Antidepressants Asians

CYP2C19 is another example of the existence of both cross-ethnic and inter-individual variations in drug metabolism. This enzyme is involved in the metabolism of many psychotropics such as diazepam and tertiary tricyclic antidepressants, as well as one of the selective serotonin re-uptake inhibitors (SSRIs), citalopram. Using S-mephenytoin as the probe, previous studies showed that up to 20% of East Asians (Chinese, Japanese, and Koreans) are PMs, when only 3-5%... 

Non-compliance issues appear more prevalent in some non-Western cultures. One study in South Africa revealed non-compliance rates to oral neuroleptics in two-thirds of Black patients and one-half of colored patients compared to only one-quarter of Caucasians (Gillis.Trollip, Jakoet etal., 1987). Cultural and communication factors were considered to be significant barriers apart from those related to cost and social factors. Kinzie et al. (1987) reported that despite prescribing adequate doses of tricyclic antidepressants (TCAs) to depressed Asian refugees,... 

Kinzie, J. D., Leung, P., Boehnlein, J. K. Fleck, J. (1987). Antidepressant blood levels in Southeast Asians. Clinical and cultural implications. J. Nerv. Ment. Dis., 175(8), 480-5. 

Compared to antipsychotics, there are even fewer studies on the prescribing patterns of antidepressants done in Asian countries. Pi etal. (1985) conducted a survey of psychotropic prescribing practices reported by psychiatrists in 29 medical schools in 9 Asian countries. Daily dose range of tricyclic antidepressants (TCAs) such as amitriptyline, imipramine, and nortriptyline in Asian countries was comparable to the practice in USA. This is despite differences found between Asian and non-Asian populations in the pharmacokinetics of TCAs (Pi et al, 1993). A questionnaire on the practical prescribing approaches in mood disorders administered to 298 Japanese psychiatrists was reported by Oshima et al. (1999). As first-line treatment, the majority of respondents chose newer TCAs or non-TCAs for moderate depression and older TCAs for severe depression. Combination of antidepressants and anxiolytics was preferred in moderate depression, while an antidepressant and antipsychotic combination was common in severe psychotic depression. Surprisingly, sulpiride was the most favored drug for dysthymia. In a naturalistic, prospective follow-up of 95 patients with major depression in Japan, the proportion of patients receiving 125 mg/day or less of imipramine was 69% at one month and 67% at six months (Furukawa et al., 2000). 

Chinese depressed patients appeared to require lower dosages, with consequently lower plasma concentrations of sertraline compared to Caucasian patients to achieve clinical efficacy (Ng et al, 2006). Again, this finding has supported the fact that Asian patients, especially Chinese, need lower doses of antidepressant drugs than their Western counterparts. 

Pi, E. H., Wang, A. L. Gray, G. E. (1993). Asian/non-Asian transcultural tricyclic antidepressant psychopharmacology a review. Prog. Neuropsychopharmacol. Biol. Psychiatry, 17(5), 691-702. 

The ICD-10 is used in most European, and Asian, and African countries for clinical purposes however, most clinical and epidemiological research in Europe is based on the DSM-IV. To date, no pharmacological studies involving antidepressants, antipsy-chotics, or antianxiety agents have been based on ICD-10 criteria. 

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. 

Drugs that are metabolized by the cytochrome P-450 (CYP) isoenzymes CYP2D6, CYP2C9, and CYP2C19 also exhibit genetic polymorphisms. An example of CYP2D6 metabolism is debrisoquine. In about 5-10 /o of Caucasians in North America and Europe and about 1% of Asians, 4-hydroxylation of debrisoquine is reduced, and such individuals are at increased risk for toxicity (orthostatic hypotension). Beta blockers (metoprolol and timolol), antiarrhythmic drugs (encainide and flecainide), tricyclic antidepressants... 

Although you see many patients on meds, Harry s side effects seem extreme, and you place a call to his physician later in the day. She is appreciative of your call and agrees with your concerns. She decides to lower Harry s nortriptyline dose until she receives pending lab results of his nortriptyline level. She also shares with you information that indicates certain Asian populations may be unable to effectively metabolize tricyclic antidepressants and antipsychotics, necessitating lower than average doses. She promises to call you after further evaluation (Shimoda et al. 1993). 

A genetic factor in Asians causes an undesirable side effect when administered the standard dose of benzodiazepines (diazepam [Valium]) alprazolam [Xanax], tricyclic antidepressants, atropine, and propranolol [Inderal],... 

CYP2C19 Benzodiazepines diazepam Antidepressants imipramine, amitriptyline, clomipramine, citalopram Others propranolol, hexobarbital, mephobarbital, proguanil, omeprazole, S-mephenytoin 2 no activity 23%-39% in Asians 13% in Caucasians 25% in African Americans 3 no activity 6%-10% in Asians 0% in others... 

CYP2D6 Antidepressants amitriptyline, clomipramine, imipramine, desipramine, nortriptyline, trimipramine, N-desmethyl-clomipramine, fluoxetine, norfluoxetine, paroxetine, venlafaxine, sertraline Neuroleptics chlorpromazine, thioridazine, perphenazine, haloperidol, reduced haloperidol, risperidone, clozapine, sertindole Others codeine, opiate, propranolol, dextromethorphan 4 no activity 25% in Caucasians 0%-10% in others 5 no activity 2%-10% in all groups 10 reduced activity 47%-70% in Asians <5% in others 17 reduced activity 25%-40% in blacks 0% in others 2XN increased activity 19%-29% in Arabs and Ethiopians <5% in others... 

CYP2C19 (mephenytoin hydroxylase) is also associated with marked interethnic differences. This enzyme metabolizes diazepam and several antidepressants (Pi and Gray 1998). Between 2% and 10% of whites have little or no activity of this enzyme, whereas 15%-25% of Asians maybe PMs (Horaietal. 1989 Kupfer and Preisig 1984 Pi and Gray 1998). In addition, there is also evidence of polymorphism among EMs, with some Asian EMs having a form of the enzyme with less activity than that of the form commonly found in Caucasian EMs (Sjoqvist et al. 1997). 

There have been no pharmacokinetic studies of SSRIs and other newer antidepressants in which Asians and non-Asians were compared. Further research into the pharmacokinetics and pharmacodynamics of antidepressants, including these newer agents, among ethnic groups is necessary (Sramek and Pi 1996,1999). 

Kinzie JD, Leung P, Boehnlein JK, et al Antidepressant blood levels in Southeast Asians clinical and cultural implications. J Nerv Ment Dis 175 480-485,1987... 

In the fourth chapter, Drs. Edmond H. Pi and Gregory E. Gray review the pharmacokinetics, pharmacodynamics, and sociocultural influences on the psychotropic responses among Asian American populations. Particular consideration is given to anti-psychotics, antidepressants, benzodiazepines, and lithium. The authors stress the importance of prescribing the lowest possible effective dose, to minimize untoward side effects and thus ensure treatment compliance. 

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