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PubMed1994

[General practice of acute inpatient treatment of mania. Retrospective comparative study of 100 patients at each of 2 psychiatric centers].

We reviewed the literature regarding acute therapy of manic patients and compared these recommendations with actual practice by reviewing 399 therapies in 100 patients each from two psychiatric care centres between 1975 und 1991. Higher age, more serious disease and a higher percentage of compulsory commitments are typical of patients treated in institutions with a mandatory admission policy as compared to university clinics, which are not compelled to admit patients. The treatment methods practised in both centres deviated greatly from recommendations in the literature. In spite of widespread therapeutic recommendations, lithium and carbamazepin are seldom employed for acute treatment; neuroleptic agents were preferred for all grades of severity. Combinations of more potent antipsychotics with more sedative neuroleptics were preferred. In contrast, the chosen substances, the preferred combinations and the application form varied considerably. The state mental hospital preferred haloperidol and levomepromazin; in the university clinic clozapin and perphenazineoenanthate were important adjuncts. Both clinics remained in the low therapeutic range of dose recommendations. There were no statistically meaningful differences with regard to either the total amount of chlorpromazine equivalents applied or the duration of inpatient care. In the first one-tenth of the total treatment period, 85% of the maximal dose reached in the second tenth is already given. A continual reduction begins thereafter, until app. 40% of the peak dose in reached. Active treatment of side effects as well as more common use of depot neuroleptics in order to minimize custodial treatment, may explain the lower number of compulsory admissions in the university hospital. Extreme interindividual differences in both dosage and length of stay help in elucidating the apparently contradictory results of comparative investigations with small patient groups. Previous treatments have little or no predictive value due to large intraindividual variations.

Adult↗
PubMed1991

Low melanin content of substantia nigra in a case of neuroleptic malignant syndrome.

A 19-year-old man suffering from a first episode of schizophrenia developed a neuroleptic malignant syndrome (NMS) after administration of haloperidol and levomepromazine. After five weeks of neuroleptic treatment he died of an unknown cause. Histological examination of the brain revealed a low melanin content in neurons in the substantia nigra (SN). Since neuromelanin in SN is the end-product of nonenzymatic dopamine degradation, the amount of melanin probably depends on the overall amount of dopamine produced during life. Thus, dopamine production must have been low in the reported case. In addition, ectopic neurons were found in subcortical white matter.

Adult↗
PubMed1999

Psychotropic drug prescription in a psychiatric university hospital.

A retrospective survey on drug prescription over a one-year period (1989) in 1083 patients (48.3% of whom were male) hospitalized in a psychiatric university hospital in Switzerland and a 35-day prospective study (1992) on the prescription of "as needed" (prn) medication in a closed and an open ward were carried out. Their aim was to establish a basis for a monitoring of prescription habits and for pharmacoeconomic considerations. In the retrospective study, 48.3% of the patients were male. The mean duration of hospitalization of the patients was 47.0 +/- 68.1 days (mean +/- s.d.). Only 11 out of the 1083 patients (1%) were without psychotropic medication. The mean (+/- SD) number of drugs/day the patients were prescribed was 4.6 +/- 2.8, including 3.2 +/- 1.7 psychotropic drugs. Patients suffering from schizophrenia (67 d) or from unipolar depression (67.4 d) were hospitalized for the longest periods. Antipsychotics (67.5% of the patients) were the most frequently prescribed psychotropic drugs, followed by anxiolytics (42.2%), antidepressants (28.3%), hypnotics (31.4%) and mood stabilizers (7.1%). Antiparkinsonian agents accounted for 4.6% of all prescriptions. Levomepromazine, haloperidol (30.9% of all patients) and clotiapine were the most often prescribed neuroleptics, and clozapine was administered to only 6.4% of all patients. Among the antidepressants, maprotiline (11.9% of all patients) was more frequently prescribed than the classical tricyclic antidepressant amitriptyline, while the only available SSRI fluvoxamine and MAO inhibitors were rarely used. The most frequently prescribed anxiolytics were clorazepate (28.2% of all patients), lorazepam, bromazepam, and prazepam. Among the hypnotic drugs, chloral hydrate (11.5%) was more frequently administered than the first-ranking benzodiazepine flunitrazepam (7.8%). In the prospective study, 97% and 77% of the patients (n = 55) of the closed (n = 29) and of the open ward, respectively, were prescribed "as needed" (prn) drugs. However, only 71 and 80%, respectively, of these patients finally received the drug. The frequency of prescription was 34.9% for neuroleptics, 15.1% for anxiolytic drugs, 8.2% for non-benzodiazepine hypnotics and only 2.1% for benzodiazepine hypnotics. The most frequently prescribed neuroleptic drug was clotiapine (18% of all patients), but finally, only 29% of the prescribed doses were administered. Studies of this type are biased by the fact that local habits of prescription do not allow generalisation of the findings. Such surveys should be carried out more frequently and simultaneously in different centers. Critical comparisons could help to optimize treatment.

Adult↗
PubMed1995

[The neuroleptic malignant syndrome].

HISTORY AND CLINICAL FINDINGS: A 22-year-old oligophrenic patient had on several occasions over several months been given various neuroleptics (haloperidol, benperidol, levomepromazine) for exacerbations of paranoid schizophrenia. For a few days before hospitalization he had become quiet and withdrawn, but on the day of admission 100 mg chlorprothixene was administered intramuscularly when he had become agitated. At admission he was somnolent, his general condition was disturbed. He had hyperhidrosis and hypersalivation, as well as tachycardia (112/min) with a normal body temperature of 37.8 degrees C. He also exhibited the cogwheel phenomenon of the limbs and neck, as well as tremor of the hands. The differential diagnosis included inflammatory disease of the brain, sinus thrombosis and, especially, malignant neuroleptic syndrome and febrile catatonia. INVESTIGATIONS: The activities of creatine kinase (3840 U/l), GOT (75 U/l) and GPT (88 U/l) were all increased. Serum myoglobin was 77 micrograms/l. CSF contained blood and there was pleocytosis of 50/3 cells. The ECG showed sinus tachycardia. EEG, chest radiogram, computed tomography, magnetic resonance imaging and cerebral angiography showed no abnormalities. Febrile catatonia could not be excluded. TREATMENT AND COURSE: 4 hours after admission the patient began to respond with normal orientation. Shortly afterwards he was able to walk a few steps, i.e. there was no catatonia. But rigor, tremor, hypersalivation and tachycardia persisted and 12 hours later he developed a fever (up to 39.2 degrees C). Blood pressure varied with peak pressures up to 190/110 mm Hg. After 2 days muscle tone had clearly increased so much that voluntary movement was hardly possible. After amantadine administration (200 mg daily) the rigor improved and for the first time body temperature became normal again. There were no signs pointing to psychotic symptoms. CONCLUSION: Neuroleptic malignant syndrome is difficult to distinguish from febrile catatonia and the diagnosis can often only be made through the clinical course.

Adult↗
PubMed2000

Determination of methotrimeprazine in pharmaceutical preparations by visible spectrophotometry.

A spectrophotometric method is described for determination of methotrimeprazine (levomepromazine). The aim of this work was to develop a simple, rapid, precise, and accurate visible spectrophotometric method for determination of methotrimeprazine in tablet, oral solution, and injection. The method is based on methotrimeprazine reaction with bromophenol blue, resulting in a stable, light yellow-green ion-pair complex that, after extraction with chloroform, presented maximum absorption at 409 nm. Beer's law was obeyed in the concentration range from 5.0 to 25.0 micrograms/ml. The proposed standardized method was applied to commercially available and simulated samples. The accuracy of the method was confirmed by recovery tests.

Antipsychotic Agents↗
PubMed2002

Toxicological analysis of chlorhexidine in human serum using HPLC on a polymer-coated ODS column.

A simple and reliable high-performance liquid chromatographic (HPLC) method for analyzing chlorhexidine in human serum was developed. After the addition of an internal standard, levomepromazine, 0.2 mL serum was deproteinized with 10% perchloric acid. The acidic supernatant was neutralized with 1M potassium carbonate solution, and the insoluble salt was removed by centrifugation. An aliquot of the supernatant was applied to HPLC with UV detection (260 nm). HPLC separation was achieved on a polymer-coated ODS column equilibrated with acetonitrile/water containing 0.05% trifluoroacetic acid, 0.05% heptafluorobutyric acid, and 0.1% triethylamine (40:60, v/v). The calibration curve was linear in the concentration range from 0.05 to 50.0 microg/mL, and the lower limit of detection was 0.05 microg/mL. The accuracy and precision of the method were evaluated at concentrations of 0.5 microg/mL and 5.0 microg/mL. The coefficients of variation ranged from 4.0 to 4.5%. The concentration of chlorhexidine in the serum of a patient who died after a suspected intravenous injection of chlorhexidine gluconate was determined.

Anti-Infective Agents, Local↗
PubMed1990

Fly larvae and their relevance in forensic toxicology.

Toxicological analyses on a putrefied cadaver are sometimes difficult to perform because of the absence of blood and urine. In this study, fly larvae, being living material, are proposed as a new medium of investigation in forensic toxicology. Bromazepam and levomepromazine were identified and assayed in the remains of cerebral tissue, in the clavicle of a putrefied cadaver, and in the fly larvae found on and in the corpse.

Aged↗
PubMedDate not supplied

Intravenous administration of levodopa ameliorated a refractory akathisia case induced by interferon-alpha.

A 28 year-old man with chronic hepatitis B was administered interferon-alpha (5 x 10(6) IU) intramuscularly once a day for 28 days. Eight days after the end of interferon treatment, he showed signs of inability to sit still for ten seconds and walked around constantly. His akathisia symptoms worsened thereafter. Clonazepam, thioridazine, beta-blockers, anticholinergics, and bromocriptine did not ameliorate his akathisia. Two days' administration of levomepromazine 100 mg led him to a coma for 2 days. Intravenous levodopa 25 mg ameliorated his akathisia symptoms drastically. He became completely premorbid 2 weeks after administration of levodopa. The present report illustrates a rare case of refractory akathisia after interferon-alpha treatment and also that levodopa treatment would be theoretically and practically useful in reducing the neurotoxicity associated with interferon-alpha.

Adult↗
PubMedDate not supplied

Early and late side effects of water-soluble contrast media for myelography and cisternography: a short review.

Acute and chronic neurotoxicities of the ionic contrast media Conray, Dimer X, Dimer X and a steroid, and a nonionic contrast medium metrizamide (Amipaque) are reviewed. All ionic media induced late arachnoiditis potentiated by intrathecal steroids. Amipaque did not induce late arachnoiditis, but it produced a number of acute side effects. Myelography in patients given a phenothiazine (levomepromazine) was associated with a decreased incidence of side effects compared with a nonmedicated group.

Arachnoiditis↗
PubMed1992

Acute colitis associated with prolonged administration of neuroleptics.

We describe a 29-year-old patient who developed acute colitis limited to the sigmoid and left colon with features mimicking ischemic injury after a prolonged administration of trifluoroperazine and levomepromazine, two phenothiazines in association with haloperidol, another neuroleptic, and biperidene, an anticholinergic compound. The discontinuation of these drugs was followed by a prompt and complete recovery, and no other cause of acute colitis was found. The subsequent administration of sultopride, a neuroleptic from the benzamide family and then the readministration of haloperidol were well tolerated. No colonic disorder occurred for the following months. This case strongly supports the view that neuroleptic agents, in particular phenothiazines, may induce acute colitis and that haloperidol, a butyrophenone derivative, or sultopride, a benzamide-related neuroleptic, can be administered thereafter without recurrence of the disease.

Adult↗
PubMed1982

Active metabolites of neuroleptic drugs: possible contribution to therapeutic and toxic effects.

Recent studies demonstrating a relationship between plasma levels and effects of haloperidol, thioridazine, chlorpromazine, butaperazine, fluphenazine, and perphenazine suggest that therapeutic plasma level monitoring of neuroleptics may be clinically useful. Chlorpromazine, thioridazine, levomepromazine, and loxapine have active metabolites which attain plasma levels within the same range as that of the parent compound after therapeutic doses of the drug. The metabolites often have pharmacological profiles which are different from that of the parent drug, and some metabolites apparently contribute to the side effects of the drug but do not possess any neuroleptic potency. The ratios between the plasma levels of metabolites and the parent compound show large interpatient variations, and the metabolites should, therefore, be measured together with the parent drug by therapeutic plasma level monitoring. Accordingly, the assay method should be carefully selected in order to include metabolites which may contribute to the therapeutic or side effects of the drug.

Antipsychotic Agents↗
PubMed1982

Plasma and erythrocyte levels of methotrimeprazine and two of its nonpolar metabolites in psychiatric patients.

Methotrimeprazine (levomepromazine) has two major metabolites in man: N-monodesmethyl methotrimeprazine, which is pharmacologically active and almost as potent as the parent drug; and methotrimeprazine sulfoxide, which is much less active. Blood levels and the distribution between plasma and erythrocytes of methotrimeprazine and the two metabolites were studied in five psychiatric patients on oral methotrimeprazine and after incubation of the compounds in blood from healthy volunteers. The concentrations were measured separately in plasma and erythrocytes by gas chromatography with a nitrogen detector, and the concentrations in whole blood were calculated from the plasma and erythrocyte concentrations. In four of the five patients the blood levels of both metabolites were similar to or higher than the levels of the parent drug. A large interindividual variation was observed in the plasma-erythrocyte concentration ratios. The mean ratios in all individuals were 1.76, 0.57, and 3.02 for methotrimeprazine, N-monodesmethyl methotrimeprazine, and methotrimeprazine sulfoxide, respectively. The relatively high blood concentrations of N-monodesmethyl methotrimeprazine suggest that this metabolite may contribute significantly to the therapeutic action and side effects of oral treatment with methotrimeprazine.

Adult↗
PubMed1997

Therapeutic drug monitoring databases for postmarketing surveillance of drug-drug interactions: evaluation of a paired approach for psychotropic medication.

The present study investigated the potential of therapeutic drug monitoring data to document pharmacokinetic drug interactions with psychotropic medication, both in terms of methodology and applicability. It focused on 105 patients exposed to one of five agents known for their capacity to induce (phenytoine, phenobarbital, and carbamazepine) or to inhibit (thioridazine and levomepromazine) the metabolism of psychotropic drugs. These patients were matched by gender, age, and monitored psychotropic medication to 105 patients randomly selected from a pool of subjects nonexposed to target comedication. Such a paired approach was shown to be effective in reducing variability for a majority of substances. Power analysis suggested that eight to 10 pairs of exposed and nonexposed patients would effectively allow the detection of twofold effects of interacting substances. In keeping with the literature, analysis of the ratios of dose-normalized exposed to nonexposed concentrations indicated that phenothiazine comedication led to significantly higher concentrations of desmethylated metabolites but not parent compounds, when clomipramine, imipramine, or amitriptyline were administered. A similar, as yet undocumented interaction was observed for the tetracyclic antidepressant mianserine. In contrast, the present study revealed that maprotiline concentrations were increased, but its metabolite was largely unaffected by phenothiazine comedication. Increased concentrations were also observed for moclobemide, but not citalopram or its metabolite. In addition to its long recognized capacity to decrease haloperidol concentrations, carbamazepine was shown to induce the metabolism of clopenthixol and possibly flupenthixol. The consistency of such a picture substantiates the need to consider therapeutic drug monitoring databases as cost-effective and reliable tools for postmarketing surveillance.

Adolescent↗
PubMed2006

Pharmacokinetic characterization of amantadine in human brain tissue.

Amantadine concentrations in human brain tissue were assessed in order to estimate population pharmacokinetic parameters using the computer program NONMEM. The elimination constant in brain tissue was determined to be 0.00447 [1/h], resulting in a t1/2 of 6.5 days for the mean patient in the population investigated (n = 19). An estimate of 65.5 L was obtained for the apparent volume of distribution. The elimination half-life of amantadine from brain tissue is much longer than from blood and is comparable to the previously investigated neuroleptic drugs haloperidol and levomepromazine.

Amantadine↗
PubMed1984

Clinical efficacy, extrapyramidal symptoms and serum levels: influence of administration schedules and concomitant drugs on serum bromperidol concentrations.

Bromperidol (4 or 12 mg per day) was administered to 18 newly admitted schizophrenics and 29 chronic schizophrenic inpatients once or four times a day and the two dose schedules were compared. The bromperidol levels in the four-times-a-day group were significantly higher than those in the once-a-day group and the daily variation in the serum level of the agent was markedly wider in the latter than in the former patients. The incidence and severity of extrapyramidal symptoms were not significantly different between the two. A clear relationship was not present between the serum levels and the development of extrapyramidal symptoms. The bromperidol serum values were not correlated with the therapeutic response but, at more than 5 ng per ml, there might be a positive correlation between the bromperidol levels and clinical efficacy in the newly admitted schizophrenics. As for concomitant medication, levomepromazine may raise the bromperidol serum level. An anti-parkinson drug failed to depress the bromperidol level.

Adult↗
PubMed1992

A case of tardive Tourette-like syndrome.

We have had experience in treating tardive Tourette-like syndrome on a chronic schizophrenic patient. The patient was a 38-year-old woman. A diagnosis of schizophrenia was made in 1971 and she received repeated medications for 17 years. In 1989, she began to show vocal tic with coprolalia and motor tic. The medications were haloperidol 18 mg, zotepine 200 mg, levomepromazine 100 mg, biperiden 3 mg and nitrazepam 10 mg at the beginning of Tourette-like syndrome. We have tried to change the medications but this tardive Tourette-like syndrome continued to hang on. However, the symptoms gradually improved after a change in drugs; cessation of biperiden 3 mg and the administration of clonazepam 3 mg. The present case suggested that tardive Tourette-like syndrome might be a subtype of neuroleptic-associated tardive syndromes which might be treated with clonazepam.

Adult↗
PubMed1997

Efficacy of lithium carbonate on public and compulsive masturbation: a female case with mild mental disability.

The efficacy of lithium carbonate in the first reported case of a female with mild mental disability who engaged in public and compulsive masturbation is described. The patient was born in 1975, and was 19 years old at first admission. A diagnosis of schizophrenia was initially suspected, therefore the patient was given medication including pimozide, haloperidol, carbamazepine, diazepam and levomepromazine. These medications, however, did not control the symptoms, and the patient showed several side effects, such as incontinence. Only lithium carbonate was efficacious among the medications administered; the patient's abnormal sexual behavior was significantly reduced and no conspicuous side effects were recognized. The mechanisms of lithium carbonate in controlling abnormal sexual behavior are discussed.

Adult↗