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Haloperidol Decanoate

A Preliminary Review of Its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Use in Psychosis

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Summary

Synopsis

Haioperidol decanoate1is a depot preparation of haloperidol, a commonly used butyrophenone derivative with antipsychotic activity. Haloperidol decanoate has no intrinsic activity: its pharmacodynamic actions are those of haloperidol — primarily that of central antidopamine activity. The monthly administered depot formulation has several clinical and practical advantages over oral haloperidol: better compliance and more predictable absorption: more controlled plasma concentrations: fewer extrapyramidal side effects: less frequent reminders of condition; and reduced medical workload. In open and controlled studies, haloperidol decanoate has produced adequate maintenance or improvement of the condition of patients with psychoses (mainly schizophrenia) when an abrupt change from orally administered haloperidol or other antipsychotic drugs has been instituted. Limited comparative studies indicate that the depot and oral forms of haloperidol are equally effective, and that haloperidol decanoate is at least as effective as depot forms of fluphenazine, pipothiazine, flupenthixol and perphenazine in controlling the symptoms of psychosis. Extrapyramidal side effects and the need for concomitant anti-Parkinsonian drugs may be a problem, but may be less frequent than with oral haloperidol or other depot antipsychotics. Thus, haloperidol decanoate offers a useful alternative in the treatment of psychoses to orally administered haloperidol or to other depot antipsychotic drugs.

Pharmacodynamic Studies

Haloperidol decanoate is a depot form of haloperidol with no intrinsic activity. Its pharmacodynamic effects are those of haloperidol; it has a central antidopamine action, antagonising the effects of apomorphine and amphetamine and releasing prolactin. Dopamine turnover is also increased and dopamine metabolites accumulate. Glutamic acid decarboxylase activity in the substantia nigra is reduced (an event which may be associated with the production of tardive dyskinesia). Like haloperidol, haloperidol decanoate has little effect on the cardiovascular system or on the motility of smooth muscle.

Pharmacokinetic Studies

Haloperidol decanoate is injected in a sesame oil vehicle into muscle. It is then hydrolysed relatively slowly to haloperidol and decanoic acid. Peak plasma concentrations are not reached for 3 to 9 days and are proportional to the administered dose. Steadystate plasma concentrations are reached within 2 to 3 months (compared with 7 days for the oral preparation). The pharmacokinetic disposition appears to be essentially the same as that of oral haloperidol, which is approximately 92% bound to plasma proteins, crosses the blood-brain barrier and passes into the milk of nursing mothers. Haloperidol is metabolised mainly by oxidative dealkylation to inactive metabolites. The plasma elimination half-life of the depot preparation (about 3 weeks) is considerably longer than that of the oral form (about 24 hours).

Therapeutic Trials

Haloperidol is a widely used antipsychotic drug in the treatment of psychotic disorders. Haloperidol decanoate is a depot formulation of haloperidol, usually administered monthly, which has recently been used in the treatment of psychoses (mainly schizophrenia) in an attempt to minimise side effects and compliance problems while maintaining clinical efficacy. Open and controlled studies have shown that haloperidol decanoate is more effective than placebo, and at least as effective as oral haloperidol and a number of other depot antipsychotic agents, including fluphenazine decanoate, pipothiazine palmitate, flupenthixol decanoate and perphenazine enanthate. Symptoms of schizophrenia, such as emotional withdrawal, conceptual disorganisation, depression, paranoia, hallucinatory behaviour and catatonia, are well controlled and indeed may be improved in most patients even when previous medication, upon which they are usually stabilised, has been abruptly discontinued. Dose-ranging studies to determine the optimum dose for clinical efficacy and improved tolerance originally used a protocol of high initial doses (usually 20 times the previous daily oral haloperidol dose) which were reduced as necessary. Currently, initial doses are often lower (10 to 15 times the previous daily oral dose) and are increased if required.

Side Effects

The major unwanted effect of antipsychotic therapy, including haloperidol decanoate, is the production of extrapyramidal symptoms. The incidence and intensity of symptoms may be less with haloperidol decanoate than other antipsychotic drugs, especially when the dose is not too high. The concomitant use of anti-Parkinsonian drugs also tends to be less with the depot preparation. Other side effects reported with haloperidol decanoate, apart from 2 cases of neuroleptic malignant syndrome, have been mild and short-lived.

Dosage and Administration

Haloperidol decanoate is usually given as a monthly intramuscular injection. Although earlier investigators gave an initial dose which was 20 times the daily oral haloperidol dose, more recent investigations have tended to give a lower initial dose, often between 10 and 15 times the daily oral haloperidol dose (i.e. about 50 to 100mg). This may be increased during subsequent injections as required, and tends to maximise antipsychotic effects and minimise extrapyramidal effects.

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  1. ADIS Drug Information Services, Private Bag, Mairangi Bay, Auckland 10, New Zealand

    R. Beresford & Alan Ward

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  1. R. Beresford
  2. Alan Ward

Additional information

Various sections of the manuscript reviewed by:L.P. de C. Bechelli, Psychiatric Hospital of Ribeirao Preto, Ribeirao Preto, Brazil;G. Ghouinard, Clinical Psychopharmacology Unit, Royal Victoria Hospital, Montreal, Canada;L. Germain, Clinical Psychopharmacology Unit, Royal Victoria Hospital, Montreal, Canada;L.M. Gunne, Psychiatric Research Centre, Ullerater Hospital, Uppsala, Sweden;L.E. Hollister, Veterans Administration Medical Center, Palo Alto, California, USA;W. Kissling, Psychiatrische Klinik und Poliklinik rechts der Isar der Technischen Universität München, München, West Germany;M.H. Lader, Institute of Psychiatry, De Crespigny Park, London, England;G. Meco, Dipartimento di Scienze Neurologiche Università, Viale dell’Università, Roma, Italy;T.R. Norman, Department of Psychiatry, Austin Hospital, Heidelberg, Victoria, Australia;W. Rapp, Department of Forensic Psychiatry, Umeå, Sweden;R. Takahashi, Department of Neuropsychiatry, Tokyo Medical and Dental University, Tokyo, Japan;B. Wistedt, Department of Psychiatry, Karolinska Institutet, Danderyd, Hospital, Dan-deryd, Sweden;H.A. Youssef, Department of Psychiatry, St Davnet’s Hospital, Mon-aghan, Eire.

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