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1) Compare the 5A (Ask-Advise-Assess-Assist-Arrange) practice rates between psychiatrists and primary care physicians (PCPs) regarding smoking cessation for PWSMI. 2) Compare the 5A practice rates reported by physicians with rates reported by PWSMI. 3) Identify which specialty is perceived as primarily responsible for smoking cessation promotion for PWSMI.Telephone surveys were carried out in a large health maintenance organization (HMO) among all psychiatrists, a random sample of PCPs, and HMO members with serious mental illness who had registered/participated in a smoking cessation program. Physicians were asked how frequently they carried out each 5A practice, along with questions regarding role responsibility and interaction between the two clinical specialties. PWSMI were asked to report about each 5A practice by both PCP and treating psychiatrist.Ask-Advise-Assess rates were higher than Assist-Arrange rates for both specialties. 83% of PCPs had satisfactory 5A practice scores compared to 46% of psychiatrists (iX/isup2/sup=23.9,ip/i lt; 0.001). With the exception of Ask rates, physician rates for each 5A component were higher than those reported by PWSMI. PCPs were more likely to see smoking cessation promotion as their responsibility and did not always confer with the psychiatrist regarding referral and SCM prescription.Interventions focusing on promoting Assist-Arrange practices and better integration between the specialties are required.

Introduction People with serious mental illness (SMI) are three times more likely to smoke and be heavy smokers than smokers without SMI. Counseling combined with smoking cessation medication (SCM) is the recommended treatment. However, until 2017, SCM prescription for SMI smokers was discouraged (FDA black box warning). This study compared use of smoking cessation programs (SCP) and SCM between smokers with and without SMI. Aims and Methods Data regarding SCP and SCM use were extracted from the database of a large HMO that offers free Group and telephone SCP. SCP registration, participation, completion, and abstinence rates between July 2013 and December 2019 were compared between smokers with and without SMI, controlling for demographic and health variables. Results 48 000 smokers registered for a SCP during the study period. Smokers with SMI were 1.8 times more likely to register for a SCP than smokers without SMI. Smokers without SMI were, however, 1.2 times more likely to start the SCP, 1.5 times more likely to complete the SCP, and 1.6 times more likely to have quit by the end of the program. The strongest factors predicting abstinence were SCP completion and SCM use. Smokers with SMI were less likely to purchase SCM, although their purchase rate increased after the black box warning was lifted. Conclusions Smoking cessation programs and SCM use should be encouraged in the SMI population. Providing support during the quit attempt and adapting SCP to the needs of smokers with SMI, combined with SCM prescription promotion, should improve abstinence. Implications Smokers with serious mental illness (SMI) were more likely to seek professional help to quit smoking than non-SMI smokers, with over 30% achieving abstinence, discrediting healthcare professional beliefs that SMI smokers don’t want to and cannot quit. Smoking cessation program (SCP) completion and smoking cessation medication (SCM) utilization were the strongest predictors of abstinence. SMI smokers were more likely to drop out of SCPs and less likely to use SCMs. Providing support during the quit attempt and adapting SCPs to the needs of smokers with SMI, combined with SCM prescription promotion, should improve abstinence.

Smoking prevalence is threefold higher among people with serious mental illness (PWSMI) than in the general population, yet smoking cessation rates for PWSMI are lower. Numerous reasons have been posited as to why tobacco use is higher and abstinence rates are lower among PWSMI. This study explores smoking cessation perceptions and experiences among PWSMI and people without serious mental illness (SMI). Methods: Participants in this cross-sectional study were recruited from among members of a large health maintenance organization (HMO) in Israel who had registered for or commenced a smoking cessation program in 2015 through 2017. The sample comprised 208 PWSMI and a matched sample of people without SMI (N = 428). Telephone surveys were used to collect information about smoking status and smoking/cessation history, use of smoking cessation programs and aids (prescription medications, nicotine replacement therapy, electronic cigarettes), motivation and intention to quit, self-efficacy (to quit), smoking cessation outcome expectancies, physician support to quit, barriers and facilitators for those who had not quit, and reinforcements/challenges for those who had quit. Results: Of those without SMI, 27% quit smoking compared to 20% of PWSMI (p = .051). Irrespective of mental health status, the most significant predictor of abstinence was the use of smoking cessation prescription medications. Family physicians were significantly less likely to inquire about motivation to quit, refer to smoking cessation programs, or prescribe smoking cessation medications for PWSMI than for people without SMI. Beyond these factors, no differences were noted between respondents with and without SMI regarding motivation to quit, intention to quit, and abstinence self-efficacy. PWSMI who had not quit were more likely to be concerned about how quitting might affect their functioning and how they would pass the time without cigarettes. Conclusions: PWSMI have similar levels of motivation and intention to quit smoking as those without SMI. However, they are disadvantaged by the reduced support received from their family physicians and lower cessation medication usage. Efforts to promote the implementation of smoking cessation treatment guidelines will help promote smoking abstinence among PWSMI.

Background: Despite the high prevalence of smoking amongst people with serious mental illness (SMI), referral rates to smoking cessation programs (SCPs) are low. Mental health workers reticence to ...

Objective Evidence both from animal and human studies suggests a role for dopaminergic pathways in the treatment of depression. Ropinirole, a selective agonist of dopamine D2/D3, is in use for the treatment of parkinsonism. Preliminary evidence suggests that such agonists might be useful as antidepressants. We tested whether an add-on ropinirole is an effective in depressed patients. Methods We conducted a double-blind, randomized, placebo-controlled trial of add-on ropinirole in depressed patients unresponsive to at least one antidepressant. We recruited 32 unipolar and bipolar patients who remained depressed (modified 21-item Hamilton Depression Rating Scale) despite at least 4 weeks of treatment with an adequate dose of antidepressant medication. Patients received either 2 mg of oral ropinirole or placebo twice daily added on to their current medication and were evaluated weekly for 7 weeks using the Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale. Results No difference in primary or secondary outcome measures was detected between the treatment and control groups. Discussion These results differ from previous studies and are unexpected in light of theoretical considerations. This may indicate that there are differences in pharmacological activity between ropinirole and other dopaminergic agents such as pramipexole.

Background: The influence of ethnicity on different aspects of psychiatric hospitalization is far from clear. The Aim of the Study: The main aim of the study was to compare the Arab and the Jewish inpatients, at the time of admission, for the demographic factors, severity of psychotic, and affective psychopathology and comorbid drug abuse rate. Population, Method, and Tools: Among 250 consecutively admitted patients in the Jerusalem Mental Health Center-Kfar Shaul Hospital, 202 Jews and 42 Arabs (aged 18-65 years) were examined within 48 hours after admission. The psychiatric diagnoses were made according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. For the differential measurement of psychopathologic severity, the following rating scales were used: 21-item Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale (PANSS), and Young Mania Rating Scale. Urine tests for Δ9-tetrahydrocannabinol (THC), cocaine, opiates, amphetamines, and methamphetamine were performed using the Sure Step TM kits (Applied Biotech, Inc, San Diego, CA, USA). The Structured Clinical Interview Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for drug abuse were applied based on self-report and results of urine analysis. Results: The comparison of the 2 population showed that among the Arab inpatients, there were more males (81% vs 67.4%; P < .005). No significant difference in psychiatric diagnosis was observed. The overall severity of positive symptoms (PANSS positive) in Arab group was higher, but only slightly so (P = .05). No significant difference was observed for total rates of PANSS negative subscale. The rates of PANSS-general were also similar. The Arab patients were significantly less depressive according to 21-item Hamilton Depression Rating Scale (P = .032), and the total score of Hamilton Anxiety Rating Scale for the Jewish group was significantly higher (P = .001). No significant difference in general severity of manic symptoms for 2 groups was detected according to Young Mania Rating Scale. The rate of comorbid drug abuse for Jewish inpatients was borderline higher (P = .068). Conclusions: The issue of referral to psychiatric hospitalization could be culturally influenced; it may be the result of disparities in demographic, psychopathologic, and drug abuse comorbid presenting symptoms, which are demonstrated upon admission by patients of different ethnic origins.

Selective serotonin reuptake inhibitors (SSRIs) are suspected of increasing the risk of bone loss and osteoporotic fractures. The aim of this study was to investigate the association between adherence to SSRI treatment and the risk of bone loss-related events. The data used in this retrospective cohort study are part of the ongoing medical documentation routinely collected in a large health maintenance organization in Israel. Specifically, we used the information collected between January 2004 and April 2010. The study cohort included 10 621 women who were new users of SSRIs. Bone loss-related events were defined as fractures or initiation of bisphosphonate treatment. Adherence level was assessed by calculating the proportion of days covered (PDC) with an SSRI from the date of first dispensed SSRI (index date) to the end of follow-up and was categorized as low (PDC ≤20%), intermediate (PDC 21–79%) and high (PDC ≥80%). To validate the study model, we conducted a similar analysis on patients using antiepileptic drugs, which are known to be positively associated with an increased risk of osteoporotic fractures. Higher adherence to SSRI treatment was significantly associated with an increased risk of bone loss-related events in a dose-response manner. The adjusted hazard ratio for bone loss-related events adjusted for age, physician visits and body mass index in patients who were covered with an SSRI for 21–79% of the time and 80% or more of the time was 1.15 (95% CI 0.97, 1.37) and 1.40 (95% CI 1.14, 1.73) compared with patients who were covered for less than 21% of the follow-up period. Exposure to SSRI treatment is associated with an increased risk of bone loss-related events. Further studies are required to determine the causality of the association and its relevance to the clinical use of SSRIs.

The influence of cannabis abuse on the severity of existing psychotic and affective symptoms is still unclear. Among 470 consecutively admitted psychotic or affective patients, 54 active (in the previous month) cannabis abusers were detected via urine tests (Sure Step TM kits; Applied Biotech Inc, San Diego, Calif) and Structured Clinical Interview for DSM-IV (SCID- IV) questionnaire. In 24 cases, substances other than cannabis were abused; 392 patients were nonabusers. All patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The following rating scales were used: Hamilton Depression Rating Scale (HAM-D-21), Positive and Negative Syndrome Scale (PANSS), and Young Mania Rating Scale (YMRS). Cannabis abusers (n = 54) were significantly younger and more frequently males than nonuser patients. In this group, there were more schizophrenic patients and fewer affective and anxiety patients (chi(2) = 11.76; P < .01). The double-diagnosed patients had more prominent psychotic symptoms than the nonusers (n = 392)-PANSS positive: 19.056 +/- 8.30 vs 16.128 +/- 8.031 (P < .02; t(446) = 2.510). The difference was statistically significant for hallucinatory behavior, excitement, grandiosity, and hostility. General PANSS scale rate of abusers was lower: 33.012 +/- 9.317 vs 37.3575 +/- 11.196 (P < .01; t = 2.727), especially for depression, anxiety, somatic concern, guilt feelings, tension, motor retardation, and volition disturbances. Rates of PANSS negative scale of abusers and nonusers were not significantly different (13.815 +/- 6.868 vs 14.983 +/- 6.446) except for lower rates of social withdrawal and stereotyped thinking for abusers. No significant difference in general level of manic symptoms (YMRS) between abusers and nonusers was observed (6.778 +/- 10.826 vs 4.910 +/- 7.754), but severity of thought/language disturbances and poor insight was found significantly higher in the abusers. Cannabis abusers are obviously less depressive (HAM-D): 5.944 +/- 10.291 vs 12.896 +/- 13.946 (P < .0005, t = 3.535). Such differences were observed in the high number of the subscales. Abusers' rates were higher (although not significantly) for paranoid symptoms and general somatic symptoms. Cannabis possibly produces some antidepressive and anxiolytic effect on psychotic and affective inpatients. The "price" of this effect is often an exacerbation of psychotic and some manic symptoms.

OBJECTIVES: Selective serotonin reuptake inhibitors (SSRIs) are currently considered as the first drug of choice in the treatment of panic disorder (PD). The aim of this long-term, naturalistic comparison study was to compare 4 SSRIs with respect to tolerability and treatment outcome of PD. Outcome measures included relapse rates and adverse effects. METHODS: Two hundred patients with PD were enrolled in our study. All subjects met DSM-IV criteria for PD or PD with agoraphobia (PDA). All patients were assigned to receive SSRI monotherapy for 12 months with either citalopram (n = 50), fluoxetine (n = 50), fluvoxamine (n = 50), or paroxetine (n = 50) in a randomized, nonblinded fashion. Both the treating psychiatrist and the patients were not blind to the assigned treatment, but the clinician raters were blind to the study medication. The study design allowed for assignment of a particular SSRI as indicated according to the clinical judgment of the study psychiatrists. The Panic Self-Questionnaire, which is a self-report scale, was administered at baseline and then once per month during the duration of the 12-month study. The visual analog scale and the Clinical Global Impression Scale were administered at baseline and then once per month during the period of the study. Reports of sexual dysfunction were assessed using a nonstructured clinical interview at monthly visits. The body weight of study subjects was measured at baseline, and then at the 12th month visit end point. RESULTS: Of 200 patients who entered the study, 127 patients (63.5%) completed the full 12-month protocol. Retention rates were highest for paroxetine (76% [38/50]), intermediate for citalopram (68% [34/50]) and fluvoxamine (60% [30/50]), and lowest for fluoxetine (50% [25/50]). Patients who completed the 12-month protocol responded favorably to the study treatment. The paroxetine and the citalopram groups had significantly lower rates of panic symptoms as measured at visits on weeks 4 and 8. At visits on months 3, 6, 9, and 12, however, there were no statistically significant differences between the 4 groups in relapse rates (defined as the occurrence of 1 or more panic attacks during the previous week of treatment) (F1,127 = 0.17; P = 0.13 [not statistically significant]). At the 12th month end point, patients in all 4 treatment groups had a statistically significant increase in body weight. Body weight among the study population increased by 6.1 + 4.9 kg from a mean weight of 72.4 + 7.3 kg at the onset of treatment. Reports of sexual adverse effects at the 12th month visit were similar in the citalopram, fluoxetine, and paroxetine groups, but the fluvoxamine patient group reported fewer sexual adverse effects at the 12th month visit. CONCLUSIONS: Most of our PD patients responded well to 12-month treatment with either citalopram, fluoxetine, fluvoxamine, or paroxetine, and the overall response rate was equal after the first 4 weeks of treatment. Although patients treated with paroxetine had the lowest dropout rates during the initiation phase, they had the highest rate of adverse effects as measured at the 12th month visit. Conversely, patients in the fluvoxamine group had the highest dropout rate (which was primarily caused by adverse effects in the initiation phase of treatment.); however, patients who were able to tolerate fluvoxamine throughout the full course of the study were observed to have lower rates of sexual dysfunction and weight gain compared with patients treated with the other agents. Overall, when measured at the 12th month visit, monotherapy with paroxetine and citalopram was associated with a higher rate of sexual adverse effects than was treatment with fluoxetine or fluvoxamine. In addition, monotherapy with paroxetine, citalopram, and fluoxetine seemed to cause more weight gain than did treatment with fluvoxamine.

Converging lines of evidence suggest a role for the mesolimbic dopamine system in the response to somatic antidepressant therapies. Here, we review evidence suggesting that antidepressant treatments of different types share the effect of increasing the sensitivity of dopamine D2-like receptors in the nucleus accumbens, clinical studies suggesting that activation of these receptors has antidepressant efficacy, as well as relevant imaging and genetic data on the role of this system in the antidepressant response. We then attempt to reconcile this data with evidence of a common target of antidepressant drugs in the cyclic adenosine monophosphate (cAMP) response element binding protein-brain-derived neurotrophic factor (CREB-BDNF) pathway in a model that suggests potential directions for future inquiry.

OBJECTIVE Post Traumatic Stress Disorder (PTSD) is known to be associated with Erectile Dysfunction (ED). Sildenafil citrate was shown to be effective treatment for ED among different clinical populations. However, to date, no placebo-controlled trial has assessed sildenafil's effectiveness for treating ED in PTSD patients. The goal of the present study was to address this question using a double-blind placebo controlled crossover design. METHODS A four-week double-blind crossover trial of sildenafil (50 mg up to 100 mg per usage) versus placebo was conducted on 21 outpatients diagnosed with chronic PTSD accompanied by ED. Erectile function was assessed biweekly using the International Inventory of Erectile Function (IIEF). Depressive symptoms, PTSD symptoms and subjective well-being scores were assessed as well. RESULTS Analysis of IIEF scores revealed a main effect of treatment phase (E = 33.361, df =2, P < 0.000). Pairwise comparisons showed that sildenafil IIEF scores (mean = 45.19 +/- 15.05) were significantly higher compared to baseline scores (mean = 20.00 +/- 12.32, P = 0.000) and placebo scores (mean = 33.04 +/- 12.99). Compared to placebo, a significant improvement was also observed during the sildenafil phase in erectile function, orgasmic function and sexual desire. There was no significant change in depression, PTSD symptoms or subjective well-being. CONCLUSION The results of this study suggest that sildenafil citrate treatment for ED in PTSD patients was accompanied with improvement of ED symptoms and was found to be significantly better than placebo. Nevertheless, this effect should be considered marginal since patients still meet the criteria of ED after treatment. Larger, parallel group studies are warranted.

Objectives: The aim of this naturalistic follow-up study was to examine the effect of pregnancy as a predicting factor of relapse in patients with panic disorder (PD). Methods: Eighty-five female patients with PD (between the ages of 20 and 35 years) were included in this study. They were divided into 2 groups based on whether the onset of PD had been during pregnancy (PD-pregnancy [PD-P]) or whether the onset of PD had been while not pregnant (PD-nonpregnant [PD-NP]). Patients were treated with paroxetine up to 40 mg/day for 12 months, and the full responders were tapered off their medication and were monitored for an additional 6 years. Treatment response was assessed using the Panic Self-Questionnaire (PSQ) with full response being defined as "0" panic attacks. Assessments using the PSQ were made at baseline and every 4 weeks for the first twelve months. During the 6-year drug-free follow-up period, patients were assessed using the PSQ every 3 months. Relapse was defined as the occurrence of a panic attack in any phase of the study. The effect of group membership (PD-P vs. PD-NP) and new pregnancies as risk factors for relapse were explored. Results: Sixty-eight patients completed the 6-year follow-up, and each of the study groups (PD-P and PD-NP) was composed of 34 patients. Twenty-six of 34 (76.6%) patients in the PD-P group had another pregnancy, and 15/26 (57%) in this group experienced a relapse during the subsequent pregnancy. Three of 8 (37%) PD-P patients experienced a relapse without pregnancy. Among the second group (PD-NP), 18/34 (52.9%) became pregnant and 8/18 (44.4%) experienced a relapse at the time of pregnancy, whereas 4/16 (25%) experienced a relapse while not pregnant. Patients who relapsed during pregnancy had a more severe relapse (as defined by the severity of the PSQ score) compared with nonpregnant relapsers. Conclusions: Our naturalistic follow-up study demonstrated that pregnancy might confer an increased risk of relapse in PD. Moreover, when compared with patients who develop PD while not pregnant (PD-NP), patients who develop PD during pregnancy (PD-P) appear to have a higher risk of relapse at the time of a subsequent pregnancy (P < 0.001).

Objectives Electroconvulsive therapy (ECT) is standard treatment of severe depression. The induction of a seizure is a core event in successful ECT. Although propofol is a frequently used anesthetic agent, one of its limitations is a reduction of seizure duration. No such effects have been reported regarding remifentanil, an ultrarapid-acting opioid that is used to induce and maintain anesthesia. The simultaneous administration of propofol and remifentanil may have similar safety and efficacy in terms of induction of anesthesia during ECT as propofol alone and significantly increase seizure duration. Methods Twenty-one ECT patients (10 men, 11 women, aged 24 to 81 years) were recruited. Muscle paralysis was achieved with succinylcholine (0.5-0.75 mg/kg intravenously [IV]). Unconsciousness was induced by either propofol (1 mg/kg IV) or propofol (0.5 mg/kg IV) + remifentanil (1 microg/kg) in a crossover format. ECT was administered according to established clinical protocols at the Sheba Medical Center, Israel. No changes in ECT current were permitted in the 2 protocols of each patient. Statistical analysis was based on paired t tests. Results In all but 2 cases, seizure duration was significantly longer in the remifentanil group than in the control group (motor seizure 53.7 +/- 28.3 seconds vs. 29.5 +/- 10.9 seconds, t = 4.017, P = 0.0007; Electroencephalographic (EEG) seizures 60.8 +/- 25.1 seconds vs. 40.1 +/- 17.0 seconds, t = 3.971, P = 0.001). No significant differences were found in mean recovery time, post-treatment elevation in blood pressure, heart-beat, or oxygen saturation. Conclusion During anesthesia, the addition of remifentanil to propofol appears to be as effective as propofol alone with regard to anesthesia efficacy and cardiovascular function while significantly increasing seizure duration. Whether this discovery is of relevance to the clinical efficacy of ECT remains to be tested.

Background: Despite the previously accepted notion that panic disorder (PD) is rare in the elderly, recent data have shown that late-life PD may be more common than previously thought. Paroxetine is a selective serotonergic reuptake inhibitor which has had clear efficacy in the treatment of PD in the general adult population. In this study we aimed to examine the treatment outcome of paroxetine pharmacotherapy for late-life PD. Method: In this long-term naturalistic follow-up study, a group of 61 elderly (aged 59 years or older) PD patients were compared with a group of 95 younger (aged between 18 and 59 years) PD patients in terms of treatment response to paroxetine pharmacotherapy. The two groups were followed during both the initial short-term treatment phase (first 3 months) and throughout long-term (month 4–12) maintenance treatment. The two groups were also compared for side effects of paroxetine therapy. Results: No differences were found between the two patient groups in terms of response rate, si...

Transcranial magnetic stimulation (TMS) applied over the motor cortex depolarizes neurons and leads to motor-evoked potentials (MEP). To assess cortico-spinal excitability we compared the motor threshold (MT) and the averaged MEP amplitude generated by TMS in patients with major depression (MD) and matched controls. Nineteen patients, who where participants in a protocol comparing the antidepressant effects of rTMS with those of ECT, and thirteen age- and gender-matched normal controls were studied. MT was similar between patients and normal controls. The MEP amplitude response was significantly increased by rTMS, however, the magnitude of the response was similar in patients and normal controls. Correlations between the averaged MEP amplitude and age revealed that older subjects demonstrated significantly lower responses at all time-points. We conclude that cortico-spinal excitability is increased following rTMS, however, differences between patients and normal controls were not apparent with the paradigm used.

Despite the findings that pain and depression are not always directly linked, enough evidence suggest that a complex relationship between pain and depression exists. Using an electronic pressure algometer placed on the sternum, the changes in pressure pain threshold (PPThr) and pressure pain tolerance (PPTol) were evaluated in 19 patients affected by refractory major depression without psychotic features, throughout a full course of electroconvulsive therapy (ECT) treatment. Measurements were done before the first treatment, after the 6th treatment and after the last treatment. After the 6th treatment, mean (+/- SD) PPThr increased significantly from 11.48 (+/- 4.81) kg/cm2 at baseline, to 13.7 (+/- 5.59) kg/cm2 (p=0.0076) while PPTol did not change significantly (from 18.46 (+/- 6.75)kg/cm2 to 17.4 (+/- 8.1)kg/cm2). At the end of the treatment course, mean (+/- SD) PPThr did not increase further significantly (15.06 (+/- 5.21)kg/cm2 (p=0.0234)) while PPTol increased significantly to 21.34 (+/- 7.8)kg/cm2 (p=0.0047). ECT's efficacy was measured with the 21-item Hamilton Rating Scale for Depression (21-HAM-D). Mean (+/- SD) 21-HAM-D scores decreased significantly from 30.9 (+/- 4.15) at baseline, to 10.47 (+/- 5.78) (p=0.0001) after the 6th treatment, with no further significant change at the end of the treatment course (9.94 +/- 3.07; p=0.0254). Both pain threshold and pain tolerance increased following the alleviation of the depressive disorder and a possible usefulness of ECT may be postulated for treating severe, chronic pain syndromes. However, a more significant conclusion is that the increase of the PPThr noted early during ECT treatment may serve as an early outcome possible detector of ECT efficacy in depressed patients.

Transcranial magnetic stimulation (TMS) is a noninvasive and easily tolerated method of altering cortical physiology. The authors evaluate evidence from the last decade supporting a possible role for TMS in the treatment of depression and explore clinical and technical considerations that might bear on treatment success.The authors review English-language controlled studies of nonconvulsive TMS therapy for depression that appeared in the MEDLINE database through early 2002, as well as one study that was in press in 2002 and was published in 2003. In addition, the authors discuss studies that have examined technical, methodological, and clinical treatment parameters of TMS.Most data support an antidepressant effect of high-frequency repetitive TMS administered to the left prefrontal cortex. The absence of psychosis, younger age, and certain brain physiologic markers might predict treatment success. Technical parameters possibly affecting treatment success include intensity and duration of treatment, but these suggestions require systematic testing.TMS shows promise as a novel antidepressant treatment. Systematic and large-scale studies are needed to identify patient populations most likely to benefit and treatment parameters most likely to produce success. In addition to its potential clinical role, TMS promises to provide insights into the pathophysiology of depression through research designs in which the ability of TMS to alter brain activity is coupled with functional neuroimaging.

Background Studies published over the past few years suggest that transcranial magnetic stimulation (TMS) may have significant antidepressant actions. In a previous report, we compared electroconvulsive therapy (ECT) and repetitive TMS (rTMS) and found ECT to be superior for psychotic major depression (MD); however, ECT and rTMS had similar results in nonpsychotic MD. We now report on a controlled randomized comparison of ECT and rTMS in patients with nonpsychotic MD. Methods Forty patients with nonpsychotic MD referred for ECT were included. Electroconvulsive therapy was performed according to established protocols. Repetitive TMS was performed over the left dorsolateral prefrontal cortex at 90% motor threshold. Patients were treated with 20 sessions (five times per week for 4 weeks) of 10-Hz treatments (1200 pulses per treatment-day) at 90% motor threshold. Response to treatment was defined as a decrease of at least 50% in the Hamilton Rating Scale for Depression (HRSD) score, with a final HRSD equal or less than 10 points and a final Global Assessment of Function Scale rating of 60 or more points. Results The overall response rate was 58% (23 out of 40 patients responded to treatment). In the ECT group, 12 responded and eight did not; in the rTMS group, 11 responded and nine did not (χ2 = .10, ns). Thus, patients responded as well to either ECT or rTMS. Conclusions This study adds to the growing literature supporting an antidepressant effect for rTMS. This study is particularly relevant because it suggests that rTMS and ECT reach similar results in nonpsychotic major depressive disorder.

Auditory command hallucinations probably arise from the patient's failure to monitor his/her own 'inner speech', which is connected to activation of speech perception areas of the left cerebral cortex and to various degrees of dysfunction of cortical circuits involved in schizophrenia as supported by functional brain imaging. We hypothesized that rapid transcranial magnetic stimulation (rTMS), by increasing cortical activation of the right prefrontal brain region, would bring about a reduction of the hallucinations. We report our first schizophrenic patient affected with refractory command hallucinations treated with 10 Hz rTMS. Treatment was performed over the right dorsolateral prefrontal cortex, with 1200 magnetic stimulations administered daily for 20 days at 90% motor threshold. Regional cerebral blood flow changes were monitored with neuroSPECT. Clinical evaluation and scores on the Positive and Negative Symptoms Scale and the Brief Psychiatric Rating Scale demonstrated a global improvement in the patient's condition, with no change in the intensity and frequency of the hallucinations. NeuroSPECT performed at intervals during and after treatment indicated a general improvement in cerebral perfusion. We conclude that right prefrontal rTMS may induce a general clinical improvement of schizophrenic brain function, without directly influencing the mechanism involved in auditory command hallucinations.

Dolberg OT, Dannon PN, Schreiber S, Grunhaus L. Magnetic motor threshold and response to TMS in major depressive disorder. Acta Psychiatr Scand 2002: 106: 220–223. © Blackwell Munksgaard 2002. Objective: The aim of this study was to examine motor threshold (MT) during treatment with transcranial magnetic stimulation (TMS). Method: The TMS was administered to 46 patients with depression and 13 controls. TMS was performed at 90% power of measured MT. The stimulation frequency was 10 Hz for 6 s, for 20 trains, with 30 s inter-train intervals. The trial included 20 sessions. Patients and controls were assessed on various outcome measures. Results: The MT values were comparable between patients and controls. Neither demographic nor clinical variables were factors in determining MT. MT was not shown to have any predictive value regarding outcome of treatment. Conclusion: In this study, MT at baseline or changes in MT during the treatment period were not able to discriminate between patients and controls and were not found to have any predictive value with regard to treatment outcome.

Background and Objective Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line treatment for panic disorder, although up to 30% of patients either do not respond to SSRIs or withdraw due to adverse events. Reboxetine, a selective norepinephrine reuptake inhibitor (selective NRI), is effective in treating depression and may alleviate depression-related anxiety. This study aimed to investigate the efficacy of reboxetine in the treatment of patients with panic disorder who did not respond to SSRIs. Method In this 6-week, open-label study, 29 adult outpatients with panic disorder who had previously failed to respond to SSRI treatment received reboxetine 2 mg/day, titrated to a maximum of 8 mg/day over the first 10 days. Efficacy was assessed using the Panic Self-Questionnaire (PSQ), the Hamilton Rating Scale for Anxiety (HAM-A), the 17-item Hamilton Rating Scale for Depression (HRSD) and the Global Assessment of Functioning (GAF) Scale. Results The 24 patients who completed the study responded well to reboxetine treatment. Significant improvement (p

The aim of our study was to evaluate the effectiveness of a self-information booklet (SIB) in decreasing anxiety and panic attacks in Panic Disorder (PD) patients. Eighty-four patients attending an outpatient clinic due to panic disorder were randomly chosen to receive paroxetine with/without a friendly-designed brochure. Follow-up was done by a masked rater after 1, 3,and 12 weeks in order to evaluate whether the co-administration of paroxetine and the brochure (Group A) had a beneficial effect over the administration of paroxetine alone (Group B). After 3 weeks of therapy, Group A patients had significantly greater improvement and lower scores on the Hamilton Anxiety Scale, the Panic Self Questionnaire, and the Visual Analog Scale. After 12 weeks, the differential improvement was not statistically significant and both groups had improved as compared to baseline. The administration of a psychoeducational brochure (SIB) to PD patients at the initiation of therapy had beneficial effects during the first weeks of treatment. Although this effect fades away, the role of the SIB is overstressed in its ability to increase well being and compliance, and reduce anxiety and panic attacks.

To evaluate the prevalence of suicidal behavior in patients with panic disorder (PD) and to study the role of alexithymia (AL), an affect component, as a predictor of suicidal behavior in PD, we compared 42 patients with PD with or without agoraphobia with 24 healthy controls with regards to depression, AL and suicide risk. Only 5% of the PD patients reported previous suicide attempts. A higher frequency of positive AL (score > 73) was found among the PD patients (39% v 4% among the controls). PD patients had a higher suicide risk and AL as compared to controls, but only the increased suicide risk reached statistical significance. AL subjects had higher suicide risk scores as compared to non-AL subjects. Significant correlations were found between the AL score and suicide risk, although the most significant correlation was, as expected, between the depression level and the suicide risk. A low rate of previous suicide attempts was found in the PD group, perhaps reflecting the low comorbidity in our sample. We suggest that AL may have a role in the causation of suicidal behavior in PD patients, although further studies should re-examine this issue with larger samples.

At least 50% of patients with manic depressive disorder (MDD) treated successfully with electroconvulsive therapy (ECT) will experience a relapse within the first year of follow-up. Sleep disturbances are very common in MDD and may constitute forerunners of relapse. In this study we tested the hypothesis that melatonin, a sleep-promoting hormone, would decrease the 3-month relapse rate after successful ECT. We included in the study patients with MDD successfully treated with ECT (post-ECT Hamilton Rating Scale for Depression [HRSD] < or = 10). Patients were blindly randomized to two groups, one receiving fluoxetine + placebo and one receiving fluoxetine + melatonin. Assessments (HRSD, Brief Psychiatric Rating Scale, Global Assessment of Function Scale, Global Depression Scale, Pittsburgh Sleep Quality Index, Mini-Mental State Exam, and pill count) were performed for 12 weeks after ECT. Ten of the 35 patients (28.5%) relapsed during the follow-up period. Relapse rates were similar in both groups of patients. Sleep reports were not improved by melatonin. Patients who achieved a higher functional state post-ECT relapsed less often. We conclude that the addition of melatonin to on-going fluoxetine treatment did not have a beneficial effect either on the 3-month outcome post-ECT or on the sleep reports of these patients.

While explicit memory in amnesics is impaired, their implicit memory remains preserved. Memory impairment is one of the side effects of electroconvulsive therapy (ECT). ECT patients are expected to show impairment on explicit but not implicit tasks. The present study examined 17 normal controls and 17 patients with severe major depressive disorder who underwent right unilateral ECT. Patients were tested in three sessions: 24-48 hours prior to, 24-48 hours following the first ECT, and 24-48 hours following the eighth ECT. The controls were tested in three sessions, at time intervals that paralleled those of the patients. Implicit memory was tested by the perceptual priming task - Partial Picture-Identification (PPI). The skill learning task used entailed solving the Tower of Hanoi puzzle (TOHP). Explicit memory was tested by picture recall from the PPI task, verbal recall of information regarding the TOHP, and by the Visual Paired Association (VPA) test. Results showed that explicit questions about the implicit tasks were impaired following ECT treatment. Patients' learning ability, as measured by the VPA task, was only impaired in the first testing session, prior to ECT treatment, reflecting the effect of depression. In addition, groups only differed in the first session on the learning rate of the skill learning task. Perceptual priming was preserved in the patients' group in all sessions, indicating that it is resilient to the effect of depression and ECT. The results are interpreted in terms of the differential effect of depression and ECT on explicit and implicit memory.

Objective: Increases in adrenergic activity are associated with stress, anxiety, and other psychiatric, neurological, and medical disorders. To improve understanding of normal CNS adrenergic function, CBF responses to adrenergic stimulation were determined. Methods: Using PET, the CBF changes after intravenous yohimbine, an alpha2-adrenoreceptor antagonist that produces adrenergic activation, were compared with placebo in nine healthy humans. Heart rate, blood pressure, Paco2, plasma catecholamines, and symptom responses were also determined. Results: Among nonscan variables, yohimbine produced significant symptom increases (including a panic attack in one subject), a decrease in Paco2 due to hyperventilation, increases in systolic and diastolic blood pressure, and a trend toward a significant norepinephrine increase. Among scan results, yohimbine produced a significant decrease in whole-brain absolute CBF; regional decreases were greatest in cortical areas. Medial frontal cortex, thalamus, insular cortex, and cerebellum showed significant increases after normalization to whole brain. Medial frontal CBF change was correlated with increases in anxiety. A panic attack produced an increase instead of a decrease in whole-brain CBF. Factors potentially contributing to the observed CBF changes were critically reviewed. Specific regional increases were most likely due in large part to activation produced by adrenergically induced anxiety and visceral symptoms. Conclusions: This study supports the relationship of anxiety and interoceptive processes with medial frontal, insular, and thalamic activation and provides a baseline for comparison of normal yohimbine-induced CNS adrenergic activation, adrenergically-based symptoms, and other markers of adrenergic function to stress, emotion, and the adrenergic pathophysiologies of various CNS-related disorders.

INTRODUCTION: The aim of this preliminary report is to demonstrate the efficacy of rapid transcranial magnetic stimulation (rTMS) in the treatment of relapsed major depressive disorder (MDD) patients. METHODS: Four patients with major depressive disorder who were successfully treated with rTMS received a second course of rTMS treatment. Patients were evaluated with the Hamilton Depression Rating Scale &#45 21 items, the Brief Psychiatric Rating Scale, the Global Depression Scale and the Global Assessment Scale in both trials. The statistical analysis was performed with paired t-tests and chi squares. RESULTS: Clinical ratings demonstrated a significant improvement at the end of both trials. No significant differences were found between the ratings at the end of the treatment courses. CONCLUSION: rTMS was successfully used in the treatment of relapsed MDD patients who had previously responsed to rTMS. ( Int J Psych Clin Pract 2000; 4: 223 - 226)

Background: Studies in laboratory animals suggest that repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive shock (ECS) increase seizure inhibition acutely. This study was designed to explore whether chronic rTMS would also have seizure inhibition properties. Methods: To this purpose we administered rTMS (Magstim Rapid) and sham rTMS twice daily (2.5 T, 4-sec train duration, 20 Hz) to two groups of 10 rats for 16 days. The rTMS coil was a 50-mm figure-8 coil held directly over the rat’s head. Raters were blind to experimental groups. On days 11, 17, and 21 (5 days after the last rTMS) ECS was administered with a Siemens convulsator using three electrical charge levels. Variables examined were the presence or absence of seizures and seizure length (measured from the initiation of the tonic contraction until the end of the limb movement). Results: At day 11 rTMS had no effect on seizures, and both rTMS and sham rTMS animals convulsed equally. At day 17, however, rTMS-treated animals convulsed significantly less (both at presence/absence of seizures, and at seizure length) than sham rTMS animals. At day 21 the effects of rTMS had disappeared. Conclusions: These findings suggest that rTMS administered chronically leads to changes in seizure threshold similar to those reported for ECS and ECT; however, these effects were short-lived.

The response to electroconvulsive therapy (ECT) was monitored with sleep polysomnography studies (SPS) performed pre- and post-ECT, in 25 patients with major depressive disorder (MDD). Patients included in this study met research diagnostic criteria for MDD and had been free of psychotropic medication for at least 10 days before SPS were performed. We compared ECT responders and nonresponders on SPS, demographic, and clinical parameters. Many SPS parameters, regardless of the clinical response, changed significantly with ECT. The presence of delusions was significantly associated with SOREM post-ECT. The presence of sleep-onset REM periods post-ECT was associated with poor response to ECT. SPS performed during a course of ECT may help identify patients at risk of responding less well to this modality of treatment.

While diagnosing schizophrenia, clinicians focus on feeling the quality and nature of the internal motivation of patients. This motivational quality was theoretically conceptualized by Self Determination Theory (SDT). In this article we will review some of the basics of this theory, which focuses on motivational variables assessing behavior on an internal-external axis. Then, we will review prominent findings in the topic of using SDT concepts for the treatment of schizophrenia. The next stage will include a discussion as to the relationship between intrinsic and extrinsic motivators as well as possible neuroanatomy of these behavioral variables. Finally, directions for research will be offered in the field of schizophrenia diagnosis and treatment.

Grunhaus L, Schreiber S, Dolberg OT, Hirshman S, Dannon PN. Response to ECT in major depression: are there differences between unipolar and bipolar depression? Bipolar Disord 2002: 4(Suppl. 1): 91–93. © Blackwell Munksgaard, 2002

Since its introduction to the clinical realm in 1985, transcranial magnetic stimulation (TMS) has rapidly developed into a tool for exploring central nervous system function in both health and disease. The antidepressant effects of TMS were initially observed in 1993. Since then, a solid body of evidence has accumulated suggesting antidepressant effects for both slow TMS (sTMS) and repetitive TMS (rTMS). This review is divided into four parts. First, it addresses the basic concepts governing TMS, and then, second, it discusses the technical parameters involved in administering TMS. Knowledge of these parameters is necessary for understanding how TMS is administered, and how manipulation of the technique impacts on the results obtained. Third, we review the most relevant studies on the antidepressant effects of sTMS and rTMS published to date. Finally, we discuss cortical excitability and how the understanding of this basic neurophysiological function of cortical neurons can be used for monitoring the effects of TMS. In our discussion, we conclude that the time has arrived for TMS to be offered to depressed patients as a treatment.

Some specialists and policy makers advocate progression of the mental health reform in Israel by transferring beds from psychiatric to general hospitals.To compare the demographic, diagnostic and psychopathological profiles of psychiatric inpatients hospitalized in psychiatric and general hospitals, as well as their patterns of drug abuse, and to estimate the preparedness of general hospitals for the possible expansion of their psychiatric services.Between 2002 and 2006 a total of 250 patients were consecutively admitted to the Jerusalem Mental Health Center-Kfar Shaul Hospital and 220 to the psychiatric department of Sheba Medical Center, a general hospital in central Israel; the patients' ages ranged from 18 to 65. The two groups were compared for demographic features, psychiatric diagnoses and severity of psychopathology (utilizing PANSS, HAD-21, YMRS rating scales). Drug abuse was diagnosed by urine analyses and self-report.The patients in the psychiatric hospital were significantly younger, predominantly male, and more dependent on social security payments. In the general hospital, diagnoses of affective and anxiety disorders prevailed, while in the psychiatric hospital schizophrenic and other psychotic patients constituted the majority. The patients in the general hospital were decidedly more depressed; in the psychiatric hospital, notably higher rates of manic symptoms as well as positive, negative and general schizophrenic symptoms were reported. For the most abused substances (opiates, cannabis and methamphetamines) the rates in the psychiatric hospital were significantly higher.The differences between the two groups of inpatients were very pronounced, and therefore, the transferring of psychiatric beds to general hospitals could not be done without serious and profound organizational, educational and financial changes in the psychiatric services of general hospitals. Since each of the two inpatient systems has particular specializations and experience with the different subgroups of patients, they could coexist for a long time.

Adrenergic response following infusions of yohimbine or normal saline was evaluated in 9 control subjects, 8 patients suffering from a major depressive episode (MDE), and 12 patients suffering from concurrent MDE and panic disorder (MDE + P). Blood was drawn at -20, 0, 5, 10, 20, 45, and 90 min following the infusions, and assayed for norepinephrine (NE) and 3-methoxy-4-hydroxy-phenyl glycol (MHPG). Although the patient groups exhibited higher baseline NE concentrations, and a greater NE area under the plasma concentration versus time curve (AUC0-90) during the yohimbine infusion, the differences were not statistically significant. Baseline NE was significantly correlated with the NE AUC0-90 in all three groups, suggesting that, although the NE system may be dysregulated in the MDE and MDE + P patients, the NE system still appears to respond somewhat predictably following a challenge, even though the actual magnitude of response may vary.

We have previously shown that a number of depressed patients demonstrated a failure to suppress corticotrophic secretion, as measured by beta-Endorphin/beta-Lipotropin (beta-End/beta-LPH levels), following dexamethasone challenge. The current study is an extension and replication of these findings, as well as an analysis of some of the biological variables which may contribute to the variance in beta-End/beta-LPH nonsuppression. We continue to observe a high rate of beta-End/beta-LPH nonsuppression in depressed patients following dexamethasone; this escape at the pituitary level is even observed in a number of patients who demonstrate normal cortisol suppression. Advancing age, particularly in women, led to higher baseline cortisol, lower baseline beta-End/beta-LPH, and a greater likelihood of being a nonsuppressor on one or both measures.

Background:Transcranial magnetic stimulation is a novel, experimental procedure in the treatment of psychiatric disorders, most notably mood disorders. Transcranial magnetic stimulation is currently being widely studied in other applications, and its efficacies and potential side effects are being investigated. Methods:Transcranial magnetic stimulation was administered five times a week for 4 weeks. Results:In this report, a manic episode followed treatment with transcranial magnetic stimulation in two patients. Conclusions:Clinicians should be aware that, like with other antidepressive treatments, a switch into mania might complicate treatment with transcranial magnetic stimulation in bipolar patients.

Because patients with Cushing' syndrome (CS) and Major depressive disorder (MDD) share features of hypercortisolism and the depressive syndrome, we compared electro-encephalographic (EEG) sleep in patients with pituitary-ACTH-dependent Cushing's syndrome (Cushing's disease, CD), patients with ACTH-independent Cushing's syndrome (AICS), patients with major depressive disorder (MDD), and normal subjects. There were substantial similarities in the abnormal polysomnography profiles of patients with CD, AICS, and MDD. All three patient groups demonstrated poorer sleep continuity, shortened rapid eye movement (REM) latency, and increased first REM period density compared with normal subjects. In addition, AICS patients and MDD patients had elevated REM activity and density. These findings are discussed in terms of models of pathophysiology that relate abnormalities in sleep, mood, and hypothalamic-pituitary-adrenal function.

Aims To evaluate the effect of repeated high-frequency transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC), combined with either smoking or neutral cues, on cigarette consumption, dependence and craving. Design Participants were divided randomly to real and sham stimulation groups. Each group was subdivided randomly into two subgroups presented with either smoking-related or neutral pictures just before the daily TMS intervention. Ten daily rTMS sessions were applied every week-day and then a maintenance phase was conducted in which rTMS sessions were less frequent. Setting Single-site, out-patient, randomized, double-blind, sham-controlled. Participants Forty-eight chronic smokers who smoked at least 20 cigarettes per day and were motivated to quit smoking. Healthy males and females were recruited from the general population using advertisements in newspapers and on internet websites. Intervention Ten daily rTMS sessions were administered using a standard figure-8 coil over the DLPFC. Stimulation included 20 trains/day at 100% of motor threshold. Each train consisted of 50 pulses at 10 Hz with an inter-train interval of 15 seconds. Measurements Cigarette consumption was evaluated objectively by measuring cotinine levels in urine samples and subjectively by participants' self-reports. Dependence and craving were evaluated by standard questionnaires. Findings Ten daily rTMS sessions over the DLPFC reduced cigarette consumption and nicotine dependence. Furthermore, treatment blocked the craving induced by daily presentation of smoking-related pictures. However, these effects tended to dissipate over time. Conclusions Multiple high-frequency rTMS of the DLPFC can attenuate nicotine craving.

The blood pressure (BP) and heart rate changes that occur upon standing and following a short walk were evaluated in 21 depressed inpatients. Measurements were obtained at baseline and following 7 days of treatment at a constant dose with tricyclic antidepressants. Heart rate and BP were measured in the supine and standing positions, and following a 72-yard walk. Antidepressants caused a significant increase in supine heart rate (P < .005) over values obtained at baseline, but no increase in the standing or postwalking heart rate. At baseline the diastolic blood pressure (DBP) increased following both standing and exercise, but during antidepressant treatment the mean change in BP following both standing (P < .005) and exercise (P < .01) decreased rather than increased. The changes in heart rate and both systolic and DBP that occurred when the patient stood were significantly correlated with age.

The ability to elicit symptoms by means of verbal communication is one of the basic requirements of psychiatric interviews. Whenever the verbal capacity of the patient is diminished, diagnosis may become difficult. A variety of medications have been used to facilitate interviews of difficult psychiatric patients including barbiturates, stimulants, and more recently, benzodiazepines. We report our experience in the interviews or eight diagnostically difficult patients while administering intravenous diazepam. We found this procedure to be both safe and effective in eliciting symptoms. The information obtained with the diazepam interview was valuable in clarifying diagnoses, which included major depression, dementia, conversion disorder, and psychotic and dissociative states.

Earlier HPLC fluorometric, ultraviolet and amperometric detector methods are not simple and sensitive for the assay of yohimbine for both therapeutic drug monitoring and pharmacokinetic studies. A simple and a very senitive HPLC coulometric assay has been developed using a C-8 column and a mobile phase of water and acetonitrile 65:35 (v/v) containing 1.8g/L of tetraethylammonium perchlorate. the optimum oxidation potential for yohimbine was 0.8 V against a Ag/AgCl electrode. Reserpiline was used as the internal standard. the sensitivity of the assay is 200 pg using 1 mL of plasma. the average inter-assay CV was 7 % and the recovery relative to the internal standard was 100 %. the assay method was used to determine the pharmacokinetics of the drug after an oral and IV dose in an individual.

Kleptomania is an impulse control disorder and that can be treated with the combination of pharmacotherapy and psychotherapy. The most common drug regimens include antidepressants, especially SSRIs and mood stabilizers. However, the low efficacy rates with these drugs urge research for new treatment regimens. Natrexone, an opioid receptor antagonist, which has been used in the treatment of substance abuse and impulse control disorders, may be also useful in the treatment of kleptomania. In this study we report two kleptomanic patients successfully treated with naltrexone. Copyright © 1999 John Wiley & Sons, Ltd.

The co-morbidity rate of illicit substance abuse and major mental problems in Israel is far from clear.To investigate the extent of drug abuse in a sample of psychiatric patients hospitalized in a psychiatric hospital and in the psychiatric department of a general hospital in Israel, to compare demographic and other background factors in dual-diagnosis patients with those of abuse-free mental inpatients, and to examine the time correlation between drug abuse and the appearance of major mental problems.Our data were derived from self-report and urine tests. The study population comprised 470 consecutively admitted patients--250 patients in the mental health center and 220 patients in the psychiatric department of the general hospital.The lifetime prevalence of drug abuse was 24%; cannabis abuse was found in 19.7%, opiates in 5.7%, cocaine in 2.7%, amphetamines in 3.4% and methamphetamine in 1.1%. Active abuse of drugs (during the last month) was registered in 17.3%, cannabis in 11.5%, opiates in 4.9%, amphetamine in 3.8%, cocaine in 1.3% and methamphetamine in 1.1%. We also found that 28.2% of active abusers used two or more substances. In 41.6% the drug abuse appeared prior to symptoms of the mental disorder; in 37.1% the duration of the mental disorders and the drug abuse was relatively similar, and in 21.3% of cases the duration of mental problems was longer than the duration of drug abuse. Dual-diagnosis patients were younger than non-abusers, more often male, unmarried, and of western origin.Substance abuse (especially cannabis) among hospitalized psychiatric patients in Israel is a growing problem.

Background Major depression disorder is a syndrome that involves impairment of cognitive functions such as memory, attention, and plasticity. In this study, we explored whether depression affects perception as well. Methods We used a recently developed paradigm that assesses the filling-in process by probing false-positive reports (false alarm [FA]), hit rates (pHit), sensitivity (d′), and decision criteria (Cr). We used a Yes-No paradigm in a low-level detection task involving a Gabor target, in the presence of collinear flankers, inducing filling-in, with differing target-flanker separations of 3–15 λ(wavelength). The depressive state of patients was assessed using the Hamilton Depression Rating Scale. Two groups were tested: an experimental group with major depression ( n = 27) and a control group ( n = 32). Results The performances of the control and the experimental groups were not significantly different regarding d′. In contrast, a specific pattern of significant differences between the control group and the hospitalized group was found for the decision criterion, pHit, and pFA, but only for target-flanker separations of 3 λ, whereas the results for the other separations were insignificant. The differences between the control and the depressed groups are not due to a global cognitive dysfunction in depression. Conclusions The results suggest that the filling-in process is deficient, probably because of reduced excitation among neurons. Neural excitation is a key factor in the neural processing involved in memory and decision making. In addition, it is still possible that the patients may be unable to match their internal representation to the changing sensory information.

Defrin R, Grunhaus L, Zamir D, Zeilig G. The effect of a series of repetitive transcranial magnetic stimula- tions of the motor cortex on central pain after spinal cord injury. Arch Phys Med Rehabil 2007;88:1574-80. Objective: To study the analgesic effect of repetitive trans- cranial magnetic stimulation (rTMS) of the motor cortex on central pain in patients with chronic spinal cord injury (SCI). Design: Double-blind randomized controlled trial. Mean follow-up period was 4.5 weeks. Setting: General hospital. Participants: Twelve paraplegic patients due to thoracic SCI suffering chronic central pain (11 completed the study) who were randomly selected from a list of eligible patients. Intervention: Real or sham 10 daily motor rTMS treatments (500 trains at 5Hz for 10s; total of 500 pulses at intensity of 115% of motor threshold) using figure-of-8 coil over the vertex. Main Outcome Measures: Chronic pain intensity (visual analog scale (VAS), McGill Pain Questionnaire (MPQ)), pain threshold, and level of depression (Beck Depression Inventory). Results: Both real and sham TMS induced a similar, signif- icant reduction in VAS scores (P.001) immediately after each of the 10 treatment sessions and in VAS and MPQ scores after the end of the treatment series. However, only real rTMS conferred a significant increase in heat-pain threshold (4°C, P.05) by the end of the series. Most important, the reduction in MPQ scores in the real rTMS group continued during the follow-up period. Depression scores were equally reduced in both groups but similar to pain relief, depression continued to improve at follow-up in the real rTMS group. Conclusions: Whereas the pain alleviation induced by a single rTMS treatment is probably due to placebo, patients with SCI may benefit from a series of rTMS treatments.

The authors' goal was to examine the hypnotic effects of slow-release melatonin during the initial 4 weeks of treatment with fluoxetine in 19 patients with major depressive disorder.Twenty-four outpatients with major depressive disorder were included in the study; 19 completed the study. Ten patients were treated with fluoxetine plus slow-release melatonin and nine were given fluoxetine plus placebo in a double-blind protocol for 4 weeks. Response was assessed by using rating scales for depression and sleep.The 10 patients given slow-release melatonin reported significantly better scores on the Pittsburgh Sleep Quality Index than the nine patients given placebo. No significant differences in the rate of improvement in depressive symptoms were noted between the two groups. No particular side effects were noted from the combination of fluoxetine and slow-release melatonin.Slow-release melatonin was effective in improving the sleep of patients with major depressive disorder. Slow-release melatonin had no effect on the rate of improvement in symptoms of major depressive disorder. The authors conclude that the role of slow-release melatonin for sleep disturbances in major depressive disorder should be investigated further.

Objectives: Agitation after electroconvulsive therapy (ECT) is observed in approximately 7% of patients. Promethazine is an antihistamine with sedative properties that has no antiseizure effects and therefore can be administered before ECT to prevent the onset of agitation. In the current study, we present a series of 8 patients who reacted to ECT with severe agitation and improved under the treatment of promethazine. Methods: Eight patients were included (5 women, 3 men), ages 22 to 77 years. All patients showed severe post-ECT agitation as demonstrated by severe restlessness, crying, or mumbling loudly. Seven of them required the administration of intravenous midazolam. ECT was given according to established clinical protocols at the Sheba Medical Center. All patients were prescribed either 25 to 50 mg of promethazine 2 hours before the treatment to avoid agitation. Results: All 8 patients suffered from extreme agitation after ECT treatment, and 7 required the administration of intravenous midazolam. After a clinical protocol, these patients were prescribed 25-50 mg of promethazine orally 60-120 minutes before the ECT. Improvement was observed in all patients both immediately post-ECT and also in their overall sense of well-being after the ECT. No patient complained of adverse reactions to the promethazine. Most patients reported a relief in pre-ECT fears. Conclusion: In this small case series, we found that promethazine can be used to prevent post-ECT agitation. Further double-blind controlled studies are needed to better evaluate the usefulness and appropriateness of promethazine in the prevention of pre-ECT fears and post-ECT agitation.

Background This naturalistic open label follow-up study had three objectives: 1) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment 2) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia. 3) To observe paroxetine's tolerability over a 24 month period. Methods 143 patients with panic disorder (PD), with or without agoraphobia, successfully finished a short-term (ie 12 week) trial of paroxetine treatment. All patients then continued to receive paroxetine maintenance therapy for a total of 12 months. At the end of this period, 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase. The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored, as in the first group, for another year while medication-free. The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a randomized manner. Results Only 21 of 143 patients (14%) relapsed during the one year medication discontinuation follow-up phase. There were no significant differences in relapse rates between the patients who received intermediate-term (up to 12 months) paroxetine and those who chose the long-term course (24 month paroxetine treatment). 43 patients (30.1%) reported sexual dysfunction. The patients exhibited an average weight gain of 5.06 kg. All patients who eventually relapsed demonstrated significantly greater weight increase (7.3 kg) during the treatment phase. Conclusions The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation. Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment.