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Chlorprothixene

Chlorprothixene is a typical antipsychotic drug of the thioxanthine class. It has a low antipsychotic potency (half to 2/3 of chlorpromazine). Its principal indications are the treatment of psychotic disorders (e.g. schizophrenia) and of acute mania occurring as part of bipolar disorders. more...

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The drug was introduced 1959 to the market on a global scale and is hence a first generation antipsychotic with 45+ years of clinical experience. It is still today of clinical and also some research interest.

Mechanisms of Action

Chlorprothixene exerts strong blocking effects at the following postsynaptic receptors:

  • 5-HT2 : anxiolysis, antipsychotic effects
  • D1, D2, D3 : antipsychotic effects
  • H1 : sedation, weight gain
  • muscarinic : anticholinergic side-effects, extrapyramidal side-effects attenuated
  • Alpha1 : hypotension, tachycardia

Uses

Other uses are pre- and postoperative states with anxiety and insomnia, severe nausea / emesis (in hospitalized patients), the amelioration of anxiety and agitation linked due to use of selective serotonin reuptake inhibitors for depression and, off-label, the amelioration of alcohol and opioid withdrawal. It may also be used cautiously to treat nonpsychotic irritability, aggression, and insomnia in pediatric patients.

An intrinsic antidepressant effect of chlorprothixene has been discussed, but not proven yet. Likewise, it is unclear, if chlorprothixene has genuine (intrinsic) analgesic effects. However, Chlorprothixene can be used as comedication in severe chronic pain. An antiemetic effect, as with most antipsychotics, exists.

Side-effects

Chlorprothixene has a strong sedative activity with a high incidence of anticholinergic side-effects. The types of side effects encountered (dry mouth, massive hypotension and tachycardia, hyperhidrosis, substantial weight gain etc.) normally do not allow a full effective dose for the remission of psychotic disorders to be given. So cotreatment with another, more potent, antipsychotic agent is needed.

Chlorprothixene is structurally related to chlorpromazine, with which it shares in principal all side effects. Allergic side-effects and liver damage seem to appear with an appreciable lower frequency. The elderly are particularly sensitive to anticholinergic side-effects of chlorprothixene (precipitation of narrow angle glaucoma, severe obstipation, difficulities in urinating, confusional and delirant states). In patients >60 years the doses should be particularly low.

Early and late extrapyramidal side-effects may occur but have been noted with a low frequency (one study with a great number of participants has delivered a total number of only 1%).

Dosage

In any case, the initial doses of chlorprothixene should be as low as possible (e.g. 30mg at bedtime, 15mg morning dose) and be increased gradually. Patients receiving 90mg daily (and more) of the drug should be hospitalized, particularly during the initial phase of treatment. The theoretical maximum is 800mg daily which can usually not been given due to side-effects as stated above. Elderly and pediatric patients should be treated with particular low initial doses. Dose increments should be done slowly.

Read more at Wikipedia.org


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Antipsychotic use and cardiac events
From American Family Physician, 11/15/05 by Karl E. Miller

Patients treated with some antipsychotic medications have been shown to be at increased risk for ventricular arrhythmias, cardiac arrest, and sudden death. This includes patients with schizophrenia who are treated with thioridazine (Mellaril), haloperidol (Haldol), and other conventional antipsychotics (see accompanying table). This increased risk has been attributed to the QT-prolonging properties of conventional antipsychotics. The newer atypical antipsychotics may be more effective in the treatment of negative symptoms in schizophrenia, and they may have a lower risk of extrapyramidal side effects and tardive dyskinesia compared with conventional antipsychotics. Because of this improved side effect profile, the use of atypical antipsychotics has increased. The effects of atypical antipsychotics on cardiac events and sudden death has not been established. Liperoti and associates performed a case-control study to compare the effects of conventional and atypical antipsychotics on the risk of hospitalization for ventricular arrhythmias or cardiac arrest among older patients.

The authors collected data from the Systematic Assessment of Geriatric Drug Use via Epidemiology database for patients at Medicaid- and Medicare-certified nursing homes in six states. This information is linked to the Medicare inpatient claim files. Patients were included in the study if they had a primary diagnosis of cardiac arrest or ventricular arrhythmia. A control group consisting of residents in the same facilities was selected from the database.

A total of 649 patients had used antipsychotic medication within seven days of admission, and 2,962 patients were included in the control group. The use of conventional antipsychotics was associated with an increased risk of hospitalizations for cardiac arrest or ventricular arrhythmias (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.27 to 2.74). The use of atypical antipsychotics was not associated with an increased risk for hospitalization. Patients with cardiac disease who took conventional antipsychotics were at increased risk of hospitalizations for ventricular arrhythmias compared with the control group (OR, 3.27; 95% CI, 1.95 to 5.47). The synergy index for this data was 1.19, indicating that there was no interaction between conventional antipsychotic use and preexisting cardiac disease.

The authors conclude that the use of conventional antipsychotic medications is associated with an increased risk of hospitalizations for cardiac arrest and ventricular arrhythmias, and that atypical antipsychotics are not associated with increased risk. They add that the use of conventional antipsychotics should be avoided, if possible, in patients with cardiac disease.

KARL E. MILLER, M.D. Liperoti R, et al. Conventional and atypical antipsychotics and the risk of hospitalization for ventricular arrhythmias or cardiac arrest. Arch Intern Med March 28, 2005;165:696-701.

Antipsychotic Medications

Atypical

Clozapine (Clozaril) Olanzapine (Zyprexa) Quetiapine (Seroquel) Risperidone (Risperdal)

Conventional

Chlorpromazine (Thorazine) Chlorprothixene (Taractan) Fluphenazine (Prolixin) Haloperidol (Haldol) Loxapine (Loxitane) Molindone (Moban) Perphenazine (Trilafon) Promazine * Thioridazine (Mellaril) Thiothixene (Navane) Trifluoperazine (Stelazine)

*--Not available in the United States.

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2006 Gale Group

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