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PubMed2004

Prevalence of diabetes mellitus among outpatients with severe mental disorders receiving atypical antipsychotic drugs.

BACKGROUND: Recent studies have suggested that patients receiving atypical antipsychotic drugs are at increased risk for developing diabetes mellitus. The purpose of this study is to examine the prevalence of diabetes in a group of adults with schizophrenia and other severe mental disorders receiving atypical antipsychotic drugs within a community mental health center setting. METHOD: A retrospective chart review was conducted on 436 outpatients receiving either atypical antipsychotic or decanoate antipsychotic drugs at a community mental health center. Diagnosis of diabetes was established through the presence of documentation in the medical record. Patients with a history of diabetes prior to age 18 years were excluded. Data were gathered from April 2001 through September 2002. RESULTS: The mean (SD) age of patients was 42.5 (10.8) years, and 57.3% were men. Patients were 61.5% white, 31.8% black, 5.3% Hispanic, and 2.3% other. Seventeen percent of patients had a positive family history of diabetes. Point prevalence of diabetes was 14.2% for the entire group. Chi-square analysis for the group revealed significant effects of age (chi(2) = 16.514, p <.001), family history of diabetes (chi(2) = 27.128, p <.001), and gender (chi(2) = 14.114, p <.001). A trend was noted toward a higher prevalence of diabetes among patients receiving atypical drugs (15.2%) compared with those receiving decanoate drugs (6.3%) (chi(2) = 2.984, p =.078). CONCLUSION: Prevalence of diabetes mellitus among outpatients with severe mental disorders receiving atypical antipsychotic drugs is substantially higher than that reported in the general population. Results of this study are limited by the retrospective methodology, which may underestimate actual prevalence by failing to detect undiagnosed cases.

Adolescent↗
PubMed1976

[Influence of homologous n-alkanoic on functional properties of isolated skeletal muscles. II. Membrane resting potential and the osmotic effectiveness of alkanoic acid].

The influence of butyric, hexanoic, octanoic, and decanoic acid on the membrane resting potential of isolated frog skeletal muscles were studied and the osmotic effects of n-alkanoic acids tested. 1. n-alkanoic acids cause osmotic effects like impermeable non-electrolytes (sucrose). Therefore, the permeability to alkanoic acids of the resting muscle cell membrane seems to be small. There are no differences between the acids tested. 2. The membrane resting potential is differently affected. Butyric acid in high concentration effects a hyperpolarization of the membrane whereas higher homologues (C6--C10) cause a depolarization. The depolarizing action increases with increasing concentration, exposure, and with the length of the hydrocarbon chain of the alkanoic acids. 3. It is suggested that osmotic effects are the cause for hyperpolarization of the membrane by high concentrations of butyric acid. 4. The depolarizing action of hexanoic, octanoic, and decanoic acid is discussed with regard to alterations induced by alkanoic acids in the membrane permeability and/or in the metabolism of the cells.

Alkanes↗
PubMed1999

Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients.

BACKGROUND: Nearly one third of patients suffering from schizophrenia do not fully respond to antipsychotic medication. Safe, effective, and cost-efficient methods to reduce symptoms are clearly needed; therefore, lithium as an adjunct to fluphenazine decanoate was tested in a placebo-controlled trial in outpatients who were part of the Treatment Strategies of Schizophrenia (TSS) study. METHOD: Forty-one patients with DSM-III schizophrenia or schizoaffective disorder were assigned to either adjunctive lithium or placebo after at least 6 months of fluphenazine decanoate treatment to stabilize symptoms had failed. The trial was designed for 8 weeks of treatment, and patients assigned to placebo could afterward be administered lithium in an 8-week, open-label study. RESULTS: Assessment of the intent-to-treat analysis revealed no significant differences in demographic variables between the lithium and placebo groups. Although both groups showed significant (p = .00135) improvement as measured by total scores on the Brief Psychiatric Rating Scale (BPRS), there were no significant differences in response between the lithium and placebo groups. Patients originally treated with placebo added to neuroleptic did not have significantly greater improvement when receiving open-label adjunctive lithium. CONCLUSION: Although success with lithium augmentation therapy for persistent psychosis has been reported in the past, this study of well-characterized patients showed no benefit for this common strategy, thus indicating that care be used in utilizing lithium augmentation.

Ambulatory Care↗
PubMed2004

Biosynthesis of poly(3-hydroxybutyrate- co-3-hydroxyalkanoates) by metabolically engineered Escherichia coli strains.

Biosynthesis of polyhydroxyalkanoates (PHAs) consisting of 3-hydroxy-alkanoates (3HAs) of 4 to 10 carbon atoms was examined in metabolically engineered Escherichia coli strains. When the fadA and/or fadB mutant E. coli strains harboring the plasmid containing the Pseudomonas sp. 61-3 phaC2 gene and the Ralstonia eutropha phaAB genes were cultured in Luria-Bertani (LB) medium supplemented with 2 g/L of sodium decanoate, all the recombinant E. coli strains synthesized PHAs consisting of C4, C6, C8, and C10 monomer units. The monomer composition of PHA was dependent on the E. coli strain used. When the fadA mutant E. coli was employed, PHA containing up to 63 mol% of 3-hydroyhexanoate was produced. In fadB and fadAB mutant E. coli strains, 3-hydroxybutyrate (3HB) was efficiently incorporated into PHA up to 86 mol%. Cultivation of recombinant fadA and/or fadB mutant E. coli strains in LB medium containing 10 g/L of sodium gluconate and 2 g/L of sodium decanoate resulted in the production of PHA copolymer containing a very high fraction of 3HB up to 95 mol%. Since the material properties of PHA copolymer consisting of a large fraction of 3HB and a small fraction of medium-chain-length 3HA are similar to those of low-density polyethylene, recombinant E. coli strains constructed in this study should be useful for the production of PHAs suitable for various commercial applications.

3-Hydroxybutyric Acid↗
PubMed1991

Side effects during long-term treatment with depot antipsychotic medication.

During long-term treatment of schizophrenia with antipsychotic medication, side effects such as weight gain and tardive dyskinesia may develop, while other extrapyramidal side effects may continue. A large multicenter, double-blind, comparative trial of haloperidol decanoate and fluphenazine decanoate has been completed, in which 181 patients took part. The study lasted for 1 year and patients were assessed using the Krawiecka scale, the Montgomery-Asberg scales for schizophrenia and depression, the Simpson-Angus scale for parkinsonism, the AIMS for tardive dyskinesia, and a scale for akathisia. Patients were also weighed at each assessment. The results provide further evidence about the occurrence of weight changes, extrapyramidal side effects, and depression during long-term treatment and about the relative benefits of the two treatments.

Akathisia, Drug-Induced↗
PubMed1986

Depot neuroleptics: side effects and safety.

Long-acting depot neuroleptics are likely to receive increasing consideration in the maintenance treatment of schizophrenia because of the growing recognition of noncompliance with daily oral medication in this patient population. The impending availability of haloperidol decanoate in the United States may also increase the use of long-acting neuroleptics. The long-term safety of these drugs, therefore, deserves close scrutiny. Based on experiences with other depot neuroleptics, the safety profile of haloperidol decanoate is unlikely to differ from short-acting formulations of haloperidol. In general, tardive dyskinesia remains the most troubling problem associated with long-term neuroleptic treatment. The available information indicates that all neuroleptics, including long-acting preparations, share the same propensity for causing tardive dyskinesia. Furthermore, the use of the lowest effective dose of a neuroleptic appears to minimize the severity of tardive dyskinesia should it develop. Extrapyramidal symptoms, notably akinesia and akathisia, are also potential concerns of maintenance treatment with oral and depot neuroleptics; however, the occurrence of these side effects appears dose related. Thus, the clinician can favorably influence the benefit-to-risk ratio of long-acting depot neuroleptics by minimizing potential side effects through the use of a low dose strategy.

Antipsychotic Agents↗
PubMed1977

[Influence of homologous n-alcanoic acids on the function properties of isolated skeletal muscles. III. Contractures by fatty acids and relations to the effects of caffeine].

The influences of octanoic, decanoic, and hexadencanoic acid were tested on the contracture capability of isolated skeletal muscle of frogs and rats. 1. 100 mM octanoic or 10mM decanoic acid induce contractures in skeletal mucles after 20-30 min of exposure. 2. The time of exposure necessary for induction of contractures is shortened by an increase of bath temperature, electrical stimulation or KCl-depolarization of muscles. 3. Simultaneous addition of fatty acid and caffeine (10 mM) effects a depression and a delay of the caffeine contracture. The contractures evoked by 5 mM caffeine are inhibited by lower concentrations of fatty acids (1 mM octaonoic acid, 0,1 mM hexadecanoic acid). 4. After the complete development of a caffeine (or fatty acid) contracture the muscle is not able to develop an identical contracture by a second application of the same drug, even after intermediate treatment during one or two hours in Ringer solution. If the contracture is interrupted one minute after the caffeine application by changing the solution, the tension returns quickly to the resting level. A subsequent addition of caffeine (10 mM) after about 10 minutes effects an identical contracture. Thus the effect of fatty acids on caffeine contracture may be studied on the same muscle which served as its own control. 5. As mechanisms involved in the development of fatty acid contractures and in the inhibition of caffeine contractures, interactions of free fatty acids and lipids of biological membranes are disucssed. Especially, there may be changes of the calcium affinity of cellular membranes.

Animals↗
PubMed1985

Plasma levels of neuroleptic in patients receiving depot fluphenazine.

Depot forms of fluphenazine are frequently used in the outpatient treatment of psychiatric patients. To gather relevant data on pharmacokinetic characteristics of depot fluphenazines, the authors measured plasma levels of neuroleptic activity in 76 clinic patients on stable dosage regimens of fluphenazine decanoate or fluphenazine enanthate. Dose and plasma neuroleptic activity level were highly correlated for both forms of depot fluphenazine. Furthermore, the slope of the regression of log dose to the log plasma neuroleptic activity was the same for both drug forms. However, doses of enanthate twice those of decanoate were associated with the same mean plasma level of neuroleptic activity. Finally, while blood levels of drug overlapped markedly in cohorts of patients receiving different doses of depot medication, the assumption of recent studies that, on the average, patients in such cohorts have different blood and tissue levels of drug was confirmed.

Delayed-Action Preparations↗
PubMed1979

[Effect of a single dose of some long-acting neuroleptics on the estrus cycle and the mammary gland of the rat].

The effects of two neuroleptics (pipotiazine and fluphenazine) and five long-acting neuroleptics (pipotiazine undecylenate and palmitate, fluphenazine enanthate and decanoate, fluopentixol decanoate) are tested in the rat, during an observation period of 20 to 40 days following only one injection of compound. The compounds administered at three different and non toxic doses, are showing effects, the intensity and duration of which are different according to the dose and the compound: diestrus of pseudo-gestation or more than 15 days, hypertrophy of mammary gland, decreasing of the uterine weight. Some long-acting neuroleptics are active during more than forty days.

Animals↗
PubMedDate not supplied

Social aspects of therapy with depot neuroleptics in the Federal Republic of Germany.

The authors compare 76 patients (50% paranoid schizophrenics, 30% residual psychotics) successively treated with oral and depot neuroleptics: the mean number of rehospitalizations has dropped from 2.5 to 0.8, while the mean duration of hospital treatment has dropped from 34 to 8 weeks (t test significant). The relationship between the type of treatment and sociodemographic data was analyzed by means of correlation coefficients and variance analyses. There was no relation of age, sex, age of onset, school background, social class and professional achievement, but a significant superiority of depot medication in single patients. The choice of the depot preparation depends on habits, scientific attitudes and year: in 1976-1977, fluphenazine decanoate was prescribed in 70% of all cases; but penfluridol, fluspirilene and to a lesser extent flupentixol decanoate were also administered. Depot forms make for 32% of all neuroleptics. There is no evidence as to whether long-term neuroleptic medication has a prophylactic effect on relapses beyond the third year of treatment; but, without these drugs, it would have been impossible to return many patients to their environment; social psychiatry has received a new impetus from depot neuroleptics; the size of psychiatric hospitals could be reduced by one-third.

Adolescent↗
PubMed1978

Stimulation of prostaglandin synthesis by tumor-promoting phorbol-12, 13-diesters in canine kidney (MDCK) cells. Cycloheximide inhibits the stimulated prostaglandin synthesis, deacylation of lipids, and morphological changes.

Tumor-promoting 12-O-tetradecanoyl-phorbol-13-acetate and phorbol-12, 13-di-decanoate, but not the non-tumor-promoting 4alpha-phorbol-12, 13-di-decanoate, stimulated deacylation of cellular lipids, prostaglandin biosynthesis, and morphological changes in cultured MDCK cells. The increased prostaglandin biosynthesis and morphological changes required at least 24 h for expression. Cycloheximide inhibited the stimulated prostaglandin biosynthesis, the changes in morphology, and the increased lipid deacylation, but hydrocortisone (1.0 microgram/ml) did not. Indomethacin (0.5 microgram/ml) completely inhibited the stimulated prostaglandin biosynthesis and also inhibited some deacylation of cellular lipids. Indomethacin, however, did not effect the 12-O-tetradecanoyl-phorbol-13-acetate-stimulated changes in morphology.

Cell Line↗
PubMed1983

Depressive symptoms in chronic schizophrenic patients after withdrawal of long-acting neuroleptics.

A double-blind randomized investigation compared withdrawal (placebo) with continued use of long-acting neuroleptics (fluphenazine decanoate or flupenthixol decanoate) in 41 chronic schizophrenic outpatients. After 6 weeks there was a tendency toward higher depressive scores in the placebo group, a difference which became statistically significant (p less than .05) at week 24. These results do not support earlier observations that neuroleptic drugs cause depression. Further analyses of the data indicated that depressive symptomatology could be an early sign of relapse.

Adult↗
PubMed1981

[Use of the ex vivo vascular perfusion technique in the rat for the study of the intestinal absorption of fatty acids into the blood].

Lipid emulsion containing tritiated decanoic or oleic acid was infused in an isolated intestinal loop in situ. An ex vivo vascular perfusion technique has been used, allowing the continuous sampling of mesenteric portal blood. With decanoic acid the amount of radioactivity recovered in portal blood was high and similar for actidione-cycloheximide treated and control Rats. On the contrary the amount of radioactivity recovered in control Rats after oleic acid absorption was low. These results show that the ex vivo vascular perfusion technique can be used to study the non-esterified fatty acid intestinal absorption.

Animals↗
PubMed1983

Medium chain fatty acids as specific substrates for diglyceride acyltransferase in cultured hepatocytes.

The fatty acyl substrate specificity for de novo diglyceride, triglyceride, and phospholipid synthesis in cultured hepatocytes was evaluated. The fatty acyl availability for diglyceride and phospholipid synthesis is restricted to fatty acids longer than myristic acid with octanoic and decanoic acids being excluded. On the other hand, octanoic and decanoic acids may serve as substrates for the diglyceride acyltransferase. Dodecanoic acid appears to occupy an intermediate position between medium and long chain fatty acids with respect to its availability as substrate for the esterification sites concerned. The availability of octanoate as a specific substrate for the diglyceride acyltransferase reaction in cultured hepatocytes enables the measurement of this activity in situ under conditions of overall triglyceride synthesis.

Acyltransferases↗
PubMed1979

Direct hydroxylation in the biosynthesis of hydroxy fatty acid in lipid a of Pseudomonas ovalis.

It was found that Pseudomonas ovalis IAM 1177 had an abundance of hydroxy fatty acids such as 3-hydroxy-decanoic acid, 3-hydroxy-dodecanoic acid and 2-hydroxy-dodecanoic acid in the lipophilic part of the lipopolysaccharide fraction, which comprise 80% of total fatty acids. By using 18O2, it was shown that one oxygen atom from molecular oxygen was incorporated into 2-hydroxy-dodecanoic acid, but not into 3-hydroxy-decanoic acid. The incorporated oxygen atom was specifically located at the hydroxyl group of 2-hydroxy-dodecanoic acid. The biosynthetic pathways of these hydroxy fatty acids are discussed.

Fatty Acids↗
PubMed1976

The initiation of long-term pharmacotherapy in schizophrenia: dosage and side effect comparisons between oral and depot fluphenazine.

This report focuses on two comparisons between oral and depot fluphenazine specifically FPZ decanoate: 1) can equivalent dosages for the two drugs be established and do these equivalencies change over six months of treatment; 2) what are the side effects seen with the two drugs during the early weeks of administration. Patients in the study receive either oral or depot FPZ as the active treatment but in order to preserve double blind conditions, they are also given the other treatment in placebo form. No dosage equivalence is established by the protocol, however, if dosage is adjusted, both forms must be changed and in the same direction. During the first weeks of treatment there is a linear relationship between the two dosage forms but a range of relatively low dosages of the oral compound (5-20 mg) is associated with a single dose (25 mg/q 3 weeks) of FPZ decanoate. At higher dosages of the oral drug the relationship is linear. Side effects of some kind are noted in over 60 percent of patients in both treatment groups after four weeks of treatment, while symptoms of at least moderate severity occur in almost 40 percent. Only symptoms involving the extrapyramidal system and sleep disturbance are observed in more than 20 percent of the patients. Benztropine was prescribed only if needed and was administered to 65% of patients. In general, those receiving benztropine had more side effects than those who did not. These differences reached significance for extrapyramidal symptoms and depression. Based on these data, we conclude that at the dosages used in this study there are no side effect differences between these two forms of fluphenazine in the early weeks of administration. Dosage equivalence between the two drugs can be set within the range of 5-60 mg/day oral and 12.5-100 mg/three weeks depot.

Administration, Oral↗
PubMed1994

Impact of clinical pharmacokinetics on neuroleptic therapy in patients with schizophrenia.

This review covers some recent work on: 1. The effects of route of administration on the pharmacokinetics of fluphenazine and some of its metabolites; 2. The clinical pharmacokinetics of fluphenazine in acute patients medicated with oral fluphenazine; 3. The clinical pharmacokinetics of haloperidol in acute patients medicated with oral haloperidol; 4. The clinical pharmacokinetics of fluphenazine in the maintenance of individuals with chronic schizophrenia with fluphenazine decanoate; 5. A systematic dose reduction study in maintenance treatment refractory patients with oral haloperidol. A study in which plasma levels of fluphenazine and fluphenazine sulfoxide were measured in a group of DSM-III-R patients with schizophrenia before and after switching from oral fluphenazine to depot fluphenazine, decanoate revealed much higher levels of fluphenazine sulfoxide with oral medication compared with those found with depot fluphenazine. These data illustrate the effect of "first pass" metabolism after oral fluphenazine. Thus in a group of 33 patients randomly assigned to receive 5 mg, 10 mg or 25 mg oral fluphenazine daily, steady state plasma fluphenazine levels at each dose were significantly lower that those of fluphenazine sulfoxide or 7-hydroxy-fluphenazine, although there were no significant differences between the levels of fluphenazine and fluphenazine N4-oxide. On the other hand, plasma levels of the parent drug were significantly higher than those of any metabolite in a corresponding group of patients at steady state on depot medication. These observations underscore the importance of route dependent differences in the pharmacokinetics of fluphenazine which can lead to problems when switching patients from oral to depot neuroleptics. The concept of "disabling side-effects" is an important development in understanding relationships between plasma levels of neuroleptic drugs and clinical response in patients with schizophrenia. Risk-benefit analysis shows clearly that evaluation of relationships between plasma levels and clinical response must take into account the consequences of side-effects which the patient feels have a negating effect on therapy. Emerging data on putative therapeutic plasma level ranges in maintenance therapy are potentially important and may be particularly useful in the maintenance of patients on low dose therapy. It is noteworthy that in a carefully executed dose reduction study in treatment resistant patients under medication with haloperidol, the mean lowest effective dose (8.7 ng/mL) lay within the optimal therapeutic range (5 ng/mL to 12 ng/mL) found in acutely psychotic patients. The study showed that gradual dose reduction of neuroleptic was possible in chronic treatment resistant patients with schizophrenia who were originally thought by ward staff to require high doses of neuroleptic.(ABSTRACT TRUNCATED AT 400 WORDS)

Antipsychotic Agents↗
PubMed1976

Double-blind investigation of two corticoid preparations for the treatment of eczematous skin disorders. Short communication.

In a double blind fully randomised trial, three Belgian dermatologists independently treated 81 patients suffering from various eczematous skin disorders. After four weeks both the dermatologists and their patients assessed the results of a twice-daily topical application of an ointment containing 17 beta-hydroxy-4-estren-3-one-17-decanoate (nandrolone decanoate, Dexatopic) ointment or a reference ointment. Both the dermatologists' and the patients' assessments of the two preparations showed that there was no significant difference between the two treatments although Dexatopic did seem to have a more favourable profile in the "much improved" area. In the total score decrease, there was an indication that Dexatopic had a more favourable effect than the reference preparation.

Clinical Trials as Topic↗