Factors associated with response after deep transcranial magnetic stimulation in a real-world clinical setting: Results from the first 40 cases of treatment-resistant depression.

BACKGROUND: Deep transcranial magnetic stimulation (dTMS) has been sanctioned by the United States Food and Drug Administration for treatment-resistant depression. In a retrospective cohort study, we evaluated response and effectiveness of dTMS in real-world practice, as an add-on treatment for resistant depression. METHODS: Forty adult outpatients suffering from depression, all taking psychiatric medications, underwent 20 dTMS treatments over a 4-6 week period. At baseline (T0), visit 10 (T1), and visit 20 (T2), the Clinical Global Impression-Severity (CGI-S) scale was administered, and the Clinical Global Impression Improvement (CGI-I) scale was completed at T1 and T2; the Hamilton Depression Rating Scale (HDRS-21) was administrated at T0 and T2 only. The patients also completed the Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR) at T0, T1, and T2. RESULTS: Depressive symptoms (HDRS-21 total score) decreased significantly following treatment. The HDRS total score decreased from an average of 21.22 (±6.09) at T0, to 13.95 (±7.24) at T2. Correspondingly, at T2, 32.5% were responders to the treatment and 20% were in remission, based on the HDRS-21. Treatment was well tolerated, with a discontinuation rate of 7.5%. While depressive symptoms at baseline did not predict remission/response at T2, higher HDRS scores at T0 were associated with a larger decrease in depressive symptoms during the study. CONCLUSIONS: Significant antidepressant effects were seen following 20 dTMS treatments, given as augmentation to ongoing medications in treatment-resistant depression. The findings suggest that among patients with TRD, the severity of the depressive episode (and not necessarily the number of failed antidepressant medication trials) is associated with a positive therapeutic effect of dTMS. Hence, the initial severity of the depressive episode may guide clinicians in referring patients for dTMS.

Executive dysfunction in bipolar disorder and borderline personality disorder.

OBJECTIVE: The boundary between bipolar disorder (BD) and borderline personality disorder is a controversial one. Despite the importance of the topic, few studies have directly compared these patient groups. The aim of the study was to compare the executive functioning profile of BD and BPD patients. METHOD: Executive functioning (sustained attention, problem-solving, planning, strategy formation, cognitive flexibility and working memory) was assessed in BD (n=30) and BPD outpatients (n=32) using a computerized assessment battery (Cambridge Neuropsychological Test Automated Battery, CANTAB). The groups were compared to one another as well as to healthy controls. RESULTS: BD patients showed deficits in strategy formation and in planning (indicated by longer execution time in the ToL task) in comparison to BPD patients and healthy controls. BPD patients showed deficits in planning (short deliberation time in the ToL task) in comparison to BD patients and in comparison to healthy controls. In comparison to healthy controls, BPD patients displayed deficits in problem-solving. CONCLUSIONS: Differences in executive dysfunction between BD and BPD patients suggest that this cognitive dimension may be relevant for the clarification of the boundary between the disorders.

Remission of positive symptoms according to the "remission in Schizophrenia Working Group" criteria: a longitudinal study of cognitive functioning.

Schizophrenia patients in positive symptomatic remission (PSR; n=39) were assessed using a longitudinal research design. The patients were found to exhibit widespread cognitive impairments that were stable over the three-year follow-up period. The findings support a generalized and stable cognitive impairment profile among schizophrenia patients in partial symptomatic remission.

Comparison of insight among schizophrenia and bipolar disorder patients in remission of affective and positive symptoms: analysis and critique.

BACKGROUND: Schizophrenia and bipolar disorder are associated with impairments in insight, leading to a poorer clinical outcome and functioning. Earlier studies comparing the two disorders on the basis of insight included inpatients or patients who were clinically symptomatic. The current study therefore assessed patients in remission of affective symptoms and positive symptoms of schizophrenia. METHODS: Schizophrenia and bipolar disorder patients (n=32, n=34; respectively) underwent clinical and functional evaluations. Insight was assessed using the Scale to assess Unawareness of Mental Disorder (SUMD) and the positive and negative syndrome scale (PANSS). Attention was assessed using a continuous performance task (CANTAB's rapid visual information processing). RESULTS: Schizophrenia patients displayed poorer insight into having a mental disorder and into the social consequences thereof compared to the bipolar disorder patients. They were also less aware of their anhedonia-asociality. Age, however, was significantly correlated with insight and differences in insight between the patient groups became nonsignificant when age was used as a covariate in the statistical analyses. Age was not a moderating variable of the relationship between diagnosis and insight. CONCLUSIONS: Significant differences in insight held by the two patient groups might be related to age disparities between patient groups. Earlier studies did not adequately address these age differences, their cause and their potential effects on findings. These issues are explored with regard to the findings of the current study, as well as earlier studies, emphasizing the need for further research of the relationship between age and insight.

Positive effects of repetitive transcranial magnetic stimulation on attention in ADHD Subjects: a randomized controlled pilot study.

OBJECTIVES: Repetitive transcranial stimulation (rTMS) affects dopaminergic secretion in the prefrontal cortex. Attention deficit hyperactivity disorder (ADHD) had been suggested to involve dopaminergic prefrontal abnormalities. METHODS: In this crossover double-blind randomized, sham-controlled pilot study, patients diagnosed as having adult ADHD received either a single session of high-frequency rTMS directed to the right prefrontal cortex (real rTMS) or a single session of sham rTMS. RESULTS: A total of 13 patients (seven males, six females) who fulfilled the criteria for adult ADHD, according to DSM-IV criteria gave informed consent and were enrolled. There was a specific beneficial effect on attention 10 minutes after a real rTMS course. The post-real rTMS attention score improved significantly (M=3.56, SD=0.39) compared to the pre-real rTMS attention score (M=3.31, SD=0.5) [t(12)=2.235, P < 0.05]. TMS had no effect on measures of mood and anxiety. The sham rTMS had no effect whatsoever. CONCLUSIONS: Our findings should encourage future research on the possibility of amelioration of attention difficulties in patients suffering from ADHD by using high frequency rTMS directed to the right dorsolateral prefrontal cortex. (NIH registry NCT00825708).

Olanzapine, risperidone and haloperidol in the treatment of adolescent patients with schizophrenia.

OBJECTIVES: To evaluate and compare the drug response and side effects of adolescents with schizophrenia treated with olanzapine, risperidone, and haloperidol. METHODS: Forty-three patients were treated with olanzapine (n = 19), risperidone (n = 17) and haloperidol (n = 7) for 8 weeks in an open clinical trial. Clinical improvement was evaluated with the Positive and Negative Syndrome Scale (PANSS), and side effects with the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale. RESULTS: Significant clinical improvement was observed by week 4 for all medications. Olanzapine and haloperidol induced fatigability more frequently than risperidone. Haloperidol was associated with a higher frequency of depression and more severe extrapyramidal symptoms. CONCLUSIONS: To the best of our knowledge this is the first study in adolescents to compare the efficacy and side effects of three most commonly prescribed antipsychotic medications. Olanzapine, risperidone and haloperidol appear to be equally effective for the treatment of schizophrenia in adolescent inpatients but have different side effect profiles.

Electroconvulsive therapy in adolescents: similarities to and differences from adults.

OBJECTIVE: Information on the indications, technique, and effectiveness of electroconvulsive therapy (ECT) in adolescent patients is scarce. The recommendations for the use of ECT in this age group are similar to those in adults. This study compares the experience with ECT in the two age groups in the same community psychiatric institution, which adheres to the accepted protocols for diagnosis and treatment. METHOD: The files of 24 consecutive adolescent patients treated in an ECT unit located in the center of Israel in the years 1991-1995 were retrospectively examined, and the findings were compared with those in 33 adult patients who started their ECT course on the same day. The technique for applying ECT was essentially the same in the two age groups. RESULTS: ECT was equally effective for adolescents and adults (58% in each group achieved remission). The main difference was the diagnosis for which patients were referred: most of the adolescents were in the "psychotic spectrum, whereas most of the adults were in the "affective spectrum." CONCLUSIONS: The findings support the current medical recommendations for the use of ECT in adolescents. Possible explanations for the differences in diagnosis between the two age groups are discussed.

Injections of depot antipsychotic medications in patients suffering from schizophrenia: do they hurt?

INTRODUCTION: Long-acting depot injections of antipsychotic medications are an important way to monitor treatment noncompliance in patients suffering from schizophrenia. Pain and discomfort at the injection site may result in patients' refusal of depot injections. The present study is a pilot study that attempts a systematic characterization of injection site pain. METHOD: Thirty-four consecutive outpatients suffering from DSM-IV-defined schizophrenia or schizoaffective disorder and treated with depot antipsychotic medications were evaluated. The pain they suffered from the injections was quantified using a visual analog scale. This evaluation was made 5 minutes before the injection, 5 minutes after. 2 days after, 10 days after, and before the next injection. Patients were also administered a modified version of the Rating of Medication Influences scale that included a specific question on the possible relationship between injection-associated pain and future compliance to depot treatment. RESULTS: The depot injections cause pain, which is maximal immediately after the injection, declines substantially 2 days after, and disappears by the tenth day after the injection. A correlation exists between reported injection site pain and the effect it has on patients' attitude toward the depot injection as reported by the patients. Zuclopenthixol depot injection is more painful than other depot medications. CONCLUSION: Depot injections are painful. The pain they inflict has a typical course, and medication type is among the factors that influence this pain. This pain might have an effect on patients' attitude toward depot injections and thus is of importance in the management of patients suffering from schizophrenia.

Assessment of a creatine kinase-MB/myoglobin kit in the prehospital setting in patients presenting with acute nontraumatic chest pain: the "Shahal" experience.

OBJECTIVES: To evaluate the usefulness of a novel qualitative, rapid, bedside immunoassay device for the detection of elevated creatine kinase MBmass (CK-MB) and myoglobin as a supportive tool for decision-making by the physician who is evaluating patients who present with chest pain. DESIGN: Prospective study. SETTING: Prehospital (mobile intensive care units). PATIENTS: Three hundred twenty-eight consecutive patients, age 71+/-13 yrs (64% males), who were admitted to the hospital via Shahal's mobile intensive care units. INTERVENTION: During a 6-month period, based on clinical presentations and electrocardiograms, the mobile's physicians classified patients into groups of high or low probability of having an acute myocardial infarction and, thereafter, used a rapid bedside STATus kit (Spectral Diagnostics, Toronto, Ontario, Canada) to determine blood creatine kinase/MB and myoglobin. MEASUREMENTS AND MAIN RESULTS: Myocardial infarction was confirmed in 59 (18%) patients. If measured >2 hrs after onset, diagnostic sensitivities, specificities, and positive and negative predictive values for physicians were as follows: 71%, 90%, 46%, and 96%, respectively, compared with 100%, 85%, 44%, and 100%, respectively, if assessed by the kit. CONCLUSIONS: If used 2 to 12 hrs from the onset of symptoms, this device is a convenient diagnostic aid to prevent a misdiagnosis of acute myocardial infarction or unnecessary hospitalization to exclude infarction. This tool may be a promising cost-cutting factor in these days of escalating expenses and dwindling resources.

Protein tyrosine kinases in bacterial pathogens are associated with virulence and production of exopolysaccharide.

In eukaryotes, tyrosine protein phosphorylation has been studied extensively, while in bacteria, it is considered rare and is poorly defined. We demonstrate that Escherichia coli possesses a gene, etk, encoding an inner membrane protein that catalyses tyrosine autophosphorylation and phosphorylation of a synthetic co-polymer poly(Glu:Tyr). This protein tyrosine kinase (PTK) was termed Ep85 or Etk. All the E.coli strains examined possessed etk; however, only a subset of pathogenic strains expressed it. Etk is homologous to several bacterial proteins including the Ptk protein of Acinetobacter johnsonii, which is the only other known prokaryotic PTK. Other Etk homologues are AmsA of the plant pathogen Erwinia amylovora and Orf6 of the human pathogen Klebsiella pneumoniae. These proteins are involved in the production of exopolysaccharide (EPS) required for virulence. We demonstrated that like Etk, AmsA and probably also Orf6 are PTKs. Taken together, these findings suggest that tyrosine protein phosphorylation in prokaryotes is more common than was appreciated previously, and that Etk and its homologues define a distinct protein family of prokaryotic membrane-associated PTKs involved in EPS production and virulence. These prokaryotic PTKs may serve as a new target for the development of new antibiotics.

The CB-12L: a new device for transtelephonic transmission of a 12-lead electrocardiogram.

The value of transtelephonic transmission of ECG information is well established, and technological advances have continuously provided improved state-of-the-art equipment. Shahal Medical Services provides professional care to subscribers who call the medical center and describe their symptoms, whereupon therapeutic measures are decided upon. A new 12-lead patient controlled device for telephonically transmitting an ECG (GB-12L) has become available; the aim of this study was to evaluate its accuracy and practicability. Forty tracings (20 standard ECG tracings obtained under medical supervision in the physician's office and 20 by the patient in his home using the new CB-12L ECG device and transmitted by telephone to the center) from 20 subjects with various electrocardiographic pathologies were reviewed by 19 experienced physicians who were asked to interpret the results and identify the recording device. In 82% of the possibilities, the interpretation of the tracings was identical for both those recorded by the standard ECG recorder and the CB-12L ECG. An equal number of physicians could not identify the means by which device the tracings were taken. Proper placement of the electrodes did not prove to be a problem for the patient. Thus, the CB-12L ECG was found to be an easily operable and reliable tool which may be of value for early and prompt diagnosis of threatening cardiac situations in the prehospital setting.

Usefulness of self-administration of intramuscular lidocaine in the prehospital setting for ventricular tachyarrhythmias unassociated with acute myocardial infarction (the "Shahal" experience in Israel).

We report on the experience accumulated by the subscribers of SHAHAL cardiac services who self-injected intramuscular lidocaine (using an automatic injector "LidoPen") for documented ventricular tachyarrhythmias which were not associated with an acute myocardial infarction. SHAHAL provides professional care to its subscribers who telephone a monitor center and describe their symptoms, whereupon therapeutic measures are decided upon. Patient data are stored in a central computer, and the center can dispatch mobile intensive care units. All subscribers carry a portable transtelephonic electrocardiographic transmitter and are provided with the LidoPen. Indications for self-injection were: transmission of a wide-QRS tachycardia (rate > 100 beats/min), symptomatic multiple or complex ventricular premature complexes in association with chest discomfort, and when the time of arrival of a medical team to the patient was estimated to be at least 8 to 10 minutes. Successful usage of the LidoPen was reported in 137 cases (123 patients). An additional 11 patients failed to use the injector properly. There was a success rate in abolishing rapid sustained ventricular tachycardia (27 of 76 patients) and nonsustained ventricular tachycardia and/or multiple and complex ventricular ectopic activity (8 of 30 patients) of 33% (total 35 of 106 patients). In another 9%, those arrhythmias were slowed markedly. The remaining 31 cases were eventually interpreted as being of supraventricular origin. No complications attributed to the use of the injector were reported and its use was found to be both feasible and effective in the prehospital setting.

Albuminuria in diabetes mellitus: relation to ambulatory versus office blood pressure and effects of cilazapril.

This study aimed to investigate the relationship between microalbuminuria and office blood pressure (BP) as compared with ambulatory BP in patients with diabetes mellitus under everyday practice conditions. It was also undertaken to assess the effect of the angiotensin converting enzyme inhibitor cilazapril on diabetes-associated albuminuria. Ambulatory BP was recorded during daytime in 54 patients with type II diabetes mellitus at the end of a 4-week period during which they received no vasoactive drug. The difference between office and ambulatory BP was unpredictable in the individual patient. There was no significant correlation between either ambulatory or office BP and urinary albumin/p5eatinine ratio. Fifty-one patients underwent a 40-week treatment with 5 mg/day of cilazapril. There was, in the absence of satisfactory BP control, the possibility of adding the calcium antagonist amlodipine (5 mg/day) from the 10th week onward and 12.5 mg/day of hydrochlorothiazide from the 20th week onward. Office mean BP was significantly reduced after 30 to 40 weeks of therapy in patients with normoalbuminuria (n = 19, -14%, P < .001), in those with microalbuminuria (n = 22, -6.6%, P < .01), as well as in those with clinical proteinuria (n = 9, -11.4%, P < .01). During the same time, the urinary albumin/creatinine ratio was not modified in normoalbuminuric patients (n = 19, +24.6%, P = .72) as well as in those with clinical proteinuria (n = 9, -29.4%, P = .09). On the other hand this value was significantly reduced for the group with microalbuminuria (n = 23, -24.3%, P < .05). In the overall population, as well as in hyperalbuminuric patients (patients with microalbuminuria + patients with clinical proteinuria), the reduction of the albumin/ creatinine ratio was also significant (n = 51, -7%, P < .01 and n = 32, -25,7%, P < .01, respectively). In conclusion, the findings of this study performed by practicing physicians show that ambulatory BP may differ greatly from office BP in diabetic patients. They also indicate that urinary albumin excretion is poorly correlated with office and ambulatory BP in type II diabetics. Finally, they demonstrate the antiproteinuric action of prolonged treatment with the angiotensin converting enzyme inhibitor cilazapril, whether given alone or combined with amlodipine.

Dibenzepin overdose causing pulmonary edema.

OBJECTIVE: To report a case of pulmonary edema due to dibenzepin overdose. CASE SUMMARY: A 39-year-old woman was hospitalized 24 hours after she ingested eight tablets of dibenzepin hydrochloride delayed-release 240 mg/tablet (approximately 35 mg/kg body weight). On admission the patient was confused, and physical examination revealed sinus tachycardia (HR 130 beats/min). Forty-five hours after ingestion of the dibenzepin she developed pulmonary edema and was treated with furosemide, morphine, and mechanical ventilation through an endotracheal tube for 48 hours. Repeated echocardiography revealed left ventricular dysfunction that resolved as the medical condition of the patient improved. Appropriate studies excluded pneumonia, pneumonitis, adult respiratory distress syndrome, myocardial infarction, and pulmonary emboli as contributing factors to this patient's condition. DISCUSSION: Tricyclic antidepressant overdose is known to cause cardiopulmonary complications, including pulmonary edema. To the best of our knowledge, this is the first reported case of pulmonary edema as a result of dibenzepin overdose. The most probable mechanism for this complication is depression of the left ventricular function. CONCLUSIONS: As with other tricyclic antidepressants, dibenzepin toxicity may cause pulmonary edema. Close patient monitoring is essential for at least 48-72 hours after the overdose.

[Hemodynamic effects of milrinone in the treatment of cardiac insufficiency after heart surgery with extracorporeal circulation]. / Effets hémodynamiques de la milrinone dans le traitement de l'insuffisance cardique après chirurgie cardiaque sous circulation extracorporelle.

Milrinone is an inotropic agent of the phosphodiesterase inhibitor family. In common with all molecules of this class it has both positive inotropic and vasodilator effects. The haemodynamic effects of 3 dosages of milrinone were studied in 25 patients with low output states after open heart surgery. The low cardiac output was defined as a cardiac index of less than 2.5/min/m2 and pulmonary capillary pressures greater than 8 mmHg. Milrinone was administered as a bolus of 50 micrograms/kg/min over 10 minutes followed by a continuous infusion for at least 12 hours. Six patients were given 0.375 micrograms/kg/min, six patients 0.5 micrograms/kg/min, and 13 patients 0.75 g/kg/min. A significant increase in cardiac index was observed but without any difference between the 3 groups. The heart rate and stroke volumes were increased. There was a mild reduction in systemic blood pressure with a decrease in systemic arterial resistances which returned to almost normal values. Left and right filling pressures did not decrease significantly from the initial values until the end of the bolus injection. Indirect measurements of myocardial oxygen consumption showed an increase in this parameter. There were no changes in blood gas concentrations. The treatment was stopped in only one patient because of peripheral vasodilation. Two patients developed supraventricular tachycardia of no consequence. Milrinone may therefore be proposed as treatment of first intention of low cardiac output states after open heart surgery. It is associated with a mild vasodilatory effect. Improved myocardial function is observed providing attention is paid to vascular filling. None of the maintenance doses used after the bolus injection was shown to be more effective than the others.