Chapter 12 Clinical Management Methamphetamine

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DOI: 10.1176/appi.books.9781585623440.349963

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Chapter 12. Clinical Management: Methamphetamine

CLINICAL MANAGEMENT: METHAMPHETAMINE: INTRODUCTION

One of the fastest growing illicit drug problems in the world between 1995 and 2005 has been the

use and abuse of methamphetamine (MA). According to estimates by the United Nations Office on

Drugs and Crime (2005), approximately 26 million people around the world used amphetamines in

a 12-month period during 2003–2004. In contrast, approximately 11 million people used heroin and

14 million used cocaine. Statistics on the extent of the MA problem within the United States create

a somewhat mixed picture. According to the National Survey of Drug Use and Health, in 2004 an

estimated 12 million people had used MA at least once in their lifetime, 1.4 million had used it in

the previous year, and 600,000 had used it in the previous 30 days (SAMHSA Office of Applied

Studies 2005). Although these estimates have been stable since 2002, the number of

previous-month users who met criteria for stimulant abuse or dependence increased from 63,000 in

2002 to 130,000 in 2004. Therefore, according to National Survey of Drug Use and Health data,

although the number of new users remains relatively stable, a higher percentage of people who use

MA are developing significant clinical disorders as a result of their use.

Treatment admission data for adults from the Substance Abuse and Mental Health Services

Administration (SAMHSA) indicate that the number of individuals reporting MA as their primary

drug of use increased from 41,000 in 1996 to 152,000 in 2005 (SAMHSA Office of Applied Studies

2006a), an increase of 370%. On a percentage basis, treatment admissions for MA, which was cited

as the primary drug used, represented 2.5% of total admissions in 1996, and the percentage

increased to 8.2% in 2005 (SAMHSA Office of Applied Studies 2006a).

The MA problem in the United States has spread from the western states to the midwestern states

and, most recently, to the southeastern states since 1997. At present, the only regions in the

United States without substantial rates of MA use are the Northeast and major urban centers in the

East and Midwest. However, recent media reports have suggested that even in some of these cities

(e.g., New York), there is evidence of considerable MA use among some men who have sex with

men (MSM) (Jacobs 2006).

HOW METHAMPHETAMINE WORKS

MA can be injected, smoked, snorted, or taken orally, and the method of use determines the

intensity of the drug’s effects. When smoked or injected, the effects of MA are almost

instantaneous because it enters the bloodstream very quickly, resulting in the release of high levels

of dopamine in the brain and a rapid, powerful, and euphoric “rush” (Matsumoto et al. 2002). In

oral use, MA takes about 20 minutes for effects to be felt, whereas effects after nasal insufflation

(snorting) are felt after 3–5 minutes (National Institute on Drug Abuse 2002).

MA enters the brain and increases the levels of norepinephrine, dopamine, and serotonin in the

neuronal synapse by preventing neurotransmitter reuptake (Han and Gu 2006). The combined

acute effects are similar to the fight-or-flight response and include increased blood pressure and

heart rate; relaxation of bronchioles; activation of fat breakdown; increase in body temperature;

locomotor activation; arousal, attention, and appetite effects; and euphoria.

MA is often compared with cocaine, but there are important differences in their mechanisms of

action. Cocaine acts primarily by blocking the reuptake of released dopamine in the synaptic clefts

of the mesolimbic dopamine neurons. MA also inhibits reuptake of the released dopamine, but is

carried into the dopaminergic neurons and, unlike cocaine, exerts its action intracellularly. MA

causes docking of the intracellular dopamine-containing vesicles at the membrane, leading toPrint: Chapter 12. Clinical Management: Methamphetamine http://www.psychiatryonline.com/popup.aspx?aID=349967&print=yes…

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leakage of dopamine into the synaptic cleft. Additionally, it interferes with dopamine transport into

the storage vesicles, thus increasing the cytoplasmic concentration of dopamine, which undergoes

oxidation and produces oxidation products that are toxic to the nerve terminals (Hanson et al.

2004; Pierce and Kumaresan 2006; Sandoval et al. 2003). The neurotoxicity of MA is further

accentuated by its prolonged half-life and long duration of action, which exceeds 6 hours.

Acute Physiological Effects

The acute physiological effects of MA use include increased blood pressure, body temperature,

heart rate, and breathing rate (National Institute on Drug Abuse 2006). The positive or rewarding

effects include euphoria, reduced fatigue, reduced hunger, increased energy, increased sex drive,

and increased self-confidence. Negative acute effects include stomach cramps, shaking, high body

temperature, bruxism, stroke, and cardiac arrhythmia, as well as increased anxiety, insomnia,

aggressive tendencies, paranoia, and hallucinations.

MA-associated psychiatric impairment may be cognitive, intellectual, or affective. The impairment

may be acute (intoxication), delayed (withdrawal), or protracted. The severity of psychiatric

impairment appears to correlate with duration of use as well as dosage, in terms of total absorbed

and peak amounts, which can vary according to route of administration (intravenous administration

seems to have greater impact than oral or smoking administration).

Adverse Effects on Health

Chronic use of MA may lead to drug tolerance (Matsumoto et al. 2002, National Institute on Drug

Abuse 2002), in which larger doses of the drug are required to obtain previous effects, and

frequently leads to psychological and physical dependence. Tolerance may also develop to some of

the drug’s effects, such as appetite suppression, whereas other effects, such as locomotor

stimulation, may become greater over time. Repeated, continuous MA use is also associated with

physical and psychological damage (McCann and Ricaurte 2004). The alertness provided by casual

use of the drug can evolve into paranoia, which is often exacerbated by lack of sleep. Chronic MA

use also results in changes in the brain, which may be reflected by cognitive dysfunction

concomitant with dependence. These changes in the brain may remain even after use of the drug

has ceased.

Among the consequences experienced by chronic users is damage to blood vessels in the brain,

strokes, respiratory problems including pneumonia, irregular heartbeat, extreme anorexia,

cardiovascular collapse, inflammation of the heart lining, liver disease, and death (National

Institute on Drug Abuse 2002). A wide range of negative health effects may result from chronic MA

use, although some effects can occur even with one-time or occasional use. Adverse effects are

listed in Table 12–1 (Albertson et al. 1999).

TABLE 12–1. Adverse effects of methamphetamine abuse

Cardiovascular

Myocardial infarction, cardiomyopathy, myocarditis, hypertension, arrhythmia and palpitations, tachycardia

Psychiatric and neurologic

Headache, seizures, cerebral edema, cerebral hemorrhage, paranoia, psychosis, depression, anxiety,

suicidality, delirium/hallucinations, aggression and violence, damage to small blood vessels in the brain

Respiratory

Pulmonary edema, dyspnea, bronchitis, pulmonary hypertension, pleuritic chest pain, exacerbation of asthma

Other

Skin ulcers and infections, dental problems, anorexia/weight problems, obstetric complications, hyperpyrexia,

renal failure, infectious diseases, rhabdomyolysis

SCREENING OF METHAMPHETAMINE PROBLEMSPrint: Chapter 12. Clinical Management: Methamphetamine http://www.psychiatryonline.com/popup.aspx?aID=349967&print=yes…

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Clinicians encountering a possibly stimulant-involved patient who is not forthcoming about

self-reporting MA abuse are faced with such a wide array of conditions within the DSM-IV-TR

criteria (American Psychiatric Association 2000) that the guidelines may not be sufficiently helpful

in isolating the contribution of MA versus the presence of other disorders and psychiatric

conditions. The DSM-IV-TR criteria for MA intoxication, for example, include the following

conditions:

Clinically significant maladaptive behavioral or psychological changes (e.g., euphoria or affective

blunting; changes in sociability; hypervigilance; interpersonal sensitivity; anxiety, tension, or anger;

stereotyped behaviors; impaired judgment; or impaired social or occupational functioning) that

developed during, or shortly after, use of amphetamine or a related substance. (American Psychiatric

Association 2000, p. 227)

If a clinician is relying solely on DSM-IV-TR criteria, the results of a medical workup could be

inconclusive regarding an MA-related diagnosis. MA intoxication can produce, for example, either

tachycardia or bradycardia, elevated or lowered blood pressure (Haning and Goebert 2007),

psychomotor agitation (National Institute on Drug Abuse 2006) or retardation (Volkow et al.

2001)— posing a muddle that defies a definitive diagnosis if regarded without sufficient context.

When a patient presents with the symptoms discussed above, consideration should be given to a

possible MA-induced state, absent a history of other Axis I or II disorders that preceded MA use.

Medications prescribed for a misdiagnosed psychiatric condition would be inappropriate for most

MA-intoxicated individuals, especially youth, whose developing brains could be negatively affected

by medications commonly prescribed for psychosis. A clinician lacking extensive experience with

individuals who abuse MA may be best advised to treat acute symptoms conservatively and rely on

the confirming results of a blood test or urine analysis.

METHAMPHETAMINE-RELATED SYNDROMES AND THERAPEUTIC

APPROACHES

Intoxication and Withdrawal

The typical syndrome associated with MA intoxication that leads patients to seek or need medical

attention is acute agitation, which may often best be handled by talking down the patient, assuring

them that the condition will pass in time, while observing them and ensuring a calm environment.

If recent MA administration indicates the possibility of toxicity, measures may be taken to promote

clearance of the drug; emetics or lavage may be useful in removing amphetamine pills, but much

more common is toxicity from intravenous or smoked MA. Currently, there are no medications that

can quickly and safely reverse a life-threatening MA overdose. In severe cases, when potential for

harm to self or others is manifest, either a benzodiazepine or an antipsychotic may be used.

Although little formal research has established the efficacy of any pharmacotherapeutic regimen

for MA overdose, the traditional approach is to provide 5 mg of haloperidol, frequently in

combination with 1–2 mg of lorazepam, administered orally or parenterally in repeated doses.

Other approaches include providing 1–2 mg of risperidone orally or parenterally, with 1–2 mg of

lorazepam orally, administered in several doses over a 12-hour period, with the patient evaluated

for 12 hours. Clinicians should observe for and treat possible dehydration and hyperthermia (Brown

and Yamamoto 2003).

Early abstinence symptoms, primarily severe fatigue, depressed mood, and clouded thinking,

resolve in a short time for most MA-dependent individuals (Table 12–2). Indeed, rest, exercise, and

a healthy diet may be the most appropriate management approach for the majority of individuals

experiencing withdrawal. Extreme agitation and sleep disturbance may respond to short-acting

benzodiazepines, but withdrawal-associated depressed mood and the most severe cognitive deficits

generally resolve without intervention. Drug craving is currently only managed through behavioral

treatment, given that no specific medications have proven effective.

TABLE 12–2. Early abstinence/withdrawal from methamphetamine: symptoms and clinicalPrint: Chapter 12. Clinical Management: Methamphetamine http://www.psychiatryonline.com/popup.aspx?aID=349967&print=yes…

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challenges (duration 2–10 days)

Symptoms Clinical challenges

Depressed mood Poor treatment engagement rates

Paranoia

High dropout rates

Fatigue

Severe paranoia

Cognitive impairment High relapse rates

Anxiety

Ongoing episodes of psychosis

Agitation

Severe craving

Anergia

Protracted dysphoria

Confusion

Anhedonia

Managing Acute and Persistent Methamphetamine Psychosis

MA-induced psychosis symptoms (Table 12–3) can be difficult to distinguish from preexisting

disorders or disorders concomitant with drug abuse; thus, the clinician must conduct a thorough

assessment of the patient before making a definitive diagnosis and treatment plan. Persons with

MA abuse disorders frequently report auditory hallucinations in addition to visual (e.g., flashing

lights, peripheral artifacts), olfactory, and tactile sensations (e.g., the sense of bugs crawling on or

below the skin). Disorientation, a symptom typical of schizophrenia, is said to not be characteristic

of MA psychosis, but in reality it is often difficult to differentiate the two conditions.

TABLE 12–3. Methamphetamine psychosis symptoms

Persecutory delusions

Ideas of reference

Hallucinations (visual, auditory, olfactory, tactile)

Relative clear sensorium

Stereotypical and compulsive acts

Anhedonia and depression

Blunt affect, poverty of speech

Prone to excited delirium and violence

MA-induced acute psychosis can require more intensive treatment approaches involving use of

either a benzodiazepine or an antipsychotic. Such psychosis is generally short-lived, at least as it is

documented in the United States. In Japan, the Philippines, Korea, and Thailand, however, the

symptoms often persist; in one Japanese study, 28% of the patients had psychosis lasting longer

than 6 months (Ujike and Sato 2004). As with the treatment of MA intoxication, low-dose

antipsychotics may be useful in treating psychosis, but there is no research guidance on efficacy or

appropriateness. It is important to note that these drugs have not been carefully tested in

adolescents and young adults (Cooper et al. 2006). Long-term effects of exposure to such

medications (Curtis et al. 2005) during these formative years are unknown but may be profound

and long-lasting. Caution in prescribing antipsychotics for younger patients is justified.

Persistent psychosis in the presence of MA abuse has been regarded by some clinicians and

researchers as latent schizophrenia made manifest by MA, whereas others assert that MA can

produce a persistent psychosis that resembles schizophrenia (Curran et al. 2004). In fact, the set of

symptoms of MA psychosis is frequently so similar to that of schizophrenia as to cause the clinician

to see the two conditions as equivalent. Research findings appear to support the position that MA

abuse can be the genesis of a persistent psychotic state (Iwanami et al. 1994; Sato 1992).

Clinicians should be aware of the documented close relationship between MA-induced psychosisPrint: Chapter 12. Clinical Management: Methamphetamine http://www.psychiatryonline.com/popup.aspx?aID=349967&print=yes…

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and schizophrenia. For example, Chen et al. (2005) showed that relatives of MA users with

MA-related psychosis had a significantly higher morbid risk for schizophrenia than the relatives of

those MA users who never became psychotic. Conclusions indicated that greater familial propensity

for schizophrenia yielded higher likelihood that an MA user will develop psychosis and that the

psychosis will be more persistent.

TREATMENT FOR METHAMPHETAMINE ABUSE AND DEPENDENCE

Contrary to some popular but errant notions, treatment for MA dependence does work. Although

there are some specific populations and clinical issues that may pose special challenges, treatment

outcomes for MA-dependent patients are comparable with those for other substance-dependent

patients involved in similar treatment programs. For example, research on the Matrix Model and

other behavioral strategies (cognitive-behavioral therapy [CBT] and contingency management

[CM]) revealed that treatment responses of MA users appeared indistinguishable from those of

cocaine users (Obert et al. 2000). However, a number of populations present particular treatment

challenges and several clinical issues are particularly important when treating MA-dependent

individuals.

Methamphetamine Populations With Unique Clinical Concerns

Methamphetamine injectors

Recently, some states (e.g., South Dakota and Oregon) have reported elevated rates of MA

injection. Smoking and, especially, injecting MA appears to lead to a more difficult drug-related

disorder. Injection users tend to report far more severe craving during their recovery and higher

rates of depression and other psychological symptoms before, during, and after treatment

(Hillhouse et al. 2007).

Injection users also have higher dropout rates and exhibit higher rates of MA use during treatment.

In a recent sample of MA-dependent users who entered treatment in the Midwest, Hawaii, or

California, the rate of hepatitis C infection was 15% (Gonzales et al. 2006). Of the MA injectors,

over 45% were infected with hepatitis C. Clearly, preventive efforts that address behaviors that

expose individuals to hepatitis C infection (blood-to-blood transfers or sharing drug paraphernalia)

should be incorporated into treatment protocols.

Men who have sex with men

Use of MA by MSM is one of the most significant public health problems associated with the

increased use of MA. Elevated rates of MA use and associated high-risk sexual behavior have been

reported in many MSM communities throughout the United States (Halkitis et al. 2005; Patterson et

1. 2005; Shoptaw et al. 2005). Rates of HIV seroprevalence have been reported to be threefold

higher among MA-using MSM than among non-MA-using MSM (Halkitis et al., in press). A report by

the Centers for Disease Control and Prevention on the connection between MA-use, high-risk sexual

behavior, and HIV transmission in MSM communities suggests that this combination of factors

poses a major threat of a renewed increase in rates of HIV infection among MSM (Centers for

Disease Control and Prevention 2007). The development of treatment materials for this population

has progressed in recent years, with evaluation of MSM-oriented programs showing that successful

treatment of MA dependence is an extremely effective HIV prevention strategy (Shoptaw et al.

2005).

Women

Women use MA at rates approaching those of men (Brecht et al. 2004; Freese et al. 2000). Use of

two other major illicit drugs, heroin and cocaine, is roughly characterized by a 2:1 ratio (men to

women; SAMHSA Office of Applied Studies 2006b). In contrast, the male-to-female ratio for MA

users approaches 1:1. Surveys among women suggest that they are more likely than men to be

attracted to MA for weight loss and to control symptoms of depression. MA-related drug disorders

may present different challenges to women’s health, may progress differently, and may requirePrint: Chapter 12. Clinical Management: Methamphetamine http://www.psychiatryonline.com/popup.aspx?aID=349967&print=yes…

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different treatment approaches. Over 70% of MA-dependent women report histories of physical and

sexual abuse; and women are more likely than men to present for treatment with greater

psychological distress (Brecht et al. 2004). Treatment materials that address the extensive

historical and current trauma-related problems of these women (e.g., Najavits 2002) are likely to

be valuable to people addressing these clinical issues. Many women with young children do not

seek treatment or they drop out early because of the fear of not being able to take care of or keep

their children, as well as the fear of punishment from authorities. Consequently, women may

require treatment that identifies and addresses women’s specific needs.

Children and perinatal issues

MA poses significant threats to the health of children in communities with high levels of MA

availability and abuse. The effects of MA use by pregnant women on their fetuses are currently

being studied (Smith et al. 2006). At present, it appears that such use can cause growth

retardation, premature birth and, possibly, neurological disorders (Lucas 1997). Children of

MA-abusing parents are at high risk of negligence and abuse as a result of the parents’ drug

preoccupation, erratic behavior, and psychiatric instability. Children who live in environments

where MA is manufactured are at particularly high risk for exposure to the toxic precursors of MA

(Swetlow 2003).

Adolescents

Although patterns of adolescent MA use have been reported to be relatively low in national surveys

(lifetime use of 3% by tenth graders and 3.4% by twelfth graders) as measured by the Monitoring

the Future study in 2004, in communities where MA-use levels are high, adolescent MA users have

been seen in treatment centers in significant numbers (Johnston et al. 2005). Of particular note is

the very high rate of MA use among teen girls admitted for substance abuse treatment. One study

(Rawson et al. 2005) found that 63.7% of adolescent females seeking treatment reported MA as

their primary drug of choice. In several clinical samples, the rates of MA abuse or dependence for

girls have been double that of boys (Gonzales et al., in press). MA use among adolescents has been

shown to be associated with higher levels of emotional, psychiatric, and delinquency problems

compared with adolescents given other drug abuse diagnoses (Rawson et al. 2005).

Noteworthy Clinical Issues

Cognitive impairment

Chronic use of MA has been documented to produce profound disruption of cognitive functions

(Barr et al. 2006). Verbal and working memory, response inhibition, perceptual speed, attention,

and fluency are some of the cognitive processes that are known to be impaired in newly abstinent

MA users. Although many of these processes appear to recover within the first several weeks of

abstinence, clinical experience suggests that residual cognitive impairment can be present for

several months following discontinuation of MA use. To accommodate these cognitive limitations,

treatment strategies should not emphasize extensive information acquisition or intellectually

complex activities, because memory impairment will result in poor retention of such material.

Treatment programs should employ simple, clear, directive behavioral techniques, accompanied by

reminders and repetition that promote acquisition and retention of treatment materials.

Sexual behavior

The hypersexuality of MA-using MSM represents a significant HIV transmission threat. However,

MSM are not unique in indicating that they associate MA use and sexual behavior. Rawson et al.

(2002) reported that in a comparison of four groups of substance-dependent individuals in

treatment (alcohol-, opiate-, cocaine-, and MA-dependent individuals), there was a significantly

greater association between drug use and sexual behavior among the MA-dependent group than

among the other three substance-dependent groups. Sexual pleasure and sexual drive, as well as

frequency, intensity, variety, and riskiness of sexual activity, were greater for MA-users than forPrint: Chapter 12. Clinical Management: Methamphetamine http://www.psychiatryonline.com/popup.aspx?aID=349967&print=yes…

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other groups. These reported elevations of sexual associations between drug use and sexual

responses applied to both men and women. Frequently, anxieties and concerns over sexual issues

are reported by individuals in the early months of recovery from MA. Decreased libido, inability to

function sexually, loss of sexual pleasure, and reduced frequency of sexual activity are all common

clinical concerns of individuals during the early months of abstinence from MA. Relapse to MA can

be a consequence of these patient concerns unless the patient is educated about the transience of

these phenomena and reassured that return to a satisfying sexual life is possible in the future.

Overview of Treatment for Methamphetamine Problems

Treatment outcomes for MA-dependent patients have been shown to be comparable with those for

individuals treated for other substance dependence disorders. Several studies have documented

that when using standard community treatments, the response of MA-dependent patients was

comparable with patient groups who were admitted for other substance dependence disorders

(Copeland and Sorensen 2001; Luchansky et al. 2007). Research on the Matrix Model and other

behavioral strategies (CBT and CM) found similar treatment responses for MA users and cocaine

users in evaluations of specific behavioral and cognitive behavioral protocols (Huber et al. 1997;

Rawson et al. 2006). Clearly, MA users do respond to current psychosocial treatments as

implemented in real-world settings.

At present, only two specific psychosocial treatment protocols (CM and the Matrix Model) have

been evaluated in randomized, controlled clinical trials with MA-dependent participant samples.

These studies are reviewed below. However, comparisons of treatment responses by MA users and

cocaine users to the specific behavioral protocols mentioned above suggest that there is a very

high likelihood that psychosocial treatments with demonstrated efficacy for cocaine dependence

can be useful for individuals with MA dependence, although an optimum approach would address

clinical concerns that are salient to MA dependence, as noted above. Treatments including CBT

(Morgenstern et al. 2001; Rawson et al. 2006), community reinforcement approach (Higgins et al.

2003), 12-step facilitation (Nowinski et al. 1992), and the National Institute on Drug Abuse drug

counseling approach (Daley et al. 1999) should be considered for treating MA-dependent

individuals.

Behavioral Treatment

Contingency management

CM applies the principles of positive reinforcement for performance of desired behaviors consistent

with MA abstinence. CM typically involves the contingent delivery of a voucher (which can be

traded for desired items or privileges) or other incentives for behaviors, such as attendance at

treatment sessions or production of a drug-negative urine specimen. CM has been widely applied to

other drug dependence disorders, and a meta-analysis of research findings has documented strong

evidence of efficacy across many studies, types of disorders, and populations. Petry (2006) has

written on how this technique can be used efficiently and cost-effectively.

The validity of CM for the treatment of MA dependence has been confirmed in a study conducted

within the National Institute on Drug Abuse Clinical Trials Network in which a CM procedure was

combined with counseling for a group of 113 MA-dependent individuals (Roll et al. 2006). Study

participants were randomly assigned to receive a structured counseling program (Matrix Model, see

below; n = 62) or structured counseling plus a CM condition (n = 51). In the CM condition,

individuals could earn small incentives for providing MA-free urine samples on a variable ratio

schedule of reinforcement. Study results indicated that participants who received CM intervention

had more drug-free urine test results than counseling-only individuals, the CM group had longer

periods of abstinence, and a higher percentage of the CM group were abstinent during the study

period. At follow-up, 12 months posttreatment, both CM and standard counseling participants had

comparable outcomes.

Another study compared the effectiveness of CM and CBT for treating cocaine- and MA-dependentPrint: Chapter 12. Clinical Management: Methamphetamine http://www.psychiatryonline.com/popup.aspx?aID=349967&print=yes…

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individuals (Rawson et al. 2006) over a 16-week outpatient trial. Stimulant-dependent individuals

(N = 177) were randomly assigned to receive one of three therapy programs: 1) group-based,

three-times-per-week CBT program (n = 58); 2) CM program for provision of stimulant-free urine

samples, with no counseling (n = 60); or 3) combination of CM and CBT conditions (n = 59). Study

results demonstrated that all groups had a significant reduction in MA use during treatment, when

compared with pretreatment levels. Participants receiving CM were retained for significantly longer

than those receiving only CBT, and they provided more drug-free urine samples during treatment.

The gains from CM and CBT were sustained at 6- and 12-month follow-ups. Clearly, the CM

approach is a validated, powerful tool in the armamentarium.

Matrix Model

The Matrix Model is a blended treatment approach that incorporates principles of CBT in individual

and group settings, family education, motivational interviewing, and 12-step program participation.

This stimulant treatment protocol, organized into a set of manuals and published by SAMHSA,

provides the structure and content for a multi-element, three-visit-per-week, 16-week outpatient

treatment experience, followed by a weekly social support group for 1 year. Although it is not a

pure CBT intervention, Matrix extensively employs CBT principles and strategies. In addition to CBT

materials delivered primarily in group sessions, the Matrix Model emphasizes that clinicians employ

a style of interacting with patients that incorporates many of the skills taught as part of

motivational interviewing. Family members are involved in a set of psychoeducation sessions and

conjoint sessions.

The Matrix Model has numerous central therapeutic constructs. These include the following:

Establishing a positive and collaborative relationship with the client

Creating explicit structure and expectations

Teaching psycho-educational information (including information on brain chemistry and other

research-derived, clinically relevant knowledge)

Introducing and applying cognitive-behavioral concepts

Positively reinforcing desired behavioral change

Educating family members regarding the expected course of recovery

Introducing and encouraging self-help participation

Monitoring drug use through the use of urinalyses

This manualized therapy has been proven effective in reducing MA use during the 16-week

application of the intervention, in comparison with a “treatment as usual” program (Rawson et al.

2004). At 6- and 12-month follow-ups, the reductions in MA use achieved by employment of the

Matrix Model and treatment-as-usual were substantial and comparable. Shoptaw et al. (2005) have

modified the Matrix Model for the treatment of MA-dependent MSM. Their study results suggest that

the Matrix approach produces outcomes that are equivalent at 1 year posttreatment to CM only and

CBT combined with CM. The CBT group component of the Matrix Model has also been extensively

employed as the behavioral treatment platform in pharmacotherapy trials for MA dependence

(Johnson et al. 2006).

Pharmacological Treatment

Several compounds have shown some promise as potential medications for MA treatment,

particularly bupropion (Wellbutrin) and modafinil (Provigil). Other medications (e.g.,

methylphenidate, topiramate, lobeline, vigabatrin) are under consideration.

Bupropion

Bupropion shows promise as a pharmacotherapy for preventing relapse among MA-dependent

individuals. Laboratory studies have indicated that bupropion can reduce the subjective effects of

MA and reduces MA cue-induced craving (Newton et al. 2006). Recent research in six

community-based clinics in California, Hawaii, Iowa, and Missouri showed that bupropion produced

significant reductions in MA use compared with placebo treatment in subjects. The dosage was 150Print: Chapter 12. Clinical Management: Methamphetamine http://www.psychiatryonline.com/popup.aspx?aID=349967&print=yes…

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mg, two times a day. The authors concluded that bupropion, in combination with behavioral group

therapy, was more effective for patients with low/moderate MA dependence (i.e., fewer than 18

days of use in the past month).

Modafinil

Modafinil is a nonamphetamine stimulant that is prescribed for controlling symptoms of narcolepsy

(i.e., daytime somnolence). Although the neuropharmacologic effects of modafinil are not entirely

clear, its stimulant properties may reduce the craving, dysphoria, and anhedonia experienced

during initial stages of MA abstinence (Menza et al. 2000; Simon et al. 1994). Furthermore,

modafinil has been shown to improve cognitive functioning, which may be useful in alleviating the

cognitive impairment that has been associated with MA withdrawal.

Methylphenidate

Methylphenidate is a stimulant used to treat attention-deficit/hyperactivity disorder. Preclinical

research has revealed a potential role for methylphenidate, acting as a dopamine transporter

reuptake inhibitor, in counteracting dopamine deficits resulting from MA abuse (Sandoval et al.

2002). A Finnish study reported that treatment with methylphenidate reduced MA injection in an

early-stage trial (Tiihonen et al. 2007).

Lobeline

Lobeline is a nicotinic receptor antagonist that has been tested as a smoking cessation agent.

Lobeline inhibits dopamine reuptake and has been shown to attenuate MA-induced hyperactivity

and reduce the self-administration of MA in rodents (Harrod et al. 2001; Miller et al. 2001; Teng et

1. 1997). In addition, there is evidence that lobeline may have neuroprotective properties against

the effects of MA (Eyerman and Yamamoto 2005). Testing lobeline in humans as a treatment agent

is in an early stage of development

Topiramate

Topiramate is an anticonvulsant that has also been approved for migraine prophylaxis. The exact

neuropharmacologic mechanisms underlying the benefits of topiramate are not entirely understood.

However, it has been shown to reduce alcohol consumption and craving in alcohol-dependent

individuals and to reduce cigarette smoking. Kampman et al. (2004) have reported that topiramate

reduced cocaine consumption in cocaine-dependent subjects; Johnson et al. (2007) have reported

that topiramate appears safe in Phase I interaction studies with MA administration.

Vigabatrin

-Vinyl- -aminobutyric acid (GVG) is an anticonvulsant licensed in Europe and Canada (not the

United States). It has been shown to block MA-induced increases in dopamine in the nucleus

accumbens and thereby blunt the euphoria and positive-subjective effects of MA (Gerasimov et al.

1999). Several open clinical trials involving cocaine-dependent and MA-dependent individuals have

revealed positive findings (Brodie et al. 2003, 2005). Systematic study of the safety and efficacy of

GVG for the treatment of MA dependence is at an early stage of development.

CONCLUSION

Abuse of MA increased between 1995 and 2005, creating substantial public health problems and

imposing considerable burdens on social service agencies. Those involved in development of

prevention and treatment interventions must consider recent epidemiological trends (e.g.,

increasing numbers of younger users and women users, increased risks for HIV infection among

MSM) in order to efficiently reduce MA-associated harm. Research has improved the neurobiological

understanding of MA abuse, and emerging knowledge about associated brain processes provides

new opportunities for development of pharmacological and behavioral treatments. It is likely that

the distribution and use of MA in the United States and around the world has become so extensive

that it will continue to be a problem of considerable significance for the foreseeable future.

KEY POINTSPrint: Chapter 12. Clinical Management: Methamphetamine http://www.psychiatryonline.com/popup.aspx?aID=349967&print=yes…

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Methamphetamine use, abuse, and dependence in the United States has increased from 1995–2005.

Chronic methamphetamine use produces significant medical and psychiatric symptoms, including

cardiovascular and respiratory system irregularities, neurological abnormalities, skin and dental problems, as

well as psychosis, dysphoria, and anhedonia.

Symptomatic treatment for methamphetamine-related psychosis, intoxication, and withdrawal using

antipsychotics and benzodiazepines is the current accepted practice.

Numerous groups require special attention regarding methamphetamine-related consequences. They are

methamphetamine injectors, adolescents, women, and men who have sex with men.

Current psychosocial treatments with demonstrated efficacy for the treatment of cocaine disorders appear

appropriate for treatment of methamphetamine users. These include: cognitive-behavioral therapy,

community reinforcement approach, contingency management, 12-step facilitation, and the National Institute

on Drug Abuse drug counseling approach.

Contingency management and the Matrix Model are the only two psychosocial approaches with data to

support their efficacy for the treatment of methamphetamine dependence.

Many medications currently show promise as pharmacotherapies for the treatment of methamphetamine

dependence, but currently none have clearly demonstrated efficacy.

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