[Intoxication of female patient with generalised cancer in hospital--a case report]. / Zatrucie pacjentki z uogólniona choroba nowotworowa w szpitalu--opis przypadku.

Medical errors are crucial factors influencing hospital mortality. We present a case of 79-year-old female, who was admitted to the hospital due to complications associated with advanced cancer disease. After several days of hospitalization, the woman died as a result of cancer as well as severe drugs intoxication. The investigation showed extremely high concentrations of chlorprothixen and tramadol in the. blood of the patient. This paper describes a number of medical errors made by hospital staff, of which the most significant was an inappropriate drugs policy.

Solvent dependence of the photophysical properties of 2-chlorothioxanthone, the principal photoproduct of chlorprothixene.

2-chlorothioxanthone (CTX) is used as photoinitiator for the reticulation of synthetic resins and for the preparation of pharmaceuticals. It was previously determined that CTX is the primary photoproduct of z-chlorprothixene (CPTX) when irradiated at 313 nm and is formed in an autocatalyzed reaction through an energy-transfer mechanism (Piñero et al. [2009] Photochem. Photobiol., 85, 895-900). In this work, the photophysical properties of CTX were measured in acetonitrile/water solutions to determine if their magnitude can affect the side effects of CPTX. The results show that CTX has higher absorption coefficients in the visible region (400-420 nm) and higher triplet quantum yields than its parent compound. Similar to TX, both properties strongly depend on the solvent polarity/hydroxylicity. The quantum yield of the triplet intermediate is very close to the value of the phenothiazine triplets. The phenothiazines are the most phototoxic antidepressants. Therefore, given the appropriate microenvironment, the photosensitization side effects of CPTX can be intensified on the production of CTX.

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.

Gamma-hydroxybutyrate versus chlorprothixene/phenobarbital sedation in children undergoing MRI studies.

BACKGROUND: Few clinical studies have assessed gamma-hydroxybutyrate and chlorprothixene/phenobarbital sedation in children. This prospective trial compared the two regimes in children, in particular concerning differences in recovery time. METHODS: 28 pediatric oncology patients undergoing elective MRI studies at a university hospital were randomly assigned to either receive gamma-hydroxybutyrate or chlorprothixene/phenobarbital sedation. Time to induce deep sedation (Ramsay score of 5) and recovery time, the incidence of failure of sedation, the frequency of side effects, the need for therapeutic interventions, and the number of patients receiving additional midazolam were recorded. Analysis of hemodynamic parameters was performed at five defined time points. RESULTS: All 28 MRI studies were successfully completed. Recovery time was significantly shorter with gamma-hydroxybutyrate (p < 0.01). There were more side effects with chlorprothixene/phenobarbital, in particular tachycardia and hyperexcitation. Vomiting was the side effect most often seen in gamma-hydroxybutyrate sedation. Therapeutic interventions were not required in any patient. Additional midazolam was necessary to maintain satisfactory sedation in six children receiving gamma-hydroxybutyrate and four receiving chlorprothixene/phenobarbital. CONCLUSIONS: Due to its significantly shorter recovery time, gamma-hydroxybutyrate is a reasonable sedative drug for children undergoing non-invasive diagnostic procedures, and is superior to chlorprothixene/phenobarbital. In pediatric oncology patients gamma-hydroxybutyrate appears to be associated more often with vomiting. The long recovery time and its great variability make chlorprothixene/phenobarbital a less valuable alternative.

Phototoxic properties of neuroleptic drugs.

BACKGROUND: Photo-induced eruptions are well-known adverse effects of some neuroleptic drugs, particularly chlorpromazine. OBJECTIVE: By a photohemolysis test we assessed in vitro the phototoxic properties of 12 phenothiazines (chlorpromazine, dixyrazine, fluphenazine, levomepromazine, perazine, perphenazine, promazine, promethazine, prothipendyl, thioridazine, trifluoperazine, triflupromazine) and 5 thioxanthenes (chlorprothixene, clopenthixol, flupenthixol, thiothixene, zuclopenthixol). METHODS: Human erythrocytes from 3 donors were incubated with the compounds and irradiated with light sources rich in UVA or UVB, respectively. Doses were up to 100 J/cm2 UVA or up to 1,600 mJ/cm2 UVB. Photo-induced hemolysis was calculated as percentage of complete hemolysis. RESULTS: Photo-induced hemolysis >10% due to radiation rich in UVA was found with chlorpromazine (maximal median: 98%), dixyrazine (100%), fluphenazine (84%), perazine (100%), perphenazine (100%), promazine (16%), promethazine (25%), prothipendyl (96%), trifluoperazine (100%), triflupromazine (76%), chlorprothixene (100%) and thiothixene (31%). UVB-rich radiation induced hemolysis only with chlorpromazine (73%), dixyrazine (45%) and perazine (60%). CONCLUSION: Most neuroleptics are strongly phototoxic in vitro indicating a potential risk for photo-induced reactions also to occur in patients treated with these drugs.

[Polytrauma and malignant neuroleptic syndrome. Case presentation with diagnostic problems]. / Polytrauma und malignes neuroleptisches Syndrom. Kasuistische Darstellung diagnostischer Probleme.

The neuroleptic malignant syndrome (NMS) is a rare but potentially fatal reaction associated with neuroleptic drugs. The role of an acute reduction in brain dopamine activity in the development of NMS is commonly accepted as underlying pathogenesis. The diagnosis is maintained by the classic findings of extrapyramidal signs, hyperthermia and autonomic dysfunction. Treatment consists primarily of early recognition and discontinuation of triggering drugs. We report on a young patient with an acute paranoid schizophrenia who suffered a severe polytrauma due to a jump from 10 m height initiated by acoustic hallucinations. The patient received haloperidol for psychotic symptoms in a dose of up to 65 mg/d and chlorprothixene. NMS developed during the second week after the polytrauma. Discontinuation of neuroleptic therapy was followed by complete recovery. The report underlines problems of diagnosis due to the ambiguity of the diagnostic criteria of neuroleptic malignant syndrome in the presence of polytrauma.

Polyneuropathy caused by chlorprothixene.

Seven chronic psychiatric patients developed signs of polyneuropathy mainly in the lower limbs after receiving chlorprothixene (500-1800 mg/d) from 3 to more than 24 months. The most prominent electroneuromyographic findings were decreased or not measurable motor conduction velocities of the peroneal nerves. Electromyography showed signs of denervation in the leg muscles in all the patients, and also in the upper limbs in 4 of them. The signs of polyneuropathy gradually subsided after withdrawal of chlorprothixene. Thus, chlorprothixene may cause a toxic, dose-dependent, reversible polyneuropathy.

[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.

A controlled comparative study of chlorprothixene vs. haloperidol in chronic schizophrenia.

Neurochemical distinctions have been made between neuroleptic drugs that affect D-1 receptors as well as D-2 receptors, compared with those neuroleptic drugs that affect only D-2 receptors. However, a controlled double-blind study of haloperidol vs. chlorprothixene in schizophrenic patients found no significant differences.

Bromazepam in generalized anxiety. Randomized, multi-practice comparisons with both chlorprothixene and placebo.

Bromazepam was compared with placebo and with chlorprothixene in a randomized, double-blind group-comparative multicenter trial in general practice. Two hundred and forty-five patients with generalized anxiety disorder (DSM-III 1980) were treated for 2 weeks with two daily doses of bromazepam, 3 mg or chlorprothixene, 15 mg or placebo. Median reductions in Hamilton Anxiety rating were 12 (bromazepam), 10.3 (chlorprothixene) and 7.3 (placebo). The study revealed significant superiority of bromazepam over placebo (median differences 3.3, 95% confidence limits: 0.3 and 6.1) but not over chlorprothixene (median difference 1.4, 95% confidence limits -0.8 and +3.5). Significantly higher rates of tiredness, sedation and hypersomnia were found on bromazepam and chlorprothixene compared to placebo. Tolerance was rated as "at least good" in 85.6% on bromazepam, in 86% on chlorprothixene and in 87.8% on placebo. Neither previous psychopharmacological treatment nor presence of psychosocial stress were of perceptible influence. Bromazepam and chlorprothixene are both superior to placebo in generalized anxiety states treated in general practice, but spontaneous improvements/placebo effects are substantial.

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.

Rebound insomnia in neuroleptic drug withdrawal neurophysiologic characteristics.

Rebound insomnia is one of the medical effects of reduction in dosage or discontinuation of neuroleptic drugs. The electrophysiologic features of sleep dysfunction are reported and discussed in 3 patients manifesting withdrawal-related DIMS. Electrographic anachronism and cyclic alternating pattern are signs of N-Rem sleep dysfunction. Clinical and neurophysiologic data suggest that rebound insomnia in neuroleptic withdrawal is due to an enhancement of physiologic mechanisms and rebound supersensitivity of cholinergic transmission in the ARAS.

Effect of different neuroleptics in tardive dyskinesia and parkinsonism. A video-controlled multicenter study with chlorprothixene, perphenazine, haloperidol and haloperidol + biperiden. Nordic Dyskinesia Study Group.

Thirty-three chronic psychiatric patients with tardive dyskinesia (TD) were included in a video-controlled multicenter study of the effect of chlorprothixene, perphenazine, haloperidol and haloperidol + biperiden in TD and parkinsonism. The drugs were given in a cross-over design in randomized order in dosages equipotent to the earlier neuroleptic treatment and administered for periods of 6 months with 6-week placebo periods before and after. A total of 55 treatment periods were completed; only seven patients were able to go through all three treatment phases (= 96 weeks). Perphenazine (20.5 mg/day), haloperidol (5.5 mg/day), and haloperidol (11 mg/day) + biperiden (7 mg/day) induced a moderate suppression of TD and at the same time produced a corresponding aggravation in parkinsonism. Chlorprothixene (142 mg/day) had only a slight TD reducing effect and did not change parkinsonism. Thus the TD suppressing effect was inversely related to the parkinsonian-inducing effect of the neuroleptics. Following withdrawal of the drugs, TD increased in some cases and decreased in others compared to the pretreatment level. No significant correlation was found between the intensity of the withdrawal TD and either drugs or preceding parkinsonism or TD suppression. Only in a subgroup of seven patients who consecutively received all three neuroleptics, perphenazine, but not haloperidol and chlorprothixene, produced a post-treatment aggravation which was correlated to the parkinsonsim and TD suppression during treatment. Independent of the neuroleptic given, the TD intensity increased significantly from the first to the third placebo period. This suggests that drug holidays are inappropriate to prevent TD induction/aggravation.