Finally, this book is intended to be genuinely helpful for practitioners of psychopharmacology by providing them with the mixture of facts and opinions selected by the author. Ultimately, prescribing choices are the reader’s responsibility. Every effort has been made in preparing this book to provide accurate and up-to-date information in accord with accepted standards and practice at the time of publication. Nevertheless, the psychopharmacology field is evolving rapidly and the author and publisher make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. Furthermore, the author and publisher disclaim any responsibility for the continued currency of this information and disclaim all liability for any and all damages, including direct or consequential damages, resulting from the use of information contained in this book. Doctors recommending and patients using these drugs are strongly advised to pay careful attention to, and consult information provided by, the manufacturer.
In pharmacokinetic studies, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with drugs characterized as substrates or inhibitors of CYP3A4 or CYP2D6 isoenzymes, such as itraconazole, nefazodone, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, sertraline, chlorpromazine, and promethazine.
When prolonged treatment (1 to 2 weeks) with enzyme-inducing drugs such as rifampin or carbamazepine is added to haloperidol therapy, this results in a significant reduction of haloperidol plasma levels.
In a study of 12 schizophrenic patients coadministered oral haloperidol and rifampin, plasma haloperidol levels were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale were increased from baseline. In 5 other schizophrenic patients treated with oral haloperidol and rifampin, discontinuation of rifampin produced a mean -fold increase in haloperidol concentrations.
In a study in 11 schizophrenic patients co-administered haloperidol and increasing doses of carbamazepine, haloperidol plasma concentrations decreased linearly with increasing carbamazepine concentrations.
Thus, careful monitoring of clinical status is warranted when enzyme inducing drugs such as rifampin or carbamazepine are administered or discontinued in haloperidol-treated patients. During combination treatment, the haloperidol dose should be adjusted, when necessary. After discontinuation of such drugs, it may be necessary to reduce the dosage of haloperidol.
Sodium valproate, a drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations.
Haloperidol is a typical butyrophenone type antipsychotic that exhibits high affinity dopamine D 2 receptor antagonism and slow receptor dissociation kinetics.  It has effects similar to the phenothiazines .  The drug binds preferentially to D 2 and α 1 receptors at low dose (ED 50 = and mg/kg, respectively), and 5-HT 2 receptors at a higher dose (ED 50 = mg/kg). Given that antagonism of D 2 receptors is more beneficial on the positive symptoms of schizophrenia and antagonism of 5-HT 2 receptors on the negative symptoms, this characteristic underlies haloperidol's greater effect on delusions, hallucinations and other manifestations of psychosis.  Haloperidol's negligible affinity for histamine H 1 receptors and muscarinic M 1 acetylcholine receptors yields an antipsychotic with a lower incidence of sedation, weight gain, and orthostatic hypotension though having higher rates of treatment emergent extrapyramidal symptoms .