Chlorprothixene

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 (eg. 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.

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 post-operative 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 paediatric 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, 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 (eg. 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 be given due to side effects as stated above. Elderly and paediatric 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 100mg to 200mg
exogenic psychosis (eg. drug psychosis) 100mg to 200mg
acute mania 45mg to 150mg
agitated depressions 45mg to 150mg
alcohol- and drug-withdrawal 50mg to 150mg
non-psychotic agitation and anxiety 30mg to 150mg
acute reactive state to stress/trauma 30mg to 100mg
psychoneurotic states 30mg to 100mg
insomnia 15mg to 100mg
cotreatment of severe chronic pain 30mg daily initial, increasing to 60 or 90mg (max. 120mg)
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), ECG 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®.

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