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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.

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.

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.

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.

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.

Hyperactive intracellular calcium ion (Ca) signaling in peripheral cells has been a reliable finding in bipolar disorder. Some established mood stabilizing medications, such as lithium and carbamazepine, have been found to normalize elevated intracellular Ca concentrations ([Ca]i) in platelets and lymphocytes from bipolar disorder patients, and some medications the primary effect of which is to attenuate increased [Ca]i have been reported to have mood stabilizing properties.Hyperactive intracellular Ca signaling has also been implicated in epilepsy, and some anticonvulsants have calcium antagonist properties. This study demonstrated that levetiracetam, an anticonvulsant that has been shown to block N and P/Q-type calcium channels in animal studies does not alter elevated [Ca]i in blood platelets of patients with bipolar disorder. Review of published clinical trials revealed no controlled evidence of efficacy as a mood stabilizer.This study underscores the possibility that pharmacologic actions of a medication in animals and normal subjects may not necessarily predict its pharmacologic or clinical effects in actual patients. Effects of treatments on pathophysiology that is demonstrated in clinical subtypes may be more likely to predict effectiveness in those subtypes than choosing medications based on structural similarities to established treatments.

Interest has grown in genetic testing to personalize treatment approaches in psychiatry, especially mood disorders and to a lesser extent anxiety. However, numerous studies of genetic variants of metabolizing enzymes, along with fewer studies of single nucleotide polymorphisms of drug transporter proteins, receptors, and other putative drug targets such as neurotransmitter reuptake pumps and receptors, have reported contradictory findings that have not translated into practical, cost-effective treatment recommendations. In this article, we review basic principles of genetic testing and highlight selected elements of genetic testing in cancer. We then critically review the current status of genetic research in pharmacokinetics and pharmacodynamics, as well as the few clinical trials that have been performed. After discussing the limited clinical applications of current research, we make recommendations for developing more clinically useful studies of cost-effective approaches to genetic testing in the treatment of mood and anxiety disorders.

One of the primary limitations of many psychiatric medications is weight gain, the mechanism of which remains to be fully elucidated. We conducted a 2-week double-blind placebo-controlled study on weight gain with olanzapine, which is frequently but unpredictably associated with this side effect, to address the possible mechanisms of weight gain independent of changes in the psychiatric condition for which it is prescribed. Healthy male volunteers were randomly assigned to olanzapine (5 mg/day for 7 days, then 10 mg/day for 7 days) or a matching placebo. Of the 24 participants, 19 completed the study (olanzapine, n=13; placebo, n=6). Body weight, glucose, triglyceride, total cholesterol, lipid, leptin, insulin, and aldosterone levels, resting metabolic rate, body composition, physical activity, and 24-h dietary intake were assessed. A significant increase in weight as well as triglyceride, insulin, and leptin levels were found in the olanzapine group as a whole. In participants receiving olanzapine who actually gained weight (n=8), lean but not fat mass increased, as did insulin, fasting glucose, total cholesterol, low-density lipoprotein, and non-high-density lipoprotein levels, whereas aldosterone levels decreased. There were no significant metabolic or endocrine changes in participants receiving placebo or in those receiving olanzapine who did not gain weight. Early metabolic changes appear to be independent of accumulation of fat.

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. Electronic supplementary material The online version of this article (doi:10.1186/s13104-016-2337-3) contains supplementary material, which is available to authorized users.

Background Increased baseline ([Ca2+]B) and agonist-stimulated ([Ca2+]s) free intracellular calcium ion concentrations ([Ca2+]i) are well-replicated findings in bipolar disorder, but whether this finding is specific to that condition and if so, whether it is a marker of the mood disorder or a feature seen in other disorders such as psychosis has remained unclear. Methods Platelet [Ca2+]i was assessed in 15 inpatients with psychotic and nonpsychotic mania, 17 schizophrenia inpatients, and 17 matched controls. Results Platelet [Ca2+]B and [Ca2+]s were significantly higher than controls in bipolar disorder but not schizophrenia. Variability of [Ca2+]B was significantly increased in bipolar disorder regardless of the presence of psychosis, but not in schizophrenia. Limitations Use of antipsychotic drugs by the majority of both patient groups may have obscured elevated [Ca2+]i in schizophrenia, or may have masked a difference between psychotic and nonpsychotic bipolar disorder. Measurement of [Ca2+]i is too labor intensive to become a routine test for diagnosis or prediction of treatment response. Conclusions Elevated intracellular Ca2+ signaling may be a marker of primary cellular hyperactivity that could contribute to comorbid conditions such as hypertension and neuronal apoptosis. Since lithium and carbamazepine attenuate increased [Ca2+]i, further research may demonstrate a correlation between normalization of [Ca2+]i and response to one of these medications, and further research may clarify whether a subgroup of patients may respond well to calcium channel antagonists.

Dextromethorphan/quinidine (DM/Q; NUEDEXTA) is approved by the US FDA for the treatment of pseudobulbar affect (PBA) associated with chronic neurological disorders such as multiple sclerosis, stroke, traumatic brain injury and amyotrophic lateral sclerosis. Studies of applications in other illnesses and for behavioral disinhibition are currently underway. The primary active agent is dextromethorphan, with quinidine added to inhibit its metabolism by CYP450 2D6 and increase the bioavailability of dextromethorphan. Published studies suggest reduction of episodes of PBA and improved quality of life with reasonable tolerability. However, the combination has the potential to interact with a number of other medications used by older patients. Some antidepressants may also be helpful in low doses for PBA and are easier to use, but more controlled studies with validated outcome measures are available for DM/Q. This article reviews published studies of DM/Q and addresses its use in clinical practice.

Background While it is generally acknowledged that self-prescribing among physicians poses some risk, research finds such behaviour to be common and in certain cases accepted by the medical community. Largely absent from the literature is knowledge about other activities doctors perform for their own medical care or for the informal treatment of family and friends. This study examined the variety, frequency and association of behaviours doctors report providing informally. Informal care included prescriptions, as well as any other type of personal medical treatment (eg, monitoring chronic or serious conditions). Method A survey was sent to 2500 randomly-selected physicians in Colorado, 600 individuals returned questionnaires with usable data. The authors hypothesised: (1) physicians would prescribe the same types of treatment at home as they prescribed professionally; and (2) physicians who informally prescribed addictive medications would be more likely to engage in other types of informal medical care. Results Physicians who wrote prescriptions for antibiotics, psychotropics and opioids at work were more likely to prescribe these medications at home. Those prescribing addictive drugs outside of the office treated more serious illnesses in emergency situations, more chronic conditions and more major medical/surgical conditions informally than did those not routinely prescribing addictive medications. Physicians reported a variety of informal care behaviour and high frequency of informal care to family and friends. Discussion The frequency and variety of informal care reported in this study strongly argues for profession-wide discussion about ethical and guideline considerations for such behaviour. These areas are discussed in the paper.

To examine the prevalence and treatment of typical and subsyndromal bipolar disorder (BD) in depressed primary care patients.Patients with a diagnosis of a mood disorder being treated with antidepressants in 2 academic family practice clinics underwent a structured diagnostic interview (Mini International Neuropsychiatric Inventory) for manic and hypomanic symptoms.Of 58 patients evaluated, 19% met full criteria for bipolar I disorder and 8.6% for bipolar II disorder; 31% had subsyndromal BD (ie, persistent elation or irritability accompanied by additional symptoms of hypomania but not enough symptoms to meet full criteria for bipolar I or II disorder). Only 5 patients with BD were receiving mood stabilizers, which had not been instituted in any patient by the primary care physician.The high prevalence of patients meeting full criteria for BD and the low rate of identification of BD in primary care patients are consistent with estimates using self-administered questionnaires, but the interview revealed a substantial additional population that could be considered to have subsyndromal BD. Because subsyndromal forms of BD are associated with significant impairment and comorbidity as well as progression to frank BD, recognition of both full and subthreshold BD in primary care practice should be improved.

Objectives The aim of this study was to assess the short-term tolerability of two titration schedules of sublingual asenapine in older patients with psychosis, not associated with organic brain disease, and to compare asenapine pharmacokinetics in older patients versus younger adults with schizophrenia. Methods Patients ≥65 years with psychosis without dementia were randomized for 6 weeks to two dose-escalation regimens: 2 days at 2 mg twice daily (BID), 2 days at 5 mg BID, and 10 mg BID thereafter (slow escalation); or 4 days at 5 mg BID and 10 mg BID thereafter (rapid escalation). Clinical and pharmacokinetic assessments were performed in each group. Results Of 122 randomized patients, 76 (62.3%) completed the trial. The incidence of treatment-emergent adverse events (AEs) was comparable (72.1%) with both regimens. The most frequently reported AEs were hypertension, headache, and somnolence; incidence of extrapyramidal symptom–related AEs was 5.7%. Mean end point weight change was 0.4 kg. For asenapine 5 and 10 mg BID, median times to maximum concentration were 1.00 and 1.06 h, respectively; maximum concentrations (Cmax) were 4.73 and 7.93 ng/mL; areas under the concentration versus time curve (0–12 h; AUC0−12) were 32.1 and 56.3 ng∙h/mL. Conclusions Despite 12–30% increases in asenapine Cmax and AUC0−12 in older patients compared with previously published findings in younger schizophrenia patients, possibly as a result of slower drug clearance, asenapine was generally well tolerated during both dose-escalation schedules. No dose adjustment appears to be necessary in older patients. Copyright © 2011 John Wiley & Sons, Ltd.

The authors describe the development of a comprehensive policy for relationships of full-time and volunteer faculty and residents with industry. The underlying philosophy was that an academic approach to relations with industry that emphasizes objective outcomes and internal change will be more effective than rote restrictions on behavior that assume that physicians cannot learn new behaviors and that are impossible to enforce. The policy, developed through much discussion and debate with stakeholders, involves elimination of industry-supplied meals, gifts, and favors; integration of industry-sponsored and academic research; education of faculty and residents about the ways in which industry marketing influences clinical decision making; and comprehensive disclosure by faculty, including to patients, of financial interests in industry. At occasional points in the psychopharmacology curriculum and at a departmental "pharma symposium," industry representatives or industry-sponsored guest speakers are allowed to present peer-reviewed articles followed by comments by a faculty member with relevant expertise about aspects of the presentation that are accurate or misleading and by a general discussion of research and clinical implications of the research and the manner in which it is presented. Adherence to new protocols has been high because faculty and residents participated in developing them and are involved in their implementation. Acceptance by industry representatives has been variable. Experience with this approach suggests that it is possible to develop a collaborative relationship with industry that maintains appropriate boundaries between industry and academia.

Agomelatine (beta-methyl-6-chloromelatonin), which is structurally homologous to melatonin, is a potent agonist of melatonin MT1 and MT2 receptors as well as an antagonist of serotonin 5-HT(2C) receptors. Agomelatine appears to improve sleep without causing daytime sedation. It has not been found to be associated with sexual side effects and discontinuation symptoms. Three placebo-controlled trials, one of them a dose finding study and two of them pivotal trials, suggest that agomelatine is an antidepressant at doses of 25 - 50 mg/day. Agomelatine appears to be well tolerated, without sexual or cardiac adverse effects, weight gain or discontinuation syndromes. Animal studies suggest a possible neuroprotective action of agomelatine, although there are more data in favor of an anxiolytic effect. Substantially more research is needed to establish its role in the treatment of mood and circadian rhythm disorders.

The authors aim to determine whether admission interviews predict performance in residency. The authors determined whether interview and other admission data were correlated with performance during postgraduate years 2–4 and with remaining in the residency in 544 residents enrolled in a single psychiatry residency program between 1963 and 2004. Considered together, admissions data predicted 13% of the variance in performance ratings in postgraduate year 2 (PGY-2) and 5% in PGY-4. Interview scores were moderately correlated with performance ratings in PGY-2, modestly correlated with performance in PGY-3, and not correlated with performance ratings in PGY-4. Letters of reference were moderately correlated with performance ratings in PGY-2 and modestly correlated with performance in PGY-3 and PGY-4. In PGY-2, interview scores differentiated between the top quartile of performance and the other three quartiles, while letters of reference differentiated performance in the top and bottom quartiles from the middle quartiles. Numerical differences among groups were not great enough to be practically useful, and no variables predicted which residents would leave the program before completing it. As they are currently conducted, application interviews do not have sufficient power to predict performance during residency. Letters of reference may be useful to the extent that they reflect personal experience with the applicant, but differences in ratings of these letters are not great enough to base admission decisions on them. As it is currently performed, the interview process may be more useful as a means of interesting applicants in the program than of evaluating their potential for success in the residency.

Suicidal ideation and attempts are common reasons for visits to the emergency department and critical care hospitalizations and a common public health problem. Most patients who make a suicide attempt have a psychiatric disorder, most frequently a mood, psychotic, substance use, or personality disorder. Patients who are at high risk of another attempt and cannot be transferred promptly to a psychiatric service should be managed jointly by the psychiatric and critical care teams with an emphasis on protection of the patient, identification of substance intoxication and withdrawal, making the environment safe, and instituting treatment of the psychiatric disorder. Antidepressants reduce suicide risk but their slow onset of action may make electroconvulsive therapy a desirable alternative for severely depressed patients. Parenteral treatment is possible with benzodiazepines and antipsychotic drugs but not antidepressants.

Pharmacogenomics, which is derived from genome-wide association studies (GWAS), and pharmacogenetics, which involves candidate gene association studies (CGASs), are proving increasingly useful in personalized cancer care. Research in psychiatric applications has primarily involved genetic polymorphisms of P450 CYP enzymes, which mediate oxidative metabolism, particularly CYP2D6, which is involved in the metabolism of at least 30 psychotropic medications. This work has been supplemented by genotyping of proteins for the drug efflux pump P-glycoprotein (P-gp), serotonin receptors, and the serotonin reuptake pump.This review covers principles of pharmacogenetics and pharmacogenomics, previous analyses of pharmacokinetic and pharmacodynamics studies, newer studies of the predictive value of genetic testing in the treatment of depression, obstacles to implementation of genetic testing in predicting treatment response and side effects, and suggestions for future research.Studies of multiple genes have produced some positive results in groups of patients, but genetic testing does not yet seem to be applicable to choosing medications for a specific patient.

The authors assessed whether current methods of evaluating residency applicants and residents identify psychiatrists who later develop evidence of impairment. Residency admissions and performance data for all physicians who were enrolled in a psychiatry residency between 1965 and 1994 and who were referred to an impaired physician program up to 35 years later were matched for age and gender with a nonreferred physician from the same class. There were no significant differences between groups in admission interview assessments, performance ratings, or narrative observations by faculty during residency. Standard approaches do not identify physicians at risk of later impairment.

To review the current status of psychopharmacology education for medical students, residents, and practitioners in psychiatry and other specialties.A search of the MEDLINE and PsychInfo data bases was conducted using four keywords: pharmacology, psychopharmacology, teaching, and student. Additional references were obtained from citations in these articles. Published material was supplemented with the experience of the author and others involved in psychopharmacology teaching.The majority of psychopharmacology education is provided by faculty from disciplines that include psychiatry, primary care medicine, basic science, and pharmacy. The pharmaceutical industry supports a substantial amount of continuing medical education (CME) by psychiatrists, pharmacists, and other medical practitioners, while much of the information that office practitioners receive and an increasing amount of material provided to residents comes from pharmaceutical representatives. The most important attributes of the effective psychopharmacology educator are knowledge, enthusiasm, honesty, an ability to encourage critical thinking, and genuine interest in the student. However, the primary criteria for participation in psychopharmacology education are faculty who are most available and willing in the academic medical center and those who engage in paid CME activities.Educators with clinical experience should play a core role in helping students to integrate research with actual clinical practice and should be able to teach students how to evaluate new research in psychopharmacology, especially if it is industry sponsored.

Major depressive disorder (MDD), one of the most common disorders in medical practice and one of the leading causes of disability worldwide, is frequently comorbid with anxiety disorders. Vortioxetine (Lu AA21004) is a new antidepressant that combines a number of neurotransmitter reuptake and receptor effects that have been thought to predict efficacy as a treatment for depressive and anxiety disorders.This review summarizes the pharmacology and neurobiology of vortioxetine. Studies of its efficacy and tolerability in major depression and generalized anxiety disorder are critically reviewed.Despite the fact that industry-sponsored studies are more likely than other clinical trials to support efficacy of the experimental drug, results have been mixed. Some studies supported that vortioxetine is superior to placebo in the treatment of MDD and some do not. Two studies supported the efficacy of vortioxetine in the treatment of generalized anxiety disorder and two do not. The incidence of sexual dysfunction has varied considerably in different studies, but cardiac effects and psychomotor impairment seem to be minimal. Advantages of vortioxetine over existing antidepressants are not yet clear.

Introduction: Cognitive impairment, the most important adverse effect of electroconvulsive therapy (ECT), may involve elevated intracellular calcium ion signaling. Animal research suggests that calcium channel-blocking agents, which attenuate excessive intracellular calcium activity, may reduce cognitive dysfunction caused by ECT. Method: The lipid-soluble calcium channel-blocking drug nicardipine or matching placebo were randomly assigned to 26 patients with major depressive disorder receiving ECT. A rater blind to the experimental condition administered the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, the Beck Depression Inventory, the Mini-Mental State Examination and a comprehensive battery of neuropsychological tests prior to ECT, at the completion of ECT, and 6 months after ECT completion. Results: Compared with patients receiving placebo, patients taking nicardipine had significantly lower scores on the Hamilton and Montgomery-Asberg but not the Beck Depression rating scale scores at the completion of ECT. There were no differences between placebo and nicardipine groups in depression scores 6 months after ECT. Cognitive function declined over the course of ECT and improved over the next 6 months in both groups, but changes were statistically significant for only two subtests on the neuropsychological battery. Changes in Mini-Mental State Examination scores were small and were not significant at any point There were no significant differences between nicardipine and placebo treated groups in any assessment of cognition. Discussion: Standard approaches to ECT in younger patients without preexisting neurological impairment do not produce cognitive side effects of sufficient severity for calcium channel-blocking agents to reduce these side effects demonstrably. Studies of treatments for cognitive impairment should be conducted in patients with risk factors for more severe cognitive impairment such as geriatric patients or patients with a history of interictal delirium during previous treatment with ECT. A possible effect of nicardipine in enhancing the antidepressant action of ECT requires further investigation in a study designed to test this action.

Psychiatric educators must prepare to teach in an era in which funding for education is more difficult to obtain, all forms of treatment are shorter, patients are discharged from the hospital while they are still acutely ill, the burden of paperwork and other administrative tasks is greater, psychiatrists provide less psychotherapy, and residents are no longer able to play a primary role in the treatment of patients covered by third-party payment schemes. A surcharge on a national insurance plan could make up for funding deficits, but this is not likely to occur in the near future. A more realistic model involves billing for services of faculty who integrate direct participation in patient care with teaching and better definitions of the role that residents can play in modern patient care. Overage from clinical activities driven by faculty may provide sufficient funding for resident services that provide an opportunity for longitudinal patient experiences. Strategies for political action and for better collaborations with primary care faculty are discussed.

A proprietary combination of the atypical antipsychotic drug olanzapine and the serotonin reuptake inhibitor fluoxetine (OFC, Symbyax) was approved for the treatment of bipolar depression based on a double-blind, placebo-controlled comparison of olanzapine, OFC, and placebo.This review considers published controlled and uncontrolled studies of the efficacy, pharmacodynamics, pharmacokinetics, interactions, and adverse effects of OFC. Beyond previously reviewed efficacy studies, an open-label 7-week study of 161 bipolar depressed patients (93% bipolar I), and an 8-week double-blind study of 833 bipolar I depressed patients with an open-label extension were identified. The structure and limitations of clinical trials of OFC are critically addressed.OFC trades simplicity of administration for loss of flexibility of dosing and lack of a generic preparation, both of which are available for olanzapine and fluoxetine separately. Clinical trials are limited by short-term follow-up, exclusive use of symptom rating scale scores, limitation of subjects to those with depression that is not overly complex or comorbid, lack of consideration of subsyndromal hypomania and mood cycling, and high dropout rates. In the absence of comparisons to mood stabilizers combined with each other and/or antidepressants, the role of OFC in the treatment of bipolar depression remains unclear.

Background While genome-wide association studies identified some promising candidates for schizophrenia, the majority of risk genes remained unknown. We were interested in testing whether integration gene expression and other functional information could facilitate the identification of susceptibility genes and related biological pathways. Results We conducted high throughput sequencing analyses to evaluate mRNA expression in blood samples isolated from 3 schizophrenia patients and 3 healthy controls. We also conducted pooled sequencing of 10 schizophrenic patients and matched controls. Differentially expressed genes were identified by t-test. In the individually sequenced dataset, we identified 198 genes differentially expressed between cases and controls, of them 19 had been verified by the pooled sequencing dataset and 21 reached nominal significance in gene-based association analyses of a genome wide association dataset. Pathway analysis of these differentially expressed genes revealed that they were highly enriched in the immune related pathways. Two genes, S100A8 and TYROBP, had consistent changes in expression in both individual and pooled sequencing datasets and were nominally significant in gene-based association analysis. Conclusions Integration of gene expression and pathway analyses with genome-wide association may be an efficient approach to identify risk genes for schizophrenia.

Summary Calcium channel blockers (CCBs) inhibit the influx of calcium ions into excitable cells through long-acting (L-) channels. Four classes of CCBs have been synthesised, all with greater activity in hyperactive than in normal cells in diverse systems. Although more generally used for the treatment of cardiovascular disorders, CCBs have been shown to be effective in a number of psychiatric disorders. Verapamil, the most widely studied of the CCBs, has been found to be superior to placebo and equivalent to lithium in the treatment of mania. However, most trials have been small and no multi centre studies have been performed. CCBs may prevent antidepressant-induced mania and reduce the frequency of rapid cycling in bipolar disorder, and they may have applications in panic disorder. The antidepressant properties of CCBs remain to be clearly demonstrated. CCBs generally are well tolerated, but still experimental, alternatives to lithium and anticonvulsants in the treatment of bipolar mood disorders.

The clinical significance of subthreshold bipolar disorder (SBD), which is characterized by an insufficient number or severity of hypomanic symptoms to qualify for a formal bipolar disorder diagnosis, remains to be determined.We examined the outcomes three years later (2004-2005; Wave 2) of 40,512 civilian, non-institutionalized subjects who endorsed elation and/or irritability but did not meet full criteria for lifetime mania or hypomania in 2001-2002 (Wave 1).The likelihood of developing a clear episode of mania or hypomania by Wave 2 was significantly increased in subjects with elation or only irritability at Wave 1 compared with subjects who did not endorse either (OR 2.8, p0.01 for each). Endorsement of both symptoms at Wave 1 increased the likelihood of a new episode of mania or hypomania 4.6 times, which was significantly higher than for those with only elation or irritability (p.05 for each).SBD was not limited to depression, reducing comparability to previous studies. Despite the large sample size, there were not enough subjects to determine the impact of different numbers and types of additional symptoms on bipolar outcome. Although the majority of subjects were followed between the two Waves, the total duration of follow-up was probably too short to determine the long-term conversion rate to mania or hypomania.Elation and/or irritability, especially if accompanied by trouble concentrating, racing thoughts or hyperactivity, may represent a prodrome of formal bipolar disorder that indicate close follow-up and cautious use of antidepressants.

Consistent with previous studies, elevated free intracellular calcium ion concentrations ([Ca2+]i) were found in blood platelets and lymphocytes of patients with mania and bipolar depression. Incubation with an ultrafiltrate of plasma from patients with bipolar illness had no effect on intracellular calcium ion concentration in platelets from normal subjects, suggesting that elevated [Ca2+]i is not due to a circulating factor. As was true in an earlier study of the effect of lithium on platelets, incubation with therapeutic levels of carbamazepine lowered [Ca2+]i in lymphocytes from affectively ill patients but not controls. Increased [Ca2+]i in peripheral cells may reflect a diffuse change in cellular homeostasis and may contribute to mixtures as well as rapid alternations of activity of affective, behavioral and physiologic systems in bipolar illness. Correction of the abnormality may at least be a marker of a relevant therapeutic action if it is not the action itself.

Antipsychotic drugs are increasingly used in the maintenance treatment of bipolar disorder. This review addresses the evidence supporting the use of one of these medications for this indication in order to place available data in perspective for the clinician.The approval of ziprasidone for maintenance treatment of bipolar I disorder was based on two open-label extensions of industry-sponsored 3-week monotherapy trials in mania, involving a total of 189 patients and an industry-sponsored study using sample enrichment of 584 outpatients who had either ziprasidone or a placebo added to lithium or valproate. Patients enrolled in maintenance studies did not have refractory mood disorders or comorbid conditions or risk of dangerousness, and they were able to give sustained consent. Ziprasidone is generally well tolerated, but should be taken with food. Primary interactions of concern are those with other serotonergic medications and other medications that prolong the QT interval.Although antipsychotic drugs are used frequently for maintenance treatment, current guidelines recommend that an attempt be made to withdraw them after acute treatment. The use of these medications as part of a maintenance regimen is most appropriate in cases of persistent psychosis or failure to respond to standard mood stabilizer combinations.

Psychotic depression is a unique subtype of depressive illness in which mood disturbance is accompanied by delusions, hallucinations, or both. Once considered relatively uncommon, it is frequently encountered in clinical practice, particularly in treatment-resistant depressed patients. Psychotically depressed patients respond poorly to antidepressants, but remission is likely with neuroleptic-antidepressant combinations or electroconvulsive therapy. Psychotic depression may be unipolar or bipolar with early or late onset and may be more likely to occur in patients with a history of childhood psychic trauma. Much is known about the course and treatment response of obvious presentations of psychotic depression, but more must be learned about depressed patients who have intermittent, subtle, or mild psychotic symptoms and about the ways in which the capacity to become psychotic interacts with the capacity to become depressed to produce a syndrome greater than the sum of its parts.

Psychiatric disorders are common in neurological patients, and psychopharmacological agents are frequently used to treat agitation and other problems in neurological practice. Antidepressants are effective for depression caused by neurological illness, but they can interact with other medications. Antianxiety drugs can aggravate cognitive disorders and should be used cautiously in this context. Antipsychotic drugs can be useful for acute agitation, but they are being found to be neither effective nor safe for chronic nonpsychotic agitation. Other agents such as beta blockers and serotonergic agents are being found to be more useful. Uses, doses, adverse effects, and interactions of psychiatric medications in neurology are summarized in this article, and suggestions are provided for the practical application of these treatments.

To the Editor: Psychotropic drugs are well known to affect sexual functioning1 and may contribute to patient noncompliance. The serotonin reuptake inhibitor antidepressants are particularly known for their effects on orgasm.2 Much less is known about adverse sexual effects of anticonvulsants, although a few case reports suggest that topiramate,3 gabapentin,4 and carbamazepine5 may cause ejaculatory failure, though these cases are mainly from patient populations with epilepsy. Here, we report a case of oxcarbazepine-induced anorgasmia and ejaculatory failure in a patient with schizoaffective disorder. Case report. Mr A, a 28-year-old man, has a long history of DSM-IV schizoaffective disorder. Upon his initial presentation to the outpatient mental health clinic in 2008, he was being prescribed quetiapine 600 mg/d and paliperidone 6 mg/d. Despite this, he remained preoccupied by paranoid delusions and complained of feeling depressed and hopeless with neurovegetative symptoms, sleep disturbance, and severe anxiety. Though he endorsed intermittent passive death wishes, he denied suicidal thoughts, intent, or plan to harm himself or others. His history revealed episodic increased energy, decreased need for sleep, increased goal-directed activities, disorganized behavior, and worsening psychotic symptoms that seemed consistent with mania. To better control the psychotic symptoms, Mr A's paliperidone was increased to 9 mg/d. At his next appointment, Mr A felt his psychotic symptoms were largely under control with the paliperidone and the quetiapine but continued to complain of low mood, anxiety, sleep disturbance, and low energy. It was recommended that Mr A undergo a trial with a mood stabilizer. Mr A initially refused to take lithium, valproic acid, or carbamazepine, as he did not want to undergo the laboratory work required to monitor the blood levels of these drugs. However, he was agreeable to a trial of oxcarbazepine 300 mg PO bid, despite the fact that this medication would still require occasional laboratory work. Within a week, Mr A felt that his mood had improved, but he complained of concerning sexual side effects, specifically an inability to experience orgasm or ejaculate. He denied having cloudy urine after sexual activity, making retrograde ejaculation less likely. Neither libido nor erection was affected. Mr A stopped oxcarbazepine treatment due to these concerns, and within a few days the sexual side effects abated. After a few days, he resumed oxcarbazepine 300 mg twice daily. Again, he experienced anorgasmia and ejaculatory failure. Due to these symptoms, which Mr A found intolerable, oxcarbazepine treatment was stopped at the next visit. At the following appointment, orgasm and ejaculatory abilities had returned to normal. During this time period, Mr A denied taking any illicit drugs or any alcohol abuse, and no other new medications had been initiated. This case demonstrated a clear on/off phenomenon of anorgasmia and ejaculatory failure related to oxcarbazepine. We have found no previous reports of anorgasmia and ejaculatory failure associated with oxcarbazepine, although it has been associated with sexual side effects. In a study of its use in epilepsy, 17% of men reported sexual dysfunction.6 Anticonvulsant medications may interact with sex hormones,6 and central-acting drugs such as oxcarbazepine may cause anorgasmia in conjunction with sedation. It is difficult to determine a mechanism by which oxcarbazepine (keto analogue of carbamazepine with no significant anticholinergic or sympatholytic activity) could cause ejaculatory failure, but its use should be reconsidered if troublesome ejaculatory failure develops. We usually ask questions about decreased sexual function with selective serotonin reuptake inhibitors, but not with anticonvulsants. Physicians should be vigilant and should evaluate patients for sexual dysfunction with anticonvulsant treatment.