Antipsychotic drugs interactions

Most antipsychotic drug interactions are relatively minor and often involve additive CNS, ACh, or sedative effects. 

Antipsychotic pharmacokinetics can be significantly affected by concomitantly administered enzyme inducers or inhibitors. Smoking is a potent inducer of hepatic enzymes and may increase antipsychotic clearance by as much as 50%. The published literature may be consulted for a listing of antipsychotic drug interactions. 

CofflerDE. Antipsychotic drug interaction. Drug Intell Clin Pharm 916) 10,114-15. 

List the uses, general drug actions, general adverse reactions, contraindications, precautions, and interactions associated with the administration of the antipsychotic drugs. 

TABLE 34-9. Metabolism and Drug Interactions with Antipsychotics... 

Drug Interactions Carbamazepine induces the hepatic metabolism of many drugs, including other antiepileptic drugs, antipsychotics, some antidepressants, oral contraceptives, and... 

Murray, M. (2006). Role of CYP pharmacogenetics and drug-drug interactions in the efficacy and safety of atypical and other antipsychotic agents. /. Pharm. Pharmacol, 58, 871— 85. 

On the other hand, the effects of two medications can counteract one another. The result is usually that both medications are rendered less effective. A common example is the patient with Parkinson s disease. On occasion, the L-DOPA that is the mainstay of treatment causes hallucinations. The treatment for hallucinations is an antipsychotic, which blocks the activity of dopamine. The problem is that using a typical antipsychotic to treat L-DOPA-induced hallucinations will interfere with the therapeutic effect of the L-DOPA, thereby worsening the symptoms of the Parkinson s disease. Fortunately, the advent of the newer atypical antipsychotics has provided a remedy to this particular Catch-22 drug interaction dilemma. 

It may be fair to ask, Is this much ado about nothing Although test tube studies have shown that particular drugs interact, it is seldom that this causes problems for patients taking the medications. For example, the antidepressant fluvoxamine inhibits the enzyme that deactivates the antipsychotic haloperidol (Haldol). Does this mean that fluvoxamine and haloperidol cannot be taken together By no means. Although this would probably raise the blood level of haloperidol somewhat, the main effect if any would be that a smaller dose of haloperidol would be more effective. 

Carbamazepine is also most beneficial for patients with mixed episodes and rapid cycling. However, many patients find the side effects of carbamazepine more troublesome than those of valproate, and becanse carbamazepine has a penchant for nntoward drug-drug interactions, we reserve the use of carbamazepine for those patients who are unable to tolerate valproate, lithium, and the atypical antipsychotic... 

See the Antipsychotic Agents monograph for drug interactions that relate to promethazine. 

There are some clinically important pharmacodynamic drug-drug interactions to be mentioned. Antipsychotics will potentiate the central depressant effects of sedatives and of alcohol. They will also increase the risk of respiratory-depressant effects of opiates. Inducers of drug metabolic enzymes like for example rifampicin and several antiepileptics, may increase the elimination rate of antipsychotic agents and thus decrease their efficacy. 

Tricyclic antidepressants are notorious for their risk to be involved in drug-drug interactions. Additive anticholinergic effects can be expected in combination with antihistamines, antipsychotics and anticholinergic-type anti-Parkinson agents. Hepatic enzyme-inducing agents increase their hepatic metabolism while enzyme inhibitors may potentiate the effects of tricyclics. Concomitant use with monoamine oxidase inhibitors will produce hypertension, hyperpyrexia and convulsions. 

Extrapyramidal side effects (EPS) associated with SSRI medications used as single agents were reported as early as 1979 (Meltzer et ah, 1979). Since then, several case reports have been published on use of fluoxetine (Elamilton and Opler, 1992), paroxetine (Nicholson, 1992), and sertraline (Opler 1994). The SSRI medications in combination with neuroleptics can cause severe EPS (Tate, 1989 Ketai, 1993) above and beyond what may be associated with increased levels of antipsychotic medications (Goff et ah, 1991), and are perhaps related to pharmacokinetic drug interactions. 

Numerous drug-drug interactions have been reported with the antipsychotic agents. These may be mediated through pharmacodynamic effects. For example, antipsychotics that block aj-adrenergic receptors may potentiate the antihypertensive effects of prazosin, labetalol, and some other antihypertensive agents. Conversely, antipsychotics associated with a2-adrenergic receptor blockade may interfere with the antihypertensive effects of clonidine and methyldopa (Richelson, 1999). 

Fang, J. and Gorrod, J.W (1999) Metabolism, pharmacogenetics, and metabolic drug-drug interactions of antipsychotic drugs. Cell Mol Neurobiol 19 491—510. 

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