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Background: Associations between the crude capture of polyallergy-also known as multiple chemical sensitivity or multiple drug intolerance syndrome-and mental health/functional somatic syndrome disorders, healthcare utilization, or other clinical phenomenon have not been examined extensively., Methods: An IRB-approved retrospective chart review of all patients between age 18 and 70 who had a clinical encounter at a large medical center between 2009 and 2014. Patients were stratified into 4 categories based on the absolute number of chart-documented allergies: (1) no allergies; (2) normal allergy (1-4 allergies); (3) polyallergy (5-9 allergies); and (4) "ultrapolyallergy," (≥10 allergies), which were corroborated through a sensitivity analysis. Demographics, comorbidities, and medications were clustered per allergy grouping. Analysis of variance, chi-square, and multivariable logistic regression analyses were employed to test for associations., Results: 2,007,434 patients were examined ("no allergy" group, n = 1,423,631, 70.9%; "normal allergy" group: n = 549,927, 27.4%; "polyallergy" group n = 29,453, 1.5%; "ultrapolyallergy" group, n = 4,423, 0.22%). Proportion of females increased from 51% in the "no allergy" group to 89.6% in the "ultrapolyallergy" group (p < 0.001). Rates of mental health and functional somatic syndrome disorder diagnoses increased significantly across allergy groups (p < 0.001). All psychotropic medication classes were increased significantly across allergy groups (p < 0.001). Healthcare utilization was also significantly elevated across allergy cohorts (p <0.001)., Conclusions: This study demonstrates that polyallergy/multiple chemical sensitivity may serve as a crude yet meaningful indicator of comorbid psychopathology. Drug intolerance mechanisms are reviewed, and both clinical and investigational implications are examined., (Copyright © 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Divalproex sodium/valproic acid (VPA) is an antiepileptic drug approved for use in epilepsy and bipolar disorder. Valproate-induced hyperammonemia occurs in up to 50% of VPA-treated patients, some of whom may become encephalopathic. Valproate-induced hyperammonemic encephalopathy (VHE) is thought to be rare, and for a variety of reasons, the diagnosis requires a high index of suspicion., Objective: The study's goals are to determine how common VHE is, and the quality of treatment provided when diagnosed., Methods: Retrospective, cross-sectional survey of general hospital patients. The hospital's laboratory and pharmacy databases were combined to identify a cohort of all VPA-treated patients who developed hyperammonemia during a 5-year period. Hospital records of the subset of patients with a psychiatric disorder were selected and reviewed for data collection., Results: Twenty of 793 (2.52%) VPA-treated patients had signs and symptoms consistent with VHE. The majority were White males on multiple psychotropic agents. Valproate was appropriately discontinued in 8 (40%) patients. Lactulose was the only ammonia-lowering drug used, and it was administered to 6 patients and only one among them had VPA discontinued., Conclusion: Study results indicate that VHE may be more common in psychiatric patients than previously assumed but underrecognized and inadequately treated. The diagnosis of VHE requires a high index of suspicion. Outcome is favorable once it is recognized and treated appropriately., (Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Management of psychogenic nonepileptic seizures (PNES) is complex, requiring multidisciplinary care. A standardized assessment and formulation approach to PNES is lacking, yet use of a comprehensive model may alleviate problems such as mental health aftercare noncompliance. Although a biopsychosocial (BPS) approach to PNES balancing predisposing, precipitating, and perpetuating (PPP) variables has been described and has been recently tested in pilot form, it is unclear how this assessment style is perceived among community mental health practitioners such as psychotherapists (including psychologists, counselors, and social workers). We predicted preference of a comprehensive "BPS/PPP" assessment style by those most involved in PNES care (i.e., community psychotherapists). One hundred and forty-three community-based social workers and counselors completed a survey featuring a fictional PNES case followed by assessment style options ("Multiaxial," "Narrative," and "BPS/PPP"). Respondents clearly preferred the robust BPS/PPP approach over less-comprehensive multiaxial and narrative assessments (p<0.0001). Reasons for choosing the BPS/PPP by respondents include ease of organization, clear therapeutic goals, and comprehensive nature. This assessment of acceptability of a BPS/PPP approach to PNES assessment among community mental health practitioners may provide a patient-centered mechanism to enhance referrals from the neurological to mental health setting. Implications and future directions are explored., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Video electroencephalography (vEEG) is the gold-standard method for diagnosing psychogenic nonepileptic seizures (PNES), but such assessment is expensive, unavailable in many centers, requires prolonged hospitalization, and many times is unable to capture an actual seizure episode. This paper systematically reviews other non-vEEG candidate biomarkers that may facilitate both diagnosis and study of PNES as differentiated from epileptic seizures (ES)., Methods: PubMed database was searched to identify articles between 1980 and 2015 (inclusion: adult PNES population with or without controls, English language; exclusion: review articles, meta-analyses, single case reports)., Results: A total of 49 studies were examined, including neuroimaging, autonomic nervous system, prolactin, other (non-prolactin) hormonal, enzyme, and miscellaneous marker studies. Functional MRI studies have shown PNES is hyperlinked with dissociation and emotional dysregulation centers in the brain, although conflicting findings are seen across studies and none used psychiatric comparators. Heart rate variability suggests increased vagal tone in PNES when compared to ES. Prolactin is elevated in ES but not PNES, although shows low diagnostic sensitivity. Postictal cortisol and creatine kinase are nonspecific. Other miscellaneous biomarkers (neuron specific enolase, brain derived neurotropic factor, ghrelin, leptin, leukocytosis) showed no conclusive evidence of utility. Many studies are limited by lack of psychiatric comparators, size, and other methodological issues., Conclusion: No single biomarker successfully differentiates PNES from ES; in fact, PNES is only diagnosed via the negation of ES. Clinical assessment and rigorous investigation of psychosocial variables specific to PNES remain critical, and subtyping of PNES is warranted. Future investigational and clinical imperatives are discussed., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Management of psychogenic nonepileptic seizures (PNES) is complex, requiring multidisciplinary care. A standardized assessment approach to PNES is lacking, yet use of a comprehensive model may alleviate problems such as mental health aftercare noncompliance. Although a biopsychosocial (BPS) approach to PNES balancing predisposing, precipitating, and perpetuating (PPP) variables has been described, it is unclear how this formulation style is perceived amongst clinicians. We predicted preference of a comprehensive, "BPS/PPP" assessment style by those most involved in PNES diagnosis and care (i.e., neurologists and psychologists). Sixty epileptologists, psychiatrists, and psychologists completed a survey featuring a fictional PNES case followed by assessment style options ("Multiaxial," "Narrative," and "BPS/PPP"). Epileptologists and psychologists ("nonpsychiatrists") differed from psychiatrists in PNES case formulation choice, with nonpsychiatrists preferring the robust BPS/PPP approach and with psychiatrists opting for less comprehensive Multiaxial and Narrative assessments (p=0.0009). Reasons for choosing the BPS/PPP by nonpsychiatrists included ease of organization, clear therapeutic goals, and comprehensive nature. Alternatively, psychiatrists cited time constraints and familiarity as reasons to prefer briefer Multiaxial or Narrative approaches. This pilot assessment of acceptability of a BPS/PPP approach to PNES case formulation, thus, reveals important gaps in formulation priorities between neurologists and psychiatrists. Implications and future directions are explored., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Electronic health records (EHRs) present an opportunity to access large stores of data for research, but mapping raw EHR data to clinical phenotypes is complex. We propose adding patient-reported data to the EHR to improve phenotyping performance and describe a retrospective cohort study demonstrating a test case in depressive disorder., Methods: We compared four EHR-phenotyping methods based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, medication records, and the Patient Health Questionnaire 9 (PHQ-9) regarding the ability to identify cases with depression and characteristics of patients identified with depression. Our sample included 168,884 patients seen (2007-2013) at our neurological institute. We assessed the diagnostic performance in a subset of 225 patients who had a reference standard measurement available., Results: ICD-9-CM codes identified the fewest number of patients as depressed (4,658), followed by PHQ-9 (46,565), and medication data (50,505). The presence of at least one of these criteria identified the largest number (78,322). The PHQ-9 identified a higher proportion of elderly, disabled, Medicaid, and rural patients, as compared to ICD-9-CM codes. ICD-9-CM codes were least sensitive (6.7% sensitivity), whereas the method using at least one of the criteria identified the highest number of truly depressed patients (93.3% sensitivity); however, specificity dropped from 97.7 to 58.1%., Conclusions: The choice of phenotyping method may disproportionately exclude patient groups from research. Patient-reported data hold potential to improve sensitivity while maintaining an acceptable loss of specificity, depending on the context. Researchers should consider including patient-reported data in EHR-driven phenotyping methods.

Objective: This study aimed to assess the accuracy and operating characteristics of the Patient Health Questionnaire-9 (PHQ-9) for depression screening in adults with epilepsy., Methods: Tertiary epilepsy center patients served as the study population, with 237 agreeing to structured interview using the Mini-International Neuropsychiatric Interview (MINI), a "gold standard" instrument developed for rapid diagnosis of neuropsychiatric disorders, including major depressive disorder (MDD); 172 also completed the PHQ-9, and 127 completed both the PHQ-9 and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) within two days of the MINI. Sensitivity, specificity, positive and negative predictive values, and areas under the ROC curves for each instrument were determined. Cut-points of 10 for the PHQ-9 and 15 for the NDDI-E were used, and ratings at or above the cut-points were considered screen-positive. The PHQ-9 was divided into cognitive/affective (PHQ-9/CA) and somatic (PHQ-9/S) subscales to determine comparative depression screening accuracy., Results: The calculated areas under the ROC curves for the PHQ-9 (n=172) and the PHQ-9/CA and PHQ-9/S subscales were 0.914, 0.924, and 0.846, respectively, with the PHQ-9 more accurate than the PHQ-9/S (p=0.002) but not different from the PHQ-9/CA (p=0.378). At cut-points of 10 and 15, respectively, the PHQ-9 had higher sensitivity (0.92 vs 0.87) but lower specificity (0.74 vs 0.89) compared with the NDDI-E. The areas under the ROC curves of the PHQ-9 and the NDDI-E showed similar accuracy (n=127; 0.930 vs 0.934; p=0.864)., Significance: The PHQ-9 is an efficient and nonproprietary depression screening instrument with excellent accuracy validated for use in adult patients with epilepsy as well as multiple other medical populations., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: This brief review presents a comprehensive evaluation of valproate-induced encephalopathy (VHE) and also discusses potential mechanisms of the condition., Scope: Sodium valproate (VPA) is an effective antiepileptic drug used in neurology as well as in psychiatry, in adults and children. VHE requires early diagnosis and management. Focused research efforts in understanding the condition will help decrease its incidence. Delay in recognition of VHE can result in the development of potentially life-threatening complications., Findings: Management options are described. Since VPA frequently causes a modest rise in plasma ammonia levels which is asymptomatic, it is important to recognize the symptoms of VHE promptly and to correlate them with the plasma ammonia levels., Conclusions: Although there are several case reports on VHE, this review is a comprehensive evaluation of its causes and potential mechanisms. Rapid diagnosis and management will help in reducing VHE-related morbidity.

The current study sought to characterize and compare personality traits of patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE). Ninety-seven adults with medically intractable epilepsy (TLE n=58, FLE n=39) completed the Personality Assessment Inventory (PAI) as part of routine preoperative investigations. Not surprisingly, both epilepsy groups endorsed significantly more symptoms across PAI clinical scales than the normative sample, most notably on scales assessing Depression and Somatic Complaints. Direct comparison of personality profiles of people with FLE and TLE revealed that FLE was associated with relative elevations on scales assessing emotional lability and relationship difficulties (i.e., Mania, Borderline Features, Antisocial, Stress, and Nonsupport). Although effect sizes were moderate to large, the clinical significance of these differences was questionable (<1 SD). However, results of a logistic regression suggested that the Borderline Features and Anxiety scales have incremental validity in predicting seizure site (FLE vs TLE) above education and duration of recurrent seizures. These results suggest that patients with FLE may exhibit more behavioral traits associated with frontal dysfunction than patients with TLE.

If psychiatrists are to bring value to the health care team, training a renewable force of such psychiatrists is essential. Have psychiatrists been trained to bring maximal value to the health care team? Is such training being provided now? Given the current health care climate, will sufficient funding be available to train this renewable force optimally? This article addresses these questions from an historical-developmental perspective, identifies current challenges, and outlines opportunities for further growth and development.

What should one do with a depressed patient who does not get better? If depression does not respond to an antidepressant given in adequate doses for an adequate time, logical next steps include increasing the dose, adding a different medication, or adding a nonpharmacologic therapy. Or one can reconsider the diagnosis.

Forty percent of the mental health care in this country is provided by primary care practitioners alone, and another 20% is provided by primary care practitioners working with mental health professionals. Primary care physicians can serve a valuable role by educating their patients about various forms of psychotherapy. Finding a good "fit" between patient and therapist is crucial to a good outcome. We discuss which psychotherapeutic techniques are appropriate for various emotional problems and the advantages and disadvantages of each.

Expanding scientific evidence supports a long-recognized link between cardiovascular disease and depression. As an independent risk factor, depression increases patient vulnerability to both cardiac events and mortality. Several important pathophysiologic mechanisms have been proposed, including hypothalamic-pituitary axis hyperactivity, autonomic nervous system dysfunction, and increased platelet reactivity, among others. The recently completed Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) inaugurates a series of studies intended to address the impact of antidepressant therapy on cardiovascular risk.

This article discusses the use of psychostimulants, such as dextroamphetamine, methylphenidate, and pemoline, in a variety of illnesses, including depression in the medically ill, cancer, HIV, and AIDS. The chemistry and pharmacology, side effects, drug interactions, dosing, and abuse potential also are reviewed.

The relative effectiveness of the available treatments for panic disorder may best be understood in the context of the longitudinal course of the disorder. This study examines a number of clinically relevant issues, including long-term outcome after acute treatment, the proportion of patients remaining on single-agent treatment or requiring multiple medications or nonpharmacologic interventions over time, evidence for dose escalation during maintenance high-potency benzodiazepine therapy, and predictors of acute and long-term response to treatment. Fifty-nine panic disorder patients originally randomized to treatment in a controlled trial comparing alprazolam, clonazepam, and placebo were reevaluated in a follow-up study. At a mean follow-up of 1.5 years, 78% of patients remained on medication and the mean dosage of alprazolam and clonazepam did not increase. Our data suggest that most patients maintain benefit with long-term pharmacotherapy but that residual symptomatology may require more intensive or additional treatment strategies. Response at the endpoint of the acute trial was significantly associated with pretrial baseline Clinical Global Impression Scale score and the presence of dysthymia. Poor outcome at follow-up was associated with total duration of the disorder, agoraphobic subtype, and the presence of comorbid social phobia. We underscore the potential importance of comorbid affective and anxiety disorders as well as phobic patterns in determining long-term response to treatment.

To test the reported antipanic efficacy of clonazepam, the authors randomized 72 subjects with panic disorder to 6 weeks of treatment with either alprazolam, clonazepam, or placebo. Endpoint analysis demonstrated a significant beneficial effect of both active treatments, but not placebo treatment, on the frequency of panic attacks, overall phobia ratings, and the extent of disability. Comparison of the two active treatments revealed no significant differences and no consistent tendency for one agent to be favored over another, although power to detect small differences was limited. Sedation and ataxia were the most common side effects reported, but these effects were mild and transient and did not interfere with treatment outcome. The results of this double-blind, placebo-controlled trial are consistent with previous reports of clonazepam's antipanic efficacy.

Interest in benzodiazepines for treatment of panic attacks followed a report of the success of alprazolam, used for generalized anxiety, in blocking such attacks. Twelve controlled trials and several open studies have substantiated the antipanic and antiphobic activity of alprazolam and concluded it is comparable to but more rapid than antidepressants in its effects and better tolerated. In a controlled trial of clonazepam, alprazolam, and placebo, the two active agents had similar positive effects. Diazepam and lorazepam have been effective in other studies. Clonazepam, with its relatively long half-life, permits less frequent dosing than possible with benzodiazepines with shorter half-lives and more continuous control of anxiety, although around 20% of patients experience unacceptable sedative effects or no reduction in anxiety. In general, benzodiazepines are safe and well tolerated. The most common adverse effects are intoxication, dependence, rebound, withdrawal, hostility, and affective disturbances. Discontinuation of alprazolam is particularly difficult and is sometimes associated with serious rebound and withdrawal symptoms. The morbidity and mortality associated with panic disorder suggest that the benefits of benzodiazepine treatment outweigh its risks.

Fifty patients with panic disorder or agoraphobia with panic attacks with treated with clonazepam, a high potency benzodiazepine. The authors report on the outcome of these patients after an average follow-up interval of 1 year, suggesting that clonazepam is a safe, effective, and easy to administer medication in a relatively treatment-refractory population of nondepressed patients with panic disorder and agoraphobia.

The authors present interim results of a prospective, random assignment, double-blind, placebo-controlled trial conducted to determine whether clonazepam is as effective as alprazolam in reducing the frequency of panic attacks and whether both agents are superior to placebo. Analysis on 44 of 60 randomized subjects showed no statistically significant differences between the clonazepam and alprazolam groups on the following clinically meaningful outcome measures: total number of panic attacks and percent of time subjects experienced anticipatory anxiety, extent of phobic avoidance, and fear. Statistically significant differences did exist among the drug and placebo groups on these measures. The authors conclude that this interim analysis of the data supports the inclusion of clonazepam in the treatment of panic disorder.

Ten cases are presented--two in detail--in which clonazepam was used successfully in patients with treatment-resistant panic disorder with or without agoraphobia. Seven of 10 patients who had been resistant to standard pharmacological treatments of panic attacks and agoraphobia achieved cessation of their attacks while three had mild to moderate symptom persistence. These data underscore other reports of clonazepam's usefulness in the treatment of panic disorder. Clinical use of clonazepam is discussed.

Although previous reports have documented the safe and effective use of intravenous haloperidol in agitated cardiac patients, the dosages advocated have in general been relatively low: 1 to 2 mg every 2 to 4 hours. In this report, the authors demonstrate that such doses may be insufficient to control severe agitation in coronary care unit patients. Four cases are presented in which more than 100 mg/day of intravenous haloperidol were required for safe and effective control of confusion and agitation.

Atherosclerosis results from a precise sequence of endothelial interaction with platelets or thrombocytes and mononuclear cells, uptake of specific lipoproteins, cholesteryl ester removal, production of collagen, elastin ad proteoglycans by activated smooth muscle cells. Thus, both the filtration hypothesis and the thrombogenic hypothesis for the pathogenesis of atherosclerosis appear to be correct.

Hospital charts were reviewed for 66 medical and surgical patients who received dextroamphetamine or methylphenidate to treat a depressive disorder. Approximately three-fourths showed some improvement; in half of the sample, improvement was marked or moderate. Of those who improved, 93% reached their peak response within the first 2 days. Relapse occurred in only 5 patients. Side effects were minimal. Nonsignificant trends suggested that dextroamphetamine was more effective for major depression than adjustment disorder, while methylphenidate tended to be more effective for adjustment disorder. Psychostimulants appear to be a therapeutic option in the medically ill depressed population and may be more rapidly effective with fewer side effects than tricyclic antidepressants.

Sudan staining of gross specimens with correlated histologic sections was used to localize the accumulation of fat in the aortas of genetically susceptible and resistant strains of pigeons. The birds were maintained on a cholesterol-free grain diet, and studies were done sequentially from ages 1 month to 4 years. Evidence suggests that the accumulation of lipids in musculoelastic cushions located at the origin of small branches is not necessarily a precursor of complicated lesions, but that it occurs concurrently in susceptible and resistant strains. In contrast, in the "lesion area," lipid accumulation is more striking and occurs earlier in the susceptible strain. It precedes proliferation by three to six months. Thus, in this model, two distinct types of fatty streaks can be identified and their biologic features can be defined and related to their propensity for atherogenesis.

Clonazepam, a high-potency benzodiazepine marketed for the treatment of minor motor epilepsy, was used to treat 50 patients with panic disorder (N = 22) or agoraphobia with panic attacks (N = 28). Of the 50 patients, 41 had previously been poorly responsive to standard pharmacologic therapies. At a mean dose of only 1.9 (+/- 1.0) mg/day, 39 patients (78%) responded. No serious adverse effects were encountered. This study, although retrospective and uncontrolled, suggests that clonazepam, like alprazolam, may be effective in blocking panic attacks. A possible common mechanism for the two drugs as high-potency benzodiazepines is discussed.

Because of the anxiety accompanying his obsessions and a prior panic attack, an obsessive-compulsive man was given alprazolam, which reduced his obsessions and eliminated his compulsions. The authors discuss links between obsessive-compulsive disorder and other psychiatric disorders.

We hypothesized that the dehydroepiandrosterone-sulfate (DHEA-S)/cortisol ratio, which has been used as an index of adrenocortical function, would be altered in panic disorder patients and would change after treatment. We evaluated 10 male and 14 female outpatients meeting DSM-III-R criteria for panic disorder. Of these 24 subjects, 13 were treated with clonazepam, 8 were treated with alprazolam, and 3 were treated with placebo as part of a double-blind study. The DHEA-S/cortisol ratio values in the 24 patients with panic disorder (mean = 20.5, SD = 11.6) were significantly higher than those of a group of 60 normal controls (mean = 11.5, SD = 6.01) and were also significantly higher than those of a group of 22 depressed patients (mean = 10.6, SD = 6.33). Although there was no significant difference in the pretreatment DHEA-S/cortisol ratio values between male (mean = 23.6, SD = 11.8) and female (mean = 18.2, SD = 11.3) panic disorder patients, the effects of treatment on this ratio differed between the two sexes. In fact, in the female patients there was a significant decrease in the DHEA-S/cortisol ratio at the end of the study (mean = 15.1, SD = 7.9), while in the male patients there was no significant change in this ratio at the end of the study (mean = 30.2, SD = 21.4). No significant differences were noted between pretreatment and posttreatment DHEA-S/cortisol ratio values in patients treated with alprazolam (n = 8), in patients treated with clonazepam (n = 13), or in patients treated with placebo (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)