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...

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.

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