Comparison of Smoking Cessation Program Registration, Participation, Smoking Cessation Medication Utilization, and Abstinence Rates Between Smokers With and Without Schizophrenia, Schizo-affective Disorder, or Bipolar Disorder.

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.

Adherence to smoking cessation guidelines (5As) by psychiatrists and primary care physicians for persons with serious mental illness.

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 (X2=23.9, p < 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.

Comparison of Perceptions and Smoking Cessation Experiences Between Smokers With and Without Serious Mental Illness in a Large Health Maintenance Organization.

OBJECTIVE: 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.

The Impact of Smoking Cessation on Hospitalization and Psychiatric Medication Utilization among People with Serious Mental Illness.

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 refer to SCPs has been attributed, in part, to their belief that quitting will have a deleterious effect on their patients' mental health status. Objectives: This study's objective was to determine if participating in a smoking cessation program had an adverse effect on mental health status among people with SMI, measured here by a change in hospitalization occurrence or psychiatric medication utilization. People with SMI who had participated in at least one SCP session in a large health maintenance organization (n = 403) were compared to an age-gender-diagnosis matched sample of SMI smokers (1,209) who had never participated. Results: No change in psychiatric hospitalization occurrence pre- versus post-SCP participation was found among participants (Pre:7.2% vs. Post:5.2, p = 0.2) or nonparticipants (Pre:7.0% vs. Post:6.0%, p = 0.2). Mean defined daily dose (DDD) for anti-psychotic, mood stabilizer, anti-depressant and anxiolytic medications also did not change over time for participants and nonparticipants. However, participants who did not complete the SCP and didn't quit had a 0.35 higher mean DDD for anti-psychotic medications compared with participants who had completed the SCP or quit, and with nonparticipants (p = 0.006), and were the only group to exhibit an increase in mean antipsychotic DDD over time (Pre:1.42, Post:1.63). SCP participation was not associated with hospitalization occurrence or psychiatric medication utilization. Conclusions/Importance: Smoking cessation should be encouraged, with close monitoring during the quit process.

Ropinirole Augmentation for Depression: A Randomized Controlled Trial Pilot Study.

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.

[Intrinsic motivation: a new direction of understanding and treatment of schizophrenia?].

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.

Adherence to treatment with selective serotonin reuptake inhibitors and the risk for fractures and bone loss: a population-based cohort study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are suspected of increasing the risk of bone loss and osteoporotic fractures. OBJECTIVE: The aim of this study was to investigate the association between adherence to SSRI treatment and the risk of bone loss-related events. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A comparative study of Arab and Jewish patients admitted for psychiatric hospitalization in Jerusalem: the demographic, psychopathologic aspects, and the drug abuse comorbidity.

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.

A comparative study of psychiatric inpatients in a general hospital and a psychiatric hospital in Israel: demographics, psychopathological aspects and drug abuse patterns.

BACKGROUND: Some specialists and policy makers advocate progression of the mental health reform in Israel by transferring beds from psychiatric to general hospitals. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cannabis abuse and severity of psychotic and affective disorders in Israeli psychiatric inpatients.

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.

Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption.

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.

Substance abuse in hospitalized psychiatric patients.

BACKGROUND: The co-morbidity rate of illicit substance abuse and major mental problems in Israel is far from clear. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Substance abuse (especially cannabis) among hospitalized psychiatric patients in Israel is a growing problem.

Major depression affects perceptual filling-in.

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 lambda(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 lambda, 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.

The effect of a series of repetitive transcranial magnetic stimulations of the motor cortex on central pain after spinal cord injury.

OBJECTIVE: To study the analgesic effect of repetitive transcranial 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 5 Hz for 10 s; 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, significant 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 degrees 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.

A naturalistic long-term comparison study of selective serotonin reuptake inhibitors in the treatment of panic disorder.

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.

Dopamine D2-like receptors and the antidepressant response.

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.

Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation.

Although previous clinical trials have suggested that repetitive transcranial magnetic stimulation (rTMS) has a significant antidepressant effect, the results of these trials are heterogeneous. We hypothesized that individual patients' characteristics might contribute to such heterogeneity. Our aim was to identify predictors of antidepressant response to rTMS. We pooled data from six separate clinical trials conducted independently, which evaluated the effects of rapid rTMS of the left dorsolateral prefrontal cortex in patients with major depression. We investigated 195 patients with regard to demographic, depression and treatment characteristics, psychiatric and drug history. Results showed that age and treatment refractoriness were significant negative predictors of depression improvement when adjusting these variables to other significant predictors and confounders. These findings were not confounded by methodological differences from the six studies, as the results were adjusted for the study site. In conclusion TMS antidepressant therapy in younger and less treatment-resistant patients is associated with better outcome.

Effectiveness of sildenafil in treating erectile dysfunction in PTSD patients: a double-blind, placebo-controlled crossover study.

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.

Recurrence of panic disorder during pregnancy: a 7-year naturalistic follow-up study.

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).