Health care disparities among persons with comorbid schizophrenia and cardiovascular disease: a case-control epidemiological study.

AIMS: Studies showed health care disparities among persons with comorbid schizophrenia and cardiovascular disease (CVD), including in countries with universal health care. However, the potential positive effect of specific mental health legislation has not been reported. This study aimed to investigate the health care of persons with comorbid schizophrenia and CVD in a country with both a national health insurance and a comprehensive rehabilitation law for persons with mental disabilities. METHOD: This study builds on a large case-control epidemiological sample (N = 52 189) of service users. Within the sample we identified a sub-group of persons with CVD diagnoses (n = 8208) and compared service users with and without schizophrenia on drug utilisation, laboratory tests, visits to specialists and surgical interventions. RESULTS: Service users with schizophrenia were less likely to meet similar indexes of care as their counterparts: 91% cholesterol tests (p < 0.001), 60% stress tests (p < 0.001), 93% visits to specialists (p = 0.001), 93% drug utilisation (p < 0.001) and 55% CVD surgical interventions (odds ratio 0.55, 95% confidence intervals 0.49-0.61). CONCLUSIONS: In Israel, a country with a national health insurance and a rehabilitation law specific for persons with mental disabilities, service users with schizophrenia still fail to receive equitable levels of health care for CVD. However, the disparities appear to be smaller than in other countries with universal health insurance.

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.

Abnormal thermoregulation in drug-free male schizophrenia patients.

Schizophrenia patients may develop various thermoregulatory disturbances. We hypothesized that a standardized exercise-heat tolerance test [two 50-min bouts of walking a motor-driven treadmill at 40 degrees C (relative humidity=40%)] would reveal abnormal thermoregulation in drug-free schizophrenia patients. Six drug-free schizophrenia outpatients and seven healthy comparison subjects participated in this study. The schizophrenia patients exhibited significantly higher baseline and exertion-related rectal temperature. The relevance of these findings to the pathophysiology of schizophrenia-related thermoregulatory disorders is as yet unclear.

[Antidepressive effect of pyridoxine (vitamin B6) in neuroleptic-treated schizophrenic patients with co-morbid minor depression--preliminary open-label trial].

BACKGROUND: Minor depression is reported in 20-60% of schizophrenic patients during various stages of their disorders; impairing patients' compliance, response to treatment and worsening their overall prognosis. Various anti-depressive treatments have been proposed for such cases but response rates are usually poor. Pyridoxine (Vitamin B6) in essential for the proper metabolism of various neurotransmitters that are considered relevant to the pathophysiology of depression and/or schizophrenia and it has been reported beneficial in ameliorating depressive symptoms as part of major depression, premenstrual syndrome or 'Chinese restaurant syndrome'. We hypothesized that addition of pyridoxine to on-going neuroleptic treatment could improve minor depression in schizophrenic patients. METHOD: Nine schizophrenic patients with co-morbid minor depression participated in this study. All participants had a stable unchanged clinical state (changes in Brief Psychiatric Rating Scale (BPRS). Scale for the Assessment of Positive Symptoms (SAPS), and Scale for the Assessment of Negative symptoms (SANS) scores < 5%) and all were maintained on unchanged doses of anti-psychotic drugs for at least 4 consecutive weeks prior to initiation of the study. Participants received, open-label, pyridoxine 150 mg/day in addition to their anti-psychotic treatment for 4 consecutive weeks. Mental status was evaluated before, during, and at the end of 4 weeks of pyridoxine administration using the BPRS, SAPS, SANS and HAM-D. RESULTS: Two of the nine patients (22%), characterized by higher initial HAM-D and SANS scores, and by older age and longer duration of illness, experienced marked improvements in depressive symptoms (23% and 28% decrease in HAM-D scores) following 4 weeks of pyridoxine administration. In one of these two, the improvement in depressive symptoms was accompanied by a parallel decrease in SANS Scores. CONCLUSION: A subgroup of schizophrenic patients with comorbid minor depression may benefit from pyridoxine addition to their on-going anti-psychotic treatment.

Low-dose clozapine for the treatment of Parkinson's disease in a patient with schizophrenia.

Clozapine is known to be beneficial for the treatment of dopamine agonist-induced psychotic states in patients with Parkinson's disease (PD). Many reports have suggested that it may also be efficacious for the treatment of parkinsonian tremor. We describe a patient with schizophrenia in whom early-onset PD appeared after treatment with antipsychotic drugs. When the parkinsonian symptoms proved resistant to anticholinergic agents, we introduced a trial with up to 50 mg clozapine daily, which yielded a prompt and dramatic response. Thereafter, the parkinsonian symptoms reappeared each time the patient discontinued clozapine and rapidly disappeared on its repeat initiation. There was also a marked improvement in his psychotic and depressive symptoms. This report suggests that some patients with concomitant schizophrenia and PD-a difficult treatment challenge-may benefit from clozapine treatment alone for both disorders.

Absence of myoglobinuria in acute psychotic patients with marked elevation in serum creatine phosphokinase level.

Elevated levels of serum creatine phosphokinase, muscular type (CK(MM)) are caused primarily by diseased muscle fiber. Acute psychoses are often associated with a marked increase in serum CK(MM) levels, though the reason remains obscure. Since striated muscle damage is also associated with pigmenturia and myoglobinuria, we sought to determine whether the markedly high serum CK level of acute psychosis reflects skeletal muscle damage by evaluating urinary myoglobin in affected patients. Baseline serum CK was measured on admission in 713 consecutive acute psychotic inpatients (BPRS> or =40). Those showing a serum CK levels above 1000 IU/l on the first 2 days of hospitalization underwent urine collection for myoglobin testing. Patients with physical trauma or medical conditions known to cause CKemia were excluded. Twenty-five patients were eligible for the study. In no case did myoglobinuria or pigmenturia accompany the marked CKemia. There is an unexpected dissociation between the robust increase in the serum CK(MM) levels and the absence of myoglobinuria in acute psychosis. Our negative finding may indicate that the serum CK threshold for myoglobinuria is very high (above 10000 IU/l). Alternatively, psychosis-associated CKemia may be related to an unknown, nontraumatic, pathophysiological mechanism(s).

Association between severity of schizophrenic symptoms and urinary retention.

A case is presented in which severe urinary retention (UR) occurred during an acute psychotic exacerbation of paranoid schizophrenia. The voiding dysfunction was apparent during continuous treatment with unchanged doses of haloperidol, and it completely resolved with the remission of the psychotic symptoms. A clear temporal correlation was evident between the patient's mental status, the Brief Psychiatric Rating Scale (BPRS) score and the degree of the UR as assessed by quantitatively measuring the total daily post-voiding urine residues. We could not relate the UR to any apparent general medical condition or to the haloperidol treatment. The presented data suggests that UR in schizophrenic patients might be the end-result of various psychosis-related mechanisms.

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.

Acute antipsychotic drug administration lowers body temperature in drug-free male schizophrenic patients.

We examined, in a controlled design, potential alterations in body temperature of male schizophrenic patients following acute antipsychotic drug (APD) administration. Fourteen drug-free (study group) and seven schizophrenic patients maintained on APDs (comparison group) initiated or received higher dose of their APD, respectively, for 27 days. Initial body temperature was 0.36 degrees C higher in the study group (P=0.01) and decreased within 24 h to values comparable to that of the comparison group (all within normal range).

The effectiveness of olanzapine in treatment-refractory schizophrenia when patients are nonresponsive to or unable to tolerate clozapine.

OBJECTIVE: This multicenter, open-label study was designed to assess the efficacy and tolerability of olanzapine in patients with chronic schizophrenia who are resistant to therapy with classic neuroleptic agents and are either not responsive to or unable to tolerate clozapine. METHODS: Patients received olanzapine orally once daily for 18 weeks at doses ranging from 5 to 25 mg. The primary efficacy measure was change in the total score on the Positive and Negative Syndrome Scale (PANSS) from baseline to end point. Secondary efficacy measures were the total score on the Brief Psychiatric Rating Scale (BPRS); the PANSS positive, negative, general psychopathology, and mood subscores; and the Clinical Global Impression improvement score. Also recorded were spontaneously reported adverse events; extrapyramidal symptoms (assessed by the Abnormal Involuntary Movement Scale, Simpson-Angus Scale, and Barnes Akathisia Scale); vital signs; and clinical laboratory test results. RESULTS: Forty-eight patients were treated with olanzapine; of these, 45 were assessable over the full 18-week study period. Total scores on the PANSS and BPRS were reduced from baseline by an average of 17.7 (14.2%) and 9.8 points (20.2%), respectively. Eighteen patients (40.0%) experienced a treatment response, defined as a reduction in PANSS total score of > or = 20%. A total of 25 patients (55.6%) achieved a similar reduction in BPRS total score. Significant reductions were seen in both the positive and negative symptom scores on the PANSS (P < 0.001). Olanzapine was well tolerated, with minimal treatment-emergent adverse events or clinically relevant changes in vital signs or clinical laboratory test results. No clinically significant blood dyscrasias were observed in olanzapine-treated patients, including those who had discontinued clozapine because of treatment-associated leukopenia or neutropenia. CONCLUSION: The results of this study suggest that olanzapine may be of benefit in patients who are refractory to or unable to tolerate clozapine.

Heat intolerance in patients with chronic schizophrenia maintained with antipsychotic drugs.

OBJECTIVE: Schizophrenia may be associated with hyperthermic syndromes such as febrile catatonia, neuroleptic malignant syndrome, and heatstroke. The authors hypothesized that an exercise-heat tolerance test would disclose abnormal thermoregulation in schizophrenic patients. METHOD: Seven male schizophrenic outpatients in remission maintained on depot antipsychotic treatment and eight healthy comparison subjects completed a heat tolerance test that consisted of two 50-minute bouts of walking a motor-driven treadmill at 40xC (relative humidity=40%). RESULTS: A significantly higher rise in rectal and skin temperatures was observed in the patient group. No differences in heart rate, blood pressure, or perspiration were detected. CONCLUSIONS: Schizophrenic patients maintained on antipsychotic drugs exhibit impaired heat tolerance. Possible explanations are a reduced ability to convey heat from the body's core to the periphery with or without excessive heat production. The hyperthermic response to the heat tolerance test may reflect a dysfunction associated with schizophrenia, a neuroleptic-induced side effect, or both.

Beneficial effect of olanzapine in schizophrenic patients with obsessive-compulsive symptoms.

Some studies suggest that obsessive-compulsive symptoms may be common (7.8-46%) in schizophrenic patients and seem to be poorly responsive to drug therapy. Conventional neuroleptics are of limited value, but adjunctive anti-obsessive agents (clomipramine, fluvoxamine) may be an option. Although novel atypical antipsychotics (clozapine, risperidone) reportedly aggravate the obsessive-compulsive symptoms, a recent trial has shown that olanzapine did not induce new-onset obsessive-compulsive symptoms in schizophrenic patients. We report our experience with three schizophrenic patients with obsessive-compulsive symptoms who were unsuccessfully treated with various conventional neuroleptics in combination with anti-obsessive agents and subsequently showed resistance or intolerance to clozapine. All of them were switched to olanzapine (10-20 mg/ day). All patients demonstrated a significant improvement in both schizophrenic and obsessive-compulsive symptoms as measured by the Brief Psychiatric Rating Scale (BPRS) and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Within 5-8 weeks of initiation of olanzapine, the BPRS scores of the three patient decreased by 53%, 51% and 48%, and the Y-BOCS scores by 68%, 73% and 85%. Olanzapine was well tolerated. These preliminary results suggest that olanzapine may be a therapeutic option in schizophrenic patients with obsessive-compulsive symptoms.

The biopsychosocial model of medicine revisited: a meta-theoretical excursion.

Engel's biopsychosocial model of medicine has been widely endorsed by contemporary medicine, at least in theory. Yet, whereas Engel's notion refers mainly to physician-patient communication, the prevalent interpretation of this model is mainly etiological. The present meta-theoretical study examines the relation between the different notions of the model. Using logical analysis and the theory of (critical) rationality, in particular Wettersten's theory of (complementary) styles of rationality, it is argued that the different notions of the model may be complementary, rather than contradictory or incommensurable as usually implied by those holding them.

Hair loss associated with paroxetine treatment: a case report.

Alopecia and hair loss are rare side effects of psychotropic drugs. There are a few case reports on hair loss associated with tricyclic antidepressants and serotonin selective reuptake inhibitors (SSRIs), but none deal specifically with paroxetine. We report on a 37-year-old female who complained of moderate hair loss during paroxetine treatment. Findings on discontinuation and rechallenge supported the assumption that the hair loss was a side effect of the paroxetine. Further investigation is needed to determine the scope of this troubling side effect.

Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome.

Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion in the long arm of chromosome 22 and is associated with an increased frequency of schizophrenia and bipolar mood disorder. The purpose of this study was to investigate the genetic, physical, developmental and psychiatric features of schizophrenic patients with VCFS microdeletion. It describes the clinical findings in four schizophrenic inpatients with the characteristic chromosomal deletion. The four patients displayed delayed motor development, language deficits, learning disabilities, mental retardation, early age of onset, chronic and disabling course of illness and poor response to classical neuroleptic drugs and electroconvulsive therapy. Two patients benefited from treatment with clozapine. We suggest that schizophrenic patients with a history of delayed motor development, early onset of the disorder, history of learning disability, mental retardation, congenital cardiac anomalies and/or hypernasal speech should be screened for the velo-cardio-facial syndrome deletion. The implications of this study for psychiatric phenotype, nosology, disease mechanism, and possible new treatments in the future are discussed.

The effect of vitamin E addition to acute neuroleptic treatment on the emergence of extrapyramidal side effects in schizophrenic patients: an open label study.

The anti-oxidant vitamin E has been reported to be effective in the treatment of tardive dyskinesia. The present open label study examined the effect of supplemental therapy with vitamin E on acute extrapyramidal symptoms and cell enzymes in patients receiving neuroleptic drugs. Thirty-nine hospitalized schizophrenic patients were randomly assigned to two groups: group 1 (n = 20) was treated with neuroleptics, and group 2 (n = 19) with neuroleptics combined with a fixed dose of vitamin E (600 IU/day), administered for two weeks. All patients were assessed with the Simpson-Angus Rating Scale (Simpson and Angus, 1970) for neuroleptic induced Parkinsonism (NIP), Barnes' Akathisia Scale (Barnes, 1989), and Brief Psychiatric Rating Scale: laboratory parameters included serum creatine kinase (CK) activity, serum glutamate oxaloacetic transaminase (SGOT) and white blood cell count (WBC). The addition of vitamin E to neuroleptic agents was associated with a trend (p = 0.08) towards prevention of the emergence of NIP compared to neuroleptic treatment alone. Addition of vitamin E to neuroleptics may reduce the severity of acute NIP in schizophrenic patients.