The interactions where effects of antipsychotic, anxiolytic and hypnotic drugs are affected are covered in this section but there are other monographs elsewhere in this publication where effects of other drugs are altered by a benzodiazepine or antipsychotic.
The antipsychotics are represented by chlorpromazine (and other phenothiazines), haloperidol (and other butyrophenones) and thioxanthenes, and atypical, or newer, antipsychotic drugs, such as clozapine and risperidone. Their major use is in treatment of psychoses such as schizophrenia and mania. These are listed in table 1 below,(below). Some of antipsychotics are also used as antiemetics, and for motor tics and hiccups.
The majority of interactions between older antipsychotics are pharmacodynamic, relating to their effect on dopamine, whilst several of newer atypical antipsychotics are metabolised to a significant extent by cytochrome P450 isoenzymes. The concurrent use of other drugs which are inhibitors or inducers of these isoenzymes may result in large changes in plasma levels. In particular, tobacco smoking and caffeine can have an effect on pharmacokinetics of some of these drugs, leading to adverse effects or lack of therapeutic effect following lifestyle changes.
The anxiolytics include benzodiazepines and related drugs, cloral hydrate and other drugs used to treat psychoneuroses such as anxiety and tension, and are intended to induce calm without causing drowsiness and sleep. Some of benzodiazepines and related drugs are also used as antiepileptics and hypnotics. table 1 below, (below) contains a list of benzodiazepines and related drugs. Many benzodiazepines undergo phase I metabolism by N-dealkylation and hydroxylation and many of metabolites are active. They may then undergo phase II conjugation,mainly to form glucuronides before being excreted. For example,diazepam is metabolised to nordazepam (desmethyldiazepam), temazepam and oxazepam. The metabolism of diazepam in liver is also mediated by cytochrome P450 isoenzymes, particularly CYP2C19, and diazepam is excreted mainly as free or conjugated metabolites.
The triazolo-and related benzodiazepines,such as alprazolam, midazolam and triazolam, are mainly metabolised by hydroxylation, mediated by CYP3A4, to active compounds, which then rapidly undergo glucuronide conjugation.
Benzodiazepines such as lorazepam,oxazepam and temazepam, which are mainly conjugated without prior phase I metabolism, are unlikely to be involved in interactions with inhibitors or inducers of cytochrome P450. Benzodiazepines themselves do not significantly induce cytochrome P450 isoenzymes,so interactions involving enhanced metabolism of other drugs are not usual.
Zaleplon,zolpidem and zopiclone are metabolised by several cytochrome CYP450 isoenzymes and it has been suggested that because of this, other drugs which affect a particular isoenzyme such as CYP3A4, may have less effect on their metabolism. However, their pharmacokinetics are affected by potent inducers such as rifampicin and by inhibitors such as azole antifungals. Buspirone undergoes CYP3A4-mediated metabolism in liver.
table 1 below Antipsychotics,anxiolytics, and hypnotics
Amisulpride,Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone, Sertindole, Ziprasidone, Zotepine
Butaperazine,Chlorpromazine, Fluphenazine, Levomepromazine, Mesoridazine, Pericyazine, Perphenazine, Prochlorperazine, Promazine, Thioridazine, Trifluoperazine
Benperidol,Bromperidol, Droperidol, Haloperidol
Chlorprothixene,Flupentixol, Tiotixene, Zuclopenthixol
Loxapine,Molindone, Pimozide, Sulpiride
Alprazolam,Bromazepam, Brotizolam, Chlordiazepoxide, Clobazam, Clonazepam, Clorazepate, Clotiazepam, Diazepam, Flunitrazepam, Flurazepam, Ketazolam, Loprazolam, Lorazepam, Lormetazepam, Medazepam, Midazolam, Nitrazepam, Oxazepam, Oxazolam, Quazepam, Temazepam, Triazolam
Buspirone,Clomethiazole, Cloral betaine, Cloral hydrate, Eszopiclone, Glutethimide, Hydroxyzine, Meprobamate, Promethazine, Triclofos, Zaleplon, Zolpidem, Zopiclone
| Table 1 Antipsychotics, anxiolytics, and hypnotics | |
|---|---|
| Group | Drugs |
| Antipsychotics | |
| Atypical antipsychotics | Amisulpride, Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone, Sertindole, Ziprasidone, Zotepine |
| Phenothiazines | Butaperazine, Chlorpromazine, Fluphenazine, Levomepromazine, Mesoridazine, Pericyazine, Perphenazine, Prochlorperazine, Promazine, Thioridazine, Trifluoperazine |
| Butyrophenones | Benperidol, Bromperidol, Droperidol, Haloperidol |
| Thioxanthenes | Chlorprothixene, Flupentixol, Tiotixene, Zuclopenthixol |
| Miscellaneous | Loxapine, Molindone, Pimozide, Sulpiride |
| Anxiolytics and hypnotics | |
| Benzodiazepines | Alprazolam, Bromazepam, Brotizolam, Chlordiazepoxide, Clobazam, Clonazepam, Clorazepate, Clotiazepam, Diazepam, Flunitrazepam, Flurazepam, Ketazolam, Loprazolam, Lorazepam, Lormetazepam, Medazepam, Midazolam, Nitrazepam, Oxazepam, Oxazolam, Quazepam, Temazepam, Triazolam |
| Miscellaneous | Buspirone, Clomethiazole, Cloral betaine, Cloral hydrate, Eszopiclone, Glutethimide, Hydroxyzine, Meprobamate, Promethazine, Triclofos, Zaleplon, Zolpidem, Zopiclone |
| Table 2 Antipsychotics, anxiolytics, and hypnotics | |
|---|---|
| Group | Drugs |
| Antipsychotics | |
| Atypical antipsychotics | Amisulpride, Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone, Sertindole, Ziprasidone, Zotepine |
| Phenothiazines | Butaperazine, Chlorpromazine, Fluphenazine, Levomepromazine, Mesoridazine, Pericyazine, Perphenazine, Prochlorperazine, Promazine, Thioridazine, Trifluoperazine |
| Butyrophenones | Benperidol, Bromperidol, Droperidol, Haloperidol |
| Thioxanthenes | Chlorprothixene, Flupentixol, Tiotixene, Zuclopenthixol |
| Miscellaneous | Loxapine, Molindone, Pimozide, Sulpiride |
| Anxiolytics and hypnotics | |
| Benzodiazepines | Alprazolam, Bromazepam, Brotizolam, Chlordiazepoxide, Clobazam, Clonazepam, Clorazepate, Clotiazepam, Diazepam, Flunitrazepam, Flurazepam, Ketazolam, Loprazolam, Lorazepam, Lormetazepam, Medazepam, Midazolam, Nitrazepam, Oxazepam, Oxazolam, Quazepam, Temazepam, Triazolam |
| Miscellaneous | Buspirone, Clomethiazole, Cloral betaine, Cloral hydrate, Eszopiclone, Glutethimide, Hydroxyzine, Meprobamate, Promethazine, Triclofos, Zaleplon, Zolpidem, Zopiclone |
| Table 3 Antipsychotics, anxiolytics, and hypnotics | |
|---|---|
| Group | Drugs |
| Antipsychotics | |
| Atypical antipsychotics | Amisulpride, Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone, Sertindole, Ziprasidone, Zotepine |
| Phenothiazines | Butaperazine, Chlorpromazine, Fluphenazine, Levomepromazine, Mesoridazine, Pericyazine, Perphenazine, Prochlorperazine, Promazine, Thioridazine, Trifluoperazine |
| Butyrophenones | Benperidol, Bromperidol, Droperidol, Haloperidol |
| Thioxanthenes | Chlorprothixene, Flupentixol, Tiotixene, Zuclopenthixol |
| Miscellaneous | Loxapine, Molindone, Pimozide, Sulpiride |
| Anxiolytics and hypnotics | |
| Benzodiazepines | Alprazolam, Bromazepam, Brotizolam, Chlordiazepoxide, Clobazam, Clonazepam, Clorazepate, Clotiazepam, Diazepam, Flunitrazepam, Flurazepam, Ketazolam, Loprazolam, Lorazepam, Lormetazepam, Medazepam, Midazolam, Nitrazepam, Oxazepam, Oxazolam, Quazepam, Temazepam, Triazolam |
| Miscellaneous | Buspirone, Clomethiazole, Cloral betaine, Cloral hydrate, Eszopiclone, Glutethimide, Hydroxyzine, Meprobamate, Promethazine, Triclofos, Zaleplon, Zolpidem, Zopiclone |