Methadone chemical structure
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Methadone

Methadone is a synthetic opioid analgesic synthesized in 1937 by German scientists Max Bockmühl and Gustav Ehrhart at IG Farben (Hoechst-Am-Main) who were searching for an analgesic that would be easier to use during surgery and also have low addiction potential. Methadone is a Schedule II drug under the Single Convention on Narcotic Drugs. more...

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On September 11, 1941 Bockmühl and Ehrhart filed an application for a patent for a synthetic substance they called Hoechst 10820 or polamidon and whose structure had no relation to morphine or the opioid alkaloids (Bockmühl and Ehrhart, 1949). Although chemically unlike morphine or heroin, methadone also acts on the opioid receptors and thus produces many of the same effects. Chemically, methadone is the simplest of the opioids.

Methadone was introduced into the United States in 1947 by Eli Lilly and Company as an analgesic (They gave it the trade name Dolophine® which is now registered to Roxane Laboratories). Since then, it has been best known for its use in treating narcotic addiction, though it is also used in managing chronic pain due to its long duration of action and very low cost. In late 2004, the cost of a one month supply of methadone is 20 USD, as compared to an equivalent analgesic amount of Demerol at 120 USD. The old name Dolophine comes from the German Dolphium. The name derives from the Latin "dolor" (pain).

Methadone (as Dolophine) was first manufactured in the USA by Mallinckrodt pharmaceuticals, a St. Louis-based subsidiary of the Tyco International corporation. Mallinckrodt held the patent up until the early 1990s. Today a number of pharmaceutical companies produce and distribute methadone. However, the major producer remains Mallinckrodt. Mallinckrodt sells bulk methadone to most of the producers of generic preparations and also distributes its own brand name product in the form of tablets, dispersable tablets and oral concentrate under the name "Methadose" in the United States. Generally, one will only hear "dolophine" used by older addicts who used the product in the 1960's and 1970's. Medical professionals who believe that dolophine is the generic name for methadone, when actually it is the reverse, may also use the old brand name.

Methadone has a slow metabolism and very high lipid solubility making it longer lasting than morphine-based drugs. Methadone has a typical half life of 24-48 hours, permitting the administration only once a day in heroin detoxification and maintenance programs. The most common mode of delivery at a Methadone clinic is in an oral solution. Methadone is almost as effective when administered orally as by injection. Just like heroin, tolerance and dependence frequently develop. Current research in this area shows methadone has a unique affinity for the NMDA brain receptor. Some researchers propose that NMDA (N-methyl-D-aspartic acid) may regulate psychic dependence and tolerance by exhibiting opioid antagonist-like activity. Withdrawal symptoms are generally less acutely severe than those of morphine and heroin at equivalent doses, but are significantly more prolonged. Considered generally effective in management of heroin addiction and harm reduction (reduction of HIV rates, etc...). At proper dosing, it reduces the appetite for heroin. However, some heroin addicts feel that it is actually harder to quit methadone than heroin itself. Treatment at a methadone maintenance clinic is intended to be for an indefinite duration, as the treatment is not curative.

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A psychometric study of the prevalence of DSM-IV personality disorders among office-based methadone maintenance patients
From American Journal of Drug and Alcohol Abuse, 8/1/04 by David Teplin

INTRODUCTION

The literature regarding co-occurring disorders reveals the notable role of Axis II personality disorders in the dual diagnoses of substance dependent individuals in general, and in opiate-dependent individuals in particular. It is arguable that personality disorders have a notable role based on the degree to which, and ways in which, the personality disorder is implicated in the etiology, the diagnosis, the treatment, and the prognosis of the co-occurring substance use disorders (1-8).

Substance dependence and personality disorders frequently exist in multiple forms, and personality disorders are highly prevalent comorbid conditions among addicted individuals (7,9). Rates vary from 50% (10,11) to 86% (12). Nace (11) theorizes that the most severe levels of substance abuse are associated with a character pathology rather than serious mental illness.

It also has been suggested that people with a personality disorder use substances for purposes related to the personality disorder, such as diminishing or managing the symptoms of the personality disorder, enhancing self-esteem, decreasing feelings of guilt, managing negative affect, and amplifying feelings of diminished individuality (13).

Substance abuse by individuals with a comorbid personality disorder has been considered an indication of a greater personality disturbance and predictor of a higher likelihood that there will be poor outcome of therapy and greater global impairment (1,6,14). There is the suggestion that individuals with a personality disorder are more vulnerable to substance abuse than are nonpersonality-disordered individuals and that they are more likely to engage in substance abuse at an earlier age and polydrug use with greater frequency than individuals without a personality disorder (11).

There are several societal, diagnostic, and treatment features that are common to both substance dependence and personality disorders. In the dually diagnosed individual these factors interact and mutually reinforce each other (9). In most cases the personality disorder is thought to precede the substance abuse. However, the substance abuse can trigger or worsen personality disorders, or produce a syndrome that is diagnostically compatible with personality disorders (13,15,16). Illicit substances can produce toxic effects on the brain and also reinforce regressive behavior, a combination that may result in a personality disorder secondary to substance dependence (16).

The personality characteristics most representative of this acquired "addictive personality" are narcissistic, antisocial, and histrionic characteristics (17). Such an addictive personality is marked by impulsivity, decreased frustration tolerance, self-centeredness, grandiosity, passivity, and affect intolerance (16,18).

There is the suggestion that when a personality disorder contributes to drug use, the pattern becomes more compulsive and rigid and more likely to continue to become a full-blown addiction (19). Richards (20) suggests that addiction is related to failures in self-regulation and notes that the most important mediator of self-regulation is the personality. Therefore, personality pathologies related to cognitive style, affective tolerance, activity, interpersonal style, and relationships all contribute to vulnerability to addiction (20).

It also has been shown that presence of personality disorders substantially increases the individual's risk of failure to achieve abstinence and to relapse. Moreover, these individuals have difficulty working cooperatively and collaboratively with service providers (5,9,14,19).

Personality pathology is thought to be especially common in opiate addicts, a finding that has been present in the literature for some time (21-26). Such studies have used psychometrically based self-report questionnaires [such as the Millon Clinical Multiaxial Inventory-III (MCMI-III)] or a structured clinical interview (such as the SCID) to define the presence of personality disorders in such populations.

Personality disorders in opiate addicts have been found to be heterogeneous (2,5,27). In general, there is also no single pattern of substance abuse or uniform choice of one drug (or even class of drugs) over the others for a given personality disorder, though there are many notable patterns (9,17).

Axis II, Cluster B personality disorders, that is, those characterized by dramatic, emotional, or erratic traits, appear to be common in dual disorders encountered in substance abuse treatment (8,28,29). Such Cluster B disorders include antisocial, borderline, narcissistic, and histrionic personality disorders (30). In particular, the antisocial and borderline personality disorders have been associated with a wide range of substance use disorders (6,24,25,27-29,31).

The prevalence of antisocial and borderline personality disorders has been reported to be particularly high in opiate dependent individuals, including those participating in methadone maintenance treatment programs (12,13,20,22,24,27,32-38). Lifetime prevalence rates for antisocial personality disorder have been reported to be as high as 69% in such populations (15).

This study sought to demonstrate the high prevalence of personality disorders that exist in an opiate-dependent population. It also hopes to demonstrate the heterogeneous nature of such disorders. High rates of antisocial and borderline personality disorders are also to be expected in such a population.

METHOD

Cases

Cases (N=38) were outpatients in an office-based methadone maintenance program in Canada who met the DSM-IV-TR (2000) (46) diagnostic criteria for opiate dependence. All cases had been referred for a clinical assessment to an experienced doctoral-level clinical psychologist in the program. All were maintained on a stabilized dose of opiate agonist medication (methadone). The cases were 100% Caucasian, men (60%), women (40%), with a mean age of 37.5 years. A total of 34% of the cases were married, 26% never married, 23% cohabiting, 11% divorced, and 6% separated. Three cases were excluded, as their MCMI-III profiles were psychometrically invalid.

Assessment of Personality Disorders

The Millon Clinical Multiaxial Inventory (MCMI-III), the foremost personality assessment instrument in use today, was used to diagnose Axis II personality disorders (39) The MCMI-III is a 175-item, psychometrically based, self-report questionnaire, with demonstrated reliability and validity (40-43). The MCMI-III consists of 28 scales, four of which are designed to measure validity and response style, 14 of which are designed to measure personality disorders, and 10 of which are designed to measure clinical syndromes. For the purposes of this study, we defined a base rate score above 84 as reflecting the presence of a personality disorder (39,42).

The MCMI-III personality disorder scales are divided into basic and severe pathology. The basic personality disorder scales include schizoid, avoidant, depressive, dependent, histrionic, narcissistic, antisocial, sadistic, compulsive, negativistic, and self-defeating personality disorders. The severe personality disorder scales include schizotypal, borderline, and paranoid personality disorders (42).

The MCMI-III personality disorder scales are consonant with the DSM-IV (30) personality disorders and include the depressive and negativistic (passive-aggressive) personality disorders, currently found in the DSM-IV (30). Research Criteria. The MCMI-III also includes the self-defeating and sadistic personality disorders, consonant with the DSM-III-R (44) personality disorders, and dropped in the DSM-IV (30,39).

RESULTS

Results demonstrated that 23% of patients had base rate scores of below 84, indicating that they did not meet the threshold for a personality disorder in this study. However, 77% did meet the study criteria (base rates of above 84) for at least one personality disorder. Of those who had a personality disorder, 20% had two personality disorders, 14% had three personality disorders, and 6% had four personality disorders.

Overall, depressive personality disorder was most commonly diagnosed (31%), followed by: dependent personality disorder (26%); masochistic (self-defeating) personality disorder (20%); antisocial personality disorder (17%); avoidant personality disorder (11%); schizoid and histrionic personality disorder (9%, respectively); borderline and sadistic personality disorder (6%, respectively); and narcissistic personality disorder (3%). It should be noted that the percentages add up to more than 100% because there is overlap among categories.

DISCUSSION

Our findings, which are consistent with the literature, report the presence of a high rate of personality disorders in an opiate-dependent population. Also. as is consistent with previous research, our study found the personality disorders to be heterogeneous in such a population. However, the lower prevalence rates of borderline and antisocial personality disorders than were reported in some previous studies were of some surprise.

Several alternative hypotheses may explain the divergence of our findings from some past findings. First among these is the possibility of false positive Axis II diagnoses of antisocial and borderline personality disorders on data gathered from structured clinical interviews. Substance abuse can produce a syndrome that is diagnostically compatible with personality disorders. Characteristics of such a syndrome include low frustration tolerance, affect intolerance, impulsivity, and self-centredness, all of which can mimic a borderline and/or antisocial personality presentation.

Since the criteria necessary to make personality diagnoses are often not clear, depend upon the perspective of the clinician, and change with time and changing situations (45), use of a structured clinical interview may impact accuracy of the diagnosis.

Furthermore, in the addiction population, antisocial personality disorder in particular is often misdiagnosed based on the substance abuse, dependence, and related behaviors (e.g., legal problems, interpersonal violence) rather than lifelong personality patterns (45). Clinician bias is avoided when administering a psychometrically based self-report questionnaire like the MCMI-III.

Alternatively, individuals seen at the clinic employed in this study, who were more florid and obvious in their borderline and/or antisocial personality diagnosis, may not have been referred for a clinical assessment to help tease out their Axis II diagnosis. This would serve as a kind of filtering process. excluding more straightforward personality diagnoses.

It is also possible that the MCMI-III taps into slightly different constructs, as far as borderline and antisocial personality disorders are concerned. In other words, test items on the MCMI-III personality scales may be consonant with the DSM-IV (30) diagnostic criteria for personality disorders, but may not be identical in their emphasis.

The findings of this study are important in that personality disorders have a notable role based on the degree to which, and ways in which, the personality disorder component plays a role not only in the etiology of the co-occurring substance use disorder but also its impact on diagnosis, treatment, and prognosis of the individuals in question.

This study is also important because such data indicate that opiate addicts should be evaluated for multiple nonsubstance use disorders, including Axis II personality disorders, as such disorders are highly prevalent comorbid conditions among such individuals.

One limitation of this study is the small sample size, which limited the ability to apply the findings to the general opiate-dependent population. Another limitation was that the sample was 100% Caucasian, similarly limiting the ability to generalize the findings to a more heterogeneous patient population. It should also be noted that geographically, this office-based clinic is a located in a middle-class neighborhood in Canada and, therefore, treats mainly middle-class patients. As a result, the socioeconomic status of patients in this study differs considerably from studies conducted with populations drawn from inner-city methadone maintenance clinics in the United States.

Future research might look at this issue of dual diagnosis, comparing psychometrically based self-report questionnaires to a structured clinical interview format, within the same clinical population. This would clarify the nature and extent of discrepancies between psychometric (e.g., MCMI-III) and interview (e.g., SCID) approaches to personality disorder diagnosis in substance abuse populations.

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David Teplin, Psy.D., C.Psych., * Tara O'Connell, M.A., Jeff Daiter, M.D., C.C.F.P., D.A.B.S.M., C.A.S.A.M., C.C.S.A.M., M.R.O., and Michael Varenbut, M.D., C.C.F.P., D.A.B.S.M., C.A.S.A.M., C.C.S.A.M., M.R.O.

Ontario Addiction Treatment Centres, Ontario, Canada

* Correspondence: David Teplin, Psy.D., C.Psych., Ontario Addiction Treatment Centres, 13085 Yonge St., Suite 205, Richmond Hill, L4E 3S8, Ontario, Canada.

COPYRIGHT 2004 Taylor & Francis Ltd.
COPYRIGHT 2004 Gale Group

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