Treatment of Clozapine-Associated Sialorrhea: The Role of Benzamide Derivatives.

PURPOSE: Hypersalivation is one of the most prevalent and distressing adverse effects associated with clozapine treatment. Currently, there is no standard therapeutic approach toward how to overcome it. Clinicians use various medications for managing this adverse effect. However, some of the agents are not effective enough, whereas others can induce other adverse effects. Recently, several reviews have been published on the treatment of clozapine-associated hypersalivation, in which the focus was on drugs from various pharmacological groups, and little attention was paid to drugs from the group of substituted benzamides. The intention of this brief narrative review is to draw the attention of clinicians to the use of the benzamide group for the treatment of this unpleasant adverse effect. METHODS: A MEDLINE search was conducted to identify published treatment studies and case reports in the literature from 2000 to September 2021, concerning a treatment of clozapine-associated hypersalivation, mainly substituted benzamides. RESULTS: Accumulating evidence during the last 2 decades indicates that agents derived from the benzamide group may be effective and safe agents for treatment of clozapine-associated hypersalivation. Whether with a psychotropic effect or without, medications from this group may produce a beneficial response. CONCLUSIONS: Substitute benzamide derivatives have emerged as effective and well-tolerated agents for treatment clozapine-associated hypersalivation.

Double-Blind, Randomized, Placebo-Controlled Trial of Metoclopramide for Hypersalivation Associated With Clozapine.

Hypersalivation is a frequent, disturbing, and uncomfortable adverse effect of clozapine therapy that frequently leads to noncompliance. The aim of this study was to examine the efficacy of metoclopramide (dopamine D2 antagonist, antiemetic medication) as an option for management of hypersalivation associated with clozapine (HAC). A 3-week, double-blind, placebo-controlled trial was conducted in university-based research clinics from January 2012 to May 2014, on 58 inpatients treated with clozapine who were experiencing hypersalivation. The subjects were randomly divided into placebo and metoclopramide groups. The starting dose was 10 mg/d. Participants who did not respond were up-titrated 10 mg/d weekly to a total of 30 mg/d during the third week. The number of placebo capsules was increased accordingly up to 3 capsules per day. Primary outcome was the change from baseline to the end of study in the severity of hypersalivation as measured with the Nocturnal Hypersalivation Rating Scale and the Drooling Severity Scale. Secondary outcomes included Clinical Global Impression of Improvement scale and adverse effect scales. Significant improvement on the Nocturnal Hypersalivation Rating Scale was demonstrated in the metoclopramide group from the end of the second week (P < 0.004), and on the Drooling Severity Scale (P < 0.02) in the third week. Clinical Global Impression-Improvement scale scores revealed major improvement. Twenty subjects (66.7%) treated with metoclopramide reported significant decline or total disappearance of HAC in comparison to 8 patients (28.6%) who received placebo (P = 0.031). No adverse effects to metoclopramide were reported. Metoclopramide was found to be safe and effective for the treatment of HAC.

Pavel Ivanovich Karpov (1873-1932?)--the Russian Prinzhorn: art of the insane in Russia.

The complicated relationship between the discipline of mental health and the arts has barely been studied systematically. Mental hospitals, shelters and prisons--institutions that accommodate the mentally ill--sometimes promote but often discourage and disrupt the patients' artistic creativity and the images created. In psychiatric circles, the recognition of patient art was a long, slow and frustrating process. Among the Western psychiatrists who studied the creative activity of the mentally ill, researchers usually mention such names as C. Lombroso, M. Shearing, V. Morgentaller, H. Prinzhorn and others, but rarely refer to their Russian colleagues and contemporaries. Pavel Ivanovich Karpov (1873-1932?), a Russian psychiatrist, was one of the most extensive researchers in the field of the art of the insane, but unfortunately his name is little known among modern psychiatrists. For his clinical and scientific contributions, he deserves to be remembered in the history of psychiatry.

Tardive dyskinesia (syndrome): Current concept and modern approaches to its management.

Tardive dyskinesia is a serious, disabling and potentially permanent, neurological hyperkinetic movement disorder that occurs after months or years of taking psychotropic drugs. The pathophysiology of tardive dyskinesia is complex, multifactorial and still not fully understood. A number of drugs were tried for the management of this motor disturbance, yet until now no effective and standard treatment has been found. It is very disappointing to realize that the introduction of antipsychotics from the second generation has not significantly decreased the prevalence and incidence of tardive dyskinesia. Therefore, the management of this motor disturbance remains an actual topic as well as a challenge for clinicians. This review summarizes recent relevant publications concerning the treatment of tardive dyskinesia.

Risk factors for coercion length at psychiatric hospitals in Israel: Relationship with staff.

Background: Coercive interventions continue to be applied frequently in psychiatric care when patients are at imminent risk of harming themselves and/or others. Aim: The purpose of this study was to demonstrate the relationship between the length of coercion and a variety of factors, including the sociodemographic background of patients, their diagnoses and the characteristics of hospital staff. Methods: This is a one-year cross-sectional retrospective study, including records of 298 patients who underwent restraint and/or seclusion interventions in male acute, closed wards in two psychiatric hospitals in Israel. Results: A higher proportion of academic nurses to nonacademic nurses on duty leads to a shorter coercion time (P < 0.000). The number of male staff on duty, without any relation to their level of education, also leads to the shortening of the coercion time. Conclusion: The presence of registered, academic female nurses, male staff on duty and the administration of medication before coercive measures can reduce the length of restriction.

Victor Kandinsky (1849-89): pioneer of modern Russian forensic psychiatry.

The paper describes Victor Kandinsky's professional achievements within nineteenth-century Russian forensic psychiatry. A thorough review of nineteenth-century Russian psychiatry is presented, followed by a short biographical account of Kandinsky's personal life. Within the backdrop of Russian forensic psychiatry toward the end of nineteenth century, Kandinsky's pioneer innovations in psychopathology and classification as well as his contributions to Russian forensic psychiatry are reviewed. These are exemplified by two of his forensic case studies relating to forensic responsibility and malingering, which are included in his famous book 'On Irresponsibility'.

Motor symptoms of schizophrenia: is tardive dyskinesia a symptom or side effect? A modern treatment.

Abnormal involuntary dyskinetic movements in schizophrenia patients have been documented for more than 140 years. Clinicians should distinguish between two kinds of disturbances-spontaneous dyskinetic movements and movements induced by psychotropic medications-which may look familiar clinically. As a modern term, tardive dyskinesia (TD) is a potentially permanent neurological hyperkinetic movement disorder that occurs after months or years of taking psychotropic drugs. Several distinct forms of TD exist, specifically tardive akathisia, tardive blepharospasm, tardive dystonia, tardive gait, tardive myoclonus, tardive tremor, and tardive tics, and they have different pathophysiologies and treatment. The pathogenesis of TD remains unclear, and the pathophysiology is complex and multifactorial. Moreover, there is solid evidence of a genetic predisposition to TD. This article summarizes recent relevant publications concerning TD and the most recent studies regarding treatment of this disorder with antioxidative agents.

Shared obsessive-compulsive disorder: broadening the concept of shared psychotic disorder.

OBJECTIVE: Folie a deux (shared psychotic disorder) is often described in the context of schizophrenia. In this article we present this syndrome in a non psychotic context. METHOD: We report a case of induced obsessive-compulsive disorder (OCD) in a married couple. Six months after the deterioration in the patient's OCD, his wife developed the same symptoms with no preceding history of an Axis I disorder. Neither spouse demonstrated psychotic symptomatology. The husband was successfully treated on an outpatient basis with Citalopram and Clonazepam. His wife's OCD spontaneously resolved without medication in parallel with the resolution of her husband's OCD. RESULTS: We highlight the uncommon phenomenon of shared psychiatric disorder occurring in the context of OCD. In the current psychiatric diagnostic nomenclature, (DSM IV and ICD10), there is no category for a non-psychotic shared psychiatric disorder. We raise the question of broadening the concept of shared disorder so as to include shared OCD and perhaps other shared psychiatric syndromes. CONCLUSIONS: More controlled studies are required in order to better understand the psychopathology and mechanisms of psychotic and non-psychotic shared disorders in psychiatry. We believe there are important treatment implications of such an understanding.

Clinical and demographic characteristics of secluded and mechanically restrained mentally ill patients: a retrospective study.

BACKGROUND: Restraint or seclusion measures in acute psychiatric care are used as a last resort when all other methods for removal of physical threat have failed. The purpose of this study is to find a correlation between coercive measures, demographic characteristics within this patient group, and factors associated with shortened periods of restriction. METHODS: This is a one-year retrospective study conducted in a male acute closed ward of a psychiatric hospital in Israel. The data from January 1, 2014 to December 31, 2014 were retrieved from the records of patients who underwent restraint and/or seclusion interventions during this period. The analyzed data included age, psychiatric diagnosis, marital status, education, race, ethnicity, length of hospital stay, legal status during admission, type of coercive measure (mechanical restraint, seclusion), number and duration of coercive episodes, reasons for coercion, time of event, number of previous hospitalizations, aggression in past and present treatment, and treatment during events. RESULTS: During this time period, there were 563 admissions in the study ward. Over this period, 176 subjects (31.3%) underwent 488 restraints and/or seclusions. 98% were aggressive in the past. (Although some results reached statistical significance, we prefer to emphasize here only the most important results, while the others will be presented in the text.) Patients with personality disorders were physically limited for the longest time, while schizophrenia patients were restricted for the shortest time compared with other diagnoses (p = 0.007). A negative correlation was found between the length of coercion and the number of academic female nurses on duty (p = 0.005), as well as the administration of sedative medications during the restricting procedure. CONCLUSIONS: We believe that the presence of registered, academic female nurses on duty and medication administration during coercive measures can reduce the length of restriction.

Curcumin as Add-On to Antipsychotic Treatment in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Introduction of old and new generations of antipsychotics leads to significant improvements in the positive symptoms of schizophrenia. However, negative symptoms remain refractory to conventional trials of antipsychotic therapy. Recently, there were several open clinical human trials with curcumin. Curcumin is a natural polyphenol, which has a variety of pharmacological activities, including antioxidative and neuroprotective effects. The studies showed that curcumin improved the negative symptoms of schizophrenia. The purpose of our study was to examine the efficacy of curcumin as an add-on agent to regular antipsychotic medications in patients with chronic schizophrenia. METHODS: Thirty-eight patients with chronic schizophrenia were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 3000 mg/d curcumin or placebo combined with antipsychotics from January 2015 to February 2017. The outcome measures were the Positive and Negative Symptoms Scale (PANSS) and the Calgary Depression Scale for Schizophrenia. RESULTS: Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. There was a significant response to curcumin within 6 months in total PANSS (P = 0.02) and in the negative symptoms subscale (P = 0.04). There were no differences in the positive and general PANSS subscales, and the Calgary Depression Scale for Schizophrenia scores between the treatment and placebo groups. No patient complained of any adverse effect. CONCLUSIONS: The promising results of curcumin as an add-on to antipsychotics in the treatment of negative symptoms may open a new and safe therapeutic option for the management of schizophrenia. However, these results should be replicated in further studies.ClinicalTrials.gov Identifier: NCT02298985.

Psychologists' and social workers' self-descriptions using DSM-IV psychopathology.

There is limited information on mental health of psychologists and social workers despite their rendering mental health services, so their subjective perception of mental disorder was explored via a self-evaluation survey in which they self-diagnosed the presence of DSM-IV disorders within themselves. The sample of 128 professionals included 63 psychologists and 65 social workers. The presence of Axis I traits was reported by 81.2%, the three most frequent traits being mood, obsessive-compulsive disorder, and eating disorder. Axis II traits were reported by 73.4% of subjects, the three most frequent conditions being narcissistic, avoidant, and obsessive-compulsive personality traits. While a high percentage of subjects reported the presence of either an Axis I or Axis II disorder, the average severity reported was low. More psychologists reported on mood, social phobia, and eating problems than social workers, while the latter reported more on psychotic problems. Psychologists reported more Axis II traits, especially paranoid, narcissistic, and avoidant subtypes. More women than men reported eating problems, while more men reported schizoid and avoidant personality traits. In conclusion, manifestations of subthreshold psychiatric conditions were prominently reported. These findings suggest encouraging mental health care professionals to explore treatment for problems if present.

The influence of immigration on the mental health of those seeking psychiatric care in southern Israel: a comparison of new immigrants to veteran residents.

OBJECTIVE: The wave of immigration from the countries of the former Soviet Union from 1990 to 2006 brought to Israel over 1,000,000 people. Many of them suffer from different diseases including mental disorders. Although the majority of older persons are free of serious psychopathology, 15-20% of the elderly people may be in need of psychiatric services. The aim of the study is to compare the mental health parameters of two elderly groups living in the southern part of Israel who suffer from severe mental problems: new immigrants from the former USSR (NI) in contrast to veteran Israelis (VR). METHOD: In this retrospective study we compare two groups of aged inhabitants (NI and VR) from the southern region of Israel who sought psychiatric services (both outpatient and inpatient). The comparison concerns socio-demographic characteristics of people in care in a mental health center, rate of use of these services and diagnoses of the patients. RESULTS: One hundred and fifty-six (1.2%) NI sought psychiatric help versus 584 (2.1%) VR. The major findings include the significantly increased number of adjustment disorders and the significantly lower number of organo-mental diagnoses among psychiatrically hospitalized NI in comparison to VR. No differences were found in the frequency of mood or psychotic disorders between the two groups. CONCLUSIONS: Immigration is acknowledged to be a major stressor which may increase the emotional distress of an immigrant and in some cases may even lead to psychopathological reactions. NI are prone not to seek medical aid in outpatient facilities until a real worsening of mental health status compels them to be hospitalized.

High-dose vitamin B6 decreases homocysteine serum levels in patients with schizophrenia and schizoaffective disorders: a preliminary study.

UNLABELLED: Vitamin B6 plays an essential role in the normal functioning of the central nervous system. Normal homocysteine (Hcy) serum level is maintained by remethylation of Hcy to methionine by enzymes that require folic acid and vitamin B12 and by catabolism to cysteine by a vitamin B6-dependent enzyme. These findings may be consistent with the hypothesis that the vitamin B6 status may influence plasma Hcy levels. The aims of this preliminary study were (1) to determine whether a correlation exists between Hcy and vitamin B6 levels in patients with schizophrenia and schizoaffective disorders and (2) to investigate whether treatment with high-dose vitamin B6 may reduce Hcy levels in these patients. METHODS: In this preliminary study, we enrolled 11 patients with schizophrenia or schizoaffective disorders (7 men and 4 women; mean age +/- SD, 50 +/- 12 years) receiving high doses of vitamin B6 treatment (1200 mg/d) for 12 weeks. Blood samples for the assessment of pyridoxal-5-phosphate and Hcy serum levels were obtained at baseline and after 12 weeks of treatment. RESULTS: Age was significantly positively correlated with Hcy levels at baseline (r = 0.392, P = 0.004). All other parameters, including diagnosis, disease duration, and pyridoxal-5-phosphate serum level, were not correlated with Hcy serum levels at baseline. After vitamin B6 treatment, Hcy serum levels significantly decreased (14.2 +/- 3.4 vs. 11.8 +/- 2.0 micromol/L, respectively, t = 2.679, P = 0.023); this decrease being statistically significant in men but not in women. CONCLUSIONS: High doses of vitamin B6 lead to a decrease in Hcy serum level in male patients with schizophrenia or schizoaffective disorder.

Education and postgraduate education of psychiatrists in the Soviet Union and their integration into a new milieu. A view from the present to the past of former Soviet psychiatrists.

The article presents the problems and difficulties that psychiatrists from the former Soviet Union (FSU) have to cope with in Israel. Immigration and acculturation in a new milieu is a complex process and even more complicated for those whose specialty is medicine and particularly psychiatry. There is a wide gap between the skills and knowledge that new immigrants brought with them from the FSU and the professional demands in the new country. Psychiatry and psychiatric education in the FSU were determined by the cultural practices and traditions of the region and the organizational principles of the USSR which were very different than those of western society and the State of Israel. In comparison to the West, postgraduate psychiatric training in the USSR was shorter and less rigorous with an emphasis on biological therapy. Soviet "psychotherapy" was more reality oriented and more authoritarian than in the West, stressing "collective" group therapy. We describe the basic principles of Soviet medical education and the radically different social, intellectual and political history of the former Soviet Union. We relate the experiences of psychiatrists in the FSU in learning dynamic psychotherapy and the difficulties connected with this education. Moreover, the process of educating psychiatric residents is described from a supervisor's point of view. This complex process led to some major difficulties. In order to cope with the difficulties the supervisor employed a broad variety of means and techniques: an introductory course and a basic seminar about fundamental cornerstones of psychotherapy were offered.

The prevalence of neuroleptic drug-induced tardive movement subsyndromes among schizophrenic and schizoaffective patients residing in the southern region of Israel.

The aim of the current study was to assess the prevalence of tardive movement disorders (TMD) among a group of institutionalized schizophrenic and schizoaffective patients in southern region of Israel. Chronic schizophrenic and schizoaffective inpatients of a psychiatric hospital and its affiliated hostels were screened for the presence of TMD subsyndromes. Twenty percent (107 patients) of 523 patients with schizophrenia and schizoaffective disorder exhibited TMD. Of those with TMD, 36% had only one subsyndrome, whereas 64% had a combination of several TMD subsyndromes. With regard to patients with TMD, the most frequent TMD subsyndrome was tardive tremor (TT). TT appeared more often in males compared to females and at a younger age (44.3+/-8 vs. 54.3+/-11 years, P<0.04). TD appearing in combination with other TMD subsyndromes was significantly more prevalent among females than in males (57% vs. 35%; P<0.02). TMD generally appears in a combined fashion. Further prospective studies from different geographical areas are recommended.

Alexey Kondratyevich Savrasov (1830-1897): the muse and the bottle.

The Russian landscape painter Alexey Savrasov lived in the middle of the 19th century. He was overwhelmed with grief at the loss of several of his children and he used alcohol to blunt the pain and anguish. The effects of psychoactive substances and especially alcohol have been linked closely to creativity. His life story demonstrates the bitter relationship between the bottle and the muse. He became dependent on alcohol, his family broke up and he was fired from work, his creativity declined and his health deteriorated. At death, he was a lonely and a forgotten man and only two persons attended his funeral.

Creativity and mood disorders: The enigmatic case of Isaak Il'ich Levitan (1860-1900).

Isaak Levitan (1860-1900) was one of Russia's most influential landscape artists. He lived a very short life, only 40 years, but left more than 1000 paintings. He suffered from mood fluctuations, and died as a result of serious heart disease. After an introduction related to the issue of creativity and mental disorders, a short biography of Levitan's life is outlined, followed by some examples of his mood and behavior. A section on the mood's reflection in Levitan's professional work is followed by a description of his romantic loves and disappointments and his relationship with his contemporary Russian, the writer Anton Chekhov.

Successful Use of Escitalopram for the Treatment of Visual Hallucinations in Patients With Parkinson Disease.

INTRODUCTION: Patients with Parkinson disease (PD) frequently experience visual hallucinations (VH). Visual hallucinations are most often viewed as an adverse effect of antiparkinsonian treatment. Possible treatments for this disturbance include a reduction of antiparkinsonian medications, adding atypical antipsychotics, or cholinesterase inhibitors. Some studies demonstrated that selective serotonin reuptake inhibitors may be an optional treatment for patients experiencing psychosis or agitation in dementia. Currently, there is no standard recommended treatment for VH in patients with PD. We present here our clinical experience with escitalopram (selective serotonin reuptake inhibitor) for treating this disturbance. METHODS: Thirteen patients with PD (8 men and 5 women; age range 67-83 years) experiencing VH were openly treated with escitalopram 10 or 15 mg/d as add-on. Efficacy was assessed at baseline, then after 4 and 8 weeks of treatment using Clinical Global Impression-Severity and Clinical Global Impression-Improvement. RESULTS: At the end of the 4th week of treatment, of 13 patients, 11 subjects demonstrated improvement, and in only 2 patients were there no changes in their condition. After an additional 4 weeks, 2 of the responders showed very significant improvement, 6 demonstrated much improvement, and 3 patients demonstrated minimal improvement. Only 1 patient showed no change in his condition. One additional patient stopped taking escitalopram after 5 weeks because of an absence of improvement in his state. CONCLUSIONS: Escitalopram was well tolerated as treatment of VH in PD patients. This medication could be a promising optional therapy for this disturbance; however, further randomized controlled and bigger studies are necessary.

The effect of sudden clozapine discontinuation on management of schizophrenic patients: A retrospective controlled study.

BACKGROUND: The aims of our study were (1) to compare the dose of clozapine needed to achieve remission in patients who stopped their treatment (study group) versus patients who continued taking this medication (control group) and (2) to compare the clinical characteristics of remission between these 2 groups. METHOD: We retrospectively reviewed the medical records of all treatment-resistant schizophrenic and schizoaffective patients (according to DSM-IV criteria) who were treated with clozapine over a period of 9 years, from January 1995 through December 2003. The study group consisted of 43 patients and the control group of 12 patients. All patients' files from both groups were examined, and each patient's remission was scored twice--initially on discharge from the hospital and subsequently after final discharge for the study group, or at the end of the study for the control group. RESULTS: The change of clozapine dose from the first to the last remission expressed by percentage shows a significant difference between the 43% increase in clozapine dose in the study group and the 12.5% decrease in clozapine dose in the control group (p < .001). Quality of remission assessment showed deterioration in the global remission score in the study group, while the quality of remission assessment in the control group did not show any change. CONCLUSIONS: Our findings suggest that the discontinuation of clozapine treatment leads to a deterioration in the quality of remission, with a need for an increased dose of clozapine. Further prospective studies on larger samples are needed to confirm these findings.

Vitamin B12 and folate serum levels in newly admitted psychiatric patients.

BACKGROUND & AIMS: Deficiencies of cobalamin and folate may play a causal role in the development or exacerbation of psychiatric illnesses. We compared cobalamin and folate levels in newly admitted psychiatric patients to mentally healthy controls and assessed their correlation with various psychiatric conditions. METHODS: All patients consecutively admitted to a psychiatric hospital were examined for serum cobalamin and folate levels. Controls were obtained from a population with no known mental illness. Values were considered to be below normal if cobalamin was <223 pg/ml and folate <3.1 ng/ml. RESULTS: The 224 newly admitted patients did not differ significantly from controls, both with regard to the mean cobalamin level and to the prevalence of lower than normal levels. About 30% of patients had low folate values compared to 2.5% in the control group (P<0.0001). Mean folate level in controls was significantly higher than in patients (P<0.0001), where a positive correlation was found between low folate levels and depression. CONCLUSIONS: The results of our study suggest that folate levels be assessed in patients admitted to psychiatric wards, especially in those with depression. Further study is needed to evaluate the role of folate and cobalamin in psychiatric illness.