, hypertension and dizziness. Three studies also reported the onset of a withdrawal dyskinesia characterised by abnormal choreiform movements as well as confusion and speech disturbance in some cases. However, these findings were limited by the number and quality of case reports identified. CONCLUSION: Discontinuation symptoms are an uncommon side effect of quetiapine cessation, which may have clinical implications. Clinicians should therefore be alert to the possibility of quetiapine withdrawal in individuals who present with somatic symptoms or choreiform movements. However, large prospective studies are required to clarify this association.
The Australian and New Zealand Journal of Psychiatry
Antipsychotics: History, Science, and Issues
Quetiapine Misuse and Abuse: Is it an Atypical Paradigm of Drug Seeking Behavior? - PMC
WMA - The World Medical Association-Declaración de Helsinki de la AMM – Principios éticos para las investigaciones médicas en seres humanos
Antipsychotic prescription patterns in patients affiliated to the Social Security Health System in Colombia
Introduction: Schizophrenia alters individual perception, thought, affection and behavior. Drug therapy can improve these manifestations.Objective: To determine prescription patterns of antipsychotic drugs in a group of patients affiliated to the Social Security Health System in Colombia.Materials and methods: This was a descriptive study with a 6.2 million people database. We selected 3,075 patients medicated with antipsychotics, of both sexes, and all ages, with continuous treatment from March to June, 2012, and residing in 57 Colombian cities. We designed a database on drug consumption, obtained by the company that distributes the drugs to the patients.Results: A total of 3,075 patients were studied, with an age mean of 55.8 ± 21.5 years; 50.3% of the participants were women. Of all patients, 81.9% were receiving monotherapy and 18.1% two or more antipsychotics. Prescription order was 77.1% atypical and 31.9% conventional. The most frequently used drugs were: quetiapine (on 30.3% of the patients), clozapine (23.7%), levomepropamize (18.4%),and risperidone (14.9%). The most common combinations were: haloperidol + levomepromazine (n=67,12.1%), clozapine + pipotiazine (n=54, 9.7%), clozapine + risperidone (n=45, 8.1%), and quetiapine +levomepromazine (n=40, 7.2%). The most prescribed co-medications were: antidepressants (n=998,32.5%), anxiolytic (n=799, 26.0%), statins (n=672, 21.9%); antiparkinsonians (n=341, 11.1%), and antidiabetic drugs (n=327, 10.6%).Conclusions: The practice of prescribing drugs with a high therapeutic value predominates mainly inantipsychotic monotherapy. Most agents were used in higher doses than recommended. This raises the need to design educational strategies to address these prescribing habits and research for evaluating the effectiveness of the treatment. doi: http://dx.doi.org/10.7705/biomedica.v33i3.1529
Meerbeke - Investigación con población vulnerable.pdf
ICMJE | Recommendations | Defining the Role of Authors and Contributors
Abuse and misuse of second-generation antipsychotics: An analysis using VigiBase, the World Health Organisation pharmacovigilance database
The study aim was to assess the abuse/misuse potential of second-generation antipsychotics (SGAPs) using VigiBase data. We extracted individual case safety reports of “Drug abuse, dependence and withdrawal” involving SGAPs up to June 2018. We assessed disproportionate reporting by calculating the information component, considering the lower end of the 95% credibility interval for the information component (IC025), and the proportional reporting ratio. We identified 1683 individual case safety reports recorded as “abuse, dependence and withdrawal” involving SGAPs, mainly quetiapine (n = 1089) and olanzapine (n = 209). The disproportional reporting indicators highlighted an association between “Drug abuse and dependence”, and quetiapine, olanzapine and ziprasidone, as indicated by the IC025 (2.263, 0.259 and 1.051, respectively) and proportional reporting ratio values (3.929, 1.020 and 1.334, respectively). The abuse/misuse potential is confirmed for quetiapine and olanzapine and highlighted for the first time for ziprasidone. Physicians should consider these risks when prescribing these antipsychotics, especially to patients with history of drug abuse.
Abuse and misuse of second-generation antipsychotics
_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/bcp.15420
British Journal of Clinical Pharmacology
INCREASING OFF-LABEL USE OF ANTIPSYCHOTIC MEDICATIONS IN THE UNITED STATES, 1995-2008
Objective To evaluate patterns of antipsychotic use. Design, setting, and measurements We used nationally representative data from the IMS Health National Disease and Therapeutic Index to describe outpatient antipsychotic use. The primary outcome was the volume of visits where antipsychotics were used for specific indications (treatment visits). We also quantified use without U.S. Food and Drug Administration approval (off-label use) and off-label use with compendium data suggesting an uncertain evidence base. Results Antipsychotic use increased from 6.2 million (M) treatment visits (95% CI, 5.4-7.0) in 1995 to 16.7M visits (15.5-18.2) in 2006, then declined to 14.3M visits (13.0-15.6) by 2008. A shift occurred from typical agents in 1995 (84% of all antipsychotic visits) to atypical agents by 2008 (93%). As they declined, typical medications shifted towards use in schizophrenia (30% in 1995 to 48% 2008). In contrast, use of atypical agents expanded for bipolar affective disorder (10% to 34%), remained stable for depression (12% to 14%), and declined for schizophrenia (56% to 23%). Overall, antipsychotic use for indications without FDA approval increased from 4.4M visits in 1995 to 9.0M in 2008. The estimated cost associated with off-label use in 2008 was US$6.0 billion. Conclusions Atypical use has grown far beyond substitution for the now infrequently used typical agents. Antipsychotics are increasingly used for conditions where FDA approval and associated clinical evidence is less certain. Despite the value of innovation, the benefits of widening atypical antipsychotic use should be weighed against their cost, regulatory status, and incomplete nature of available evidence.
Metabolic Consequences of Using Low-Dose Quetiapine for Insomnia in Psychiatric Patients
Quetiapine is frequently prescribed for insomnia that is comorbid with psychiatric disorders, but there has been no documentation of metabolic adverse effects associated with this practice. The objective of this study was to document changes in weight, body mass index, and waist circumference that occurred when low-dose quetiapine was used at bedtime for insomnia. The study was a retrospective chart review conducted at a community mental health center. Patients were non-elderly (19–65 years old) psychiatric patients who received quetiapine at ≤200 mg at bedtime for the explicit indication of insomnia. Forty-three patients were included in the study. Weight and BMI increased by an average of 4.9 lb. (P = 0.037) and 0.8 points (P = 0.048), respectively. Males experienced statistically significant increases in weight and BMI, and Caucasians experienced a statistically significant increase in BMI. There were no significant differences between baseline and endpoint metabolic parameters when examined by baseline BMI, age category, psychiatric diagnosis, or concomitant psychotropic medication. Despite the low doses typically used when quetiapine is prescribed for insomnia, metabolic adverse effects can occur and should be considered in the overall benefit to risk analysis.
Inappropriate long-term use of antipsychotic drugs is common among people with dementia living in specialized care units
Background Antipsychotic drugs are widely used for the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD), despite their limited efficacy and concerns about safety. The aim of this study was to describe antipsychotic drug therapy among people with dementia living in specialized care units in northern Sweden. Methods This study was conducted in 40 specialized care units in northern Sweden, with a total study population of 344 people with dementia. The study population was described in regard to antipsychotic drug use, ADL function, cognitive function and BPSD, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). These data were collected at baseline and six months later. Detailed data about antipsychotic prescribing were collected from prescription records. Results This study showed that 132 persons (38%) in the study population used antipsychotic drugs at the start of the study. Of these, 52/132 (39%) had prescriptions that followed national guidelines with regard to dose and substance., After six months, there were 111 of 132 persons left because of deaths and dropouts. Of these 111 people, 80 (72%) were still being treated with antipsychotics, 63/111 (57%) with the same dose. People who exhibited aggressive behavior (OR: 1.980, CI: 1.515-2.588), or passiveness (OR: 1.548, CI: 1.150-2.083), or had mild cognitive impairment (OR: 2.284 CI: 1.046-4.988), were at increased risk of being prescribed antipsychotics. Conclusion The prevalence of antipsychotic drug use among people with dementia living in specialized care units was high and inappropriate long-term use of antipsychotic drugs was common.
Behavioral and Psychological Symptoms of Dementia
Behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms, represent a heterogeneous group of non-cognitive symptoms and behaviors occurring in subjects with dementia. BPSD constitute a major component of the dementia syndrome irrespective of its subtype. They are as clinically relevant as cognitive symptoms as they strongly correlate with the degree of functional and cognitive impairment. BPSD include agitation, aberrant motor behavior, anxiety, elation, irritability, depression, apathy, disinhibition, delusions, hallucinations, and sleep or appetite changes. It is estimated that BPSD affect up to 90% of all dementia subjects over the course of their illness, and is independently associated with poor outcomes, including distress among patients and caregivers, long-term hospitalization, misuse of medication, and increased health care costs. Although these symptoms can be present individually it is more common that various psychopathological features co-occur simultaneously in the same patient. Thus, categorization of BPSD in clusters taking into account their natural course, prognosis, and treatment response may be useful in the clinical practice. The pathogenesis of BPSD has not been clearly delineated but it is probably the result of a complex interplay of psychological, social, and biological factors. Recent studies have emphasized the role of neurochemical, neuropathological, and genetic factors underlying the clinical manifestations of BPSD. A high degree of clinical expertise is crucial to appropriately recognize and manage the neuropsychiatric symptoms in a patient with dementia. Combination of non-pharmacological and careful use of pharmacological interventions is the recommended therapeutic for managing BPSD. Given the modest efficacy of current strategies, there is an urgent need to identify novel pharmacological targets and develop new non-pharmacological approaches to improve the adverse outcomes associated with BPSD.
Purpose. The diagnostic criteria and treatment of insomnia are reviewed.Summary. Insomnia is most often described as a subjective complaint of poor sleep quality or quantity despite adequate time for sleep, resulting in daytime fatigue, irritability, and decreased concentration. Insomnia is classified as idiopathic or comorbid. Comorbid insomnias are associated with psychiatric disorders, medical disorders, substance abuse, and specific sleep disorders. Idiopathic insomnia is essentially a diagnosis of exclusion. A wide array of terminology exists for defining the duration of insomnia symptoms, which may add to the confusion regarding insomnia classification. Acute insomnia refers to sleep problems lasting from one night to a few weeks, whereas chronic insomnia refers to sleep problems lasting at least three nights weekly for at least one month. Diagnostic tools for identifying insomnia are multifactorial. Nonpharmacologic interventions for insomnia include sleep-hygiene education, stimulus-control therapy, relaxation therapy, and sleep-restriction therapy. The most effective pharmacologic therapies for insomnia are benzodiazepines, benzodiazepine-receptor agonists, melatonin-receptor agonists, and antidepressants. Choice of a specific agent should be based on patient-specific factors, including age, proposed length of treatment, primary sleep complaint, history of drug or alcohol abuse, and cost.Conclusion. Many treatment options are available for patients with insomnia. Behavioral therapies should be initiated as first-line treatment in most patients. For patients who require the addition of pharmacologic therapy, the drugs with the most evidence for benefit include benzodiazepines, benzodiazepine-receptor agonists, melatonin-receptor agonists, and antidepressants. Selection of a specific agent must take into account numerous patient-specific factors.
American Journal of Health-System Pharmacy
United States Department of Veterans Affairs
United States Food and Drug Administration
After the black box warning: predictors of psychotropic treatment choices for older patients with dementia
OBJECTIVES: This study aimed to evaluate factors associated with the selection of pharmacological treatments often given as first-line treatments to elderly patients with neuropsychiatric symptoms associated with dementia. It also evaluated patterns of medication usage over time in the year preceding and three years after the U.S. Food and Drug Administration issued a black box warning for antipsychotic usage. METHODS: A retrospective cohort consisted of 19,517 Veterans Affairs patients with diagnosed dementia and a new outpatient start with an antipsychotic agent (haloperidol, olanzapine, quetiapine, or risperidone) or valproic acid and its derivatives between May 1, 2004, and September 30, 2008. Patient and facility characteristics were examined for their association with the new starts of these medications. RESULTS: Trends in the rate of fills for psychotropic medications varied, with yearly increases in the use of quetiapine, haloperidol, and valproic acid and decreasing use of olanzapine and risperidone. Predictors of haloperidol use included a new start in nonpsychiatric settings, prior benzodiazepine use, and any prior-year hospitalization. Anxiety disorder and major depression were predictive of not receiving haloperidol. Parkinson's disease was predictive of quetiapine use, whereas bipolar disorder was predictive of valproic acid use. Older age was predictive of use of antipsychotics rather than valproic acid. Urban facilities were less likely to use olanzapine, and significant regional variations were seen. CONCLUSIONS: Important patient and facility characteristics were associated with initiating different psychotropic agents among elderly dementia patients. In addition, the rate of use and the factors predictive of use varied across the study years.
International trends in antipsychotic use: A study in 16 countries, 2005–2014
The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0–19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20–64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring.
International trends in antipsychotic use
Effects of quetiapine on sleep: A systematic review and meta-analysis of clinical trials
Quetiapine is a common off-label antipsychotic drug for treating insomnia. Its effects in different disease conditions and dosages remain unclear. We conducted a systematic review and meta-analysis in clinical trials examining the efficacy of low-dose quetiapine in sleep. We obtained 21 clinical trials. Mean difference (MD), standard mean difference (SMD), and odds ratio (OR) were used to estimate the effect sizes using a random-effects model. The pooled results showed that quetiapine improved sleep quality compared with placebo (SMD: -0.57 [95%CI: -0.75, -0.4]). The SMD of sleep quality was correlated with age (coefficient: -0.0174) and sex (coefficient: -0.012). The significant effects were observed in the general anxiety disorder (SMD: -0.59 [95%CI: -0.92, -0.27]), major depressive disorder (SMD: -0.47 [95%CI: -0.66, -0.28]), and healthy (SMD: -1.33, [95%CI [-2.12, -0.54]) subgroups, at the dosage of 50 mg (SMD: -0.36 [95%CI: -0.36, -0.11]), 150 mg (SMD: -0.4 [95%CI: -0.52, -0.29]), and 300 mg (SMD: -0.17 [95%CI: -0.31,-0.04]). Quetiapine increased total sleep time compared with placebo (MD: 47.91 [95%CI: 28.06, 67.76]) but not when compared with other psychiatric drugs (MD: -4.19 [95%CI: -19.43, 11.05]). Adverse events (AEs) and discontinuation due to AEs were common among the quetiapine users. Quetiapine is effective as a sleep-helping drug. Precaution is suggested when interpreting the results on the elderly due to the high heterogeneity caused by incorporating patients over 66 years in the meta-analyses. We recommend an initial dosage of 50-150 mg/day with priority consideration for the elderly with GAD or MDD while monitoring its potential AEs.