Monitoring long-term court order psychiatric hospitalization: a pilot project in Israel.

BACKGROUND: In Israel, the rules of compulsory psychiatric hospitalization, including hospitalization under a court order, are set out in the Israel Mental Health Act, 1991 (MHA). The MHA does not specifically define the time limits of hospitalization by Court Order, though every patient, by law has to be brought before the Regional Psychiatric Board (RPB) once every six months for reevaluation. The Supreme Court recently addressed this issue and suggested that by having no specific time span, the way lies open for infringement of individual rights (Criminal Appeals 3854\02). Consequently the Supreme Court suggested that some court committed patients should be moved from the criminal to the civil track which inflicts less severe infringement of the mentally ill patient's rights. This ruling generated rethinking at the ministerial level aimed at improving the monitoring of the care of long-term psychiatric hospitalization in criminal cases. The Ministry of Health initiated a project designed to study this issue. OBJECTIVES: The main objective of this project, which is described below, is to monitor the type and incidence of forensic mental patients hospitalized in Israel for more than 10 years, and to propose alternatives to replace this untenable situation. METHODS: All the 12 psychiatric hospitals in Israel which hospitalize forensic patients were sent written requests for data on criminal patients hospitalized under court orders, including demographic data, diagnosis and type of offense. We identified in all 65 such patients. The data received were compared with the National Psychiatric Register databank of the Ministry of Health and divided in subgroups according to diagnosis, type of offence, demographic variables and length of hospitalization. RESULTS: Most of the subjects of the sample (89%) suffered from psychotic disorder mainly schizophrenia of the paranoid type. 95.5% were male. The most prominent type of offense was assault against family members (37%), which is in keeping with statistics reported in the relevant literature. The profile of the typical patient of this sample is: male, aged 45-65, unmarried, with 8 years of education and suffering from paranoid schizophrenia. DISCUSSION: No correlation between type and severity of offense and length of involuntary forensic hospitalization was found. We suggest some possible alternatives to improve the current handling of the group of long term hospitalized forensic patients. We also feel that a further study should be carried out on forensic patients hospitalized for a period of five to ten years.

Platelet serotonin transporter in drug-naive migrainous children and adolescents.

Platelet [3H]imipramine binding was measured in 17 children and adolescents suffering from common (n = 10) and classical (n = 7) migraine and 10 healthy control subjects. All patients had more than a 1-year history of the disease and suffered at least one attack per month. All subjects had been drug-free for at least 4 weeks prior to the study and had never been treated with drugs active at the serotonergic system. An increased density in [3H]imipramine binding sites was detected in the migraine patients (+51%; p < 0.05). The increase in maximal binding was more prominent in the classical migraine group (+63%) than in the common migraine group (+43%). These results disagree with previous studies that reported decreased platelet imipramine binding in adult migraine patients. The discrepancy may be related to chronicity of drug treatment, long-term duration of disease and comorbidity of depression and anxiety disorders in adult migrainous patients.

Decreased platelet imipramine binding in Tourette syndrome children with obsessive-compulsive disorder.

[3H]Imipramine binding to blood platelets was assessed in eight untreated Tourette syndrome (TS) children, nine drug-free TS children with obsessive-compulsive disorder (OCD), and nine age-matched and gender-matched control subjects. The density of [3H]imipramine binding sites in TS + OCD patients was significantly lower compared with TS-OCD patients (28%) as well as when compared with controls (31%). This alteration was not accompanied by differences in the affinity of the binding site to the ligand. The decreased density of the platelet serotonin "transporter" might implicate the involvement of the serotonergic system in the pathophysiology of OCD in TS patients, but not in TS per se.

Low platelet-poor plasma concentrations of serotonin in patients with combat-related posttraumatic stress disorder.

BACKGROUND: Combat-related posttraumatic stress disorder (CR-PTSD) is associated with a dysregulation of various neurotransmitter systems. METHODS: We assessed levels of platelet-poor plasma (PPP) norepinephrine (NE), and serotonin (5-HT), and 24-hour urinary excretion of NE, dopamine (DA), and homovanillic acid (HVA) in 17 male outpatients with untreated chronic CR-PTSD (age, 33.1 +/- 7.4 years) and 10 normal control subjects (age, 35.8 +/- 2.7 years). RESULTS: Compared with the control subjects, the PTSD patients showed significantly lower PPP 5-HT levels, elevated PPP NE levels, and significantly higher mean 24-hour urinary excretion of all three catecholamines (NE, DA, and HVA). The 24-hour urinary HVA values of the CR-PTSD patients correlated significantly and positively with the total Impact of Event Scale scores and the avoidance symptoms cluster scores, and the PPP 5-HT levels correlated negatively with the Hamilton Anxiety Rating Scale scores. The PPP NE/5-HT ratio was significantly higher in the study group than in the control subjects. CONCLUSIONS: We believe this combined enhanced noradrenergic activity and diminished 5-HT activity may be relevant to the neurobiology of CR-PTSD.

Elevated levels of serum interleukin-1 beta in combat-related posttraumatic stress disorder.

Levels of serum interleukin-1 beta (IL-1 beta) and soluble interleukin-2 receptor (sIL-2R) were assessed in 19 male patients with combat-related posttraumatic stress disorder (PTSD) in comparison to 19 age- and sex-matched healthy volunteers. Serum IL-1 beta levels (but not sIL-2R) were significantly higher (p < .001) in the PTSD patients than in the controls. IL-1 beta levels did not correlate with cortisol levels, severity of PTSD, anxiety, depressive symptoms, or alexithymia score; however, they did correlate significantly (r = .54, p < .005) with the duration of PTSD symptoms. It is possible that desensitization of the hypothalamic-pituitary-adrenal axis in chronic PTSD patients counteracts the stimulatory effect of IL-1 beta on cortisol secretion.

Clozapine treatment for neuroleptic-induced tardive dyskinesia, parkinsonism, and chronic akathisia in schizophrenic patients.

BACKGROUND: Previous studies on the use of clozapine in neuroleptic-resistant chronic schizophrenic patients have demonstrated positive effects on tardive dyskinesia but were less conclusive about chronic akathisia and parkinsonism. The aim of the present study was to investigate the short-term (18 weeks) efficacy of clozapine in neuroleptic-resistant chronic schizophrenic patients with coexisting tardive dyskinesia, chronic akathisia, and parkinsonism. METHOD: Twenty chronic, neuroleptic-resistant schizophrenic patients with coexisting tardive dyskinesia, parkinsonism, and chronic akathisia were treated with clozapine. Assessment of tardive dyskinesia, parkinsonism, and chronic akathisia was made once weekly for 18 weeks with the Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Rating Scale for Extrapyramidal Side Effects, and Barnes Rating Scale for Drug-Induced Akathisia (BAS). RESULTS: At the end of 18 weeks of clozapine treatment, improvement rates were 74% for tardive dyskinesia, 69% for parkinsonism, and 78% for chronic akathisia. A statistically significant reduction in the scores on the AIMS and Simpson-Angus Scale was achieved at Week 5 and on the BAS at Week 6 (p < .0001). CONCLUSION: Relatively low doses of clozapine are effective for the treatment of neuroleptic-induced extrapyramidal syndromes in neuroleptic-resistant chronic schizophrenic patients. The relief of tardive dyskinesia, parkinsonism, and chronic akathisia in this group of patients occurs more rapidly than the reduction in psychotic symptoms. Disturbing, long-term extrapyramidal syndromes in chronic schizophrenic patients should be considered an indication for clozapine treatment.

Increased serotonin 5-HT2 receptor binding on blood platelets of suicidal men.

In search of a physiological marker of depression and suicidal behavior, serotonin receptors of the 5-HT2 type were studied on platelet membranes from 19 control and 22 suicidal subjects. All were young, drug- and medication free men (18-21-years-old). 5-HT2 receptor binding was assayed using tritiated ketanserin at two concentrations. Receptor binding in the suicidal subjects was significantly higher than controls at both concentrations, the mean difference being around 50%. A similar difference between patients with major depressive disorder and matched controls has been observed previously. These findings support the use of 5-HT2 receptors on platelets as a research and diagnostic tool in depression and suicide.

Chronic GnRH agonist administration down-regulates platelet serotonin transporter in women undergoing assisted reproductive treatment.

The effect of pretreatment with the gonadotropin releasing hormone (GnRH) agonist D-Trp6-LHRH (Decapeptyl) on platelet serotonin transporter in women undergoing assisted reproductive treatment (ART) was investigated and compared with women treated with human menopausal gonadotropin (Pergonal). The study group (n = 10) was exposed for 12 days to 3.2 mg Decapeptyl C.R. while a comparison group (n = 9) was exposed to 11 days of human meno-pausal gonadotropin (Pergonal). All patients were assessed with the Hamilton depression and anxiety scales before and after treatment, and platelet and plasma samples were collected at the same time points. Plasma levels of estradiol, progesterone. FSH and LH were determined by radioimmunoassay (RIA). Platelet serotonin transporter was labeled using high affinity [3H]imipramine binding. The GnRH analogue induced ovarian suppression as reflected by low plasma estradiol levels, while Pergonal administration induced ovarian stimulation. An elevation in the Hamilton depression and anxiety scale scores was observed in the Decapeptyl treated group; this mood alteration was associated with a significant decrease (19%, P < 0.05) in the density (Bmax) of platelet [3H]imipramine binding sites. No significant change was observed in the Bmax of the Pergonal treated group. These results indicate that ovarian suppression (menopausal-like state) in young women is associated with depressed and anxious mood and decreased serotonin transporter density.

Clozapine treatment in very early onset schizophrenia.

Very early onset schizophrenic patients only partially benefit from conventional antipsychotic treatment and are at increased risk for developing tardive dyskinesia (TD). Clozapine, which lacks extrapyramidal side effects including TD, has been proved effective for adult schizophrenic patients who are resistant to other neuroleptics. Clozapine, therefore, may offer an alternative treatment for these patients. The authors report four successful trials of clozapine in children aged 10 to 12 years old with schizophrenia, the youngest group reported on to date, who were unresponsive to conventional neuroleptic treatment.

Lifetime psychiatric comorbidity rate in Israeli non-help-seeking patients with combat-related post-traumatic stress disorder.

BACKGROUND: Most of the data on lifetime psychiatric comorbidity in combat-related posttraumatic stress disorder (CR-PTSD) were collected in help-seeking patients. METHODS: In the present study we used the Schedule for Affective Disorder and Schizophrenia-Lifetime Version to examine a relatively large sample (n=80) of Israeli non-help-seeking CR-PTSD patients. The diagnosis of PTSD was based on the DSM-III-R criteria. RESULTS: We found a low rate of lifetime psychiatric comorbidity, especially drug dependence (2.25%), alcoholism (2.25%) and major depressive disorders (5%). CONCLUSION: It seems that in contrast to help-seeking CR-PTSD, non-help-seeking CR-PTSD is associated with a low frequency of comorbid psychiatric disorders. LIMITATION: Only non-help seeking CR-PTSD patients who agreed to participate in the study were included in this investigation. CLINICAL RELEVANCE: The detection and diagnosis of CR-PTSD comorbidity is important for establishing appropriate psychotherapeutic and pharmacological treatment.

Psychiatric and polysomnographic evaluation of sleep disturbances.

BACKGROUND: We evaluated psychiatrically 100 subjects, who were referred to a sleep laboratory in a general hospital because of sleep complaints. METHODS: All subjects were interviewed using a Structured Clinical Interview for DSM-III-R and underwent one night of standard polysomnography (PSG) examination. RESULTS: Forty three percent of the population had at least one Axis I DSM-III-R disorder. High rate of depressive mood disorder (24%) was observed in our sample, in contrast to low prevalence of alcohol and drug abuse (4%). Our results of a Israeli population are different from the United States studies in respect to alcohol and drug abuse. Furthermore, 11% of patients with PSG diagnosis exhibited comorbid psychiatric disorder. CONCLUSION: it appears that individuals with sleep complaints have high rate of psychiatric morbidity, especially mood disorders. LIMITATION: The rapid eye movement (REM) latency, a biological marker for depression, was not investigated. CLINICAL RELEVANCE: it seems that both PSG and psychiatric evaluation of sleep disturbance are of importance for appropriate therapeutic strategy for individuals with sleep complaints, especially in those with features of suspected depressive mood disorders.

Reduction of aggressiveness and impulsiveness during clozapine treatment in chronic neuroleptic-resistant schizophrenic patients.

Aggressive and impulsive behavior is frequently observed in schizophrenic patients. Previous studies suggest that impulsive aggression may be the most common behavioral correlate of central serotonergic system dysfunction. This study was aimed to determine if clozapine, an atypical antipsychotic agent with potent serotonergic antagonistic properties, can reduce impulsiveness and aggression in neuroleptic-resistant chronic schizophrenic patients. Fourteen neuroleptic-resistant chronic schizophrenic patients were treated with clozapine and prospectively evaluated for aggressiveness and impulsiveness for 18 weeks. Clozapine treatment induced a marked decrease in impulsiveness (32% on the Impulsivity Scale; p < 0.0001) and aggressiveness (98% on the Overt Aggression Scale; p < 0.0001). We conclude that clozapine treatment may be effective in reducing psychotic symptoms as well as in controlling aggressive and impulsive behavior in neuroleptic-resistant chronic schizophrenic patients.

Verapamil is not an antidepressant in patients resistant to tricyclic antidepressants.

The effects of a calcium channel blocker (verapamil, 160-320 mg/day for 4 weeks) were studied in seven unipolar major-depressed patients resistant to treatment with tricyclic antidepressants. This regimen of verapamil did not alter either the Hamilton rating scales for depression and anxiety or the Beck depression inventory score in these patients. Thus, verapamil appears devoid of antidepressant properties in patients resistant to tricyclic antidepressants.

Myotoxicity and neurotoxicity during clozapine treatment.

Some recent studies have shown that clozapine (CLZ) has myopathic side effects and causes alterations in motor force control. The aim of this study was to evaluate the neurologic and electrophysiologic characteristics of patients with schizophrenia who are undergoing long-term CLZ treatment. Ninety-four patients with schizophrenia treated with CLZ for 18.2 +/- 15.5 months were studied retrospectively and prospectively (40% and 60%, respectively) for serum creatine kinase (CK) levels before and after initiation of CLZ treatment. An electrodiagnostic study was performed on patients with CK elevation above normal limits, complained of general weakness or muscle pains, and/or had abnormal clinically significant findings. In 13 patients (13.8%), abnormal CK levels were found. Six patients complained of some muscular weakness. In two patients, clinical assessment revealed mild general muscular weakness; one revealed decreased tendon reflexes and, in both, CK levels were above 1,750 IU/L. On electrophysiologic examinations performed in the six patients with abnormal neurologic findings, the motor and sensory nerve conduction velocity were within normal range in all but one patient, who exhibited some prolongation of distal latency in the lower limbs. In two patients, the electromyography demonstrated a myopathic pattern. In 2.1% of medically healthy patients with schizophrenia treated with clozapine on a long-term basis, signs of myotoxicity were found. It seems warranted to discontinue CLZ therapy in patients who exhibit abnormal CK levels and myopathic features during treatment. Further studies are needed to provide more objective data on the impact of CLZ treatment on muscle tissue.

Combined electroconvulsive-clozapine therapy.

We reviewed 36 reported psychiatric patients who were treated with a combination of electroconvulsive therapy (ECT) and clozapine. The indication of the ECT-clozapine treatment was resistance to classical antipsychotic agents, clozapine, or ECT alone. Sixty-seven percent of the patients benefited from the combined treatment. In most of the patients, the combined treatment was safe and well tolerated. Adverse reactions occurred in 16.6% of the patients and included prolonged ECT-induced seizures (one case), supraventricular (one case) and sinus tachycardia, and blood pressure elevation. It seems that combined ECT-clozapine treatment is effective and safe. This strategy may be a therapeutic option in treatment-resistant patients.

The impact of clozapine treatment on serum lipids in chronic schizophrenic patients.

The aim of this retrospective study is to determine whether lipid levels rise in neuroleptic-resistant chronic schizophrenic patients during clozapine treatment and if this rise is correlated with a decrease in aggressive and suicidal behavior. Seventy neuroleptic-resistant schizophrenic patients treated with clozapine for at least 6 months were compared with 30 chronic schizophrenic patients treated with classic antipsychotic agents for the same length of time. Data on serum levels of cholesterol and triglycerides and on aggressive and suicidal behavior, as measured by the Overt Aggression Scale (OAS), were collected in both groups before treatment and 6 months later. A significant reduction in aggressive and suicidal behavior was noted in the clozapine-treated group but not in the classical antipsychotic-treated group. Clozapine treatment was associated with an elevation in serum triglyceride level, whereas classic antipsychotic treatment was associated with an increase in serum cholesterol level. We conclude that serum cholesterol level does not play a role in the clozapine-induced attenuation in aggressive and suicidal behavior in neuroleptic-resistant schizophrenic patients, though the accompanying elevation in triglycerides may be relevant to a behavioral effect.

Diminished suicidal and aggressive behavior, high plasma norepinephrine levels, and serum triglyceride levels in chronic neuroleptic-resistant schizophrenic patients maintained on clozapine.

Impulsiveness and aggressiveness may be the most common behavioral correlates of central serotonergic dysfunction. The aim of this study was to determine whether clozapine, an atypical antipsychotic agent with a potent serotonergic antagonistic activity, affects impulsiveness and aggression. Its effects on serum lipids, platelet-poor plasma serotonin (5-HT), and norepinephrine (NE) levels were also studied. Thirty neuroleptic-resistant chronic schizophrenic patients, maintained on clozapine for 1 year, were evaluated for aggressiveness, impulsiveness, and suicidality in comparison with 30 chronic schizophrenic patients maintained on classical antipsychotic agents for the same period of time. Clozapine treatment was associated with less impulsiveness (p < 0.05), aggressiveness (p < 0.01) and fewer suicidal attempts (p < 0.05). Serum triglycerides and plasma NE levels were significantly higher (p < 0.01 and p < 0.0001, respectively) in the patients treated with clozapine, as compared with patients treated with classical neuroleptic drugs. The authors conclude that long-term clozapine treatment may be effective in controlling aggressive, impulsive, and suicidal behavior in neuroleptic-resistant chronic schizophrenic patients. The elevated plasma NE levels in patients treated with clozapine as compared to those treated with classical neuroleptic drugs may be relevant for the anti-aggressive/antisuicidal activity of clozapine.

Seizures induced by combined levomepromazine-fluvoxamine treatment.

We report a case of combined levomepromazine-fluvoxamine treatment-induced seizures. It seems that combined treatment of fluvoxamine with phenothiazines may possess proconvulsive activity.

Trihexyphenidyl treatment of clozapine-induced hypersalivation.

The objective of this study was to investigate the efficacy of the anticholinergic agent trihexyphenidyl in the treatment of clozapine-induced hypersalivation. Fourteen chronic schizophrenic patients who exhibited nocturnal hypersalivation during clozapine treatment were coadministered trihexyphenidyl (5-15 mg/day, at bedtime) for 15 days. Salivation was assessed by a single-item 5-point scale. A reduction of 44% in the reported nocturnal hypersalivation was observed after trihexyphenidyl treatment. These results indicate that at least some chronic schizophrenic patients with clozapine-induced nocturnal hypersalivation may benefit from anticholinergic treatment.