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Biomedical subjects

G M Simpson

Publications and source records attributed to G M Simpson.

At least 55 records · Page 3Linked to original sources

Schizophrenia and smoking: an epidemiological survey in a state hospital.

OBJECTIVE: The authors sought to determine whether smoking is related to schizophrenia or neuroleptic treatment. METHOD: Cigarette smoking was measured in all patients hospitalized at a state hospital (N = 360) and compared in relation to gender and diagnosis (schizophrenic versus nonschizophrenic). RESULTS: The overall frequency of smoking was 79% (N = 284). Male schizophrenic patients had the highest frequency of smoking, followed by male nonschizophrenic patients, female schizophrenic patients, and female nonschizophrenic patients, respectively. Schizophrenia and polydipsia were associated with both smoking and heavy smoking. CONCLUSIONS: After correction for other variables, schizophrenia appears to increase the risk of being both a smoker and a heavy smoker. There was a possible association between high doses of neuroleptics and smoking but only for nonschizophrenic patients.

Adult↗

Fluphenazine plasma levels, dosage, efficacy, and side effects.

OBJECTIVE: The authors sought to determine whether fluphenazine dose or plasma level predicts clinical improvement or side effects during acute treatment. METHOD: Oral fluphenazine was given in fixed, randomized, double-blind doses (10, 20, or 30 mg/day) for 4 weeks to 72 inpatients with acute schizophrenic exacerbations. Outcome measures included percentage improvement in ratings of positive symptoms (hallucinations, delusions, and thought disorder), percentage improvement in negative symptoms, and maximum score for extrapyramidal symptoms. Response was defined as an improvement in positive symptoms of 40% or more. RESULTS: The 42 responders had a shorter duration of illness, less chronic course, and lower rate of akathisia. Plasma level and dose did not differentiate responders and nonresponders, but they did predict percentage improvement in positive symptoms within the responder subgroup. Akathisia was more common and extrapyramidal symptoms were more severe at higher plasma levels. CONCLUSIONS: Responders showed the greatest improvement at fluphenazine plasma levels above 1.0 ng/ml and doses above 0.20-0.25 mg/kg per day. Since the literature suggests that optimal plasma levels are similar during acute and maintenance treatment, monitoring of plasma levels may thus be useful. Conditions for applying the "responder-only" analytic strategy in future studies are discussed.

Acute Disease↗

Misidentification syndromes in schizophrenia: case reviews with implications for classification and prevalence.

Misidentification syndromes represent false, delusionally-based identification of self and/or others. These are variants of the Capgras Syndrome. Although the frequency of misidentification syndromes in schizophrenic populations has not yet been established, the authors believe this syndrome is more prevalent than previously described. Seven of twenty-five (28%) consecutive patients admitted to a chronic clozapine unit with a variant of misidentification syndrome will be described. Their symptoms are categorised according to traditional classification, and Silva's proposed nomenclature. Problems inherent in these classifications are discussed. The need for a more systematic classification of misidentification syndromes is emphasised. Longitudinal studies of misidentification syndrome, and the development of a standardised assessment tool for clinicians who treat chronically psychotic patients, are encouraged.

Adult↗

Polydipsia and water intoxication in psychiatric patients: a review of the epidemiological literature.

Polydipsia among chronic psychiatric patients is poorly understood and underdiagnosed. It may have three stages: simple polydipsia, polydipsia with water intoxication, and physical complications. Epidemiological surveys have used staff reports and polyuria measures to identify polydipsic patients. Water intoxication has been screened by chart review, weight, or serum sodium data. According to these surveys, polydipsia, not explained by medically induced polyuria, may be present in more than 20% of chronic inpatients. Up to 5% of chronic inpatients had episodes of water intoxication although mild cases may have been missed. Single time point surveys show that 29% of polydipsic patients had presented water intoxication. Methodologically limited clinical studies suggest that polydipsia with water intoxication rather than simple polydipsia may be associated with poor prognosis in schizophrenia. Epidemiological surveys found polydipsia with water intoxication to be associated with chronicity, schizophrenia, smoking, some medications, male gender, and white race. New pathophysiological models need to elucidate these findings.

Chronic Disease↗

Neuroendocrine factors influencing polydipsia in psychiatric patients: an hypothesis.

Polydipsia and water intoxication cause considerable morbidity and mortality in chronic psychiatric patients. The pathophysiology of the disorder is unknown, and there is no effective treatment. Angiotensin II is an important dipsogen in animals; in humans, some conditions with abnormal thirst are associated with increased angiotensin function. Chronic D2 dopamine receptor blockade increases angiotensin II-induced thirst in animals; in humans, increased peripheral response to angiotensin II is documented. Chronic D2 blockade with typical neuroleptics may increase sensitivity to angiotensin II and induce thirst. Clozapine, which has negligible D2 blocking action may improve polydipsia. Recent case reports demonstrate improvement of polydipsia during clozapine therapy. Angiotensin II releases vasopressin; this could explain water intoxication, which occurs later in the syndrome. This paper suggests an etiological model and a treatment modality for this disorder.

Antipsychotic Agents↗

The test-retest reliability of the Mini-Mental State Examination in chronic schizophrenic patients.

The test-retest reliability of the Mini-Mental State Examination (MMSE) was explored in a sample of 22 inpatients suffering from chronic schizophrenia by DSM-III-R criteria. Patients were tested 4 times during a period of 4-6 weeks. The total score for serial sevens showed consistently significant reliability at about 0.7, and the total score for spelling displayed a lower reliability at about 0.4, which was of borderline significance. In this short period of time, 36% and 27% of the patients shifted between being demented and nondemented when the serial sevens and spelling, respectively, were used to calculate total scores. The MMSE should not be used to categorize schizophrenics as demented or nondemented in biological studies using relatively stable variables.

Adult↗

The treatment and management of neuroleptic malignant syndrome.

1. The neuroleptic malignant syndrome was initially described as a disorder specifically related to neuroleptic usage with frequent fatal outcome. The observations of variant or mild cases of this syndrome as well as case reports on neuroleptic-malignant-like syndromes in the absence of neuroleptics raises the issue of the usefulness of this terminology and highlights the potential for inappropriate management of this "malignant" syndrome. It has been suggested that hypothalamic thermoregulatory responses may involve an interplay among noradrenergic, cholinergic and serotonergic pathways. Out treatment strategy is based on the pharmacology of neuroleptics and empirical data, verified in our own clinical practice and considers that it is often difficult to determine whether certain physiologic states are a consequence to or specific triggering factors. 2. If a patient's temperature is less than 101, we emphasize vigorous treatment with anticholinergic agents, while simultaneously assessing the psychiatric need for neuroleptics versus medical risks. Given that the severe rigidity of NMS represents severe extrapyramidal effects of dopamine blockade, there is no reason to withhold anticholinergics in the absence of higher temperatures. Neuroleptics can be stopped at the discretion of the clinician even during circumstances when there is fever below 101. 3. In cases of severe EPS with fever greater than or equal to 101, we recommend stopping neuroleptics, treating with anticholinergics and starting with dopamine agonists. In the event of a poor response to dopamine agonists, a brief trial of dantrolene and/or benzodiazepines is recommended. Dantrolene should not be introduced for prolonged periods, since abnormal liver function studies have been observed in approximately 1.8% of patients. 4. In cases of extreme hyperpyrexia (fever greater than 103), clinicians should consider transfer to an ICU or another medical support. Extreme temperatures have been associated with potentially irreversible cerebellar or other brain damage, if not aggressively treated. If neuroleptics are later indicated, a 2 week interval after resolution of symptoms should be maintained before reinstituting neuroleptics. 5. In patients with severe EPS without fever, we emphasize aggressive use of anticholinergic therapy, while simultaneously considering the psychiatric need for neuroleptics versus medical risks. In all cases where a patient's swallowing, respirations or physical mobility is severely compromised, we suggest stopping neuroleptics. Anticholinergic agents should be continued for 7 days after neuroleptics are stopped. If anticholinergic agents are unsuccessful after 2-3 dosages, dopamine agonists may be added, while simultaneously monitoring vital signs. It should be emphasized that severe EPS sometimes takes days to improve even after neuroleptic cessation and the addition of anticholinergics.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

Comparison of the pressor effect of tyramine after treatment with phenelzine and moclobemide in healthy male volunteers.

This study was conducted to establish the safety, tolerability, side effects, and pressor effects of tyramine on subjects treated with moclobemide, a short-acting reversible and preferential monoamine oxidase inhibitor, and to compare these responses with the responses of subjects treated with phenelzine. Twelve healthy male volunteers participated. An oral tyramine sensitivity test was performed on all subjects 24 hours before the start of a 28-day open-label treatment with phenelzine or moclobemide. A tyramine challenge was performed on day 28 on four subjects treated with phenelzine. The mean dose of oral tyramine required to increase systolic blood pressure by 30 mm Hg was 15 mg. The mean dose of tyramine that produced a clinical response (day 28) in subjects treated with moclobemide was 240 mg. No subject receiving moclobemide responded clinically on day 31 after receiving hourly doses of 20, 40, 80, 160, and 320 mg, respectively. These findings suggest that moclobemide may be used without stringent dietary precautions.

Administration, Oral↗

Timing of acute clinical response to fluphenazine.

The time course of clinical improvement was studied in 41 schizophrenic and schizoaffective acute in-patients treated for 28 days with 10, 20 or 30 mg/day of oral fluphenazine hydrochloride in a double-blind, randomised study. Significant improvement was seen in the four BPRS factors: thinking disturbance, hostile-suspiciousness, withdrawal-retardation and anxious depression. The first two of these factors were improved by day 5. Significant improvement was seen up to day 22 for three of the four factors, but without significant improvement during the last week (although scores continued to drop). The half of the sample showing greater overall improvement did not improve faster than the sample as a whole. These more improved subjects did not differ significantly from the less improved subjects in the thinking disturbance factor until day 15, suggesting that at least a two-week neuroleptic trial would be necessary to begin to differentiate more and less responsive patients. The longer-term course of improvement cannot be determined from these data. The withdrawal-retardation and anxious depression factors showed their greatest improvement later than the 'positive' symptom factors, suggesting that the former may improve as a result of change in the latter.

Acute Disease↗

Neurotoxicity related to lithium and neuroleptic combinations? A retrospective review.

The question of toxic interactions resulting from combinations of lithium and neuroleptic drugs is largely based on anecdotal reports. We replicated the methods of Miller and Menninger (1987) who reported that 27% of manic patients on treatment with lithium and neuroleptics developed toxicity. We found no cases of neurotoxicity as defined in the earlier report. Pharmacologic mechanisms and differences in the clinical findings of the two studies are discussed.

Antipsychotic Agents↗

Negative symptoms, defect state and Huber's basic symptoms: a comparison of the concepts.

Comparing Crow's schizophrenia model with the defect state and Huber's basic symptoms shows that this model is an oversimplification of the complex reality of schizophrenic outcomes. The concept of negative symptoms is undermined by several factors, such as differing definitions, other confounding cross-sectional variables (e.g., akinesia and depression), short follow-ups and lack of confirmation by factorial analysis. The longitudinal concept of a defect state, which has been used in long-term follow-up studies, includes enduring symptoms currently classified as positive and negative. Huber's conceptualization of basic symptoms describes prodromal and enduring residual symptoms of schizophrenia associated with structural brain abnormalities. The overlap and lack of equivalence of these concepts and the limited empirical evidence does not allow firm conclusions. New longitudinal studies using clinical, psychosocial, and neuropsychological measures are needed to understand the natural history and etiology of the defect state.

Cross-Sectional Studies↗