Changes of Mental State and Serum Prolactin Levels in Patients with Schizophrenia and Depression after Receiving the Combination Therapy of Amisulpride and Chloroprothixol Tablets.

OBJECTIVE: To investigate the changes in mental state and serum prolactin levels in patients with schizophrenia and depression after receiving the combination therapy of amisulpride and chloroprothixol tablets. METHODS: A total of 148 schizophrenic patients with depression were randomly divided into control group (N = 73) and study group (N = 75). The control group was treated with clopidothiol, and the study group was treated with amisulpride. Symptom scores, sleep quality, adverse reactions, therapeutic effects, prolactin, and progesterone levels, HAMD, PANSS, and PSP scores were compared between the two groups. RESULTS: The symptom scores of both groups were significantly reduced, but when compared to the control group, the symptom scores of the research group were significantly reduced more significantly (P < 0.05); serum GDNF levels of both groups were significantly increased, while serum NSE, IL-1, and MBP levels were significantly reduced (P < 0.05). However, the research group altered more substantially (P < 0.05) than the control group; the overall PSQI score of the research group was lower (P < 0.05) than the control group; and the incidence of adverse responses in the control and study groups was 12.3 percent and 4.0 percent. The research group had a lower rate of adverse responses (P < 0.05) than the control group, and the effective treatment of the control and research groups was 82.2 percent and 98.7%, respectively. The research group had a lower rate of adverse reactions (P < 0.05) than the control group, while the control and research groups' successful treatment rates were 82.2 percent and 98.7%, respectively. When compared to the control group, the research group had a greater treatment efficiency (P < 0.05); blood prolactin and progesterone levels were considerably lowered in both groups, but the reductions in the research group were more evident (P < 0.05). Both groups had considerably lower HAMD and PANSS scores, and both had significantly higher PSP scores, although the difference in the research group was more evident (P < 0.05). CONCLUSION: For people with schizophrenia and depression, a combination of amisulpride and chloroprothixol pills has a considerable effect. It can help patients with their clinical symptoms and sleep quality while also lowering their serum prolactin levels, which is favorable to their illness recovery. As a result, the combined treatment of amisulpride and chloroprothixol pills deserves to be promoted and used.

Acepromazine and Chlorpromazine as Pharmaceutical-grade Alternatives to Chlorprothixene for Pupillary Light Reflex Imaging in Mice.

Studies of visual responses in isoflurane-anesthetized mice often use the sedative chlorprothixene to decrease the amount of isoflurane used because excessive isoflurane could adversely affect light-evoked responses. However, data are not available to justify the use of this nonpharmaceutical-grade chemical. The current study tested whether pharmaceutical-grade sedatives would be appropriate alternatives for imaging pupillary light reflexes. Male 15-wk-old mice were injected intraperitoneally with 1 mg/kg chlorprothixene, 5 mg/kg acepromazine, 10 mg/kg chlorpromazine, or saline. After anesthetic induction, anesthesia maintenance used 0.5% and 1% isoflurane for sedative- and saline-injected mice, respectively. A photostimulus (16.0 log photons cm-2 s-1; 470 nm) was presented to the right eye for 20 min, during which the left eye was imaged for consensual pupillary constriction and involuntary pupil drift. Time to immobilization, loss of righting reflex, physiologic parameters, gain of righting reflex, and degree of recovery were assessed also. The sedative groups were statistically indistinguishable for all measures. By contrast, pupillary drift occurred far more often in saline-treated mice than in the sedative groups. Furthermore, saline-treated mice took longer to reach maximal pupil constriction than all sedative groups and had lower heart rates compared with chlorpromazine- and chlorprothixene-sedated mice. Full recovery (as defined by purposeful movement, response to tactile stimuli, and full alertness) was not regularly achieved in any sedative group. In conclusion, at the doses tested, acepromazine and chlorpromazine are suitable pharmaceutical-grade alternatives to chlorprothixene for pupil imaging and conceivably other in vivo photoresponse measurements; however, given the lack of full recovery, lower dosages should be investigated further for use in survival procedures.

Intrathecal chlorprothixene, cis(z)-flupenthixol, chlorpromazine and fluphenazine for prolonged spinal blockades of sensory and motor functions in rats.

The aim of this study was to examine whether thioxanthine-type antipsychotics (chlorprothixene and cis(z)-flupenthixol) and phenothiazine-type antipsychotics (chlorpromazine and fluphenazine) produced spinal anesthesia. Using a rat model of intrathecal injection, we evaluated spinal anesthesia of antipsychotic drugs (chlorprothixene, cis(z)-flupenthixol, chlorpromazine, and fluphenazine) and bupivacaine, a known local anesthetic. At a same dose of 2.31 µmol/kg, chlorprothixene had the most potent spinal blockades (P<0.001) and the longest duration of action (P<0.001) of motor function and nociception among those antipsychotic drugs. On the 50% effective dose (ED(50)) basis, the ranks of potencies were chlorprothixene=bupivacaine>cis(z)-flupenthixol>chlorpromazine>fluphenazine (P<0.01 for the differences) in dose-response studies. At an equianesthetic basis (ED(25), ED(50), and ED(75)), the spinal block duration caused by chlorprothixene, cis(z)-flupenthixol, chlorpromazine or fluphenazine was longer than that caused by bupivacaine (P<0.05). These results showed that chlorprothixene produced a similar potency and longer duration of spinal anesthesia than did bupivacaine, whereas several other antipsychotics produced less potency than did bupivacaine.

Prescription persistence and safety of antipsychotic medication: a national registry-based 3-year follow-up.

PURPOSE: Long-term persistence of use, lack of co-prescribed anticholinergic antiparkinson drugs and low mortality may indicate effectiveness and safety of antipsychotic drugs. We aimed to assess 3-year prescription persistence, concomitant use of anticholinergics and mortality related to the use of all antipsychotic agents available in Norway. METHODS: Data were drawn from the Norwegian Prescription Database on the sales of antipsychotic and anticholinergic antiparkinson agents in 2004 to a total of 52,427 patients. The primary study group was a subgroup of 34,494 patients who were prescribed only one antipsychotic agent in 2004. The patients were re-investigated in 2007. For each of the 13 antipsychotic agents studied, assumed prescription persistence was assessed in light of use of anticholinergic antiparkinson agents in 2004, and casualty rates were noted. RESULTS: The highest persistence was demonstrated for zuclopenthixol (69.8%) and clozapine (88.4%). Zuclopenthixol was often co-prescribed with anticholinergics (22.2%), in contrast to clozapine (3.6%). Ziprasidone was associated with a low mortality (OR = 0.08), while chlorprotixene and haloperidol were associated with a high mortality (OR = 1.34 and 3.97, respectively) compared to levomepromazine. CONCLUSIONS: Clozapine demonstrated a high degree of continuity of prescription and a low level of concomitant use of anticholinergics. Zuclopenthixol also demonstrated a high degree of continuity of prescription, despite a considerable degree of co-prescribed anticholinergics. We did not find that any antipsychotic other than ziprasidone was associated with a low mortality. The use of haloperidol seemed to confer a mortality risk three times that of any of the other antipsychotic agents included.

Efficacy, tolerability, and preference of mirtazapine orally disintegrating tablets in depressed patients: a 17-week naturalistic study in Lithuania.

Mirtazapine is an established antidepressant with well-documented efficacy demonstrated in controlled clinical trials. However, the gap between the results obtained in controlled clinical trials and everyday clinical practice exists. Therefore, the importance of naturalistic studies in psychiatry is becoming recognized. The aim of present naturalistic study was to acquire data on efficacy, safety, and preference of mirtazapine orally disintegrating tablets during a 17-week treatment of depression. This prospective, open-label, multicenter study in patients with mild to severe depression was conducted at 47 mental health centers of Lithuania by 78 psychiatrists. Patients were initially given 15 mg or 30 mg of mirtazapine orally disintegrating tablets; the maximum allowed dose was 45 mg per day. The primary efficacy measure was the total score on the Hamilton Depression Rating Scale-17 (HAMD-17), the Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Improvement (CGI-I) scales. Tolerability was primarily measured by assessing the incidence of treatment-emergent adverse events. Patients were evaluated at baseline, at weeks 1, 5, 9, 13, and 17. A total of 779 patients (595 women [76.4%] with a mean [SD] age of 50.2 [13.65] and 184 men [23.6%] with a mean [SD] age of 52.4 [14.6] years) were enrolled into the study; 687 (88.2%) patients completed the study. The mean (SD) daily dose of mirtazapine orally disintegrating tablets was 29.0 (3.8) mg. The mean total (SD) HAMD-17 score improved significantly from 25.7 (4.6) to 7.3 (4.3) (P<0.005). At each visit, the mean HAMD-17 score was significantly lower than that at the preceding visit. At week 17, remission (HAMD-17 score < or =7) was observed in 436 (56%) patients. The mean (SD) CGI-S score improved significantly from 4.9 (1.0) at baseline to 1.5 (0.6) at endpoint (P<0.001). According to the CGI-I assessments, 621 patients (89.4%) improved and improved very much. The vast majority of patients (80%) preferred the new formulation of mirtazapine - mirtazapine orally disintegrating tablet. Treatment-emergent adverse events occurred in 106 patients (13.6%). The most frequent adverse events were weight gain, sedation, dizziness, and dry mouth. In this study conducted in Lithuania with depressed patients, a significant improvement was shown in all efficacy measures. In addition, mirtazapine orally disintegrating tablet was a well-tolerated and preferable formulation for the treatment of depressed patients.

In-patient psychiatric-psychotherapeutic treatment of mothers with a generalized anxiety disorder--does the co-admission of their children influence the treatment results? A prospective, controlled study.

INTRODUCTION: Whether women who are admitted together with their children achieve inpatient psychotherapeutic treatment results that differ significantly from the results for women who are admitted alone, is a subject of controversy. We compared both groups in a prospective, randomized, controlled study. METHODS: The monitored results of 29 female patients diagnosed with generalized anxiety disorder, 15 of whom were admitted with accompanying children and 14 without, were compared (response rate 95.3%). The period of observation amounted to six weeks. The System Checklist (SCL-90-R) and The Questionnaire of Changes in Experience and Behavior (VEV) were used as instruments of assessment. RESULTS: With respect to co-morbidity and socio-demographic data, both groups were initially comparable. During the course of six weeks' treatment, no statistically significant differences between the results for mothers with and mothers without accompanying children were measured in any of the tests we used, namely, the VEV (Difference = 0.3; 95%-CI [-5.4; 6.1]; p = 0.66) and the SCL-90-R, which includes the Global Severity Index (Difference = 4.0; 95%-CI [-1.4; 9.4]; p = 0.15), and the Anxiety Scale (Difference = 0.5; 95%-CI [-2.0; 1.0]; p = 0.63). CONCLUSION: The results indicate that mothers with generalized anxiety disorder who were accompanied by their children during in-patient psychotherapeutic treatment achieved treatment results that were just as good as mothers with the same diagnosis who were admitted without children.

Pharmacokinetic-pharmacodynamic modeling of tolerance to the prolactin-secreting effect of chlorprothixene after different modes of drug administration.

The objective of this study was the construction of a pharmacokinetic-pharmacodynamic model to describe the effects of chlorprothixene on prolactin secretion and the time-dependent alterations in the concentration-effect relationship due to tolerance development. Prolactin and chlorprothixene serum concentrations were determined in eight healthy men for up to 72 h after the intravenous and oral administration of chlorprothixene. An integrated pharmacokinetic model and a physiological indirect pharmacodynamic/tolerance model were applied to describe the prolactin-secreting effect of chlorprothixene. A three-compartment model served as pharmacokinetic model. The pharmacodynamic and tolerance model accounted for the baseline effect, the effect induced by the drug, and the regulatory mechanism that opposes the effect of the drug. This model adequately characterized the prolactin response after intravenous and oral drug administration of each individual by the sensitivity (dissociation constant), the efficacy (maximal prolactin secretion rate), the extent, and the rate of tolerance development. We speculate that this approach improves the quality of neuroendocrine challenge tests to determine the subject's sensitivity to drugs and the time course of adaptation.

Pharmacokinetics of chlorprothixene after single intravenous and oral administration of three galenic preparations.

The absolute and relative bioavailability of chlorprothixene (CAS 113-59-7, Truxal) was studied in eight healthy male volunteers with three different formulations: solution, suspension and coated tablet. An intravenous infusion and an oral aqueous solution served as references. Single doses of 100 mg were administered in a randomized complete-block design with washout periods of two weeks. Serum concentrations of chlorprothixene were assayed using a high-performance liquid chromatographic method with electrochemical detection. After a 1-h infusion period the maximum serum concentration (Cmax) of chlorprothixene was 430 +/- 81 ng/ml (mean +/- S.D.) and subsequently decreased with a terminal elimination half-life (t1/2) of 25.8 +/- 13.6 h. The total serum clearance (Cl) and the apparent volume of distribution at steady state (Vss) were 867 +/- 167 ml/min and 1035 +/- 356 l, respectively. The profiles of the chlorprothixene serum concentration vs. time and the resulting pharmacokinetic parameters were similar for all orally administered formulations. The absolute oral bioavailability of 17% of the solution indicated a marked presystemic metabolism. The bioavailability of chlorprothixene relative to the oral solution was 56.4% with the coated tablet and 67.7% with the suspension. All pharmacokinetic parameters showed wide inter-subject variations, partly attributable to the respective formulation.

ELISA screening with GC-MS confirmation of the tranquilizer chlorprothixene administered in subtherapeutic doses to horses.

A commercially available generic promazine ELISA kit is available which shows cross-reactivity for the tranquilizer chlorprothixene (CPT). The ELISA test readily detects the presence of CPT or its metabolites in equine urine for up to 24 h after the i.v. and i.m. administration of sub-therapeutic doses (4.5 mg) to three horses. Maximum concentrations (CPT equivalents) are obtained 2 h after i.v. dosing. No distinct concentration peak values are observed after i.m. administration. Following solid-phase extraction, confirmation of CPT and its metabolites by electron impact mass spectrometry after sub-therapeutic administration is not successful. The use of chemical ionization mass spectrometry however revealed the presence of at least four metabolites including; chlorprothixene sulphoxide, hydroxylated chlorprothixene and hydroxylated chlorprothixene sulphoxide.

[Malignant neuroleptic syndrome in a 15-year old girl after a single injection of a high-dose neuroleptic]. / Malignt neuroleptikasyndrom hos 15-årig pige efter enkelt injektion af højdosis-neuroleptika.

The malignant neuroleptic syndrome is a rare and fatal iatrogenic syndrome which requires rapid and effective symptomatic treatment in a somatic hospital, possibly in an intensive care unit. Relatively little medicine (neuroleptics) is employed in child psychiatry and the syndrome is, therefore, rare in child psychiatric departments. A well-defined syndrome is concerned and it is important to be able to recognise and diagnose this.

Anticonvulsants as adjuncts for the neuroleptic treatment of schizophrenic psychoses: a clinical study with beclamide.

A recent study showed an adjuvant effect of carbamazepine in the neuroleptic treatment of acute schizophrenic psychoses. Since beclamide (beta-chlorpropionamide) was reported to reduce the neuroleptic doses required, the combination haloperidol-beclamide was tested using a double-blind, placebo-controlled study in 23 inpatients with an acute schizophrenic psychosis. In both groups patients received haloperidol and either beclamide or placebo. Every 7 d the treating psychiatrist could increase the haloperidol dose by 3 mg per day if clinically necessary. Chlorprothixene and biperiden were on hand as additional medication. After 28 d beclamide or placebo were discontinued under a constant dose of haloperidol and a final rating with the Inpatient Multidimensional Rating Scale, Brief Psychiatric Rating Scale, and Extrapyramidal Symptom Scale was carried out. Without reaching statistical significance, the beclamide group needed a lower dose of neuroleptic medication, showed fewer side effects and a more pronounced psychopathological improvement.

Antidepressant combination therapy of endogenous depressions with benzodiazepines or neuroleptics--a study comparing adjuvant treatment with oxazolam versus chlorprothixene.

Antidepressants are routinely administered in combination with benzodiazepine tranquilizers or low-potency neuroleptics. A controlled study was conducted involving 40 endogenous depressive inpatients who were treated with maprotiline in combination with the benzodiazepine oxazolam or the neuroleptic chlorprothixene. After a period of two weeks there was no significant difference in the clinical ratings (HRSD, Bf-S, BL, CGI) of the two groups studied. Only in the factor "anxiety" and the adjective mood scale scores was there a tendency toward quicker onset of action (third day) in the patient group treated with oxazolam, though it was not statistically significant. The clinical global evaluation (efficacy, tolerability) showed more favorable ratings for oxazolam than for chlorprothixene. Both substances were generally tolerated well; oxazolam hardly ever caused any side effects. However, a slight deterioration of some patients' conditions was observed after discontinuation of oxazolam.

[Comparative clinical studies on parenteral and oral premedication in childhood with special regard to the volume and acidity of the gastric juice]. / Vergleichende klinische Untersuchungen zur parenteralen und oralen Prämedikation im Kindesalter unter besonderer Berücksichtigung der Magensaftmenge und Azidität.

90 children of age between 1 and 10 years who were scheduled for adenotomy were randomized into 3 premedication-groups. Group 1 received no premedication, group 2 chlorprothixene 1 mg/kg i.m. and group 3 chlorprothixene 2 mg/kg orally. Prior to induction of anaesthesia 63.3% of the unpremedicated children were anxious or crying, in contrast to 23.3% of the children given oral or i.m. premedication. With respect to the reaction on venepuncture with a Butterfly G 23, there was no significant difference between the groups. The volume of gastric acid (median values) was 0.056 ml/kg in group 1, 0.063 ml/kg in group 2, and 0.068 ml/kg in group 3, with a pH of 2.0, 1.5 and 2.0 respectively. One hour after operation 44.8% of the children in group 1, 92.6% in group 2 and 84.6% in group 3 were calm or sleeping. Premedication definitively improves the pre- and postoperative management of children. We now recommend oral chlorprothixene for the premedication of children because the effect of this oral premedication is equivalent to i.m. application, and the oral route has no influence on the quantity or acidity of gastric contents.

Clinical pharmacology and the prescription of psychotropic medication.

There are many reasons why once a day oral dosage may be advantageous in administration of psychotropic drugs to mental patients, such as convenience for the patient, avoided side effects, ease of remembering, all of which contribute to reliable dosage as well as cost savings. This paper illustrates cost data, pharmacokinetics of psychotropic drugs, and suggests a basis for determining adequate pill size for unit dosage. On a cost per milligram basis, there is economic savings if medication is prescribed in the largest size the patient can conveniently take. Pharmacological data support a rationale for higher unit dosage. They indicate a dose response relationship between dose and therapeutic effectiveness and probably a blood level relationship. The long half-life indicates that once-a-day medication is a reasonable dosage schedule. The most important evidence for once-a-day medication, however, is the empirical evidence that it works, and is safe. Dosage information from double blind investigations provides a basis for determining adequacy of pill size for antipsychotic therapy.