[Show abstract][Hide abstract] ABSTRACT: Objective. To measure the effect, over time, of a 2-year problem-based learning (PBL) sequence on the skills, knowledge, and abilities it was designed to develop and enhance.Design. At the start of each PBL semester, students were provided a "work sample" case with a main medical issue not previously covered in the curriculum. A standardized form containing 6 sections (hypotheses, learning issues to investigate, how hypotheses ruled in/out, primary-problem identification, plan, and goals of plan) was completed for each case. To rate student performance, investigators used a standardized form with 5-point Likert scale.Assessment. Sixty-seven students who completed 4 assessments were included in data analyses. Scores significantly improved for each semester compared with baseline. Minimal significant differences were observed among semesters 2, 3, and 4.Conclusion. The 2-year PBL sequence improved students' performance compared with baseline, but the performance ceiling observed in our study requires further investigation.
American journal of pharmaceutical education 11/2012; 76(9):179. DOI:10.5688/ajpe769179 · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The prevalence of transmitted drug resistance mutations (TDRMs) in HIV-infected treatment-naïve patients in the United States has been estimated to be 15-19%, but has not been previously assessed in our clinic.
Methods: The primary endpoint was the prevalence of TDRMs 2008-2011. Antiretroviral (ARV) drug susceptibility was retrospectively analyzed in treatment-naïve patients 2008-2011. Resistance was defined on the basis of the International AIDS Society 2011 definition and the 2009 CDC surveillance mutation list. Secondary endpoints included TDRM rates in recently diagnosed patients (HIV diagnosis in the last 12 months), predictors of persistence with care (12 months of follow-up data available) in patients who were initiated on ARVs 2008-2010, and virologic success (HIV-1 RNA <50 copies/mL after 12 months of therapy). Descriptive statistics, Pearson’s chi-square analysis, and logistic regression were used to analyze results.
Results: Among 189 treatment-naïve patients who entered care 2008-2011 (69% male, 87% African American, median CD4 count 299 cells/mm3), 19 (10%) had at least 1 TDRM. Year-to-year comparisons indicated a 0% TDRM rate in 2008, 12% in 2009, 8% in 2010, and 16% in 2011 (p=0.36). Among 137 recently diagnosed patients, TDRM rates were 0% in 2008, 13% in 2009, 10% in 2010, and 20% in 2011 (p=0.49). NNRTI resistance was most common (14/19; 74%), followed by NRTI (5/19; 26%); no PI TDRMs were noted. Of the 137 patients initiated on HAART; 103 (75%) demonstrated persistence in care and 81 (59%) achieved virologic success. Recent HIV diagnosis was the only factor significantly associated with persistence with care (OR 3.53; 95% CI 1.49 to 8.36; p=0.004) and with achieving virologic success (OR 3.78; 95% CI 1.68 to 8.53; p=0.001).
Conclusion: The prevalence of TDRMs in our clinic mirrors national surveillance data. Efforts must be focused on improving patient retention and virologic success rates in urban HIV clinical settings.
IDWeek 2012 Meeting of the Infectious Diseases Society of America; 10/2012
[Show abstract][Hide abstract] ABSTRACT: Mirtazapine is a commonly used antidepressant with a well-known ability to produce sedation. At the same time, its sleep-promoting effects in patients with major depressive disorder (MDD) are relatively unclear. The purpose of this article is to provide clinicians with a detailed review of mirtazapine's sleep effects in patients with MDD.
A literature search was conducted for studies involving mirtazapine in depressed patients that specifically assessed sleep.
Twenty-three studies met selection criteria and were included in this review. Of the 15 studies that included a general assessment of sleep, all noted improvement from baseline with mirtazapine. Twelve of the 23 trials were randomized, blinded, and controlled. Mirtazapine was superior to placebo but did not clearly differentiate itself from other antidepressants, with the exception of venlafaxine. Eight studies used detailed measures of sleep and consistently reported that mirtazapine produced significant improvement in sleep efficiency, total sleep time, and sleep quality. Few investigations combined detailed assessments of sleep along with a comparator antidepressant.
Mirtazapine is an antidepressant with sleep-promoting effects significantly greater than placebo, similar to tricyclic antidepressants, and somewhat similar to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. These effects must be balanced with mirtazapine's ability to cause sedation-related side effects.
Annals of Clinical Psychiatry 08/2012; 24(3):215-24. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Anticonvulsants are a class of medications that have received considerable interest as possible treatments in patients with behavioural disturbances in dementia. The role of these medications for such a use remains controversial. The current paper reviews the published evidence surrounding the safety and efficacy (i.e. as a behavioural and cognitive treatment) of newer anticonvulsants in patients with dementia. A MEDLINE, International Pharmaceutical Abstracts, PsycINFO and clinicaltrials.gov search through to December 2011 was conducted for anticonvulsants that have received regulatory approval since 1996. Studies reporting behavioural or cognitive outcomes in patients with dementia were included. Nine trials involving only four medications met selection criteria and were included: levetiracetam (n = 4), oxcarbazepine (n = 1), topiramate (n = 2) and zonisamide (n = 2). Levetiracetam may have a role in the treatment of behavioural symptoms in dementia but study limitations substantially hinder the strength of such a recommendation. Oxcarbazepine and topiramate, based on limited data, do not appear to be effective treatments of behavioural symptoms in dementia. A lack of trials do not allow for conclusions to be made regarding zonisamide. From a cognitive standpoint, levetiracetam was the anticonvulsant most examined in patients with dementia, it appears to have less deleterious effects than some anticonvulsants. Limited data are available on the safety of these medications in elderly patients; however, studies completed thus far have demonstrated some adverse events that are more common or problematic with the use of these drugs in this patient population (i.e. somnolence, dizziness, hyponatraemia, weight loss).
[Show abstract][Hide abstract] ABSTRACT: Valproic acid is widely used in the treatment of behavioral disturbances in patients with dementia; however, there is uncertainty about its dosing and studies have reported mixed findings. The current article examines published trials of valproic acid in the treatment of patients with dementia to identify whether an optimal dosing strategy exists. Secondarily, valproic acid dosing from published studies is compared with a real-world 5-year sample of valproic acid prescribing. Twenty studies met selection criteria and were included in the review. Based primarily on uncontrolled trials and the current retrospective study, valproic acid serum levels between 40 and 60 mcg/mL and relatively low doses (ie, 7-12 mg/kg per d) are associated with improvements in agitation in some patients with dementia. At the same time, similar valproic acid levels produced no significant behavioral improvements in most placebo-controlled studies and led to substantial side effects in some patients. Considerable trial design differences exist between controlled and uncontrolled trials. Overall, valproic acid appears to have limited efficacy as monotherapy in many patients with dementia. Its optimal role may be in combination with other psychotropics as a treatment of agitation associated with dementia.
Journal of Pharmacy Practice 11/2011; 25(2):142-50. DOI:10.1177/0897190011424802
[Show abstract][Hide abstract] ABSTRACT: This study describes the prevalence of antipsychotic polypharmacy in patients admitted to a geriatric psychiatry unit, compares polypharmacy by psychiatric diagnosis, explores predictors of polypharmacy, and examines changes in antipsychotic polypharmacy from baseline to discharge.
A retrospective examination was made of patients admitted to an inpatient geriatric psychiatry ward between 2006 and 2010. All patients with a diagnosis of schizophrenia, bipolar disorder, or dementia prescribed a regularly scheduled antipsychotic for at least 1 month prior to admission were included.
Of the 416 patients meeting selection criteria, nearly 13% were prescribed antipsychotic polypharmacy at the time of admission. Quetiapine was the antipsychotic most commonly involved in polypharmacy. By discharge, the rate of antipsychotic polypharmacy had decreased to 8% (X=4.74, df=1, p=0.03). Patients with a history of a severe mental illness were significantly more likely to have been prescribed antipsychotic polypharmacy compared with those with only a diagnosis of dementia (X=14.67, df=1, p=<0.001). Living situation and psychiatric diagnosis were significant predictors of antipsychotic polypharmacy.
Older adults admitted to a geriatric psychiatry ward on a scheduled antipsychotic were commonly prescribed more than one antipsychotic. This was most likely in patients living in a facility (e.g., assisted living, skilled nursing, long-term care) and in those patients with a severe mental illness. A better understanding of the efficacy and safety of antipsychotic polypharmacy in older adults, especially those with dementia, is necessary in order to use these medications rationally.
[Show abstract][Hide abstract] ABSTRACT: To describe a North Carolina Taking Antibiotic Resistance Seriously (NC Tars) project involving a student pharmacist coalition educating patients about appropriate use of antibiotics.
Charlotte, NC, metropolitan area in October 2008.
Student pharmacists from the Wingate University School of Pharmacy were educated on the importance of antibiotic safety and the threat of antibiotic resistance, and groups of students were assigned to local community pharmacies where they assessed patients' knowledge of antibiotic resistance.
Student pharmacists expanded their knowledge of antibiotic resistance and were provided an opportunity to participate in a service-learning project in their community.
Patient knowledge regarding proper antibiotic use and the threat of antibiotic resistance.
Patient knowledge was increased. Patients reported that the information provided by the student pharmacists was beneficial and would be useful in the future.
The NC Tars project is a unique, student-driven education program that has the potential to raise public awareness about the proper use of antibiotics and the threat of antibiotic resistance in the community setting. Through this experience, students were provided an opportunity to educate patients via a service-learning experience.
Journal of the American Pharmacists Association 07/2011; 51(4):539-43, 1 p following 543. DOI:10.1331/JAPhA.2011.09159
[Show abstract][Hide abstract] ABSTRACT: To implement an integrated module on death and dying into a 15-week bioethics course and determine whether it increased student pharmacists' empathy.
Students participated in a 5-week death and dying module that included presentation of the film Wit, an interactive lecture on hospice, and a lecture on the ethics of pain management.
Fifty-six students completed the 30-item Balanced Emotional Empathy Scale (BEES) before and after completing the module and wrote a reflective essay. Students demonstrated an appreciation of patient-specific values in their essay. Quantitative data collected via BEES scores demonstrated significant improvement in measured empathy.
A 5-week instructional model on death and dying significantly increased student empathy.
American journal of pharmaceutical education 05/2011; 75(4):71. DOI:10.5688/ajpe75471 · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: to examine the use of quetiapine for sleep in patients with dementia admitted to a geriatric psychiatry ward.
retrospective cross-sectional study (January 2007 to December 2009).
geriatric psychiatric unit located near a metropolitan city in North Carolina.
all patients admitted with a diagnosis of dementia who were also receiving quetiapine were eligible. One hundred one patients met the criteria and were included in the study.
descriptive statistics defining quetiapine prescribing. Based on a priori criteria, quetiapine was considered to be used for sleep if it were prescribed: 1) only at bedtime, as needed, for sleep, 2) once daily, only at bedtime, or 3) multiple times daily, but with at least 75% of the daily dose administered at bedtime.
forty-three of the 101 patients included in the study were prescribed quetiapine, probably for sleep. Quetiapine, when used as a sedative-hypnotic, was generally employed at doses between 50 mg and 100 mg nightly. Several published studies report beneficial sleep-promoting effects of quetiapine and other atypical antipsychotics for primary and secondary sleep complaints; however, most of these trials involve young and middle-aged adults, have diagnostic variability, and are limited methodologically.
quetiapine prescribed as a sedative-hypnotic in patients with dementia, while common, is understudied and not without risk.
The Consultant pharmacist: the journal of the American Society of Consultant Pharmacists 10/2010; 25(10):676-9. DOI:10.4140/TCP.n.2010.676
[Show abstract][Hide abstract] ABSTRACT: To review the efficacy and safety of psychostimulants for negative behavioral symptoms (ie, apathy, excessive daytime sedation) and cognition in patients with dementia.
Literature was accessed through PubMed and MEDLINE (1966-June 2010), using the terms stimulant, psychostimulant, methylphenidate, dexmethylphenidate, amphetamine, dextroamphetamine, lisdexamfetamine, atomoxetine, modafinil, armodafinil, dementia, Alzheimer disease, vascular dementia, Lewy body dementia, mixed dementia, frontotemporal dementia, therapy, treatment, and therapeutic. Additional references identified from the initial search were reviewed.
All relevant clinical trials published in English and involving primarily older adults with dementia were included. Case reports, review articles, and other preclinical literature were included as appropriate.
Psychostimulants have been employed as a treatment for cognitive and behavioral symptoms in dementia for decades, but the literature has lagged behind this practice. Eight reports on use of psychostimulants as a treatment of apathy in dementia were reviewed. Methylphenidate was the most frequently studied medication and improvements in apathy were consistently noted; however, the magnitude and duration of effect remain unclear. Six studies examining the cognitive effects of a variety of psychostimulants in patients with dementia were reviewed; psychostimulants had little to no effect on cognition. A lack of studies exists to draw conclusions about the use of psychostimulants for the treatment of excessive daytime sedation in dementia. The possibility of psychostimulants to increase blood pressure; elevate heart rate; and lead to irritability, agitation, and psychosis makes careful patient selection critical, especially in older adults with severe cardiovascular disease or other underlying cardiac abnormalities.
Based on limited studies, methylphenidate is a possible treatment for apathy in patients with dementia. Psychostimulants, as a group, do not appear to be broadly effective treatments for behavioral or cognitive symptoms of dementia. The potential utility of psychostimulants must be balanced with careful patient selection.
Annals of Pharmacotherapy 10/2010; 44(10):1624-32. DOI:10.1345/aph.1P341 · 2.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pharmacological treatment of older adults with major depressive disorder presents a variety of challenges, including a relative lack of high quality studies designed to measure the efficacy and safety of antidepressants specific to this patient population. Gaining a clear understanding of how to use antidepressants in elderly patients with depression, especially new and widely used agents, would provide valuable insight to clinicians. The purpose of the current article is to review the pharmacology, efficacy and safety of newer antidepressants (i.e. escitalopram, duloxetine and desvenlafaxine) in the treatment of late-life depression. To accomplish this goal, a MEDLINE and PubMed search (1966 - February 2010) was conducted for relevant articles. Animal and human studies have clearly demonstrated the effects of desvenlafaxine, duloxetine and escitalopram on monoamine reuptake transporters. The serotonergic and noradrenergic actions of desvenlafaxine and duloxetine may provide for a faster onset of antidepressant activity in the elderly, but more definitive data are needed and the clinical effects of the possible faster onset of action need to be elucidated. Duloxetine and escitalopram are extensively metabolized via cytochrome P450 (CYP) enzymes and the decreased hepatic metabolism present in many older adults should be taken into account when prescribing these medications. Duloxetine possesses the greatest likelihood of producing clinically relevant drug-drug interactions because of its inhibition of CYP2D6. All three agents must also be used cautiously in older adults with poor renal function. In terms of clinical efficacy, 14 prospective published trials involving escitalopram (n = 8) and duloxetine (n = 6) in the treatment of older adults with major depressive disorder were identified. No such studies involving desvenlafaxine were found. Of the five randomized, double-blind, controlled trials, 46% and 37% of antidepressant-treated patients were considered responders and remitters, respectively. In contrast to escitalopram, duloxetine-treated patients experienced improvements in depressive symptoms that more consistently differentiated themselves from the symptoms of placebo-treated patients. Escitalopram and duloxetine were generally well tolerated, but 5-20% and 10-27% of patients, respectively, dropped out because of medication-related adverse effects. Adverse effects experienced by older adults were generally similar to those experienced by younger adults, although indirect comparisons suggest that older adults are more likely to experience dry mouth and constipation with duloxetine and escitalopram, while orthostasis may be more common in older adults prescribed desvenlafaxine. Overall, duloxetine and escitalopram represent modestly effective treatments for late-life depression that are generally well tolerated but do produce a variety of adverse effects. Conclusions regarding desvenlafaxine cannot be made at this time because of a lack of geriatric-specific data.
[Show abstract][Hide abstract] ABSTRACT: To compare the effectiveness of an in-person versus telephone-based pharmacist-managed lipid clinic.
Retrospective examination of a pharmacist-managed lipid clinic conducted at a Veterans Affairs medical center between September 2005 and March 2008. The clinical pharmacist educated, monitored, recommended nonpharmacologic treatment, and prescribed lipid-lowering medications using an in-person or telephone-based clinic style. The primary outcomes were to compare the two clinic styles on the percent of patients who reached their low-density lipoprotein (LDL) cholesterol goal and the absolute percent of LDL cholesterol reduction.
157 patients with coronary artery disease or its risk equivalent were enrolled in the pharmacist-managed lipid clinic. Overall, patients experienced a mean 27% reduction in LDL cholesterol levels from baseline, and 76% reached their LDL cholesterol goal. No significant differences in the percent of patients reaching their LDL cholesterol goal or absolute percent reduction in LDL cholesterol levels were found between the in-person and phone-based clinics. A trend toward phone clinic patients achieving their goal LDL cholesterol levels more quickly was noted.
Both in-person and phone-based pharmacist-managed lipid clinics offer effective methods to improve the cholesterol levels of patients. Phone-based clinics may offer more advantages in efficiency for pharmacists and their patients and the potential to deliver care in a wider variety of pharmacy settings.
Journal of the American Pharmacists Association 05/2010; 50(3):375-8. DOI:10.1331/JAPhA.2010.09048
[Show abstract][Hide abstract] ABSTRACT: To review certolizumab pegol for the treatment of moderate-to-severe Crohn's disease (CD).
Clinical studies were identified through MEDLINE (1966-October 1, 2009), bibliographies of articles, International Pharmaceutical Abstracts, clinicaltrials.gov, fda.gov, and New Drug Approval documents (www.accessdata.fda.gov). Search terms were CDP 870, certolizumab pegol, Cimzia, Crohn's disease, and inflammatory bowel disease.
Human studies describing pharmacology, pharmacokinetics, efficacy, and safety of certolizumab pegol were identified. Phase 2 and Phase 3 randomized controlled trials and observational studies were reviewed, with emphasis given to Phase 2 and Phase 3 trials.
Certolizumab pegol is a tumor necrosis factor-alfa (TNF-alpha) antagonist, approved for the treatment of moderate-to-severe CD that is failing conventional therapy. It is an antigen-binding fragment (Fab') portion of an immunoglobulin G antibody attached to a polyethylene glycol moiety. In 2 Phase 3 randomized, placebo-controlled trials, certolizumab pegol was effective in inducing clinical response compared with placebo. Common adverse effects during clinical trials were upper respiratory tract infection, urinary tract infection, and arthralgia. Serious infection occurred in 3% of patients. The 4 published controlled trials for the use of certolizumab pegol in the treatment of CD share similar limitations with other studies of TNF-alpha antagonists including high placebo response, natural course of disease fluctuation, and the use of Crohn's Disease Activity Index to assess outcomes. However, certolizumab pegol is an effective agent for adults with moderate-to-severe CD with less than optimal response to conventional therapy. Long-term efficacy and safety data are unavailable. Certolizumab pegol and adalimumab, unlike infliximab, can be self-administered.
With similarity in cost and the lack of head-to-head comparisons, patient and physician preference may determine choice of TNF-alpha antagonist.
Annals of Pharmacotherapy 02/2010; 44(2):333-42. DOI:10.1345/aph.1M314 · 2.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adequate treatment of behavioral disturbances in Alzheimer's disease is both important and difficult. This report describes a case series that examined the effectiveness and safety of low-dose divalproex in the treatment of agitated patients with Alzheimer's disease who were admitted to an inpatient geriatric psychiatry unit over a 1-year period. All patients had agitation due to probable Alzheimer's disease or mixed dementia and were prescribed divalproex monotherapy at low and completely flexible doses. Patients and nursing staff were blind to study enrollment. Clinical global impression scale scores, divalproex serum levels, and a variety of medical chart data were collected. Twenty patients met selection criteria and were included in the study. Of those, 13 patients (65%) were considered responders, while 4 patients (20%) required augmentation with other psychotropic medications; divalproex was discontinued in 1 patient. Adverse events occurred in 25% of patients. This case series suggests that low-dose divalproex may offer behavioral improvement and a reduced risk of side effects for some patients with agitation in Alzheimer's disease.
[Show abstract][Hide abstract] ABSTRACT: To review pharmacologic, pharmacokinetic, efficacy, and safety data for fesoterodine and determine its role in the treatment of overactive bladder.
A MEDLINE search (1966-July 2009) was conducted using the key words fesoterodine, tolterodine, muscarinic receptor antagonist, anticholinergic, overactive bladder, urge incontinence, efficacy, safety, adverse effect, pharmacology, pharmacokinetic, and receptor binding.
All articles written in English that were identified from the data sources were evaluated, prioritizing randomized, controlled trials with human data. The references of published articles that we identified were examined for any additional studies appropriate for the review.
Fesoterodine, a competitive muscarinic receptor antagonist, is converted to its active metabolite, 5-hydroxymethyltolterodine, by nonspecific esterases, bypassing the cytochrome P450 system. Two randomized controlled Phase 3 trials examined the safety and efficacy of fesoterodine in the treatment of overactive bladder. Fesoterodine was found to produce significant improvements in the treatment of overactive bladder symptoms compared with placebo. Post hoc analysis of these trials demonstrated significant improvements in health-related quality of life in patients with overactive bladder. Only one study included tolterodine, and direct comparisons between fesoterodine and tolterodine were not conducted. The most common treatment-emergent adverse effects associated with fesoterodine included dry mouth, constipation, urinary tract infection, and headache.
Fesoterodine appears to be effective and generally safe for the treatment of overactive bladder. The efficacy and safety of fesoterodine in overactive bladder treatment seem to be at least similar to that of tolterodine. Although additional comparative trials are needed, based on available data, it does not appear that fesoterodine provides a substantial advantage over extended-release tolterodine in either efficacy or safety.
Annals of Pharmacotherapy 11/2009; 43(12):1992-2000. DOI:10.1345/aph.1M308 · 2.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the dosing of memantine in patients with dementia admitted to an inpatient geriatric psychiatry ward and review the published literature regarding the pharmacologic and clinical need to dose adjust memantine.
A retrospective study was conducted involving patients, admitted over a 2-year-period, with a diagnosis of dementia and receiving memantine. Published clinical trials, pharmacokinetic studies, and clinical trial registry data were used to investigate relationships among dose, efficacy, and side effects.
Of the 70 patients comprising the study sample, 27% were not prescribed appropriate doses of memantine at the time of admission. Notably, 60% of those patients who should had memantine renally dose-adjusted were not prescribed the adjusted dose. Trial and pharmacokinetic data support the need to renally adjust memantine.
Appropriate dosing of memantine in patients with dementia is important in an effort to maximize the medication's safety and efficacy.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 03/2009; 17(2):170-3. DOI:10.1097/JGP.0b013e318186bd7b · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To review the efficacy, safety, pharmacologic, and pharmacokinetic data of agomelatine to better understand its potential role in the treatment of patients with major depressive disorder.
A MEDLINE search (1966-October 2008) was conducted using the following terms: agomelatine, antidepressant, S20098, melatonin, serotonin, 5-HT(2C), MT, efficacy, safety, adverse effect, pharmacology, pharmacokinetic, receptor binding, depression, major depressive disorder, and mood disorder.
All articles in English identified from the data sources were evaluated. Randomized, controlled trials involving humans were prioritized in the review. The references of published articles identified in the initial search process were also examined for any additional studies appropriate for the review.
Agomelatine, a potent agonist at type 1 and 2 melatonin receptors, selectively inhibits serotonin. It is extensively metabolized via cytochrome P450 isoenyzmes 1A1, 1A2, and 2C9 to metabolites with less activity than the parent drug. Five randomized controlled studies were identified that examined the efficacy and safety of agomelatine in major depressive disorder. In general, agomelatine was found to produce significant improvements in depressive symptoms compared with placebo on many, but not all, rating scales. Three of the trials had active comparator arms (ie, venlafaxine, paroxetine). In these 3 investigations, agomelatine produced effects on depressive symptoms similar to those of the comparator drugs. A small number of studies have demonstrated sleep benefits with the use of agomelatine in depressed patients. Positive findings also exist for the use of agomelatine in seasonal affective disorder and bipolar depression. The most common adverse effects reported with agomelatine use were headache, nasopharyngitis, and gastrointestinal complaints. The magnitude of agomelatine-related adverse effects appears to be at least similar to some currently marketed antidepressants.
Overall, agomelatine is a promising and well-tolerated medication for the treatment of major depressive disorder. More large-scale controlled trials are needed to gain a better understanding of the relative efficacy and safety of agomelatine.
Annals of Pharmacotherapy 01/2009; 42(12):1822-31. DOI:10.1345/aph.1L296 · 2.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A number of news items and case reports describing complex behaviours (e.g. sleep driving, sleep cooking, sleep eating, sleep conversations, sleep sex) associated with the use of hypnosedative medications have recently received considerable attention. Regulatory agencies examining these reports have subsequently issued warnings regarding the potential of hypnosedative agents to produce complex behaviours. Despite these warnings, little is known about the likelihood, presentation, treatment or prevention of hypnosedative-induced complex behaviours. The purpose of this review is to evaluate the published evidence regarding the clinical presentation, incidence, mechanism and management of sleep-related behaviours induced by nonbenzodiazepine receptor agonists (NBRAs).
Review of the literature identified ten published case reports of NBRA-induced complex behaviours involving 17 unique patients. Fifteen of the 17 patients described in the case reports had taken zolpidem, one had taken zaleplon and one had taken zopiclone. The complex behaviours most commonly reported were sleep eating, sleepwalking with object manipulation, sleep conversations, sleep driving, sleep sex and sleep shopping. Elevated serum concentrations resulting from increased medication dose or drug-drug interactions appeared to play a role in some but not all cases. Sex, age, previous medication exposure and concomitant disease states were not consistently found to be related to the risk of experiencing a medication-induced complex behaviour.
From a pharmacological standpoint, enhancement of GABA activity at GABAA receptors (particularly α1-GABAA receptors) is a possible mechanism for hypnosedative complex behaviours and amnesia. Evidence suggests that complex behaviour risk may increase with both dose and binding affinity at α1-GABAA receptors. The amnesia that accompanies complex behaviours is possibly due to inhibition of consolidation of short- to long-term memory, suggesting that the risk may extend to non-GABAergic hypnosedatives. While amnesia and GABA-related receptor actions are the most frequently discussed mechanisms for complex behaviours in the literature, they do not fully explain such behaviours, suggesting that other mechanisms and factors probably play a role.
A number of potential strategies are available to manage or prevent hypnosedative-induced complex behaviours. These include lowering the dose of, or stopping, the offending hypnosedative, switching to a different hypnosedative, treating patients with other classes of medications, using nonpharmacological treatment strategies for patients with sleep disorders, examining drug regimens for potential drug interactions that may predispose patients to experiencing complex behaviours, administering hypnosedative medications appropriately and selecting patients more carefully for treatment in terms of their likelihood of experiencing medication adverse effects.