Antipsychotic medications drug interactions

Table 5-27 and Table 5-28 summarize the clinically relevant pharmacokinetic and pharmacodynamic properties of other novel antipsychotics ( 326). Drug interactions with these agents were not systematically evaluated because controlled clinical trials usually prohibit concurrent medications. There are also many special circumstances (e.g., patients with comorbid medical diseases, substance abuse, epilepsy, or atypical indications such as agitation associated with mental retardation or dementia) that are not usually addressed in clinical research trials. Thus, much remains to be learned about significant drug interactions in these patient groups. To our knowledge, however, no consistent, serious, clinically relevant interactions have been reported. 

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. 

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. 

Although drug interactions may occur through a variety of mechanisms, most occur because of pharmacodynamic or pharmacokinetic interactions. Common examples of pharmacodynamic interactions resulting in enhanced effect include the excess sedation that can occur when antipsychotics are used concomitantly with other medications that have sedative side effects (e.g., mood stabUizers, hypnotics, alcohol, antidepressants, anxiolytics, or antihistamines). 

I Drug-Drug Interactions. Carbamazepine induces the hepatic cytochrome P450 isoenzymes (1A2, 3A4, 2C9/10, and 2D6), which increases the metabolism of many medications, such as anticonvulsants (i.e., lamotrigine, topiramate, and valproate), antidepressants (i.e., tricyclics and bupropion), antipsychotics (i.e., clozapine, haloperi-dol, fluphenazine, olanzapine, and thiothixene), benzodiazepines, oral contraceptives, and protease inhibitors. " Women who receive carbamazepine require higher dosages of oral contraceptives or alternative contraceptive methods." ... 

Also note that the potential for an interaction between drugs does not preclude their concurrent use. Certain combinations are routinely prescribed without problems in many patients (as with lithium and antipsychotics), whereas others are contraindicated due to the severity of the interaction (for example, MAOIs and SSRIs). However, whenever psychiatric medications are coadministered, the additive potential of central nervous system depression and anticholinergic effects must be considered. 

Klonopin (clonazepam) A conunon medication used as a mood stabilizer often prescribed for the following reasons inadequate response or intolerance to antipsychotics or lithium, manic symptoms, rapid cycling of the condition, EEC abnormalities, and head trauma. The most common side effects are difficulty with balance and drowsiness. Behavioral and emotional side effects include irritability, excitement, increased anger and aggression, trouble sleeping or nightmares, and memory loss. The most serious side effect is the interaction effect if this medication is combined with alcohol or other drugs, which can result in sleepiness, unconsciousness, and death. 

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