Psychotropic agents antipsychotics

Treatment discontinuation of several psychotropic agents has been proposed to increase the risk of recurrence of morbidity to a degree greater than would be predicted by the natural history of untreated illness this risk probably extends over several months. Evidence for this phenomenon is particularly strong with lithium in bipolar disorder, is likely with some antipsychotics, and may occur with antidepressants. Such risk may be reduced by gradual discontinuation of long-term medication over at least several weeks see Chapter 18). 

As can be seen in Table 4.2, many agents commonly co-prescribed with antipsychotics may act as inducers and inhibitors. That these agents are also prone to ethnically determined variations in their own metabolism, suggests that providing the optimal dose of antipsychotics in various ethnic groups may become complex where psychotropic polypharmacy is common. 

Some of the earliest studies of psychotropic medications in preschool-age children involved neuroleptics. In autism, antipsychotics are the most frequently used psychoactive agents for the reduction of stereotypies, temper tantrums, aggressiveness against self or others, and hyperactivity (Campbell et al., 1999). There are seven studies with preschoolers with a total subject number of 59. Each of these seven studies involved medication trials with preschool children diagnosed with autism or childhood schizophrenia (Table 49.5). Only one study was a randomized, double-blind, pla-... 

Important biological differences that potentially affect the metabolism of psychotropics have been described between Japanese and non-Asian children. For example, a pharmacogenetic ethnic difference was reported in cytochrome P450 (CYP) 2D6 metabolism of several antipsychotics and antidepressants, and in the CYP 2C19 metabolism of tricyclic agents. In adults, the rate of poor metabolizers of CYP 2D6 substrates is lower in Asians (about 1%) than in Caucasians (about 7%), while that of CYP 2C19 substrates is higher in Asians (15%-30%) than in Caucasians (3%-6%) (Poolsup et ah, 2000). Clinicians may need to keep these differences in mind when they use psychotropics in Japanese and other Asian patients, since such differences can lead to different behavioral responses or toxicity. 

The first psychotropics of the modern era (e.g., lithium, neuroleptic antipsychotics, tricyclic and monoamine oxidase inhibitor antidepressants) were discovered serendipitously. These agents were not engineered to have selective actions, but instead produce a wide range of central biochemical effects and generally affect more than one neurotransmitter system simultaneously, resulting in multiple repercussions ... 

Uremia Antihistamines Antiparkinsonian agents Antispasmodics Ophthalmic preparations OTC sleep/allergy medications Tricyclic antidepressants Other medications Analgesics/NS AIDs Anticonvulsants Corticosteroids (high dose) Digoxin H2 blockers Insulin Muscle relaxants Narcotics Psychotropics (anxiolytic, antidepressant, antipsychotic) Sedative/hypnotic Sulfonylurea... 

Risperidone is an antipsychotic agent. The compound is metabolized into two major metabolites, of which the 9-hydroxy analogue is biologically active and the 7-hydroxy analogue is not. Bioanalytical methods for risperidone should have a sub-ng/ml LOQ, discriminate between the 7- and 9-hydroxy metabolites, and should be selective towards other psychotropic drugs, which may be used simultaneously by patients. 

Li often is used in conjunction with antipsychotic, sedative, antidepressant, and anticonvulsant drugs. Case reports suggesting a risk of increased CNS toxicity when Li is combined with haloperidol are at variance with many years of experience with this combination. Antipsychotic drugs may prevent nausea, which can be an early sign of Li toxicity. There is no absolute contraindication to the concurrent use of LT and psychotropic drugs. Finally, anticholinergic and other agents that alter GI motility also may alter LT concentrations in blood over time. 

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