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Differences in Methylphenidate Abuse Rates among Methadone MaintenanceTreatment Patients in two clinics

Ph.D Einat Peles, M.D. Shaul Schreiber, R.N.,.M.S. Shirley Linzy, M.D. YoavDomani, M.D. Miriam Adelson

PII: S0740-5472(14)00260-8DOI: doi: 10.1016/j.jsat.2014.12.010Reference: SAT 7256

To appear in: Journal of Substance Abuse Treatment

Received date: 18 May 2014Revised date: 13 December 2014Accepted date: 16 December 2014

Please cite this article as: Einat Peles, P.D., Shaul Schreiber, M.D., ShirleyLinzy, R.N.,.M.S., Yoav Domani, M.D. & Miriam Adelson, M.D., Differences inMethylphenidate Abuse Rates among Methadone Maintenance Treatment Patients intwo clinics, Journal of Substance Abuse Treatment (2014), doi: 10.1016/j.jsat.2014.12.010

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Differences in Methylphenidate Abuse Rates among Methadone Maintenance

Treatment Patients in two clinics

Einat Peles, (Ph.D),a*

Shaul Schreiber, (M.D.), a,b*

Shirley Linzy, (R.N., M.S.),c Yoav

Domani, (M.D),a,b

Miriam Adelson (M.D.)a,c

aDr. Miriam & Sheldon G. Adelson Clinic for Drug Abuse, Treatment & Research, and

bDepartment of Psychiatry, Tel-Aviv Sourasky Medical Center & Tel-Aviv University

Sackler Faculty of Medicine, Tel-Aviv, Israel.

cDr. Miriam & Sheldon G. Adelson Clinic for Drug Abuse, Treatment & Research, Las

Vegas, Nevada, USA

*First and second authors had equal contribution

Correspondance: Einat Peles, Ph.D.

Adelson Clinic, Tel-Aviv Sourasky Medical Center

1 Henrietta Szold St.

Tel-Aviv 6492406, Israel.

Tel: +972-3-6973226

Fax: +972-3-6973822

E-mail: einatp@tlvmc.gov.il

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Differences in Methylphenidate Abuse Rates among Methadone Maintenance

Treatment Patients in two clinics

Methylphenidate, an amphetamine-like prescription medication for attention deficit

hyperactivity disorder (ADHD) was suspected as being abused among methadone

maintenance treatment (MMT) patients. We tested its presence in the routine urine

monitoring of all patients in both Tel Aviv and Las Vegas MMT clinics. Data on

demographic and addiction history, ADHD (Wender Utah Rating Scale), cognitive

impairment (Mini Mental State Exam), and lifetime DSM-IV-TR psychiatric diagnosis from

admission were retrieved, and retention following 6 months. None of the 190 patients in Las

Vegas tested positive for methylphenidate, while 14.7% (45/306) did in Tel Aviv. Abusers

were less educated (p=0.01), had higher ADHD scores (p=0.02), lower cognitive scores

(p=0.05), and a higher benzodiazepine abuse rate (p<0.0005), with no difference in age,

gender, duration in MMT, cannabis, opiates, and cocaine abuse and infectious disease. Of the

methylphenidate abuse 42.2% have take-home methadone dose privileges. Not like opiate

use, being methylphenidate positive did not relate to 6-months retention. Compared to Tel

Aviv, Las Vegas patients were more educated, with lower BDZ, and cocaine abuse. The

greater abuse of methylphenidate among ADHD subjects might indicate their using it as self-

medication, raising a possible indication for its prescription for that subgroup of MMT

patients. The high rate of methylphenidate abuse in Israel needs future study.

Keywords: Methylphenidate; Methadone maintenance treatment; Abuse; Monitoring; ADHD;

Methylphenidate

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1. Introduction

Methylphenidate (Ritalin®), an amphetamine-like stimulant drug with dopamine and

noradrenaline reuptake inhibition properties, is mainly indicated for attention deficit

hyperactivity disorder (ADHD) (Greenhill et al., 2002). However, ADHD stimulants are

classified as Schedule II controlled substances in the United States based on their potential

for abuse, dependence, and individual and public health harm, which is consistent with the

Convention on Psychotropic Substances 1971 (Kollins et al., 2007). There is a high

comorbidity between ADHD and substance dependence (Kollins, 2008; Schubiner, 2005).

Prospective studies on ADHD patients found that the onset of substance dependence always

follows ADHD onset (Wilens, 2004; Elkins et al., 2007), suggesting that ADHD children are

more vulnerable to develop substance dependence (Elkins et al., 2007) and that treatment of

ADHD may reduce their incidence of substance abuse when grown up (Wilens et al., 2003).

However, a recent meta-analysis (Humphreys et al., 2013) that reviewed 2565 participants

from 15 different studies and evaluated the incidence of alcohol, cocaine, marijuana, nicotine,

and nonspecific drugs, concluded that diagnosing and treating children with ADHD neither

protects nor increases the risk of later substance use disorders.

Based on data for all intentional exposures from 2007 through 2009 among adolescents

from the RADARS (Researched Abuse, Diversion and Addiction-Related Surveillance) study

in the US, abuse of methylphenidate was found among 14% of the 16,209 intentional

adolescent exposures (Zosel et al., 2013). An internet survey among 4,297 non-

institutionalized adults aged 18 to 49 years in the United States (Novak et al., 2007) reported

a past-year prevalence of nonmedical use of ADHD medications to be approximately 2%,

with 4.3% reported among those aged 18 to 25 years and 1.3% among those aged 26 to 49

years. Receipt of medications for ADHD was a significant correlate of past year nonmedical

use.

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A report from France that studied patterns of methylphenidate use and abuse using a

general health insurance system database (Frauger et al., 2011) found that the subjects were

characterized as being older (aged 35.4 ± 11.3 years) and more frequent users of

benzodiazepines, antidepressants, antipsychotics and maintenance opioid treatment. The

proportion of subjects with a behavior such as higher number of dispensing, different

prescribers and pharmacies, and a greater total dispensed quantity, increased from 0.5% in

2005 to 2% in 2007 and then decreased to 1.2% in 2008. A more recent report from France

that was based on the 2008–2010 OPPIDUM survey (Frauger et al., 2013) found that

methylphenidate abusers (several misuse indicators of methylphenidate consumed the week

prior to the interview are computed to assess abuse liability) were mostly male (85.4%), had a

relatively low socioeconomic situates (70%), obtained methylphenidate illegally (68%) and

used it intravenously (52%).

In Israel, a 2009 survey among adults (aged 18-40 years) found that 1.01% reported

stimulant medications usage in the last year (an increase from the 0.5% reported in 2005),

and that it was much higher among adolescents aged 12-18 years (3.3% in 2009 and 2.7% in

2005) (Israeli Anti-drug Authority). A survey among school children in Israel aged 17-18

years that specifically asked about methylphenidate found a 0.9% rate of non-prescribed

usage in the last 30 days (Harel-Fish et al., 2013).

In the last decade, Israel has been invaded by a prominent social wave (leaded mostly by

some Media Persons and several local “Celebrities”) to legalize cannabis and other

recreational drugs. The local ministry of health authorized the prescription of

methylphenidate by all GPs, and the illicit use of this drug has expanded throughout the

country (mostly by students who use it as a ”performance enhancer” during examinations,

and by street-drug users who prefer it snorted.

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Methadone maintenance treatment (MMT), a chronic treatment for opiate addiction,

includes a routine monitoring for drug abuse as part of the treatment, in particular as a need

for privileges achievement (i.e., take home doses and treatment payment discount).

According to the regulations and procedures in the USA (SAMHSA) and in Israel (Israeli

Ministry of Health, 2004), the routinely monitored drugs are opiates, cocaine,

benzodiazepines (BDZ), amphetamines and cannabinoids (THC). Methylphenidate has never

been assessed, but is suspected to be abused among our MMT patients; as we’ve heard

patients talking about it, some of them were found with packs of pills in their pockets, some

manifested behaviors that were not explained by their negative urine tests, and some others

have confessed having used methylphenidate (or their “friends” reported on them).

The goals of the current analyses was to apply a cross-sectional design to evaluate the

point prevalence of methylphenidate abuse, and to identify the characteristics of the abusing

patients in two MMT clinics: one in Tel Aviv, Israel, and one in Las Vegas, Nevada. The

findings of this investigation were intended to help decide the need of routine monitoring of

methylphenidate abuse among our MMT patients. In order to be able to obtain the real

occurrence of the methylphenidate abuse prevalence, patients were neither informed of the

one-time performance of the methylphenidate test, nor reported about the results (even if their

test was found positive), and regardless of findings – they had no effect on patient's privileges

(i.e. take-home dose, etc.).

2. Materials and methods

2.1. Study population

This analysis was approved by the Tel Aviv Sourasky Medical Center (TASMC)

Helsinki committee (IRB) (No 111-07). The Adelson Clinic in Tel Aviv (Israel) treats about

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330 patients who meet criteria similar to those of the U.S. Federal Regulations for entering

methadone treatment (i.e., DSM-IV criteria of dependence with multiple self-administrations

of heroin per day for at least one year). Characterization, demography, and effectiveness of

the clinic have already been reported elsewhere (Peles et al., 2006; Peles et al., 2010).

The Adelson clinic in Las Vegas (Nevada, USA) treats about 190 patients. Both MMT

clinics (“twin” clinics) were established by the same physician (Tel Aviv in 1993 and Las

Vegas in 2000), they both use similar policy and procedures guidelines and principles of

treatment, and they have been accredited by the Commission Accreditation of Rehabilitation

Facilities (CARF, international, 1999) (for more details see Peles et al., 2008a). The study in

Tel Aviv was done through October 2013 and that in Las Vegas through February 2014.

2.2. Urine Toxicology

Patients in MMT undergo repeated urine tests throughout the entire length of their

treatment. In order to prevent manipulating, all urine tests are always observed.

For the purposes of this study, methylphenidate for each patient was tested in the first of

the 2-4 (80% 2 tests, mean 2±0.5) random urine samples that are routinely taken during each

month for opiates, cocaine metabolite (benzoylecgonine), BDZ, cannabinoids (THC),

methadone metabolite, tricyclic antidepressant amitriptyline (TCAs) and amphetamines,

using enzyme immunoassay systems (DRI® and CEDIA

®) (Hawks, 1986). TCAs and

amphetamines are not tested every month.

A methylphenidate cutoff urine concentration of 100 ng/ml was considered as being

positive, and a positive result was defined by at least one of the urine samples tested positive

for the substance.

Routinely, if a patient refuses to give urine for test, it is considered as positive for

cocaine, a fact that leads to immediate cancelation of both privileges for take-home doses (if

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there are any) and for a discount of the monthly payment. Therefore urine-testing refusals are

rare.

The methadone dose during the study month was recorded. Serum methadone level (the

closest serum that is taken routinely during treatment) was taken. A routine serum level is

taken at specific timing to be sure that serum level is within the safe therapeutic range (i.e.

when patient is clinically stabilized; prior to 1st take home dose; when daily methadone dose

exceeds 150 mg; annually). Serum methadone had been measured by gas

chromatography-mass spectrometry (Clinical Science Laboratory, Mansfield, MA). (For details

see Adelson et al., 2007).

2.3. Patient characteristics (Table 1)

TABLE 1 AROUND HERE

A modified addiction severity index (ASI) (McLellan et al., 1984) and other

demographic details were retrieved from the patients’ records that are part of the routine

intake upon entry to the clinic, including lifetime psychiatric diagnoses (DSM IV-TR,

determined during the psychiatric intake which includes clinical interview accompanied by

relevant questionnaires and part of the Hebrew validated version of the SCID (Shalev et al.

1996)) and the responses to the Adult ADHD Self-Report Scale (ASRS) symptom checklist

(Kessler et al., 2005; Adler et al., 2006). That questionnaire includes an 18-item scale that

rates ADHD symptoms using a 5-point Likert severity scale (from 0 = never, to 4 = very

often). A score of ≥17 is indicative of possible adult ADHD (likely to have ADHD) while a

score of ≥24 is indicative of definite ADHD (highly likely to have ADHD). Childhood

ADHD was assessed by the Wender Utah Rating Scale (Ward et al., 1993) that includes 61

questions and a 5-point Likert severity scale as in the adult ASRS. A total of ≥46 points is

indicative of childhood ADHD. As both adult and childhood ADHDs evaluations were only

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based on questionnaires and not clinically diagnosed, they were all considered “suspected” or

“possible” ADHD. Cognitive status was assessed using the Mini-Mental State Examination

(MMSE) (Folstein et al., 1975). The Fagerström nicotine score was measured with the

modified Fagerström Test for Nicotine Dependence (FTND) (Fagerström, 1978), which

consists of six questions and yields a score of 0 (no or low) to 10 (highest nicotine

dependence severity).

2.4. Data analyses

Statistical analyses were by the SPSS-21 package. The results were compared using the

Chi-square or Fisher’s Exact test in categorical variables, and one-way analysis of variance

(ANOVA) in continuous variables. A logistic regression model for urine samples positive for

methylphenidate was applied with all variables that were found to be significant (p<0.05) in

the univariate analyses. Adequacy of the model was determined with the Contingency

Hosmer and Lemeshow test (chi-square=3.2, p=0.9) (Hosmer and Lemeshow, 1980).

Kaplan Meier survival analyses was performed to evaluate retention up to 6 months,

using log rank Chi Square for significant differences between groups.

3. Results

3.1. Prevalence of methylphenidate

A total of 45 (14.7%) of the 306 study participants tested positive for methylphenidate in

Tel Aviv. None of the 190 patients in Las Vegas MMT clinic tested positive for

methylphenidate.

3.2. Tel Aviv and Las Vegas Clinics’ Characteristics Differences

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Las Vegas patients were younger (43.5 ± 14.2 vs. 48.9±8.7, F=24.8, p<0.0005), for

shorter duration in MMT (3.3 ± 3.4 vs. 9.2±5.6 years, F=170.7, p<0.0005). More of them

were females (44.7% vs. 25.5% p<0.0005), living alone (77.7% vs. 67.3%, p=0.01) and they

were more educated (12.0 ± 1.5y vs. 9.7±2.7, F=104, p<0.0005), with less hepatitis C

antibody patients (44.2% vs. 54.6%, p=0.03). Drugs in urines differed between the clinic

groups; Specifically, LV clinic had less BDZ (21.1% vs.33.6%, P=0.003) opiates (8.9% vs.

19.4%, p=0.002) and cocaine abuse (3.7% vs. 15.8%, p<0.0005), and more THC (14.2% vs.

7.6%, p=0.02), and amphetamines (6.3% vs. 2.0, p=0.03).

3.3. Similarities between the methylphenidate abusers and non-abusers

Patients with urine tests positive or negative for methylphenidate did not differ in age

(47.8 ± 10.7 years vs. 49.1 ± 9.5, years, respectively, p=0.4), duration in MMT (8.7 ± 5.8

years vs. 9.3 ± 5.6 years, p=0.5), gender (22% females vs. 26.1% females, p=0.7), proportion

of immigrants (34.1% vs. 39.6%, p=0.5), ever drug injecting (68.2% vs. 62.9%, p=0.6), rate

of patients with positive antibody to hepatitis C (HCV) (57.8% vs. 54%, p=0.7) and rate of

patients with HIV (9.1% vs. 7.0%, p=0.5). They also did not differ in any DSM-IV-TR Axis I

psychiatric diagnosis (38.6% vs. 41.6%, p=0.4) and Fagestörm smoking severity score (5.0 ±

2.1 vs. 4.7 ± 2.3, p=0.5). The mean methadone serum level did not differ between the groups

(506.6± 155.7 vs. 507.9± 216.6, p=1), nor did the rate of urine samples that tested positive for

opiates (29.3 vs. 19.6%, p=0.2) and cocaine (17.1% vs. 17.4%, p=1).

3.4. Differences between the methylphenidate abusers and non-abusers

The methylphenidate abusers were less educated than the non-abusers (8.8±2.4 years vs.

9.9±2.7 years, respectively, p=0.01), and had higher ADHD scores (50.1±21.8 vs. 41.9±21.6,

p=0.02) and higher proportion of patients with moderate/severe cognitive impaired

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(MMSE<24) (9.5% vs. 1.3%). The abusers had more than twice higher rates of urine tests

positive for BDZ than the non-abusers (68.3% vs. 30.4%, p<0.0005), and also showed a

greater trend towards abusing cannabis as well (17.1% vs. 7%, p=0.06). Privileges of take

home methadone doses (based on normative behavior in treatment) were granted to 42.2% of

the methylphenidate abusers compared to 63.6% of the non-abusers (p=0.002). The

methadone dose was higher among the methylphenidate abusers compared to the non-abusers

(132.4± 36.6 vs. 118.5± 43.9, p=0.05). Comparing the ADHD patients, their Fagerström

score was significantly higher among the patients with ADHD than the non-ADHD patients

(5.4±2.3 vs. 4.3±2.1, p=0.001).

3.5. Six months follow up

Of the methylphenidate urine positive tested patients, 6.7% (n=3) left after 6 months as

compared to 3.1% (n=8) of the methylphenidate urine negative tested patients (p=0.2).

Opiates in urine were the only substance that was associated with 6-months retention;

specifically, 10.2% (6 of 59 patients with positive urine for opiates) as compared to 2% (5 of

the 247 patients with negative urine for opiates) were not in treatment after 6 months

(p=0.008). The other substances (BDZ, cocaine, THC, and amphetamines) were not related to

6-months retention (data not shown). Significant longer retention and, cumulative retention

showed no differences in mean duration in treatment between methylphenidate positive and

negative urine groups (Figure 1) but showed shorter duration in treatment among the opiate

positive patients of 199.1 days (95% CI 189.5-208.6) vs. 208.4 days (95% CI 206.1-210.8)

among the negative urine opiate group (Log Rank Chi Square 9.2, p=0.002) (Figure 1).

3.6. Multivariate analyses

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A logistic regression (multivariate analyses) demonstrated that the methylphenidate

abusers were more likely to be BDZ abusers (OR=4.9, 95% CI 2.4-10.1) and less likely to be

educated (OR=0.85 95% CI 0.75-0.97).

3.7. Correlations

Years of education linearly correlated with the MMSE score (R=0.28, p<0.0005), and

inversely correlated with the ADHD score (R=-0.35, p<0.0005). The MMSE and ADHD

scores were inversely correlated (R=-0.28, p<0.0005).

4. Discussion

The high rate (14.7%) of methylphenidate abuse found among our patients in the Tel

Aviv MMT-center, one-month evaluation study confirmed our preliminary suspicions. The

abuse of methylphenidate was also found in the multivariate analyses to characterize BDZ

abusers with fewer years of education. Although the poor cognitive state (MMSE score) and

high ADHD score that characterized methylphenidate patients in univariate analyses, were

not significant in the multivariate analyses, each was also associated with limited education.

However, the more interesting findings are the similarities between the methylphenidate

abusers and the non-abusers. They did not differ neither in drug injecting practice, hepatitis

C, HIV antibody, nor in the abuse of other substances, such as cocaine. This raises the

possibility that methylphenidate may actually be abused (at least by some patients) mainly for

self-medication.

A six-months follow up period did not differentiate between methylphenidate positive

and negative patient groups with respect to retention in MMT. Actually, as the only substance

that significantly predicted retention was opiate, while substances such as BDZ which is

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known as a predictor of poor outcome (Peles et al., 2010) did not, a longer duration of follow

up is needed to learn about the effect of methylphenidate on outcome.

In 2008, we found a high abuse rate of tricyclic antidepressants (TCAs) in a similarly

designed study (Peles et al., 2008b), and the characteristics of the TCAs abusers group were

very different from those of the methylphenidate patients found in the present study. But both

those TCAs abusers and the methylphenidate abusers in the current study is the high rate of

urine tests positive for benzodiazepines.

Following our previous finding of high TCAs abuse among our patients (Peles et al.,

2008b), TCAs were added to the routinely monitored drugs. The take-home dose privileges

were canceled for those who continued abusing TCAs, and a substantial reduction in TCAs

abuse was demonstrated several months later, leading us to first reduce the frequency of

TCAs assessment to every other month, and currently to every 4 months (without informing

the patients of that).

An ssubstantial percent of the patients with take home dose privileges having been found

to abuse methylphenidate, similarly to the situation with TCAs at the time. Given the

association between methylphenidate and suspected ADHD, the question arose as to how

many of the abusing MMT patients might be abusing it for self-medication of

undiagnosed/untreated ADHD. Notice that although rating scales are helpful in identifying

individuals at risk of ADHD, diagnosing ADHD is a complex clinical process. A proper

diagnosis is made by taking a comprehensive history and performing a physical and

psychiatric examination, by reviewing different kinds of data (e.g. school data) and by ruling

out alternative disorders many other conditions.

Our earlier study of ADHD among a random sample of 154 of our MMT patients (Peles

et al., 2012) demonstrated that 33.1% of them had been diagnosed as having childhood-onset

ADHD (a score >46) and they, too, were characterized as having few years of education.

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They also had more severe tobacco smoking, which is well known among ADHD population

(McLernon and Kollins, 2008), and were more likely to have a DSM-IV-TR axis II disorder.

Our not having found these differences among the methylphenidate group in the present

study may be related to the fact that only 54.5% of them were found with ADHD symptoms.

A second interesting question regards the actual prevalence of methylphenidate abuse in

these MMT patients. There are several commercially available pharmacological preparations

of methylphenidate, with a large variety of half-lives (from 4 hours for the “classical”

Ritalin®

, to 6-8 hours for the Ritalin XR (extended release) type, and reaching up to 12 hours

for the Concerta®

). A single, point prevalence, cross-sectional design with such short T1/2 of

the substance assessed necessarily underestimates the real prevalence and, indeed, reports of

methylphenidate abuse among MMT patients are limited. Only one study in 1982 by Haglund

et al (1982) examined the use of methylphenidate among 192 opioid treatment patients, with

special attention given to history of use, means of supply, and adverse consequences

associated with the abuse of this substance.

Since methylphenidate’s effects are rather similar to those of cocaine, it had been

proposed as treatment for cocaine addiction. As such, the use of methylphenidate may serve

as a means for self-medication for cocaine abusers. A recent brain imaging study (Konova et

al., 2013) found that methylphenidate changes the mesocorticolimbic dopamine pathways

brain resting-state functional connectivity of cocaine addicts. Interestingly, methylphenidate

was not found to be more abused by the cocaine abusers than by our other MMT patients. On

the other hand, several clinical trials on methylphenidate among MMT patients did not find it

effective for cocaine abuse. In one double blind, three-arm, 12-week trial that aimed to

compare the efficacy of sustained-release methylphenidate or sustained-release bupropion

with that of placebo in treating adult ADHD symptoms (Levin et al., 2006), both medications

did not provide a clear advantage over placebo either in reducing ADHD symptoms or in

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reducing additional cocaine use in MMT patients. There was no evidence of misuse of

medication or worsening of cocaine use among those randomized to methylphenidate. In

support of those findings, methylphenidate reportedly did not reduce cocaine abuse in a

controlled double blind trial among diacetylmorphine-maintained patients suffering from

cocaine abuse (Dürsteler-MacFarland et al., 2013).

Unexpectedly, none of the Las Vegas clinic’s patients were found to abuse

methylphenidate. Differences may derive from the fact that in Israel, GPs prescribe

methylphenidate without effective regulatory surveillance, and the illicit use of this drug has

vastly expanded throughout the country, while in Las Vegas methylphenidate is not easily

found on the streets, or not “popular” among street-drugs users and MMT patients (or they

possibly prefer other drugs).

It should be noticed, that both Las Vegas and Tel Aviv perform a random observed urine

test collection as improper procedures may increase false negative results. There are many

ways for patients to circumvent testing (e.g. adding adulterants to urine at the time of testing,

urine dilution trough excessive water ingestion, consumption of substances that interfere with

testing, substitution of clear urine sample etc.).

There are two separate clinical implication to our findings in the Tel Aviv MMT clinic:

the 1st and most important one, is the need to develop a protocol of treatment for the ADHD

MMT patients, taking into consideration both the problematic prescription of an addictive

medication with severe abuse potential to patients with addictive disease and the potentially

hazardous addition of a medication that induces (at least) tachycardia (methylphenidate)

(Schelleman et al., 2012) to a medication known to potentially prolong the QTc on ECG

(MMT) (Mujtaba et al., 2013), blood pressure elevation and risk of prehypertension

(Martinez-Raga et al., 2013; Westover et al., 2013), marked decrease in appetite leading to

significant weight loss and episodes of depression and paranoia (Imbert et al., 2013). The

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primary clinical syndrome of methylphenidate overdose involves prominent neurological and

cardiovascular effects, while secondary complications can involve renal, muscle, pulmonary,

and gastrointestinal effects. In overdose, the patient may present with mydriasis ,tremor,

agitation, hyperreflexia, combative behavior, confusion, hallucinations ,delirium, anxiety,

paranoia, movement disorders, and seizures (Spiller et al., 2013; Marti et al., 2013). The

second (and not less important) is the urge (presented already to the regulatory authorities in

Israel) to add methylphenidate to the list of drugs of abuse checked-for in the routine urine

tests.

It could be possible that methylphenidate may also be used for “management” (by the

patients themselves) of opioid-induced- and sedative-induced sedation, meaning that

methylphenidate use might also serve as a means to reduce drowsiness resulting from opioids

(including methadone) and/or BDZ. This is consistent with the finding that the

methylphenidate group, as compared to no methylphenidate users group received a

significantly higher methadone dose and were more likely to use BDZ.

To summarize, the current study results revealed a 14.7% methylphenidate abuse rate in

MMT patients. The finding that more abusers had coexisting ADHD may indicate that

methylphenidate was intended to serve as a means of self-medication, at least among some of

these patients. Prescribed methylphenidate for those with an ADHD diagnosis should be

considered. A future study evaluating the motives, circumstances and patterns of

methylphenidate intake by patients will add insight into the phenomenon. Such a study

however, would necessitate to inform patients and would require high sensitivity and

specificity methodology for the detection of methylphenidate. This may be achieved by

detecting not only methylphenidate but its metabolite (ritalinic acid) as well, and increase

specificity by confirmation with GCMS method.

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Acknowledgments

The study was funded by the Adelson Family Foundation.

Esther Eshkol is thanked for editorial assistance.

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Legend

Figure 1 Cumulative retention in days up to 6 months from methylphenidate evaluation by

negative and positive methylphenidate in urine, and by negative and positive to opiate in

urine. Opiate groups differed significantly (Log Rank Chi Square 9.2, p=0.002).

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Table 1 Characteristics of the study groups

Tel Aviv Las Vegas

Characteristic Methylphenidate No p (F) No

Total, n (%) 45 (100) 261 (100) 190 (100)

Gender (female), n (%) 10 (22.2) 68 (26.1) 0.7 85 (44.7)

Age of opiate onset (y) 21.2 ± 7.9 22.6 ± 6.3 0.2 22.9 ± 8.9

Pre-MMT opiate abuse (y) 17.2 ± 9.4 16.8 ± 9.2 0.8

Age admission MMT (y) 38.6 ± 9.7 39.9 ± 9.7 0.4 40.4 ± 13.7

Current age (years) 47.6 ± 10.7 49.1 ± 9.5 0.4 43.6 ± 14.2

Immigrant, n (%) 15 (34.1) 103 (39.6) 0.5

Education (years) 8.8 ± 2.4 9.9 ± 2.7 0.01 (6.5) 12.0 ± 1.5

Living in couples, n (%) 9 (20.9) 90 (34.6) 0.08 146 (77.7)

Ever THD privileges, n (%) 22 (51.2) 204 (81.0) <0.0005 124 (65.7)

Working, n (%) 11 (25.6) 137 (53.9) 0.001 74 (38.9)

Methadone dose (mg/d) 132.4 ± 36.6 118.5 ± 43.9 0.05

Methadone serum (ng/ml) 506.6 ± 155.7 507.9 ± 216.6 1

Urine opiate, n (%) 13 (28.9) 46 (17.8) 0.2 17 (8.9)

Urine cocaine, n (%) 8 (17.8) 40 (15.4) 0.7 7 (3.7)

Urine cannabis, n (%) 7 (15.6) 16 (6.2) 0.06 27 (14.2)

Urine benzodiazepine, n (%) 31 (68.9) 71 (27.4) <0.0005 40 (21.1)

Ever injected, n (%) 29 (67.4) 163 (63.2) 0.7

Hepatitis C antibody, n (%) 25 (56.8) 141 (54.2) 0.9 80 (44.2)

HIV antibody (%) 3 (6.8) 18 (6.9) 1

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Tel Aviv

Characteristic Methylphenidate No p (F)

Axis I DSM-IV-TR, n (%) 17 (38.6) 106 (41.6) 0.4

Fagerstrom score 5.0 ± 2.1 4.7 ± 2.3 0.5

ADHD score 50.1 ± 21.8 41.9 ± 21.6 0.02

ADHD (scored >46), n (%) 24 (54.5) 99 (42.9) 0.2

Adult ADHD, n (%)

Yes

Possible

No

13 (34.2)

18 (36.8)

11 (28.9)

65 (30)

47 (21.7)

105 (48.4)

0.05

MMSE score 25.9 ± 3.4 26.8 ± 2.5 0.05

MMSE, n (%)

Moderate/Severe (<24)

Mild (24-26)

Normal (27-30)

4 (9.5)

14 (33.3)

24 (57.1)

3 (1.3)

87 (38.5)

136 (60.2)

0.04

MMT, methadone maintenance treatment; THD, take-home dose; MMSE, Mini Mental State

Exam; ADHD, attention deficit hyperactivity disorder

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Highlights

The high abuse of methylphenidate among ADHD subjects may suggest self-

medication

Methylphenidate abusers had lower cognitive scores and high benzodiazepine abuse

MMT clinics from Israel and US differed in presence and rate of methylphenidate

abuse

Six months retention rates were similar for Methylphenidate abusers and non-abusers