Effects of country of origin and wave of immigration on prevalence of schizophrenia among first and second-generation immigrants: A 30-year retrospective study.

OBJECTIVES: To compare the rates of schizophrenia among 1st and 2nd generation immigrants from two distinct backgrounds and across sequential periods of immigration. METHODS: A 30-years retrospective cohort study (187,184 individuals) of 1st and 2nd generation East-African immigrants (EAIs) and former Soviet-Union immigrants (FSUIs) who migrated to Israel between 1980 and 2012. EAIs were further divided according to waves of immigration. Period prevalence was calculated between the years 2002-2012. Multivariate logistic regression models were used to examine the association between immigration-related factors and prevalence of schizophrenia (Native-Born Israelis serving as reference group). RESULTS: The prevalence of schizophrenia in 1st generation EAIs and FSUIs was 1.8% and 1.2%, respectively, compared to 1.0% among NBIs (p<0.001). The prevalence of schizophrenia among 2nd generation EAIs and FSUIs was 1.3% and 0.8%, respectively, compared to 0.6% among NBIs (p<0.001). Adjusted odds ratios for developing schizophrenia compared to NBIs were 1.6 (95%CI:1.4-1.8) and 2.1 (95%CI:1.6-2.7), among 1st and 2nd generation EAIs and 1.1 (95%CI:0.9-1.2) and 1.3 (95%CI:1.0-1.8) among 1st and 2nd generation FSUIs respectively. Among EAIs, we observed the highest rate of schizophrenia in the pioneer wave of immigrants with gradual decline across subsequent waves: 2.4%, 1.9% and 1.0% for the 1st, 2nd and 3rd waves of immigration, respectively (p<0.001). CONCLUSIONS: The increased risk for developing schizophrenia among 2nd generation immigrants and among pioneer groups of immigrants emphasizes the importance of persistent investment in acculturation. Further studies elucidating the impact of country of origin and ethnic density on the risk for developing schizophrenia are warranted.

Insight into the current practice of ototoxicity monitoring during cisplatin therapy.

BACKGROUND: The aim of this study is to evaluate the current state of ototoxicity monitoring for patients receiving cisplatin chemotherapy in an academic medical center with particular attention to how closely monitoring adheres to national ototoxicity guidelines. METHODS: Case series including retrospective medical records review of patients (age > 18) treated with cisplatin at University of California Davis Medical Center between January 2014 and August 2017. Patient and ototoxicity related variables were analyzed. Patients that underwent a transfer of care during treatment and with less than 3 months of follow-up were excluded. RESULTS: Three hundred seventy-nine patients met study criteria, of which 104 (27.4%) had a prior history of hearing loss. Prior to treatment, 196 (51.7%) patients were counseled regarding the ototoxic nature of cisplatin and 92 (24.3%) patients had a pretreatment audiogram. During treatment, 91 (24%) patients had documented otologic complaints. Only 17 patients (4.5%) patients had an audiogram ordered during their cisplatin treatment period. 130 (34.3%) patients had otologic complaints following cisplatin treatment. Audiograms were ordered for 20 (7.8%), 13 (5.1%), and 16 (6.2%) patients at 1-month, 3-month, and 6-month follow-ups, respectively. No patients in the study cohort received baseline, treatment, and post-treatment audiograms as recommended by national ototoxicity monitoring protocols. Patients with Head and Neck Cancer (HNC) represented the largest subgroup that received cisplatin (n = 122, 32.2%) and demonstrated higher rates of ototoxicity counseling (n = 103, 84.4%) and pretreatment audiograms (n = 70, 57.4%) compared to the non HNC group (n = 36, 36.2%, P < 0.0001 and n = 22, 8.5%, P < 0.0001). CONCLUSIONS: There is poor adherence to national ototoxicity monitoring guidelines at a large academic medical center. This is a missed opportunity for intervention and aural rehabilitation. Improved education and collaboration between otolaryngology, audiology, and medical oncology is needed to develop and promote an effective ototoxicity-monitoring program.

Suicidality and second generation antipsychotics in schizophrenia patients: a case-controlled retrospective study during a 5-year period.

RATIONALE: Rates of attempted suicide for individuals with schizophrenia are approaching 30%. Attempted suicide is among the most potent predictors of subsequent suicide. Several studies suggest that suicide is more likely to occur in patients who are not being adequately treated or not being treated at all. An effort was made in the last decade to evaluate the antisuicide effects of pharmacological treatment in schizophrenia with emphasis on the role of the newer second-generation antipsychotics (SGA). OBJECTIVE: The aim of the present study was to assess in a large cohort of schizophrenia patients the effects of exposure to SGA on suicidality of patients suffering from schizophrenia or schizoaffective disorder. The study is a retrospective case-controlled evaluation over a 5-year period undertaken in a large university affiliated tertiary care psychiatric hospital. METHODS: Between January 1998 and December 2002, all records of admissions of schizophrenia or schizoaffective disorder patients (ICD-10) were assessed. Data as to age, gender, diagnosis, suicide attempt prior to admission, treatment with antipsychotic medication, dose and duration of treatment (mg daily, duration) with SGA was extracted from patients' files. All patients who had attempted suicide prior to admission were defined as the index group. The case-controlled group was comprised of the next admission of a patient suffering from schizophrenia (or schizoaffective disorder), matched for gender and age, who did not attempt suicide. RESULTS: Records of 756 patients (4486 admissions for said period) were analyzed (56.6% male, mean age 39.1+/-13.5 years). Amongst 378 patients who attempted suicide (index group), 16.1% were exposed to SGA while 37% were exposed in the control group (P=0.0001). The protective effect (odds ratio) of treatment by SGA was 3.54 (95%CI: 2.4-5.3). Risperidone was more frequently prescribed in the control group (54.3%) and had a larger effect-size than olanzapine (3.16 versus 1.76), although not statistically significant. Clozapine was prescribed only to a few patients. CONCLUSIONS: Schizophrenia patients exposed to both risperidone and olanzapine may gain protection from suicidality. The antisuicide effects seem to differ between SGAs. The long duration and large sample size support this finding, despite the retrospective nature of this study.

Mianserin or placebo as adjuncts to typical antipsychotics in resistant schizophrenia.

The beneficial effect of atypical antipsychotic drugs (APDs) in treatment-resistant schizophrenia patients has been attributed, mostly, to their relatively high serotonergic (5-HT)2 to dopaminergic (D)2 receptor blockade ratio. We hypothesized that a combination of typical APDs (D2 antagonists) and mianserin, a potent 5-HT2 antagonist, might also exert superior efficacy in this population. Eighteen inpatients with treatment-resistant schizophrenia who had an acute psychotic exacerbation of the disorder received, in a double-blind design, 30 mg/day mianserin (n = 9) or placebo (n = 9) in conjunction with typical neuroleptics [haloperidol (n = 9) or perphenazine (n = 9)]. Clinical status was evaluated before, during, and at the end of 6 weeks of combined treatment with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms and Hamilton Rating Scale for Depression. The typical APD/mianserin group exhibited significantly greater improvement in total BPRS scores (17.6% versus 5.5%; P= 0.03) and a trend towards greater improvement in SAPS scores (35.3% versus 13.0%; P = 0.07). Our study indicates that patients with chronic treatment-resistant schizophrenia who have an acute psychotic exacerbation ('acute-on-chronic') may benefit from the addition of a potent 5-HT2 blocker, such as mianserin, to typical antipsychotics. Our findings may further emphasize the contribution of enhanced 5-HT2 blockade to the 'atypicality' of the atypical APDs and to their greater efficacy in alleviating symptoms of chronic treatment-resistant schizophrenia.

Comparison of sexual dysfunction in male schizophrenic patients maintained on treatment with classical antipsychotics versus clozapine.

BACKGROUND: Antipsychotic treatment is frequently associated with sexual dysfunction. The objective of the present study was to evaluate and compare sexual function and behavior in male schizophrenic patients who regularly take either classical neuroleptic drugs or the prototypical atypical antipsychotic agent, clozapine. METHOD: Participants included 60 schizophrenic male patients (DSM-IV criteria); 30 maintained on treatment with classical antipsychotics and 30 on treatment with clozapine. The patients were evaluated with a detailed 18-item sexual function questionnaire. RESULTS: Both groups reported sexual dysfunction, although scores were significantly higher, indicating better functioning, in the clozapine-treated group in the domains of orgasmic function (number of orgasms per month, p = .037; frequency of orgasm during sex, p = .046), enjoyment of sex (p = .013), and sexual satisfaction (p = .0004). Equivocal results were obtained for the desire parameters. CONCLUSION: Maintenance therapy with the atypical neuroleptic clozapine may be associated with a lesser degree of sexual dysfunction than the classical antipsychotics in male outpatients with chronic schizophrenia.

Heart rate variability in elderly patients before and after electroconvulsive therapy.

Earlier studies have found major depression to be associated with increased cardiac mortality, hypothesized to result from reduced vagal modulation. Since reduced heart rate variability is part of normal aging, depression might predispose elderly patients to a higher risk. The authors investigated cardiac autonomic modulation, using spectral analysis, in 11 elderly depressed inpatients before and after electroconvulsive therapy (ECT). Cardiac vagal modulation increased significantly after ECT and was associated with symptom improvement, assessed by a significant decrease in the Hamilton Rating Scale for Depression. Further research is needed to elucidate the relationship between depression, autonomic modulation, and clinical risks in elderly patients.

Subjective effects of MDMA ('Ecstasy') on human sexual function.

Sexual function following 3,4-Methylenedioxymethamphetamine (MDMA, or 'Ecstasy') consumption was subjectively evaluated in 35 healthy recreational users (20 men and 15 women, aged 21-48 years) with regard to four major domains of sexual activity: desire, erection (lubrication in women), orgasm and satisfaction. Desire and satisfaction were moderately to profoundly increased by MDMA in more than 90% of subjects. Orgasm was delayed but perceived as more intense. Erection was impaired in 40% of the men. It seems that MDMA impairs sexual performance, in spite of enhancement of sexual desire and the perception of greater satisfaction.

Donepezil for the treatment of behavioral disturbances in Alzheimer's disease: a 6-month open trial.

Behavioral and psychological signs of dementia (BPSD) are common clinical characteristics of Alzheimer's disease (AD). They result in patient and caregivers distress, decreased quality of life and placement in nursing homes. Treatment of BPSD with antidepressant and antipsychotic medications is not without complications and serious adverse effects. The acetylcholinesterase inhibitors (AChEI) show preliminary promise as psychotropic agents possibly able to improve BPSD in AD patients. The present study aimed to evaluate the effect of donepezil (an AChEI) as an only treatment for AD patients with BPSD. Ten consecutive AD patients hospitalized at a psychogeriatric ward due to BPSD were treated with donepezil for 24 weeks. Effect was measured using the NeuroPsychiatric Inventory (NPI). Significant reduction in the presence of delusions, irritability/lability and disinhibition were achieved after 24 weeks of donepezil treatment. This was accompanied by reduction in caregivers distress. The drug was well tolerated and all patients completed the study. Our findings complement the preliminary data that donepezil as well as other AChEIs are promising candidates for further study as psychotropic agents positively affecting BPSD in AD patients.

Cyproheptadine versus propranolol for the treatment of acute neuroleptic-induced akathisia: a comparative double-blind study.

The purpose of this study was to investigate the efficacy of cyproheptadine, an antiserotonergic agent, in the treatment of neuroleptic-induced akathisia (NIA), as compared with propranolol, the current gold standard. In a double-blind trial, 30 patients with schizophrenia and NIA received either cyproheptadine 16 mg/day (N = 18) or propranolol 80 mg/day (N = 12) for 4 days, followed by 3 days without any anti-NIA treatment. The Barnes Akahisia Scale, Simpson-Angus Extrapyramidal Effects Rating Scale, and Brief Psychiatric Rating Scale were used to assess the severity of NIA, parkinsonism, and psychosis, respectively. In both groups, the severity of NIA decreased significantly over time (cyproheptadine, -46%; propranolol, -42%), with no significant intergroup difference. The NIA symptoms worsened significantly when cyproheptadine and propranolol were discontinued. We conclude that cyproheptadine 16 mg/day is as effective as propranolol for the treatment of acute NIA. The antiakathisic effect of cyproheptadine may be mostly attributable to its serotonin antagonistic activity.

Sexual dysfunction in male posttraumatic stress disorder patients.

BACKGROUND: Previous studies have suggested that sexual dysfunction may be associated with posttraumatic stress disorder (PTSD). Yet such studies have not examined a full range of sexual functioning and have not accounted for the possibility that medication used to treat PTSD may contribute to sexual dysfunction. OBJECTIVE: The current study compares the various components of sexual functioning among three groups of males: (1) untreated PTSD patients (n = 15), (2) PTSD patients currently treated with selective serotonin reuptake inhibitor (SSRI) agents (n = 27) and (3) a group of normal controls (n = 49). METHODS: All participants completed an 18-item questionnaire for assessment of sexual functioning. Those with PTSD also completed the Impact of Events Scale and the Symptom Check List-90 (SCL-90). RESULTS: Untreated and treated PTSD patients had significantly poorer sexual functioning in all domains (desire, arousal, orgasm, activity and satisfaction) as compared to normal controls. Those treated with SSRI had greater impairment in desire, arousal and frequency of sexual activity with a partner. There was a high correlation between sexual dysfunction among the PTSD group and the anger-hostility subscale of the SCL-90. CONCLUSIONS: PTSD appears to be associated with pervasive sexual dysfunction that is exacerbated by treatment with SSRIs. PTSD may represent a heterogeneous syndrome. Patients with PTSD have a high rate of comorbid panic disorder, major depression and anxiety, and it could thus be argued that these comorbid disorders, rather than PTSD, accounted for the observed result. Future research aimed at understanding comorbidity and heterogeneity should help to illuminate the psychobiology of PTSD and eventually guide both medication and psychosocial treatments.

QT dispersion in the surface electrocardiogram in elderly patients with major depression.

BACKGROUND: QT dispersion (QTd) is a measure of interlead variations of QT interval of the surface 12-lead electrocardiogram (ECG). Increased QTd, found in various cardiac diseases, reflects cardiac instability and is associated with increased cardiac death. Major depressive disorder (MDD) was found to be associated with high cardiovascular mortality rates. This study compares QTd in elderly patients with MDD to normal controls. METHODS: QTd and rate-corrected QTd of 18 physically healthy elderly patients (69.9 +/- 7.6 years) with MDD was compared to nine physically and mentally healthy age- and gender-matched controls (64.1 +/- 12.2 years). RESULTS: QTd and rate-corrected QTd were significantly higher in MDD compared to controls (68 +/- 30 vs. 40 +/- 13 ms, P=0.002 and 81 +/- 39 vs. 43 +/- 13 ms, P=0.001, respectively). Intra- and inter- observer reproducibilities were highly correlated (r=0.96, P <0.0001; r=0.88, P <0.001, respectively). LIMITATIONS AND CONCLUSIONS: The major limitations of this study are the small number of subjects and the fact that all the patients were maintained on antidepressant medication. However, it seems that QTd analysis might shed light on possible autonomic imbalance and also provide a novel cardiovascular risk factor for increased cardiac death in MDD.

Sexual function in women attending a urogynecology clinic.

The study prospectively evaluated the relationship between sexual dysfunction and urodynamic diagnoses in 100 consecutive female patients referred for urogynecologic evaluation. Sexual function was evaluated by a detailed questionnaire that addressed four phases of the sexual cycle: desire, arousal, orgasm and satisfaction. Each phase of the sexual cycle was assessed separately using a score of 1-4. Total sexual function (TSF) score was calculated by combining the scores of the four examined parameters (range 4-16). Analysis revealed statistically significant (P < 0.05) lower TSF scores in patients with detrusor instability (DI) than in those with genuine stress incontinence, sensory urge or mixed urodynamic diagnoses (8.65 +/- 4 versus 12.22 + 3.6, 10.25 +/- 4.1 and 11.47 +/- 4.1, respectively). Three per cent of the elderly women (>60 years) compared to 29% of the younger women (< or = 60 years) reported urinary incontinence during sexual activity. Sexual function should therefore be routinely evaluated in women presenting with urinary symptoms.

Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior.

OBJECTIVE: The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients. METHOD: Twenty-eight actively psychotic inpatients, aged 20-60 years, who were under treatment with neuroleptic agents were selected for the study. Each was randomly assigned on a double-blind basis to receive either 5 mg i.m. of haloperidol (N=13) or 1 mg i.m. of flunitrazepam (N=15) during an aggressive event. Verbal and physical aggression was measured over time with the Overt Aggression Scale. Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale. RESULTS: Both flunitrazepam and haloperidol exhibited acute antiaggressive activity. This beneficial effect, as assessed by the Overt Aggression Scale, was obtained within 30 minutes. CONCLUSIONS: Intramuscular flunitrazepam may serve as a convenient, rapid, safe, and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric settings.

The serotonin antagonist mianserin for treatment of serotonin reuptake inhibitor-induced sexual dysfunction in women: an open-label add-on study.

The aim of this study was to determine if the serotonin antagonist mianserin improves antidepressant-induced sexual dysfunction in women. The work was prompted by an earlier study of men by our team of researchers. The study population included 16 women aged 20-65 years undergoing treatment at a psychiatric outpatient clinic, who presented with sexual dysfunction subsequent to intake of a serotonin reuptake inhibitor (SRI) for depression. Sexual function (four domains) was evaluated by semistructured interviews before and after the administration of mianserin 15 mg/d for 3 weeks. The most prominent sexual dysfunction was anorgasmia. Clinically significant improvement was noted in all domains in two thirds of the patients, in most cases in the first or second week of treatment. None of the patients with panic disorder (PD) responded to mianserin, in contrast to those with affective disorder or obsessive compulsive disorder (OCD), indicating a possible relevance of the psychiatric diagnosis to mianserin effectiveness. There were no major adverse effects and no changes in the patients' stabilized psychiatric status. We conclude that mianserin is beneficial in reversing sexual function caused by SRI intake. Further large-scale, placebo-controlled studies are needed to confirm these findings.

Elevated adhesiveness/aggregation of peripheral blood leukocytes in patients with major depression.

A simple slide test was used to determine the effects of major depression (MD) and heterocyclic antidepressants on leukocyte adhesiveness/aggregation (LAA) in the peripheral blood. Eighty subjects were categorized into four equal groups: untreated-MD patients, treated-MD patients, nondepressed patients treated with antidepressants and healthy controls. Significantly higher LAA values were observed both in untreated- and treated-MD patients, 13.8+/-1.7% and 13.5+/-1.9% respectively, compared to nondepressed-treated patients and healthy controls, 5.4+/-0.9% and 6.4+/-0.7% respectively (P < 0.0001). Increased LAA was associated with the depressive episode, was not affected by antidepressants and may potentially serve as a useful laboratory state marker for MD.

Mianserin, a 5-HT2a/2c and alpha 2 antagonist, in the treatment of sexual dysfunction induced by serotonin reuptake inhibitors.

Sexual dysfunction is commonly encountered in patients treated with antidepressants. The exact mechanism responsible for the sexual impairment is as yet unclear, although activation of the serotonergic system has been implicated. In the present study, we examined the effect of the 5-HT2a/2c and alpha 2 antagonist mianserin in the treatment of patients with sexual dysfunction induced by serotonin reuptake inhibitors (SRIs). Mianserin 15 mg was coadministered to 15 male subjects with new-onset sexual dysfunction who were under treatment with SRIs. Four major domains of sexual activity-desire, erection, orgasm, and satisfaction-were assessed once weekly for 4 weeks. At the end of the study, 9 of the 15 subjects reported a marked improvement in their sexual functioning, 2 reported partial improvement, and only 4 subjects showed no improvement at all. The beneficial effects were prominent in the areas of orgasm and satisfaction and were usually noted within the first and second week of mianserin treatment. The addition of mianserin to the treatment regimen was not associated with either improvement or worsening of the basic psychiatric clinical status. It appears that the coadministration of low-dose mianserin may be an additional option in the treatment of sexual dysfunction induced by SRIs.

Sulpiride adjunction to clozapine in treatment-resistant schizophrenic patients: a preliminary case series study.

Six chronic neuroleptic-resistant schizophrenic patients, partial responders to clozapine, were co-administered 600 mg/day of sulpiride (a selective D(2) dopaminergic antagonist) as an augmentation to clozapine (a relatively weak D(2) blocker), for 10 weeks, open-labeled. A remarkable reduction in positive and negative symptoms was observed in four of the six patients.