Chlorprothixene
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| Image:Chlorprothixene.png | |
| Chlorprothixene
| |
| Systematic (IUPAC) name | |
| 3-(2-chlorothioxanthen-9-ylidene)-N, N-dimethyl-propan-1-amine | |
| Identifiers | |
| CAS number | |
| ATC code | N05 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C18H18ClNS |
| Mol. mass | 315.861 g/mol |
| Pharmacokinetic data | |
| Bioavailability | incomplete |
| Metabolism | hepatic |
| Half life | 8 to 12 hours |
| Excretion | feces and urine |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status |
Rx-Only |
| Routes | oral (tablets, syrup, concentrate), intramuscular (seldom) |
Chlorprothixene is a typical antipsychotic drug of the thioxanthene 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.
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.
Contents |
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 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. Also, like most antipsychotics, chlorprothixene has antiemetic effects.
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, difficulties 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. 30 mg at bedtime, 15 mg morning dose) and be increased gradually. Patients receiving 90 mg daily (and more) of the drug should be hospitalized, particularly during the initial phase of treatment. The theoretical maximum is 800 mg daily which can usually not be 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.
On the right table are some guidelines given for daily dosages as follows (dependent on the clinical situation). Some reflect extended clinical experience from decades of usage.
| schizophrenia | 100 mg to 200 mg |
| exogenic psychosis (e.g. drug psychosis) | 100 mg to 200 mg |
| acute mania | 45 mg to 150 mg |
| agitated depressions | 45 mg to 150 mg |
| alcohol- and drug-withdrawal | 50 mg to 150 mg |
| non-psychotic agitation and anxiety | 30 mg to 150 mg |
| acute reactive state to stress/trauma | 30 mg to 100 mg |
| psychoneurotic states | 30 mg to 100 mg |
| insomnia | 15 mg to 100 mg |
| cotreatment of severe chronic pain | 30 mg daily initial, increasing to 60 or 90 mg (max. 120 mg) |
If chlorprothixene is to be withdrawn, it should not be stopped abruptly, but the dose should be decreased steadily.
Additional remarks
Chlorprothixene may be particularly useful in the clinical setting, when the patient is under strict control. Blood pressure (at least daily), EKG and standard laboratory (blood cell counts, liver and kidney tests) should be monitored/assessed in close intervals during therapy as good clinical practice dictates.
Important interactions
Chlorprothixene may increase the plasma-level of concomitantly given lithium. In order to avoid lithium intoxication, lithium plasma levels should be monitored closely.
If chlorprothixene is given concomitantly with opioids, the opioid dose should be reduced (by approx. 50%), because chlorprothixene amplifies the therapeutic actions and side effects of opioids considerably.
Avoid the concomitant use of chlorprothixene and tramadol (Ultram®). Massive seizures may be encountered with this combination.
Consider additive sedative effects and confusional states to emerge, if chlorprothixene is given with benzodiazepines or barbiturates. Choose particular low doses of these drugs.
Exert particular caution in combining chlorprothixene with other anticholinergic drugs (tricyclic antidepressants and antiparkinsonian agents): Particularly the elderly may develop delirium, high fever, severe obstipation, even ileus and glaucoma.
Trade names
Chlorprothixene is marketed under the brand names Taractan® and Truxal®.
See also
References
- PubChem Substance Summary: Chlorprothixene National Center for Biotechnology Information.
- Psychopharmakotherapie in Klinik und Praxis (German), Schattauer Verlag, 1998. ISBN 3-7945-1842-X
- Truxal Prescribing Information (PDF) Lundbeck Norge.
Psycholeptics: antipsychotics (N05A) | |
|---|---|
| Phenothiazine typical antipsychotics | Chlorpromazine • Fluphenazine • Mesoridazine • Perphenazine • Prochlorperazine • Promazine • Thioridazine/Sulforidazine • Trifluoperazine • Triflupromazine |
| Other typical antipsychotics | Indoles (Molindone) • Butyrophenones (Azaperone, Benperidol, Bromperidol, Droperidol, Haloperidol, Trifluperidol) • Thioxanthenes (Flupentixol, Chlorprothixene, Thiothixene, Zuclopenthixol) • diphenylbutylpiperidines (Fluspirilene, Penfluridol, Pimozide) • other (Loxapine) |
| Atypical antipsychotics | Butyrophenones (Melperone) • Indoles (Sertindole, Ziprasidone) • Benzamides (Sulpiride, Remoxipride, Amisulpride) • diazepines/oxazepines/thiazepines (Clozapine, Olanzapine, Quetiapine) • other (Aripiprazole, Risperidone, Paliperidone, Asenapine, Iloperidone, Zotepine) |
de:Chlorprothixen hu:Klórprotixénsv:Klorprotixen
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
