Psychotropics interaction

Sandson NB, Armstrong SC, Cozza KL. An overview of psychotropic drug-drug interactions. Psychosomatics 2005 46 464M94. 

Ethnic differences have been shown to influence response to psychotropic medications. Much of the focus on the explanation for such differences has been on drug-metabolizing (CYP) enzymes of the liver and their sway over pharmacokinetic factors. It is now well recognized that differences in the distribution of polymorphic variants of CYP enzymes exist between different ethnic groups. However, within ethnic groups there are considerable inter-individual variations in drug kinetics, which may not be accounted for solely by genetic variation. Responses to pharmacotherapy are multifaceted and involve the interaction of environmental and... 

Eldefrawi, A. T., Miller, E. R., Murphy, D. L., and Eldefrawi, M. E. (1982) (3H)Phencyclidine interactions with the nicotinic acetylcholine receptor channel and its inhibition by psychotropic, antipsychotic, opiate, antidepressant, antibiotic, antiviral and antiarrhythmic drugs. Mol. Pharmacol., 22 72-81. 

What Is a Side Effect This chapter picks up where Chapters 1 and 2 left off. As we discussed in the earlier chapters, all medications, psychiatric and otherwise, have multiple effects. One takes a medication to achieve a therapeutic effect. Occasionally, a single medication may have more than one therapeutic effect. All other effects are side effects. Different medications may have differing therapeutic and side effects depending on the intended use. For example, trazodone and quetiapine are often prescribed to aid in sleep, and in this instance sedation is the desired effect, yet when used as an antidepressant and antipsychotic, respectively, the sedation is often an unwanted effect. Psychotropic medications typically have multiple effects. First, they usually interact with more than one nerve cell protein, be it a transporter or a receptor. Quite often, one of the medication s receptor or transporter interactions produces the therapeutic effect. The other interactions tend to not be involved in the therapeutic effect and only serve to produce side effects. Sometimes a neurotransmitter will have multiple different receptor types, but the medication interacts with... 

As we move forward with our discussion, we ll devote a section of this chapter to each of the key neurotransmitter systems that psychotropic medications interact with. We will discuss the following systems norepinephrine, dopamine, serotonin, GABA, acetylcholine, and histamine. Within each of the sections is a description of the effects that can be anticipated when a medication enhances the activity of that transmitter (reuptake inhibitors or agonists), and the effects to expect when a medication interferes (receptor antagonists) with the activity of that same transmitter. We will then describe strategies that can be implemented to help minimize and/or manage these side effects. 

Ensuring that other drugs or treatments are not administered which may interact with the psychotropic drug under investigation (e.g. lithium, electroconvulsive therapy). 

A summary of the main classes of psychotropic drugs metabolized by the P450 enzymes, together with some of the drugs of other classes with which they may interact, is given in Table 3.3. 

Hopefully these few examples will serve to emphasize the importance of a knowledge of the pharmacokinetic features of psychotropic drugs in order to avoid the potentially serious side effects that can result from drug interactions. 

Despite the limited value of measuring plasma psychotropic drug concentrations to assess clinical response, a knowledge of the pharmacokinetics of such a drug can be of value in predicting drug interactions. 

The decision to use a psychotropic drug must take into account the potential risks and benefits. This should be discussed with the patient and/ or carer. Before prescribing, a full evaluation of the symptoms should be made and the diagnosis confirmed. Polypharmacy should be avoided. If a drug combination is necessary, the pharmacod)mamic and pharmacokinetic interactions should be considered. 

Changes in the activity of adenosine receptors have been implicated in the stimulant effects of drugs like caffeine. Carbamazepine exhibits a partial agonist effect on adenosine receptors, and experimental evidence suggests that the reduced reuptake and release of noradrenaline caused by the drug are due to its interaction with these receptors. The precise relevance of these findings to its anticonvulsant and psychotropic effects is presently unclear. 

Gex-Fabry, M., Balant-Gorgia, A.E., and Balant, L.P. (1997) Therapeutic drug monitoring databases for postmarketing surveillance of drug-drug interactions evaluation of a paired approach for psychotropic medication. Ther Drug Monit 19 1-10. 

Any attempt to memorize hundreds of potential drug interactions to prevent dangerous interactions is unproductive. Rather, a child psychiatrist should have a basic understanding of the types and timing of possible drug interactions and then develop prevention strategies in prescribing psychotropics. These may include... 

For most child psychiatrists, the drug interactions most frequently encountered are interactions with other psychotropics. Fluoxetine inhibits the CYP3A isozymes and thus increase the plasma concentration of the tria-zolobenzodiazepines (alprazolam, midazolam, and triazolam), causing increased psychomotor effects (Shader and Greenblatt, 1995). To avoid unwanted psychomotor effects, the dosage of alprazolam should be decreased when it is coadministered with fluoxetine (Chouinard et ah, 1999). Nefazadone has also been shown to increase the pharmacodynamic effects of triazolam and, to a lesser extent, alprazolam (Chouinard et ah, 1999). 

Significant medical conditions, including head trauma, metabolic disorders, and neurologic conditions, should be identified. Eating and sleeping patterns are important to identify over time to know if these relate to the present condition and to know if medications affected them. Information about potential drug sensitivities or interactions may be obtained from a medication history that includes antibiotics commonly used, cold preparations, vitamins, health supplements, and present and past psychotropic medications. It is important to find out about previous medication trials what was tried, what worked, what did not work, and why. 

Donovan et al. (1996, 1997) completed an open study evaluating the use of valproic acid (Depakote) in adolescent outpatients with marijuana abuse or dependence and explosive mood disorder (mood symptoms were not classified using the DSM FV Diagnostic System). Eight subjects were prescribed 1000 mg of valproic acid (Depakote) for 5 weeks, in addition to regular therapy sessions, but did not receive any other psychotropic medications. All subjects showed a significant improvement in their marijuana use (p <0.007) and their affective symptoms (p < 0.001), although both outcomes were measured only by self-report. The most common adverse events were nausea and sedation. No subjects discontinued because of these side effects, nor were there any reported interactions between the valproic acid (Depakote) and substances of abuse. 

Pemoline (Cylert), (112.5 to 185.5 mg) was assessed in a 3-week open trial in 15 adolescents with CD, ADHD, and SUD (Riggs et ah, 1996). Three of the subjects were receiving other psychotropic medications (clonidine (Catapres) and paroxetine [Paxil]). All subjects had a significant improvement in ADHD symptoms (p <0.002) while 10/13 reported that the pemoline (Cylert) assisted in their substance rehabilitation. No subjects developed a significant elevation in their liver function tests, nor did any subjects test positive for substances of abuse for the duration of the study. No interactions between pemoline (Cylert) and any substances of abuse were reported. 

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