Benzodiazepines Remain Important Therapeutic Options in Psychiatric Practice.

Benzodiazepines and medications acting on benzodiazepine receptors that do not have a benzodiazepine structure (z-drugs) have been viewed by some experts and regulatory bodies as having limited benefit and significant risks. Data presented in this article support the use of these medications as treatments of choice for acute situational anxiety, chronic anxiety disorders, insomnia, alcohol withdrawal syndromes, and catatonia. They may also be useful adjuncts in the treatment of anxious depression and mania, and for medically ill patients. Tolerance develops to sedation and possibly psychomotor impairment, but not to the anxiolytic effect of benzodiazepines. Sedation can impair cognitive function in some patients, but assertions that benzodiazepines increase the risk of dementia are not supported by recent data. Contrary to popular opinion, benzodiazepines are not frequently misused or conduits to misuse of other substances in patients without substance use disorders who are prescribed these medications for appropriate indications; most benzodiazepine misuse involves medications that are obtained from other people. Benzodiazepines are usually not lethal in overdose except when ingested with other substances, especially alcohol and opioids. Benzodiazepines comprise one of the few classes of psychotropic medication the mechanisms of action of which are clearly delineated, allowing for greater precision in their clinical use. These medications, therefore, belong in the therapeutic armamentarium of the knowledgeable clinician.

Calcium Channel Antagonists for Mood Disorders.

PURPOSE: Development of new thymoleptic medications has primarily centered on anticonvulsants and antipsychotic drugs. Based on our studies of intracellular calcium ion signaling in mood disorders, we were interested in the use of novel medications that act on this mechanism of neuronal activation as potential mood stabilizers. METHOD: We reviewed the dynamics of the calcium second messenger system and the international body of data demonstrating increased baseline and stimulated intracellular calcium levels in peripheral cells of patients with bipolar mood disorders. We then examined studies of the effect of established mood stabilizers on intracellular calcium ion levels and on mechanisms of mobilization of this second messenger. After summarizing studies of calcium channel blocking agents, whose primary action is to attenuate hyperactive intracellular calcium signaling, we considered clinical experience with this class of medications and the potential for further research. FINDINGS: Established mood stabilizers normalize increased intracellular calcium ion levels in bipolar disorder patients. Most case series and controlled studies suggest an antimanic and possibly mood stabilizing effect of the calcium channel blocking medications verapamil and nimodipine, with fewer data on isradipine. A relatively low risk of teratogenicity and lack of cognitive adverse effects or weight gain suggest possible applications in pregnancy and in patients for whom these are considerations. IMPLICATIONS: Medications that antagonize hyperactive intracellular signaling warrant more interest than they have received in psychiatry. Further experience will clarify the applications of these medications alone and in combination with more established mood stabilizers.

Psychotic Depression: Diagnosis, Differential Diagnosis, and Treatment.

Psychotic depression was initially considered to be at one end of a continuum of severity of major depression. Subsequent experience demonstrated that psychosis is an independent trait that may accompany mood disorders of varying severity. While much has been learned about the impact of severe mood congruent delusions and hallucinations on the course and treatment response of depression, less is known about fleeting or mild psychosis, mood incongruent features, or psychotic symptoms that reflect traumatic experiences. Acute treatment of psychotic unipolar depression generally involves the combination of an antidepressant and an antipsychotic drug or electroconvulsive therapy. There is inadequate information about maintenance treatment of unipolar psychotic depression and acute and chronic treatment of psychotic bipolar disorder. Decision-making therefore still must rely in part on clinical experience.

Preliminary Assessment of a Novel Continuum-of-Care Model for Young People With Autism Spectrum Disorders.

Because of limited intermediate-care services, patients with autism spectrum disorders (ASDs) are increasingly being treated in emergency departments (EDs) and psychiatric hospitals. To address this growing problem, the authors developed a mobile outreach program, called Access to Psychiatry through Intermediate Care (APIC), for young (≤26 years) patients with ASD at risk for involvement with emergency medical services or the legal system. In its initial year, the average program duration per patient was 264.5 days. Clinical and Family Distress Scale scores indicated significant improvements for participating patients and caretakers. In the first year, among 40 patients with sufficient data for comparison, 13 (33%) went to the ED, and lengths of stay decreased up to 77% from pre- to postintervention. Given a cost per APIC-enrolled patient of $1,700, the net saving for the cost of ED treatment was $2,260-$2,559 per patient. The feasibility and cost-effectiveness of the APIC model has attracted additional state and county funding.

Selective serotonin reuptake inhibitors and benzodiazepines in panic disorder: A meta-analysis of common side effects in acute treatment.

BACKGROUND: Benzodiazepines (BZs) and selective serotonin reuptake inhibitors (SSRIs) are effective in the pharmacologic treatment of panic disorder (PD). However, treatment guidelines favor SSRIs over BZs based on the belief that BZs are associated with more adverse effects than SSRIs. This belief, however, is currently supported only by opinion and anecdotes. AIM: The aim of this review and meta-analysis was to determine if there truly is evidence that BZs cause more adverse effects than SSRIs in acute PD treatment. METHODS: We systematically searched Web of Science, PubMed, Cochrane Central Register of Controlled Trials, and clinical trials register databases. Short randomized clinical trials of a minimum of four weeks and a maximum of 12 weeks that studied SSRIs or BZs compared to placebo in acute PD treatment were included in a meta-analysis. The primary outcome was all-cause adverse event rate in participants who received SSRIs, BZs, or placebo. RESULTS: Overall, the meta-analysis showed that SSRIs cause more adverse events than BZs in short-term PD treatment. Specifically, SSRI treatment was a risk factor for diaphoresis, fatigue, nausea, diarrhea, and insomnia, whereas BZ treatment was a risk factor for memory problems, constipation, and dry mouth. Both classes of drugs were associated with somnolence. SSRIs were associated with abnormal ejaculation, while BZs were associated with libido reduction. BZs were protective against tachycardia, diaphoresis, fatigue, and insomnia. CONCLUSION: Randomized, blinded studies comparing SSRIs and BZs for the short-term treatment of PD should be performed. Clinical guidelines based on incontrovertible evidence are needed.

Applications of calcium channel blockers in psychiatry: pharmacokinetic and pharmacodynamic aspects of treatment of bipolar disorder.

Introduction: Calcium channel blockers (CCBs) comprise a heterogeneous group of medications that reduce calcium influx and attenuate cellular hyperactivity. Evidence of hyperactive intracellular calcium ion signaling in multiple peripheral cells of patients with bipolar disorder, calcium antagonist actions of established mood stabilizers, and a relative dearth of treatments have prompted research into potential uses of CCBs for this common and disabling condition. Areas covered: This review provides a comprehensive overview of intracellular calcium signaling in bipolar disorder, structure and function of calcium channels, pharmacology of CCBs, evidence of efficacy of CCBs in bipolar disorder, clinical applications, and directions for future research. Expert opinion: Despite mixed evidence of efficacy, CCBs are a promising novel approach to a demonstrated cellular abnormality in both poles of bipolar disorder. Potential advantages include low potential for sedation and weight gain, and possible usefulness for pregnant and neurologically impaired patients. Further research should focus on markers of a preferential response, studies in specific bipolar subtypes, development of CCBs acting preferentially in the central nervous system and on calcium channels that are primarily involved in neuronal signaling and plasticity.

Pharmacotherapy of mood disorders and psychosis in pre- and post-natal women.

INTRODUCTION: Untreated mood and psychotic disorders can have substantial adverse impacts on the patient, the fetus and the family, while treatment can ameliorate such problems. To address concerns by clinicians about the risks of psychotropic medications, this review addresses the risk/benefit analysis of somatic therapies for psychiatric disorders during pregnancy and lactation. Areas covered: All available research was reviewed on the impact on pregnancy and breastfeeding of mood and psychotic disorders, and of antidepressants, mood stabilizers, antipsychotic drugs, and electroconvulsive therapy. References cited in other reviews, case series, formal studies, pharmacologic discussions, and theoretical pieces were added. Available case control and other studies were critically reviewed and diverse explanations for their findings were considered. Expert opinion: The potential benefits of treatment of mood and psychotic disorders often outweigh the risks after alternative therapies have been considered. Some medications, particularly paroxetine and valproate, pose greater risks during pregnancy, while the teratogenic risks of lithium have probably been overstated. There is more experience with first than with second generation antipsychotic drugs during pregnancy and lactation. Nursing an infant is possible while taking a number of antidepressants, mood stabilizers or antipsychotic drugs.

A preliminary study of a novel emergency department nursing triage simulation for research applications.

BACKGROUND: Studying the effect on functioning of the emergency department of disasters with a potential impact on staff members themselves usually involves table top and simulated patient exercises. Computerized virtual reality simulations have the potential to configure a variety of scenarios to determine likely staff responses and how to address them without intensive utilization of resources. To decide whether such studies are justified, we determined whether a novel computer simulation has the potential to serve as a valid and reliable model of on essential function in a busy ED. METHODS: Ten experienced female ED triage nurses (mean age 51) mastered navigating a virtual reality model of triage of 4 patients in an ED with which they were familiar, after which they were presented in a testing session with triage of 6 patients whose cases were developed using the Emergency Severity Index to represent a range of severity and complexity. Attitudes toward the simulation, and perceived workload in the simulation and on the job, were assessed with questionnaires and the NASA task load index. Z-scores were calculated for data points reflecting subject actions, the time to perform them, patient prioritization according to severity, and the importance of the tasks. Data from questionnaires and scales were analyzed with descriptive statistics and paired t tests using SPSS v. 21. Microsoft Excel was used to compute a correlation matrix for all standardized variables and all simulation data. RESULTS: Nurses perceived their work on the simulation task to be equivalent to their workload on the job in all aspects except for physical exertion. Although they were able to work with written communications with the patients, verbal communication would have been preferable. Consistent with the workplace, variability in performance during triage reflected subject skill and experience and was correlated with comfort with the task. Time to perform triage corresponded to the time required in the ED and virtual patients were prioritized appropriately according to severity. CONCLUSIONS: This computerized simulation appears to be a reasonable accurate proxy for ED triage. If future studies of this kind of simulation with a broader range of subjects that includes verbal communication between virtual patients and subjects and interactions of multiple subjects, supports the initial impressions, the virtual ED could be used to study the impact of disaster scenarios on staff functioning.

Executive Function and Personality Predict Instrumental Activities of Daily Living in Alzheimer Disease.

OBJECTIVE: Previous research shows that executive function (EF) and personality independently predict functional decline. Our objective was to determine whether personality traits predict independence with instrumental activities of daily living (IADLs), after accounting for executive dysfunction, in a mixed sample of patients with amnestic mild cognitive impairment (MCI) and Alzheimer disease (AD). METHODS: In a cross-sectional analysis at a university medical center, 63 healthy older adults (median age: 67.6 years; 71% women) and 119 patients (median age: 75.0 years; 58% women) with varying degrees of AD (probable AD: 85; possible AD: 3; amnestic MCI: 31) were studied. Standardized neuropsychological measures, NEO Five-Factor Inventory (NEO-FFI), and informant-report Lawton and Brody IADL scales were used. All participants underwent neuropsychological evaluation, including administration of self- and informant-report NEO-FFI. Patients additionally underwent neurologic examination, and their informants completed the Lawton and Brody IADL scale. RESULTS: When testing the association between EF and personality on IADLs in the patient sample, conceptual card sorting, informant-report Openness, and informant-report Conscientiousness all significantly predicted IADLs, after accounting for age, education, and depression. In addition, a significant interaction showed that low Conscientiousness and executive dysfunction, in combination, can predict impairment of IADLs. CONCLUSION: Personality has a unique association with IADLs in patients with AD pathology that is not explained by EF. The findings confirm prior speculation that personality, in addition to cognitive dysfunction, is a risk factor for functional decline. Early identification of vulnerable individuals may allow for intervention to prolong functional independence.