Publications

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    ABSTRACT: Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD. We recruited 212 MDD outpatients, aged 22–68 years, who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode. They were randomly assigned to monotherapy with active or sham dTMS. Twenty sessions of dTMS (18 Hz over the prefrontal cortex) were applied during 4 weeks acutely, and then biweekly for 12 weeks. Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale (HDRS-21) score and response/remission rates at week 5, respectively. dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group (p=0.008), resulting in a 0.76 effect size. Response and remission rates were higher in the dTMS than in the sham group (response: 38.4 vs. 21.4%, p=0.013; remission: 32.6 vs. 14.6%, p=0.005). These differences between active and sham treatment were stable during the 12-week maintenance phase. dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred. These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, and whose effect remains stable over 3 months of maintenance treatment.
    World psychiatry: official journal of the World Psychiatric Association (WPA) 02/2015; 14(1):64. DOI:10.1002/wps.20199
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    ABSTRACT: Aims: The International Survey Informing Greater Insights in Opioid Dependence Treatment (INSIGHT) study evaluated the implementation of opioid dependence treatment across different countries to assess treatment delivery, quality of care and outcomes. Methods: A questionnaire-based survey was used to gather data in nine countries across Central and Eastern Europe, South Africa and South-East Asia, from patients with opioid dependence receiving medication-assisted treatment (MAT), healthcare professionals (HCPs) who cared for opioid-dependent patients and opioid users not receiving MAT. Findings: There was substantial variation between countries, but overall results suggest that several aspects of MAT can be improved, such as access to treatment (conditions to start or remain in treatment), quality of care (availability/awareness of treatment options and appropriate medication dosing) and treatment outcomes (on-top use, misuse and diversion). Conclusions: This analysis highlights key priorities that should improve the quality of opioid dependence care and access to treatment. These priorities include: acknowledging opioid dependence as a chronic medical condition requiring long-term treatment; recognition by policymakers of the cost-effectiveness of treatment; making available, to those who want them, psychosocial interventions and educating HCPs to prescribe the safest, least divertible forms of medications available at optimal doses in order to reduce opioid use, misuse and diversion.
    Drugs: Education Prevention and Policy 08/2014; 21(6). DOI:10.3109/09687637.2014.945511
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    ABSTRACT: Tobacco smoking is the leading cause of preventable death in developed countries. Our previous studies in animal models and humans suggest that repeated activation of cue-induced craving networks followed by electromagnetic stimulation of the dorsal prefrontal cortex (PFC) can cause lasting reductions in drug craving and consumption. We hypothesized that disruption of these circuitries by deep transcranial magnetic stimulation (TMS) of the PFC and insula bilaterally can induce smoking cessation.
    Biological Psychiatry 06/2014; 76(9). DOI:10.1016/j.biopsych.2014.05.020
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    A Weinstein, L Dinur Klein, P N Dannon
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    ABSTRACT: Gambling behavior is not a unique behavior. There are certain differences in behavior, gambling habits, gambling beliefs, and their reflection in psychosocial life. We have compared three groups of adult male gamblers-sports gamblers (n = 41), machine gamblers (n = 36), and poker gamblers (n = 35)-in regard to measures of personal status and legal-social characteristics. We found no difference between groups in terms of the length of gambling behavior, personal status, or age. We found no legal difference between groups in terms of the number of court cases for debt, stealing, or family court cases. In terms of economic circumstances, sports gamblers suffered more losses than the other groups (p < 0.0001). There were higher rates of bankruptcy among sports gamblers compared with machine gamblers (p < 0.01). Sports gamblers were more likely to borrow money from the black market compared with the other groups (p < 0.01). In terms of mental health, sports and machine gamblers had more suicidal thoughts and gestures than poker gamblers (p < 0.05), whereas the rate of suicide attempts was higher in machine gamblers compared with poker players (p < 0.05). Our results indicated higher vulnerability in sports gamblers in terms of economic problems compared with the other groups, whereas machine gamblers had vulnerability to suicidal thoughts and suicidal attempts compared with poker gamblers.
    Journal of Gambling Behavior 05/2014; DOI:10.1007/s10899-014-9462-5
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    ABSTRACT: Problematic Internet use (PIU) or Internet Addiction Disorder (IAD) is characterized by excessive or poorly controlled preoccupations, urges, or behaviors regarding Internet use that lead to impairment or distress. Due to the increased use of the Internet over the past 15 years, IAD has attracted attention of researchers and clinicians in the field. Young (1998) and Griffiths (1998; 2000) were the first who defined IAD and have done extensive research. Internet addiction has also attracted increasing coverage in the popular media and among researchers, and this attention has paralleled the growth in computer use and Internet access (Shaw & Black, 2008). Phenomenologically, there appear to be at least three IAD subtypes: excessive gaming-gambling, sexual preoccupations (cybersex), and socializing or social networking, including e-mail and messaging. Internet addicts may use the Internet for extended periods, isolating themselves from other forms of social contact, and focus almost entirely on the Internet rather than broader life events. Adolescents with problematic Internet use showed dysfunctional coping strategies with problems in school and home and showed worse interpersonal relations (Milani, Osualdella, & Di Blasio, 2009). IAD can also be explained by a need to “escape from oneself,” which may account for the excessive playing of Internet games (Kwon, Chung, & Lee, 2011).
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    Guy Sender Zahavi, Pinhas Dannon
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    ABSTRACT: Electroconvulsive therapy (ECT) is considered to be one of the most effective treatments in psychiatry. Currently, three medications for anesthesia are used routinely during ECT: propofol, etomidate, and thiopental. The objective of this study was to evaluate the effects of the anesthetics used in ECT on seizure threshold and duration, hemodynamics, recovery from ECT, and immediate side effects. Our study is a retrospective cohort study, in which a comparison was made between three groups of patients who underwent ECT and were anesthetized with propofol, etomidate, or thiopental. The main effect compared was treatment dose and seizure duration. All patients were chosen as responders to ECT. Data were gathered about 91 patients (39 were anesthetized with thiopental, 29 with etomidate, and 23 with propofol). Patients in the thiopental group received a lower electrical dose compared to the propofol and etomidate group (mean of 459 mC compared to 807 mC and 701 mC, respectively, P<0.001). Motor seizure duration was longer in the thiopental group compared to propofol and etomidate (mean of 40 seconds compared to 21 seconds and 23 seconds, respectively, P=0.018). Seizure duration recorded by electroencephalography was similar in the thiopental and etomidate groups and lower in the propofol group (mean of 57 seconds in both groups compared to 45 seconds, respectively, P=0.038). Patients who were anesthetized with thiopental received a lower electrical treatment dose without an unwanted decrease in seizure duration. Thiopental might be the anesthetic of choice when it is congruent with other medical considerations.
    Neuropsychiatric Disease and Treatment 01/2014; 10:383-9. DOI:10.2147/NDT.S58330
  • P. Dannon
    Value in Health 11/2013; 16(7):A682. DOI:10.1016/j.jval.2013.08.2014
  • Oded Rosenberg, Limor Klein Dinur, Pinhas N Dannon
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    ABSTRACT: In the past decade, we have witnessed the emergence of pharmacological treatments for pathological gambling with some success but many question marks. We aimed to explore pharmacological treatments that have been previously explored with some success, with the intent of comparing their efficacy and pave the way to larger placebo-controlled trials. In this study, we allocated 78 patients to 4 different types of psychotropic medications: naltrexone, topiramate, bupropion, and escitalopram. We treated patients for more than 2 years, with additional 2-year follow-ups without medication. The sample was evaluated using the 21-item Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Global Assessment of Functioning, and the Visual Analog Scale to measure general well-being before enrollment as well as at 1 month, 6 months, 24 months, and 48 months after beginning medication treatment. During the first 2 years of treatment, 34 patients dropped out, with one more dropping out during the additional 2 years of follow-up. Significant improvement on all rating scales was seen in all groups after 2 years, except HAMD in the group that received topiramate.We found the naltrexone-treated group of patients to have a statistically significant lower dropout rate compared with other groups, statistically significant lower HAMD scores in comparison to the group treated with bupropion, statistically significant lower Hamilton Anxiety Rating Scale score compared to the groups treated with escitalopram and topiramate, and significantly higher Visual Analog Scale scores compared to the groups treated with bupropion and topiramate. Pathological gambling is essentially a biopsychological disorder that may be attenuated provided that patients adhere to medication. In our study, among 4 medications with different mechanisms of action, naltrexone was found to be the most effective. Placebo-controlled studies involving large numbers of subjects are required before naltrexone's efficacy can be established.
    Clinical neuropharmacology 03/2013; 36(2):42-5. DOI:10.1097/WNF.0b013e31828740ea
  • Oded Rosenberg, Limor Dinur Klein, Pinhas N Dannon
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    ABSTRACT: Five pathological gamblers received deep transcranial magnetic stimulation (DTMS). Evaluations included rating scales and collateral anamnesis. Despite initial improvement in ratings, collateral anamnesis demonstrated failure to respond. DTMS to the pre-frontal cortex using an H1 coil was an ineffective treatment. Our study is preliminary, and additional studies are required.
    10/2012; DOI:10.1016/j.psychres.2012.09.045
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    ABSTRACT: Background: Football (soccer) betting, as a strategic form of betting, became one of the favorite wagers for pathological gamblers. Previous studies demonstrated the psychological and biological significance of the 'illusion of control' (personal control) and 'near miss' results in gambling. In our study, we explored whether knowledge and expertise of pathological sports gamblers can ensure a successful bet. Sample and Methods: Participants were divided into three groups of individuals - pathological gamblers, amateurs and laypersons - and were asked to predict in advance the general result and the exact result of football matches in the European Champions League Round of 16. Results: The 165 participants included 53 pathological sports gamblers (52 males and 1 female), 78 laypersons (45 females and 33 males) and 34 amateurs (all males). After a thorough statistical analysis, we found no significant differences between the groups, no matter what kind of previous knowledge they had acquired. Conclusion: This study demonstrates that the 'illusion of control' of pathological gamblers, attained by knowledge of the game and its latest data and information (especially in a strategic gamble as football betting), has no factual background. Moreover, our study demonstrates without a doubt that there is no significant difference between the male pathological sports gamblers group and the male/female laypersons group.
    Psychopathology 08/2012; 46(1). DOI:10.1159/000338614
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    ABSTRACT: About 25% of schizophrenia patients with auditory hallucinations are refractory to pharmacotherapy and electroconvulsive therapy. We conducted a deep transcranial magnetic stimulation (TMS) pilot study in order to evaluate the potential clinical benefit of repeated left temporoparietal cortex stimulation in these patients. The results were encouraging, but a sham-controlled study was needed to rule out a placebo effect. A total of 18 schizophrenic patients with refractory auditory hallucinations were recruited, from Beer Yaakov MHC and other hospitals outpatient populations. Patients received 10 daily treatment sessions with low-frequency (1 Hz for 10 min) deep TMS applied over the left temporoparietal cortex, using the H1 coil at the intensity of 110% of the motor threshold. Procedure was either real or sham according to patient randomization. Patients were evaluated via the Auditory Hallucinations Rating Scale, Scale for the Assessment of Positive Symptoms-Negative Symptoms, Clinical Global Impressions, and Quality of Life Questionnaire. In all, 10 patients completed the treatment (10 TMS sessions). Auditory hallucination scores of both groups improved; however, there was no statistical difference in any of the scales between the active and the sham treated groups. Low-frequency deep TMS to the left temporoparietal cortex using the protocol mentioned above has no statistically significant effect on auditory hallucinations or the other clinical scales measured in schizophrenic patients. Clinicaltrials.gov identifier: NCT00564096.
    Annals of General Psychiatry 05/2012; 11:13. DOI:10.1186/1744-859X-11-13
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  • Roman Gersner, Oded Rosenberg, Pinhas N Dannon
    05/2012; 9(3):269-278. DOI:10.2217/cpr.12.23
  • Oded Rosenberg, Pinhas N Dannon
    03/2012; 9(2):125-127. DOI:10.2217/cpr.12.6
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    ABSTRACT: The phenomenon of hair pulling has been recognized for centuries, yet the true prevalence of trichotillomania (TTM) is largely unknown and the topic has been sparsely studied. TTM is classified as an impulse-control disorder despite much debate about its etiology. In this review we summarize the different hypotheses, including impulse-control disorders, obsessive-compulsive disorders, behavioral problems and addiction, and the appropriate treatment methods. The combination of selective serotonin reuptake inhibitors and antipsychotic medications are shown to be most effective. Treatment with anti-addiction drugs seems relevant. Further research is needed to increase our knowledge regarding the etiology of TTM.
    The Israel Medical Association journal: IMAJ 02/2012; 14(2):125-9.
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    ABSTRACT: Pathological gambling (PG) disorder occurs when a person gambles repetitively despite severe negative effects on important aspects of life. PG tends to be a heterogonous disorder in which patients differ with respect to type and intensity of gambling behavior, psychiatric comorbidity, family history, age at onset and gender. Gamblers may accordingly be classified into three subtypes: the “impulsive”, “obsessive-compulsive” and “addicted” subtypes.Aimsto characterize a sample of Italian PG pathological gamblers and assess the prevalence of the various gambling subtypes in this population.Methods52 outpatients (44 men, 9 women), diagnosed with PG according to DSM IV-TR and SOGS criteria, were administered the Dannon Ainhold Gambling Scale (DAGS), which assesses the presence of the disorder and is useful for patient subtyping.Results37 gamblers enrolled in our study played one specific kind of game, while 15 played multiple games. 30 patients played slot machines, 18 sport betting, 11 casino and card games, 14 bingo and scratch cards. According to DAGS, 5 (9,6%) patients belonged to the “addicted” subtype, 4 (7,7%) to the “obsessive-compulsive” subtype and 9 (17,3%) to the “impulsive” subtype. 15 (28,8%) gamblers were classified as “addicted-impulsive” subtype, 10 (19,2%) as “addicted-obsessive-impulsive” subtype, while 9 (17,3%) did not belong to any specific subtype though they displayed a tendency for one of the subtypes.ConclusionDAGS allows to identify three major subtypes of gamblers and also considers possible combinations between the different subtypes. An evaluation of these aspects could be useful in treatment options based on patient subtype.
    European Psychiatry 01/2012; 27:1. DOI:10.1016/S0924-9338(12)74243-8
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    ABSTRACT: The aim of our study was to evaluate the effectiveness of Cognitive Behavioral Group Therapy (CBGT) in the treatment of Panic Disorder (PD) and to compare the treatment outcome of CBGT versus Paroxetine pharmacotherapy. Fifty seven patients referred to our anxiety disorder clinic for the treatment of PD were randomly allocated to receive either CBGT or Paroxetine. Follow up was done by a masked rater after four and twelve weeks of treatment in order to compare the efficacy of CBGT versus Paroxetine. CBGT and Paroxetine were both effective in the short-term treatment of PD. Assessments at weeks four and twelve of treatment showed no statistically significant differences between the two groups in terms of treatment outcome. Treatment with CBGT alone for the acute phase of PD appears to be equally efficacious to treatment with Paroxetine alone. Our study shows that CBGT produced beneficial results, for it was associated with a reduction in the number and frequency of panic attacks and with an improved feeling of well-being.
    Annals of Clinical Psychiatry 12/2011; 16(1):41-6.
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    ABSTRACT: Marijuana addiction is one of the most common forms of addiction worldwide. A variety of reasons for use exist, however, there are only a few tested treatments with frequent relapses. In this study, we examined the efficacy of four pharmacotherapy agents for the treatment of marijuana addiction: naltrexone, bupropion, escitalopram and bromazepam. A total of 59 patients were randomly assigned into four groups. Each group received one of the pharmacological agents for 120 days. Four types of questionnaires were employed: The Hamilton Rating Scale for Depression--21 items, the Hamilton Rating Scale for Anxiety, the Global Assessment of Functioning and a Visual Analogue Scale for perceived need of the drug. In addition, random urine tests were performed to detect tetrahydrocannabinol [THC). Naltrexone proved to be the most efficacious of the four agents, with only four dropouts. Other agents proved less efficacious with six, seven and eights dropouts for bupropion, bromazepam and escitalopram, respectively. In addition, naltrexone was most efficacious in reducing anxiety and depression rates, and increasing functioning and perceived need for drug use. Out of four pharmacological agents, naltrexone proved to be most efficacious in treating marijuana addiction and related disorders. Further studies are needed to confirm our results.
    Harefuah 12/2011; 150(12):888-92, 937.
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    ABSTRACT: Objectives: Pathological gambling (PG) is a highly prevalent and disabling impulse control disorder. A range of psychopharmacological options are available for the treatment of PG, including selective serotonin reuptake inhibitors, opioid receptor antagonists, anti-addiction drugs, and mood stabilizers. In our preliminary study, we examined the efficacy of two anti-addiction drugs, baclofen and acamprosate, in the treatment of PG. Materials and Methods: Seventeen male gamblers were randomly divided into two groups. Each group received one of the two drugs without being blind to treatment. All patients underwent a comprehensive psychiatric diagnostic evaluation and completed a series of semi-structured interviews. During the 6-months of study, monthly evaluations were carried out to assess improvement and relapses. Relapse was defined as recurrent gambling behavior. Results: None of the 17 patients reached the 6-months abstinence. One patient receiving baclofen sustained abstinence for 4 months. Fourteen patients succeeded in sustaining abstinence for 1-3 months. Two patients stopped attending monthly evaluations. Conclusion: Baclofen and acamprosate did not prove efficient in treating pathological gamblers.
    Frontiers in Psychiatry 06/2011; 2:33. DOI:10.3389/fpsyt.2011.00033
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    ABSTRACT: This work investigates whether inhibition impairments influence the decision making process in pathological gamblers (PGs). The PG (N=51) subjects performed the Iowa Gambling Task (IGT as the measure of the decision making process) and two tests of inhibition: the Stroop (interference inhibition), and the Go/NoGo (response inhibition), and were compared with demographically matched healthy subjects (N=57). Performance in the IGT block 1 and block 2 did not differ between the groups, but the differences between the PGs and healthy controls began to be significant in block 3, block 4 and block 5. PGs learned the IGT task more slowly than the healthy controls and had non-optimal outcomes (more disadvantageous choices). Impaired IGT performance in PGs was not related to an inhibition ability measured by the Stroop (interference response time) and the Go/NoGo (number of commission errors) parameters. Further controlled studies with neuroimaging techniques may help to clarify the particular brain mechanisms underlying the impaired decision making process in PGs.
    Psychiatry Research 03/2011; 188(1):71-7. DOI:10.1016/j.psychres.2011.02.021
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    ABSTRACT: Schizophrenia is a chronic and disabling disease that presents with delusions and hallucinations. Auditory hallucinations are usually expressed as voices speaking to or about the patient. Previous studies have examined the effect of repetitive transcranial magnetic stimulation (TMS) over the temporoparietal cortex on auditory hallucinations in schizophrenic patients. Our aim was to explore the potential effect of deep TMS, using the H coil over the same brain region on auditory hallucinations. Eight schizophrenic patients with refractory auditory hallucinations were recruited, mainly from Beer Ya'akov Mental Health Institution (Tel Aviv university, Israel) ambulatory clinics, as well as from other hospitals outpatient populations. Low-frequency deep TMS was applied for 10 min (600 pulses per session) to the left temporoparietal cortex for either 10 or 20 sessions. Deep TMS was applied using Brainsway's H1 coil apparatus. Patients were evaluated using the Auditory Hallucinations Rating Scale (AHRS) as well as the Scale for the Assessment of Positive Symptoms scores (SAPS), Clinical Global Impressions (CGI) scale, and the Scale for Assessment of Negative Symptoms (SANS). This preliminary study demonstrated a significant improvement in AHRS score (an average reduction of 31.7% ± 32.2%) and to a lesser extent improvement in SAPS results (an average reduction of 16.5% ± 20.3%). In this study, we have demonstrated the potential of deep TMS treatment over the temporoparietal cortex as an add-on treatment for chronic auditory hallucinations in schizophrenic patients. Larger samples in a double-blind sham-controlled design are now being preformed to evaluate the effectiveness of deep TMS treatment for auditory hallucinations. This trial is registered with clinicaltrials.gov (identifier: NCT00564096).
    Annals of General Psychiatry 02/2011; 10(1):3. DOI:10.1186/1744-859X-10-3
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