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PubMed2002

Population pharmacokinetics of haloperidol using routine clinical pharmacokinetic data in Japanese patients.

OBJECTIVE: To clarify the observed variability of haloperidol disposition in patients with psychiatric disorders. DESIGN: Retrospective population pharmacokinetic study. PARTICIPANTS: 218 Japanese patients aged 16 to 82 years who provided 391 serum haloperidol concentrations. METHODS: Routine clinical pharmacokinetic data gathered from patients receiving haloperidol were analysed to estimate population pharmacokinetic parameters with the nonlinear mixed effects model (NONMEM) computer program. RESULTS: The final pharmacokinetic model was CL = 42.4 * (TBW/60)(0.655) * 0.814(AGE> or = 55) * (DOSE/200)(0.236) * 1.32(ANTIEP) and Vd = 34.4 * TBW * 0.336( AGE> or = 65), where CL is total body clearance (L/h), Vd is apparent volume of distribution (L), TBW is total bodyweight (kg), DOSE is daily dosage (microg/kg/day), ANTIEP = 1 for concomitant administration of antiepileptic drugs (phenobarbital, phenytoin or carbamazepine) and 0 otherwise, AGE > or = 55 = 1 for patient aged 55 years or over and 0 otherwise, and AGE > or = 65 = 1 for patient aged 65 years or over and 0 otherwise. Concomitant administration of haloperidol and antiepileptic drugs resulted in a 32% increase in haloperidol clearance. Patients aged 55 years or over showed an 18.6% reduction in clearance, and elderly patients aged 65 years or over showed a 66.4% reduction in apparent volume of distribution. Inclusion of terms for the concomitant administration of haloperidol and antiparkinsonian drugs (amantadine, bromocriptine, biperiden, trihexyphenidyl or mazaticol) or cytochrome P450 (CYP) 2D6 substrates (levomepromazine, perphenazine, thioridazine, amitriptyline or clomipramine) did not significantly improve the estimate of haloperidol clearance. CONCLUSION: Application of the findings in this study to patient care may permit selection of an appropriate initial maintenance dosage to achieve target haloperidol serum concentrations, thus enabling the clinician to achieve the desired therapeutic effect.

Adolescent↗

PubMed1989

A review of trimipramine. 30 years of clinical use.

The hybrid chemical structure of trimipramine incorporates an imipramine nucleus and levomepromazine side chain. This structure predicts much of the clinical profile of trimipramine. The initial studies on trimipramine date back nearly 30 years. It now has a well-recognised clinical profile with some characteristics akin to other tricyclic antidepressants (TCA) and others which are quite distinct. It is well established as a highly effective antidepressant with an efficacy profile similar to the other TCAs. Clinically, its anxiolytic and sedative properties distinguish it from most other TCAs. Its effects on sleep architecture are unique and explain some of its unique properties. The side effect profile of trimipramine is in some ways similar to those of the tertiary amine TCAs with a preponderance of anticholinergic and sedative effects. Its cardiotoxic properties are minimal, with some findings suggesting a very favourable profile. Interactions with other drugs, psychotropic or non-psychotropic, are compatible with its pharmacological profile. These are reviewed with its clinical applications in mind. The pharmacokinetic characteristics of trimipramine differ from those of many of the other TCAs. The application of this to clinical situations is addressed. Based on experience using trimipramine, a profile of 'ideal' patient characteristics has been built up. Finally, the use of trimipramine in selected patient populations is reviewed.

Depressive Disorder↗

PubMed1990

Clozapine. A review of its pharmacological properties, and therapeutic use in schizophrenia.

Clozapine, an antipsychotic agent of the dibenzodiazepine class, is characterised by relatively weak central dopaminergic activity and displays atypical pharmacological and clinical properties in relation to the classic antipsychotics. Clinical studies have shown clozapine to be effective in suppressing both the positive and negative symptoms of schizophrenia and to be associated with an extremely low incidence of extrapyramidal side effects. Clozapine has been shown to be of comparable, or on some criteria superior, therapeutic efficacy to perphenazine, levomepromazine, haloperidol and chlorpromazine in several short term comparative studies in patients with schizophrenia of predominantly acute symptomatology. Moreover, clozapine is effective in a substantial proportion (30 to 50%) of schizophrenic patients who are refractory to or intolerant of classic antipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (1 to 2% of patients) is a major factor restricting the drug's wider use in psychiatric practice. In accordance with current guidelines, clozapine therapy, performed in conjunction with close haematological monitoring, is indicated for the management of severe and chronic schizophrenia refractory to classic antipsychotic therapy, and in those unable to tolerate such therapy. In such appropriately selected patients, clozapine represents an important alternative to the classic antipsychotics.

Clozapine↗

PubMed1996

Reversible azoospermia in a patient treated with triazolam.

This is a report of a 26-year-old schizophrenic man treated with triazolam, levomepromazine, trifluoperazine and biperiden, who showed complete absence of spermatozoa in seminal analysis with normal plasma hormone levels. Sperm count reached 151 x 10(6)/ml after 6 months of triazolam withdrawal. A reversible effect of triazolam is suggested at the level of the germinal cells which are differentiating, without affecting the stem cells.

Adult↗

PubMed1976

[Psychotropic drugs for behavior disorder treatment in oligophrenic epileptics].

Forty-one patients were treated with promazine, a phenothiazine derivative, for an average of 266 days. The average daily dose was 200 mg. Thirty patients were treated with levomepromazine for an average of 115 days, the daily dose being about 130 mg. The two groups of patients were examined for their contactual, impulsive, and affective behavior before, during, and after treatment. The positive results obtained justify the use of the above-mentioned psychopharmaceuticals for the therapy of abnormal behavior of oligophrenic epileptics.

Adult↗

PubMed1976

[Analgesic effects of Neurotropin in mice, and a comparison with analgesic effect of other drugs in SART-stressmice].

Analgesic effects of a neuroleptica "Neurotropin" (NSP) were studied in mice while the analgesic effects of other agents were studied in SART-stress mice (specific stress caused by alterating rhythm in temperature) and the results compared with those in normal mice. NSP is an extract containing many conjugated polysaccarides isolated from the skin or tissues of rabbits which had been inoculated with the living cowpox virus. (a) NSP given alone to normal mice resulted in slight analgesic effects as observed with the application of the acetic acid-, phenylquinon-writhing method or the modified Randall-Selitto method. Little effect was seen when the D'Amour-Smith was used. (b) Synergism was evident when NSP and aminopyrine or NSP and morphine were given concomitantly and the acetic acid- or phenylquinon-writhing methods were applied. (c) Analgesic effects of morphine, levomepromazine, imidazole acetic acid and particularly NSP were greater in SART-stress mice than in normal mice. With the D'Amour-Smith method, only NSP had a greater effect in SART-stress mice than in normal mice.

Aminopyrine↗

PubMedDate not supplied

[Risperidone and concept of bipolar neuroleptic].

We present a review of the stimulant properties of risperidone, analyzing them according to the model of bipolar neuroleptic proposed in 1979 by Colonna and Petit. The bipolar neuroleptics (pimozide, sulpiride) present stimulant properties at low dose and sedative effects at high dose whereas monopolar neuroleptics (levomepromazine, chlorpromazine) present from the low dose sedative effects. The stimulant properties might arise from a preferential blockade of the presynaptic dopaminergic receptors, giving and enhancement of the dopaminergic transmission. Risperidone might follow the bipolar model; we review the stimulant effects in laboratory animals and in clinical settings, showing exacerbation of manic symptoms and a possible antidepressive effect. These properties could be due to the capacity to increase the cerebral monoamines by the 5-HT2A and alpha 2 antagonism. Risperidone could be used in the treatment of clinical syndromes combining depressive and psychotic symptoms.

Antipsychotic Agents↗

PubMedDate not supplied

Skin manifestations of a case of phenylbutazone-induced serum sickness-like reactions.

Serum sickness consists of a systemic reaction resulting from the formation of soluble circulating immunocomplexes after the introduction of a foreign substance into the body We studied a 38-year-old woman diagnosed with anxiety, depression and right sacroileitis who was treated with phenylbutazone, ranitidine, clomipramine and levomepromazine. After taking this treatment for 1 month, she presented with fever, diarrhea, localized edemas, generalized pruritic papular and erythematous rash and lymphadenopathies. She presented the same symptoms after oral intake of metamizole. The diagnosis was confirmed following a single-blind, placebo-controlled provocation test with phenylbutazone and a biopsy of the affected skin.

Adult↗

PubMed2000

[A survey of drug utilization in psychiatric hospitals in Japan: comparison of 1973, 1979, and 1993].

This paper investigated the trend in prescription patterns in the treatment of psychiatric inpatients using a database of our 1993 survey as well as reports of surveys conducted by Ito et al. in 1973 and 1979. To make the database of our survey comparable with surveys in 1973 and 1979, we extracted and analyzed 1,164 cases which met the criteria of Ito's survey, requiring that patients were diagnosed as having schizophrenia and were hospitalized for two years or longer. The results were as follows: 1) The most common number of different drugs per patient increased from 4 in 1973 and 1979 to 8 in 1993. That of psychotropics increased from 2 to 5. That of neuroleptics increased from 2 to 3. 2) The most commonly prescribed neuroleptics were haloperidol followed by levomepromazine and chlorpromazine. While the top three neuroleptics had not changed, the mean daily dose of haloperidol rose from 8.4 mg in 1979 to 15.3 mg in 1993.

Databases, Factual↗

PubMed2002

[Continuous subcutaneous infusion in palliative care, an undervalued method].

Three patients, 2 men aged 55 and 54 years and a woman aged 86 years, were admitted to hospital for treatment of symptoms resulting from terminal disease (pain, agitation, nausea etc.). In all three patients, continuous subcutaneous infusion (CSI) of medication was successfully used to control the symptoms. Compared with intravenous infusion, the technique of CSI is easy to learn and is associated with fewer complications. Its reliability and ease-of-use make it a technique that can be used not only in a hospital setting, but also in general practice and nursing homes. Medication used in palliative care (e.g. morphine, haloperidol, metoclopramide, levomepromazine, midazolam) can often be administered safely by CSI. In palliative care, where goals should be accomplished with minimal burden to the patient, CSI must be considered the technique of choice in patients who are unable to swallow their medication.

Aged↗

PubMed2003

[From some experiences in pharmaco-psychotherapy].

The author had developed the anaclitic pharmaco-psychotherapy as an integrated treatment of levomepromazine (a phenothiazine derivate), psychoanalytic interviewing and intensive nursing care for severe cases. Nevertheless the author had good results by the new therapy, some severe cases were still non-responded. The author found some differences of personality pattern between responder and non-responder. Responders had hyperkinetic pattern with good verbal expression and dependent behavior. Non-responders had hypersensory pattern with holding their tongue and keeping tension. The author had tried psychotherapy under using LSD for hypersensory pattern cases and gotten good results by it. But using LSD was prohibited by legal reason, now. The author could get significant development of three areas of psychiatric treatment through our development of the pharmacopsychotherapy as follows. 1) Significance of some biological factors for personality The author has clarified that two different response types to drug, hyperkinetic-visual dominant type and hypersensory-auditory dominant type. Assessments of such personality pattern or trait are useful for selection of appropriate drug. 2) Some changes in psychoanalytic stance. The author could find some therapeutic significances of object relationship in therapeutic process. These findings have stimulated the author to shift from classic drive oriented psychoanalysis to object relation psychoanalysis. 3) Significance of psychiatric nursing, team approach and therapeutic environment. The author has convinced of importance of role of psychiatric nursing and team approach. And the author has found importance of making and maintaining of appropriate psychiatric milieu and environment.

Humans↗

PubMed2003

[Prolonged hyperthermia after isocarboxazid poisoning].

A 44-year-old unconscious man was admitted 24 hours after intake of approximately one gram of isocarboxazid. He was subsequently intubated for seven days. Muscular hyperactivity and prolonged hyperthermia were the main therapeutic problems which were treated with dantrolene, levomepromazine, pancuronium, and external cooling. Massive rhabdomyolysis was treated with forced diuresis.

Adult↗

PubMed2003

[Antipsychotic medication as a cause of deep hypothermia].

Two patients were presented at our hospital with hypothermia following dose adjustment of antipsychotic medication. The first patient, a mentally retarded 45-year-old man developed a temperature of 31.7 degrees C several days after starting of levomepromazine. The second patient, an 41-year-old schizophrenic man, whose risperidone dose had been increased following a psychotic crisis, developed deep hypothermia (temperature 29.7 degrees C) and severe respiratory insufficiency requiring pressure support ventilation. Both patients were admitted to the ICU and recovered completely. Antipsychotics influence hypothalamic thermoregulation and may induce hypothermia by stimulating dopamine (mainly D2) receptors and blocking 5-HT2 receptors. Furthermore, antipsychotics may reduce the shivering capability and can cause peripheral vasodilatation and reduced shunting by blocking skin alpha 1 receptors. Hypothermia can be a lethal condition. When a patient's clinical condition deteriorates following the start of antipsychotic medication, the presence of hypothermia should be excluded.

Adult↗

PubMed2003

Neuroleptic malignant syndrome in Mexico.

BACKGROUND: Neuroleptic Malignant Syndrome (NMS) is an uncommon but potentially fatal complication of antipsychotic and neuroleptic drug treatment. OBJECTIVES: This study estimated the frequency, clinical presentation, and outcome of NMS in a referral center for neurological, neurosurgical and psychiatric disorders in Mexico. METHODS: The authors conducted a thorough search of psychiatry, neurology, neurosurgery and intensive care unit records for cases of NMS during the 10-year period between 1990 and 1999. They examined the clinical features, course and treatment of the NMS episodes, and performed a follow-up survey for residual symptoms and clinical outcome. The mean time to follow-up assessment was 36 months. RESULTS: A total of eight of 4831 neuroleptic-treated patients had an episode of NMS (incidence 0.165%). Seven of the eight patients were treated with haloperidol. Other neuroleptics agents associated with NMS were depot pipotiazine palmitate and levomepromazine maleate. One patient received lithium concomitantly. No fatal outcome was found. Only one patient developed persistent clinical sequelae, consisting of extrapyramidal and cerebellar symptoms, three years after the NMS episode. CONCLUSIONS: The slightly low frequency of NMS found in this study compared with studies conducted in other countries may be attributable to the advent and use of newer atypical antipsychotics in Mexico, the rigorous demands for NMS diagnostic criteria and the lack of familiarity with the diagnosis between physicians.

Adolescent↗

PubMed1976

[Controlled arterial hypotension produced by nitroprusside combined with neuroleptics].

Ganglioplegic drugs, including trimetaphan, have been imperfect agents of arterial hypotension, liable to produce tachyphylaxis, and not blocking intercurrent attacks of adrenergic hypertension the dose is inconstant and reversibility sometimes doubtful. The association of neuroleptics, in particulier promazines, permits an appreciable economy in dosage, stabilises the curves of hypotension, with the disadvantage of blocking normalisation of blood pressure. Sodium nitroprusside does not have the disadvantage of ganglioplegic drugs. Although usable alone, the blood pressure graphs sometimes have a certain instability mainly due to the difficulty of regulating the ideal perfusion flow rate. The authors show that the association of neuroleptic drugs has here also an effect of economy of dosage and facilitates the rise in blood pressure. Verification of reinforcement of the effect of sodium nitroprusside by chlorpromazine, acepromazine and levomepromazine was carried out in the dog. The authors show significant graphs.

Animals↗

PubMed2005

[Palliative sedation].

Palliative sedation is the intentional lowering of the level of consciousness ofa patient in the last phase of life by means of the administration of sedatives. The objective of palliative sedation is to relieve severe physical or psychological suffering that is otherwise untreatable. Sedation is used in 12% of all patients dying in the Netherlands. Refractory delirium, dyspnoea or pain are the most common indications. If deep palliative sedation is used, the estimated life expectancy should be a few days to at most one week. Midazolam is used most often for continuous sedation, usually by subcutaneous infusion; if the response is insufficient, a combination of midazolam with levomepromazine or phenobarbital or monotreatment with propofol may be used. If continuous infusion is not desired or feasible, intermittent administration of midazolam, diazepam, lorazepam or chlorpromazine may be considered. Provided that it is used under the right circumstances, palliative sedation does not shorten life.

Humans↗

PubMedDate not supplied

Direct effects of neuroleptics on the activity of CYP2A in the liver of rats.

The aim of the present study was to investigate the influence of classic and atypical neuroleptics on the activity of rat CYP2A measured as a rate of testosterone 7alpha-hydroxylation. The reaction was studied in control liver microsomes in the presence of neuroleptics, as well as in microsomes of rats treated intraperitoneally (i.p.) for one day or two weeks (twice a day) with pharmacological doses (mg/kg) of the drugs (promazine, levomepromazine, thioridazine, perazine 10, chlorpromazine, haloperidol 0.3, risperidone 0.1, sertindole 0.05), in the absence of the neuroleptics in vitro. Most of the neuroleptics added in vitro to control liver microsomes decreased the activity of the rat CYP2A. Chlorpromazine (Ki = 11 microM) was the most potent inhibitor of the rat CYP2A among the studied drugs, whose effect was more pronounced than that of the other tested phenothiazines (Ki = 41-83 microM), haloperidol (Ki = 190 microM) or sertindole (Ki = 78 microM). Risperidone was not active in this respect. The investigated neuroleptics when given to rats in vivo for one day or two weeks--did not produce any indirect inhibitory effect on CYP2A via other mechanisms. The obtained results show direct inhibitory effects of phenothiazine neuroleptics on the activity of CYP2A in rat liver, which may be of physiological importance for the metabolism of testosterone, considering simultaneous inhibition of CYP2C11 and CYP3A by those drugs.

Animals↗

PubMedDate not supplied

Pharmacokinetic interaction between imipramine and antidepressant neuroleptics in rats.

Antidepressant neuroleptics, perazine (PZ), levomepromazine (LMZ) and flupenthixol (FPX) given to rats jointly with imipramine (IMI) for 2 weeks affected the plasma concentration of IMI only slightly but markedly elevated the concentration of its metabolite, desipramine (DMI). In the brain PZ significantly elevated both IMI and DMI concentrations while LMZ and FPX showed a tendency to increase the concentration of IMI and decrease the concentration of DMI. All three neuroleptics markedly decreased the DMI/IMI ratio in the brain and (except FPX) increased it in the plasma. Given alone for two weeks PZ, LMZ, FPX did not affect the levels of cytochromes P-450 and b-5 in liver microsomes. Chronic treatment with IMI significantly elevated the concentration of cytochrome P-450 in the liver and had a tendency to increase the concentration of cytochrome b-5. FPX, but not PZ or LMZ abolished this effect. Neuroleptics coadministered with IMI to rats did not affect the activity of the enzymes responsible for the IMI biotransformation as compared with IMI-treated animals. The neuroleptics added to the incubation mixture in vitro inhibited IMI hydroxylation noncompetitively. The demethylation was inhibited competitively by LMZ but noncompetitively by PZ and FPX. The inhibitory effect of neuroleptics on the hydroxylation was much more marked than that on the demethylation. FPX was the weakest inhibitor of IMI metabolism among the neuroleptics studied.

Administration, Oral↗