#  Chronic Substance abuse 

### OVERVIEW: What every practitioner needs to know

### Are you sure your patient has this condition? What are the typical findings for this condition?

##### What are the stages of substance abuse?

From a developmental perspective, adolescents do not always fit neatly into the criteria for substance abuse and dependence formerly defined by the Diagnostic and Statistical Manuel (DSM IV revised). Therefore, the following spectrum of use is often used to describe adolescent substance use.

Primary abstinence: This is complete abstinence from use of alcohol or drugs.

Experimentation: The adolescent is curious about certain drugs and the feelings of intoxication.

Nonproblematic use: This is defined as using substances in a social context without any complications.

Problem use: This is the stage when adolescents are using substances for reasons other than recreational use, such as for relaxation. This stage is also associated with experiencing problems, such as decreased productivity at school or arguments at home.

The latter can be defined as a substance use disorder (SUD) (as will be defined in DSM V) if the individual has at least two of the following over a 12-month period:

Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, home (poor school performance, substance-related absences, suspensions, or expulsions)

Recurrent substance use that involves physical hazard (e.g., driving a car)

Continued substance use despite having persistent or recurrent social or interpersonal problems exacerbated by the effects of the substance (e.g., arguments with parents and/or friends, physical fights

Tolerance as defined by either of the following:

A need for markedly increased amounts of the substance to achieve intoxification or desired effect markedly diminished effect with continued use of the same amount of the substance

Withdrawal, as manifested by either of the following:

The characteristic withdrawal syndrome for the substance

The same substance is taken to relieve or avoid withdrawal symptoms (not often seen in adolescents)

The substance is often taken in larger amounts or over a longer period than intended

There is persistent desire or unsuccessful efforts to cut down or control the substance use

A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects

Important social, occupational, or recreational activities are given up or reduced because of substance use

The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance

There is a craving or a strong desire or urge to use a specific substance

Severity specifiers:

Moderate: 2-3 criteria positive

Severe: 4 or more criteria positive

Specify if:

With physiologic dependence: evidence of tolerance or withdrawal

Without physiologic dependence: no evidence of tolerance or withdrawal

##### What do I need to know about consent and confidentiality when interviewing an adolescent for substance use?

Consent for treatment issues in adolescents

Informed consent implies that a patient has been given information that the patient needs to provide the consent and that the patient must be capable of understanding the information and making a decision. It also implies that the consent must be given voluntarily.

Some states allow adolescents to give consent. However, other states require the parental consent or notification. It is important to understand the laws the physician must comply with in each state when deciding to treat an adolescent in situations in which the adolescent’s life is not in danger.

Confidentiality

The Health Insurance Portability and Accountability Act (1966) and the Privacy Rule (2001) protect the rights of adolescents as much as those of adults.

If an adolescent’s behavior is sufficiently risky, as determined by the physician, the physician must discuss his or her concerns.

If the adolescent agrees to take the necessary steps to stop the behavior, (i.e., agrees to abstain and has subsequent urine drug testing), the physician may hold off on reporting. These drug screens can be explained to the parent as a precautionary procedure used for many adolescents.

However, the physician must warn the adolescent that if the drug screen result is positive, the adolescent and the physician must discuss how the adolescent would like this information to be disclosed. It is always best to encourage the adolescent to discuss this in front of the physician so that the physician can disperse emotional conflict during the disclosure and offer possible alternatives to treatment interventions.

##### How do I screen for substance use?

There are quite a few goals of the screening process:

Determine if drugs or alcohol has been used

Determine the level of risk for a substance use disorder

Give advice to those with low risk

Determine the level of intervention needed for those at risk

The physician should always begin by using open-ended questions such as “Have you ever….” or if the patient has been seen previously, “Since our last meeting….”

It is always important to do a psychosocial evaluation on the adolescent before proceeding to screening questions about substance use. Asking questions about how things are going at home and school, activities in and out of school and whether an adolescent is enjoying these activities, sexual activity, sleep, and friends can act as a guideline for a clinician to gain understanding of the adolescent before pursuing more personal questions.

The best oral screening instrument developed for adolescents is called the CRAFFT. This is a mnemonic acronym that is used as a guideline for drug and alcohol disorders.

It begins by asking, In the past 12 months have you ever:

Ridden in a car with someone, including yourself, who is high or under the influence of alcohol or drugs?

Used alcohol or drugs to feel relaxed or to fit in?

Been alone when using alcohol or drugs?

Forgotten actions you took while high on drugs or alcohol?

Had friends or family express their concern or ask you to cut down on drinking or drug use?

Gotten into trouble while using alcohol or drugs?

Each “yes” to a question is scored as 1 point.

A score of 2 or higher suggests a positive screening result and that the adolescent is at high risk for having a drug or alcohol disorder. If an adolescent states he/she is abstinent, the clinician should ask if he/she has driven in a car with someone who is high or had used drugs or alcohol so that safe ways to handle that situation can be discussed.

##### If a screen is positive, what interventions should I suggest?

Score specific interventions or strategies:

CRAFFT 0 points = no use:

Adolescents who have remained abstinent from drugs and alcohol should be given praise for their decision and encouraged to keep lines of communication open for questions should their decision change.

“Yes” to “ridden in a car” but the adolescent is abstinent:

All adolescents who say they have ridden in a car with someone who is high or under the influence of drugs or alcohol should receive risk reduction advice or information about the effects of alcohol and drugs on driving. In addition, it is important to ensure that the adolescent is capable of obtaining a safe ride home with someone who did not use or by calling their parents.

CRAFFT 1 point = brief advice:

If an adolescent has admitted to use, advice that an adolescent can personally relate to should be used. For instance, advice about possible negative consequences of use, such as trouble with the law or the effect it could have or an adolescent who is already overweight or the effect it may have on an athlete’s performance, or the effect it may have on school work are a few examples.

CRAFFT 2 points or more = appropriate referrals should be made for further evaluation

##### What techniques would I use to gather information in a nonconfrontational way that would help me to know if the adolescent is ready for treatment?

Technique: Motivational Enhancement Therapy (MET)

Miller in 1994 explained MET as a technique that can be used once a screening is done and is found to be positive or during further evaluation.

It helps to form an alliance between the adolescent and the physician and can actually help an adolescent who is not ready for treatment to question whether he/she should consider treatment. It has six components that are referred to as FRAMES:

Feedback on personal risk: discuss what effect the substance use has had on the adolescent’s personal life and discuss whether that is the direction he/she wants to continue in

Emphasis on responsibility to change: emphasis that no one else can do this and that he/she has the ability to make that decision

Clear advice on how to change: suggestchoosing nonusing friends or finding other recreational ways to occupy his/her time

Menu on treatment options: suggest random weekly urine drug screens to determine if it really is difficult for the adolescent to stop substance use, with options for helping the adolescent stop such use based on what triggered the use and when it occurs, or suggesting higher levels of treatment if the adolescent is really out of control.

Empathy as an intervention approach: using threats or anger will not help to form an alliance. Always be empathetic to the adolescent during the interview.

Self-efficacy and support: remind the adolescent that he/she is competent to quit. Provide examples from the past when the adolescent faced difficult times and was able to move through them. Continue to let the adolescent know that you will support him/her in getting future treatment if treatment is not wanted now but may be desired later.

##### How do I know whether the adolescent is motivated—what are the stages of motivation?

Prochaska and DiClemnente described the stages of change (which can be used to determine the motivation to change) and appropriate interventions for each:

Precontemplation: The adolescent is in denial of any problem. Here the intervention is to raise doubt and increase awareness of risks and problems.

Contemplation: The adolescent makes excuses, refuses to quit and will not consider making a change. He/she is ambivalent. The physician should acknowledge the adolescent’s ambivalence and evoke reasons to change by pointing outbehavior preceding substance use and behavior after such use that is detrimental to the adolescent.

Determination: The adolescent is ambivalent but is considering changing. The intervention is to find the best course of action.

Action: The adolescent is ready to change. The intervention is to provide assistance in moving forward.

Maintenance: The adolescent must maintain stability by staying away from activities involving drug use or peers who use. The emphasis is relapse prevention strategies and positive reinforcement.

Relapse: The adolescent may relapse even when motivated to change. The intervention is to avoid demoralization, enhance movement back toward action, and assist in learning what triggered the adolescent to use so that the situation can be avoided or the reaction to the situation can be different.

##### Can substance use mimic other psychiatric disorders?

For DSM V, the following substance-induced disorders have been suggested:

Psychotic disorder

Anxiety disorder

Bipolar disorder

Depressive disorder

Dissociative disorder

Sexual dysfunction disorder

Sleep-wake disorder

Delirium disorder

Obsessive-compulsive disorder

Mild and major neurocognitive disorder.

##### What are the risks factors that can lead to substance use disorder?

Although SUD begins in early to mid-adolescence and progresses in young adulthood, the risk factors that lead to SUD begin much earlier, even prenatally. Therefore, SUD is referred to as a pediatric disease.

Some risk factors have more effect during certain developmental stages. Newcomb has described these risk factors based on the developmental stage in which they are most likely to occur.

Prenatal risk factors

Most prenatal exposure can lead to learning disorders that increase the risk for substance abuse.

Prenatal exposure to marijuana: tends to affect problem solving involving visual integration (visual spatial working memory) and analytical skills as well as attention

Prenatal cigarette exposure: tends to be associated with symptoms similar to attention deficit hyperactivity disorder (ADHD) or ADHD and conduct disorders. There is also an effect on IQ, auditory function, and tasks involving visual perceptual skills.

Prenatal exposure to alcohol: includes two well-known entities known as fetal alcohol syndrome (FAS) and alcohol-related neuropsychiatric disorders (ARND). Exposure to alcohol before cells have migrated and differentiated is more likely to be associated with FAS (while still causing the neurocognitive effects) and exposure to cells after they have migrated and differentiated is not likely to have the dysmorphic effects seen with FAS but will have neurocognitive effects.

FAS is the most common nonhereditary cause for mental retardation. There was a six-fold increase in FAS between 1979 and 1993 probably because drinking was more socially acceptable in women.

ARND is obviously more difficult to identify, but the effects clearly the increase risk for adolescents ending up in the juvenile justice system. The percentage of adolescents in the juvenile justice system with ARND is 6-10 times higher than the worldwide incidence.

There are several areas affected by FAS/ARND: visual spatial functions, executive function, attention, auditory processing, processing speed, and learning and memory.

Cocaine exposure: Although cocaine can cause learning difficulties, it is now thought that alcohol, marijuana, and cigarettes can have a greater effect. The home environment, if improved, of a mother who has used cocaine, can have an effect on IQ.

Cultural factors

Parents allowing use in their home, economic deprivation, laws favorable to use or nonmonitoring of laws prohibiting use, neighborhood disorganization, and availability of drugs are the main cultural and societal risk factors that can lead to substance use.

Childhood interpersonal factors

Parent modeling during childhood can decrease the idea that substances of abuse can be harmful, harsh disciplinary techniques, sexual or physical abuse, marital and family conflict, low academic aspirations, low family bonding, poor family monitoring, and inconsistent or permissive discipline can increase the risk of developing SUD.

Adolescent interpersonal risk factors

Stress factors: relocation or peer rejection

Peer influence: adolescents associating with peers who use are six times more likely to use. Peers not only influence initiation but also relapse. The neurobiological explanation for peer influence: areas of the brain on functional magnetic resonance imaging become activated during risky behaviors when other peers are around. These areas primarily include the nucleus accumbens, which is responsible for pleasure. Also, once hormones become active, adolescents will produce oxytocin when they are engaged in risky behaviors with their peers. Oxytocin causes increased attentiveness to the social event and memory consolidation for the social bonding that occurred during the risky behavior.

Adolescent developmental increase in risky behaviors: adolescents tend to become more impulsive and engage in experimentation. The neurobiological explanation is that research has shown that the nucleus accumbens, responsible for pleasure, matures more rapidly in the adolescent brain than does the prefrontal cortex, which is responsible for inhibiting the impulse to seek out pleasurable activities. In fact, the prefrontal cortex does not fully develop until around age 22 or 23 years. Therefore, adolescents are more prone to experimentation.

The neurobiological evidence for why peers are more likely to influence initiation and relapse and the neurobiological evidence that adolescence is a developmental stage in which experimentation is more likely, along with genetic and other preadolescent risk factors, all explain why adolescence is a more vulnerable developmental period that can lead to SUD.

Psychobehavioral factors that can increase risk during childhood and adolescence

Personality: Cloninger type 2 and Babor type 1 alcoholics share common characteristics—early spontaneous seeking behavior, diagnosis during adolescence, rapid course of onset, genetic risk factors and deviancy. These are factors associated with conduct disorder, which also includes genetic vulnerability, negative environmental factors (poverty, parental neglect, marital discord, parental illness, and/or alcoholism) and are associated with frontal lobe dysfunction, which affects the ability to plan, to avoid harm, and to learn from negative consequences.

Age of first use: Schuckit has identified that those who start drinking at age 13 years are likely to have had their first inebriated episode by age 5 years, display problem use by age 18 years, and dependence by age 25 years. Earlier use also predicted a shorter time span between first use and dependence and a shorter time span between their first and second dependence during the continuum of use.

Academic failure: academic failure and/or undetected learning disorders and/or ADHD can lead to increased risk. However, attention problems can lead to risk that is not associated with ADHD, such as processing speed deficits, working memory problems, and auditory processing problems. Careful academic testing should be done early to detect these problems.

Comorbid psychiatric disorders: Referral to a psychiatrist should occur if a psychiatric disorder is detected and the adolescent does not respond to treatment or the treatment causes other problems.

Important co-occurring psychiatric disorders will be discussed below.

Biogenetics

Environmental influence on gene expression: Prenatal and postnatal stress and early life experiences may alter the pathologic characteristics of addiction later in life through changes in gene expression. These changes occur through chromatin remodeling without changes in DNA sequence. Factors such as prenatal exposure to substances of abuse, postnatal hypoxia, poor nutrition, and a history of sexual abuse during childhood or adolescence can cause these changes.

The neurobiological explanation is that alterations in genes may dysregulate the hypothalamic pituitary axis (HPA), which would increase the sensitivity to stress. This increased sensitivity to stress can lead to using substances to relieve the stress. However, the use of substances to relieve stress can also dysregulate the HPA axis, leading to a vicious cycle of worsening sensitivity.

Adoption studies:Children adopted from substance-abusing families and placed with non–substance-abusing families are more likely to acquire a substance abuse problem than are children adopted from nonusing substance-abuse families who were placed with substance-abusing families. The latter example was more likely to be associated with initiation of use. Therefore, predictors of later substance use are more strongly influenced by genetic predisposition.

##### What comorbid psychiatric disorders are more likely to be associated with substance abuse?

Conduct disorder

ADHD and conduct disorder are more likely to be associated with later substance abuse rather than ADHD alone. It is important to note that depression in boys may be linked to an earlier onset of conduct disorder. Depressed boys with substance abuse problems seem to have an earlier onset of conduct disorder.

Depressed girls with conduct disorder and SUD have more anxiety disorders than depressed girls with conduct disorder without SUD. Since anxiety disorders can influence the HPA axis and increase the sensitivity to stress and thereby increase the use of substances to relieve the stress, this may be the reason that girls with conduct disorders, depression, and SUD are more likely to use than are girls with conduct disorder, depression, and no SUD.

Bipolar disorder

Although patients report that marijuana and alcohol decrease the symptoms of the manic phase, in reality those who used marijuana and alcohol had less relief of their manic phase than did those who used alcohol alone. Use of multiple substances may indicate a more progressed addiction and a decrease in the ability to inhibit compulsive behavior, which will make it less likely to make for treatment of the mania to be effective. Geller has shown that adolescents with bipolar disorder and alcohol abuse are best treated with lithium and psychosocial therapy than with valproic acid, lithium, or psychosocial treatment alone.

Wilens reported that adolescents in whom late-onset bipolar disorder developed were eight times more likely to acquire a substance abuse disorder than were adolescents who had early-onset bipolar disorder. This may be due to the fact that adolescents may more impulsively seek out substances to medicate their bipolar symptoms.

Anxiety disorders: Merikangas found that anxiety disorders in all countries have a high association with the development of substance abuse. Anxiety disorders extend to panic attacks, obsessive compulsive disorder, and social phobia. These disorders, especially social phobia, often are not identified and go untreated because these disorders do not cause a major behavior disruption in the classroom. Cognitive behavioral therapy, relaxation techniques, and serotonin reuptake inhibitors are effective treatments for anxiety disorders. Beta-blockers are also effective for the treatment of posttraumatic stress disorder (PTSD).

PTSD: There is an increased risk for substance abuse in adolescents who experienced trauma during childhood and adolescence. This risk has already been explained under “Biogenetics”.

Social phobia: Adolescents with social phobia associated with aggression have a high risk for the development of a SUD. However, these children are not often treated.

Major depression: Substance-induced depression may be relieved once 4 weeks of abstinence is achieved. However, for those who have had a history of depression while abstinent, it is important to treat the depression because nontreatment may increase the risk for relapse.

ADHD: ADHD alone does not increase the risk of SUD during adolescence unless it is untreated in childhood. However in those adolescents that have ADHD and SUD, many questions should be considered before using a stimulant to treat the ADHD if a nonstimulant has been ineffective. For instance, is the adolescent committed to stopping the use of drugs or alcohol, are the parents aware of the risk of using stimulants when the adolescent may be using other illicit drugs or alcohol, is the adolescent compliant with taking medication and willing to allow the parent to monitor and administer the stimulant?

Learning disorders: Hops reported that learning disorders that are undetected by age 7-9 years can predict substance abuse by age 14-15 years.

Eating disorders: One fourth of patients with a diagnosis of eating disorders has a history of substance abuse or is currently using substances or alcohol. Patients with bulemia have a higher incidence of substance abuse than do patients with restrictive anorexia. Patients with bulemia with higher novelty-seeking behavior have a higher incidence of eating disorders than do bulemics without high novelty-seeking behavior. Therefore, personality disorders should be considered when treating patients with bulemia with SUD and high novelty-seeking behavior.

An important note is that girls with untreated ADHD may acquire an eating disorder.

Schizophrenia

Use of marijuana may have an effect on the development of schizophrenia in three ways:

If used for several years, marijuana may decrease the threshold for the appearance of schizophrenia and it may appear earlier than expected.

A dopamine stress factor may precipitate the onset of schizophrenia and the schizophrenia would appear the same month it is used.

Patients with schizophrenia may self-medicate the symptoms of schizophrenia once they appear.

Since marijuana and alcohol are the two most common substances to precipitate psychosis, and late adolescence is associated with the onset of symptoms associated with schizophrenia, a family history of schizophrenia in individuals using marijuana or alcohol may accelerate the onset of schizophrenia. An adolescent who uses substances of abuse should, therefore, be assessed for a family history of schizophrenia.

Continued use in individuals with a diagnosis with schizophrenia may have a worsening effect on prognosis. Effective treatment of individuals with schizophrenia and substance abuse is helped with atypical antipsychotic agents, but ongoing treatment to stop the use of substances of abuse is essential.

Suicide

Research by David Brent (1987) revealed that completed suicides among 10- to19-year-olds were 4.9 times more likely to have occurred while drinking. In youth with a history of depression, this is extremely important. Therefore, clinicians should monitor these youth alcohol use.

### What laboratory studies should you request to help confirm the diagnosis of substance use? How should these results be interpreted?

Types of Drug Testing

Urine and blood testing

There are several types of drug testing, many of which are distinguished from one another by the duration after use that drugs and drug metabolites are typically detectable, the distribution of the drugs and drug metabolites, the ease of specimen collection, and the resistance to cheating. Blood and urine can detect the largest number of drugs and alcohol.

The five most common drugs tested for in urine samples are marijuana, cocaine, phencyclidine, amphetamines, and opiates. These latter drugs are known as the SAMHSA-5 because the Federal Substance Abuse and Mental Health Services Administration manages the federal standards for regulated drug testing. Drugs can be added to urine and blood samples.

The common surveillance window for urine testing is 1-3 days and for blood testing it is 3-12 hours.

Alcohol

In regard to alcohol, blood and urine testing can detect alcohol levels only after 12 hours. However, alcohol can be detected 5-7 days after using by ordering a ethyl glucuronide or ethyl sulfate, both of which are metabolites of alcohol in the urine.

The legal limit of intoxication for blood alcohol levels in most states is 0.08%. The legal limit in all states is 0.10%-0.125%, which causes significant impairment. Speech, balance, vision, reaction time, and hearing can be affected.

At 0.13%-0.15%, dysphoria may occur.

At 0.16%-0.24%, nausea may occur.

Between 0.25% and 0.29%, vomiting, ataxia, and blackouts may occur.

Between 0.30% and 0.39%, loss of consciousness may occur.

At 0.40% and greater, apnea, coma, and death may occur from respiratory depression.

Marijuana

If marijuana is used everyday, it may take 7 days before it is is no longer detected.

Table I shows types of drug testing, substances of abuse detected, cost, resistance to cheating, and which tests can detect the difference between light, moderate, and heavy drug use.

##### Table I.

Type of Testing | Substance | Surveillance Time | Resistance to Cheating | Cost | Ability to Detect Light/Heavy Use  
---|---|---|---|---|---  
Urine* | Marijuana | 1-3 days | Low | $15-$30 | None  
Blood | Marijuana | 3-12 hours | High | $100-$200 | Yes, for short time  
Hair testing§ | Cocaine, opiates | 7-90 days | High | $40-$65 | No, but can be  
Hair testing | Amphetamines,phencyclidine | Broader than for other drugs | <$500  
Saliva testing | SAMHSA-5 | 3-24 hours | High | $15-$50 | No  
Sweat patch†,†† | SAMHSA-5 | 1-21 days | High | $35 | Yes  
  
*Obtain creatinine level to remove dilution problem or specific gravity to determine if test was tampered with.

†If a patient states the test was positive for opiates or morphine because he/she used poppy seeds, hair testing cannot detect these substances even if large amounts of poppy seeds have been used.

‡Marijuana is detected in hair samples only if used two times/week over the last 90 days.

§Although alcohol is not detected in hair testing, its metabolite ethyl glucuronide is.

**Saliva testing can also detect blood alcohol levels.

††It will pucker if taken off and put back on

### Would imaging studies be helpful? If so, which ones?

Obviously, if a patient has been intoxicated and a head injury is suspected or the patient seems to show cognitive decline days later, a computed tomographic scan should be obtained to rule out bleeding or head injury.

##### If substance abuse disorder has been diagnosed or if a patient is intoxicated, what pharmacotherapies should be used?

Reports on intoxication and pharmacotherapy for SUD have been published mostly for adults. The following information focuses on adolescents, mostly younger than 19 years of age. However, it is extended to 18- to 24-year-olds because there is increasing evidence that the brain does not reach maturity until the mid-20s.

The pharmacotherapies are categorized by the mechanisms of action: aversion, craving, detoxification, and treatment of comorbid conditions. Treatment of comorbid conditions was discussed previously.

The following is based on a review of the literature in which treatment of adolescents was pertinent.

Aversion Therapies

The goal of aversion therapy is to reduce alcohol or drug use through the development of unpleasant responses after the consumption of the abused substance. Only disulfiram for alcohol dependence strictly applies to this category.

Disulfiram acts as an inhibitor of the liver enzyme acetaldehyde dehydrogenase, resulting in an accumulation of acetaldehyde (a toxic by-product with adverse effects) when consumed with alcohol. These adverse effects may last up to 2 weeks with alcohol consumption after disulfiram is discontinued. Rare but serious adverse effects have been reported, including arrhythmias, respiratory depression, toxic hepatitis, seizures, and death. Therefore, disulfiram may be appropriate only in highly motivated adolescents.

One double-blind randomized controlled trial compared disulfiram (200 mg daily) with placebo in 49 adolescents. At 90 days, abstinence, as well as the mean cumulative duration of abstinence, was statistically higher in the group of adolescents who received disulfiram than in the group who received placebo.

Anticraving Agents

The goal of this class of agents is to assist in craving and withdrawal reduction and therefore help reduce relapse.

Alcohol

Acamprosate: The US Food and Drug Administration (FDA) has not approved acamprosate for the treatment of alcohol dependence in adolescents. Although the exact mechanism of action is not completely understood, it is thought to act by restoring the central balance between glutamate and gamma-aminobutyric acid (GABA) that are thought to be disrupted by prolonged alcohol exposure.

When drug-associated cues are recognized, there is a profound activation of the prefrontal cortex and glutamatergic drive to the core of the nucleus accumbens. Drug craving occurs in this scenario. Thus acamprosate may play a role in decreasing cravings by restoring glutamate and GABA imbalance and influencing the role that the prefrontal cortex and the core of the nucleus accumbens plays in craving after chronic use.

There has been only one study of acamprosate in adolescents. A double-blind randomized controlled trial compared acamprosate (1332 mg daily) with placebo in 26 adolescents. The proportion of subjects who remained abstinent at 90 days, as well as the mean cumulative duration of abstinence, was statistically higher in the acamprosate group than in the placebo group.

Since this medication requires three times a day dosing, only highly motivated adolescents should be considered when using this drug. It may be a better choice when it come to cost, since naltrexone is more expensive.

Naltrexone: The FDA has not approved oral or intramuscular naltrexone for the treatment of alcohol dependence in adolescents. As a pure mu opioid antagonist, it is thought to restore central balance of the endogenous opioid system that is disrupted by prolonged alcohol exposure. This restoration is thought to occur by blocking opioid peptides produced by the influence of alcohol on the arcuate nucleus, which influences the ventral tegmentum and the nucleus accumbens.

Only three studies have been published on oral naltrexone in adolescents. A 6-week open label trial using oral naltrexone (50 mg) in five adolescents demonstrated, at 6 weeks, an average drink/day decrease of 7.61 standard drinks, from 8.94 to 1.33, with a statistically significant reduction in craving. Adverse effects were minimal, although two subjects reported nausea.

Several case studies have had good results. In one case, an adolescent treated for 12 weeks (50 mg daily) remained abstinent for 26 weeks.

The FDA has not approved long-acting injectable naltrexone for adolescents. It is injected once every 4 weeks as an intramuscular injection. The use of an injectable prevents a subject from noncompliance, which is often seen with oral naltrexone. One case report of an adolescent girl diagnosed with alcohol dependence stated she remained abstinent for more than 12 months. A self-report from the subject of decreased craving was the reason the adolescent felt she no longer sought alcohol (Simkin, unpublished data).

Odansetron: Odansetron is a highly specific and selective serotonin 5-HT3 receptor antagonist and has a low affinity for dopamine. The exact mechanism for anticraving properties is not completely understood but may attenuate the rewarding effects of ethanol or of ethanol-conditioned cues that cause craving.

Only one known study has been published to date on odansetron treatment in adolescents. An 8-week prospective open label study of odansetron (4 μg/kg twice daily) in 12 alcohol-dependent adolescents was conducted. Intent-to-treat analysis showed a significant within group decrease for drinks used per day. The investigators suggested that odansetron reduced cravings as measured by the Adolescent Obsessive-Compulsive Drinking Scale (A-OCDS).

Topiramate and baclofen and selective serotonin reuptake inhibitors: Topiramate and baclofen both act on GABA. Although research has been done in adults with these agents for anticraving, no research has been published using these agents with adolescents.

Marijuana

There is no FDA-approved medications for anticraving in marijuana dependence in adults or adolescents. No systemic studies have been conducted in adults or adolescents. However, recent advances have correlated the endocannabinoid (ECS) with drug addiction and alcoholism and have implicated the role of the ECS in the development of tolerance to alcohol. Evidence points to the possibility that pharmacologic management of the ECS might not only block the direct reinforcing effect of cannabis, opioids, nicotine and ethanol but may also prevent relapse to various drugs of abuse, including opioids, cocaine, nicotine, alcohol, and amphetamines.

Only one known study has been published to date on divalproex (1000 mg daily) in eight adolescents with marijuana abuse and dependence who also reported mood irritability and temper outbursts. At the end of the 5-week trial, all subjects showed a significant decrease in marijuana use, although this was measured only by self-reporting. Whether this effect was caused by the effect of the anticraving agent or improving mood lability is unclear.

The anticraving properties of several agents, including buspirone, entacapone, mirtazapine, and oral tetrahydrocannnbinol (THC), and the experimental antiobesity agent rimonabant, are currently being explored and have shown positive preliminary results in several small studies in cannabis-dependent adults. No studies have been done in adolescents.

Cocaine

Currently, there are no FDA-approved medications for cocaine dependence in adults or adolescents, and no systemic studies have been conducted in either of these populations. Some medications have shown promise in cocaine-dependent adults for reducing withdrawal, such as beta-blockers, and for reducing craving, including antidepressants, anticonvulsants, baclofen, disulfiram, N-acetylcysteine, modafinil, and ondansetron. Results are mixed, and no medication has emerged as consistently effective.

Antipsychotic agents have been tried in cocaine-dependent adults but they did not prove any more effective than placebo. However, positive results were reported with enthixol decanoate. A promising new development still in human trials includes human cocaine vaccine (TA-CD) for treatment of cocaine dependence.

Only two known studies have been published to date on desipramine in cocaine-dependent adolescents. In one detailed case report, one adolescent was treated for cocaine craving, depression, and ADHD with desipramine on an inpatient unit. At 6 months follow-up, continued abstinence and improved life domains were observed. Another case report of two cocaine-dependent adolescents treated with desipramine reported symptom improvement in the youth who was compliant.

Nicotine

Eight treatment conditions have been used: nicotine lozenge, nicotine patch, sustained-release buproprion, nicotine patch plus nicotine lozenge, buproprion plus nicotine lozenge, cognitive behavioral therapy, nicotine replacement therapy plus cognitive behavioral therapy or placebo. In the adult literature, the greatest benefit relative to placebo for smoking cessation was the nicotine patch plus lozenge. In other adult studies, nicotine replacement therapy was not as effective as extended cognitive behavioral therapy (11 cognitive behavioral therapy sessions over a 40-week period). Nicotine use in adolescents remains high.

In three other studies using a nicotine patch or gum versus placebo, buproprion as an adjunct to nicotine replacement therapy or buproprion (150 or 300 mg) alone, none had a persistent long-term effect in reducing the use of cigarettes. Motivation and adolescent impulsive behavior from a neurobiological perspective may play a role here. Other treatment interventions, such as the ones mentioned in adults, need to be studied.

In July 2009, the FDA announced that the previously approved anticraving agents buproprion and varenicline for tobacco dependence must carry a boxed warning that the use of these medications has been associated with serious mental health events, including changes in behavior, hostility, agitation, depressed mood, suicidality, and attempted suicide. Given these warnings, studies on adolescents must be carried out with caution.

Opioids

Only two known studies have been published on anticraving agents in opioid-dependent adolescents. In a retrospective study of adolescents in a methadone program (after controlling for demographic and clinical characteristics), antidepressant treatment was not significantly associated with sobriety.

Agents of Substitution

The goal of substitution therapy allows the patients’ drug choice to be replaced with the supervised administration of a related medication, thereby shifting control of addiction back to the patients and clinicians. Agents of substitution are usually used to replace addictive substances with another substance that prevents withdrawal. However, continued use should be supervised to prevent functional impairment—for example, lethargy or cognitive decline—and misuse of the drug or other drugs.

Alcohol

The use of long-term benzodiazepine treatment poses a risk for cross-addiction and is not generally recommended for alcohol substitution in either adults or adolescents.

Marijuana

A limited number of studies with oral THC in marijuana-using adults for withdrawal symptoms have been reported. None was effective and no systemic studies have been done in adolescents.

Cocaine

No systemic data exist on medications for substitution treatment in either cocaine-dependent adults or adolescents. Some limited studies in adults using various dopamine repletion medications (levodopa, bromocriptine, amantadine, and mazindol) have mixed results. Some possible promising results for stimulants in adults have been seen. This is not recommended in adolescents with a diagnosis of cocaine dependence.

Opioids

Currently, there are five FDA-approved medications for opioid dependence in adults. They include oral methadone, oral naltrexone, oral levo-a-acetylmethadol (LAAM), sublingual buprenorphine, and a sublingual buprenorphine-naltrexone combination. Long-acting injectable naltrexone is not FDA approved but has been used off label.

Methadone is a full mu opioid agonist and also binds to glutamatergic  
N-methyl-D-aspartate receptor and thus acts as a receptor antagonist against glutamate transmission, which may be one mechanism by which methadone decreases craving for opioids and therefore would have less tolerance associated with it. LAAM is similar to methadone but has a longer duration of action and therefore may be administered three times/week versus once daily for opioid substitution.

Buprenorphine is a partial mu opioid agonist and in standard doses it acts in a manner similar to other mu opioid agonists, such as heroin or morphine, but at higher doses acts as an antagonist and precipitates withdrawal symptoms. In a 4:1 combination with naltrexone (pure mu opioid antagonist), this formulation is intended to discourage intravenous abuse of buprenorphine.

No systemic data exist on methadone treatment in opioid-dependent adolescents. In the United States according to the Panino State Methadone Treatment Guidelines (1992), methadone treatment is currently allowed for those younger than 18 years of age only if opioid treatment has failed after two attempts at medication taper or short-term rehabilitation. However, methadone maintenance, and not opioid detoxification, remains the treatment for pregnant adolescents given the risks and benefits to the fetus.

Although there are no systemic data on the use of buprenorphine or buprenorphine-naloxone in adolescents, the FDA has approved both treatments in adolescents aged 16 years and older, citing a lack of data efficacy and safety in younger adolescents. Likewise, there is no systemic data either on oral naltrexone or LAAM in opioid-dependent adolescents.

The Cochrane Database of Systemic Reviews lists two studies on substitution in adolescents with opioid dependence. One study compared methadone with LAAM in 187 adolescents for maintenance treatment for 16 weeks. The other study compared 12-week maintenance with buprenorphine-naltrexone to 2-week detoxification treatment with buprenorphine-naltrexone. Maintenance therapy seemed more efficacious for keeping patients in treatment but not for reducing positive results on urine testing at the end of the studies.

A literature search of pharmacologic treatment studies for heroin-using youth revealed only seven noncontrolled trials (six with methadone treatment and one with naloxone). Methadone maintenance had the highest retention rate.

A study comparing therapeutic detoxification to methadone maintenance treatment in153 heroin-dependent adolescents was reported. Of the 59 detoxified subjects, 41 subjects remained drug free, 12 resumed methadone maintenance, 3 began abusing substances again, and 2 died of heroin overdose. One subject was lost to follow-up.

An open label nonrandomized trial involving 5407 subjects younger than 19 years of age (897 daily opioid users, 1276 daily users of opioid and other illicit drugs, 903 subjects who used opioids and other illicit drug less often than daily, 2329 users of nonopioid illicit drugs) compared four treatment modalities. The modalities were therapeutic detoxification, methadone maintenance, therapeutic community abstinence, and outpatient abstinence.

Results revealed that retention of opioid users was greatest in the methadone maintenance group. Youth in therapeutic community treatment had superior outcomes compared with methadone maintenance when considering all opioid use, other substance use, and employment. This is probably due to the need for support and supervision during adolescence.

A study of heroin-dependent adolescents comparing methadone, buprenorphine, and nonopioid medication has been reported. The methadone maintenance group had significantly longer retention in the first treatment episode.

Detoxification

Medications for detoxification usually provide relief during withdrawal.

Opioids

A double-blind randomized controlled trial of 36 self-referred adolescents (aged 13-18 years) with opioid dependence compared oral buprenorphine (dosage based on weight and self-reported heroin intake: 6 mg/day versus 8 mg/day, then decreased by 2 mg every 7 days) and 18 subjects with transdermal clonidine treatment. Both groups had identical placebo matching and combination treatment with oral naltrexone.

The buprenorphine results favored retention in treatment and opioid-negative urinalysis results. However, opioid-negative urinalysis results for those retained in treatment with buprenorphine compared with those retained in clonidine treatment was not significant. A highly significant number of buprenorphine-treated adolescents entered oral naltrexone treatment.

Only two other known studies have been published on buprenorphine detoxification in opioid-dependent adolescents. An open label nonrandomized trial compared buprenorphine and methadone for detoxification in 93 adolescents. There were no statistically significant differences between those who finished detoxification in the two groups.

Another study compared two buprenorphine doses (2 mg versus 4 mg sublingually or 0.3 mg versus 0.6 mg intramuscularly per day) in young adults aged 18-25 years in an inpatient unit. There was a significant reduction from baseline in the mean Addiction Severity Index drug use composite score and the mean number of days of heroin and cocaine use during the previous 30 days, which was sustained at follow-up at 1 month, 3 months, and 6 months.

A double blind, randomized trail compared LAAM and methadone in a 16-week detoxification period. There was no statistical difference in either group, including opioid-positive urinalysis results, positive urinalysis results for nonprescribed drugs, and ease of withdrawal.

A multicenter randomized controlled trial in 152 self-referred adolescents (aged 15-21 years) were assigned either a 2-week detoxification program or 12-week maintenance treatment. Eighty adolescents were assigned to buprenorphine-naltrexone and 2-week detoxfication (up to 14 mg/day and then tapered until day 14) and 74 adolescents were assigned to buprenorphine-naltrexone and 12-week maintenance with subsequent detoxification (up to 24 mg/day for 9 weeks and then tapered until week 12), both in combination with behavioral therapy.

Opioid-positive urinalysis results were more prevalent in the shorter 2-week group compared with the longer 12-week group. Retention time in treatment was greater in the 12-week group. The two groups did not differ in self-reported alcohol use. One year later, 53% in the 12-week group reported opioid use in the last month compared with 72% in the 2-week group.

Alcohol

The efficacy and safety of benzodiazepines for treatment of adolescents for alcohol-withdrawal syndrome is not well established and may contribute to opioid toxicity symptoms in association with methadone and buprenorphine consumption.

For uncomplicated alcohol withdrawal without a history of seizures, oral propanolol or clonidine may be administered in a monitored setting and used for adolescents for detoxification, as is the common practice in adults. Clonidine can be titrated up to 0.14 mg/kg. Subjects should be monitored for sedation and low blood pressure.

### What are the possible outcomes of substance abuse?

The best results for adolescents recovering from substance abuse occurs when family therapy occurs along with treatment for the substance abuse.

### How can substance abuse be prevented?

Early identification of risk factors and conversion to positive risk factors and treatment of comorbid conditions, as discussed above, should be instituted.

### What is the evidence?

Armentano, M, Sohlkhah, R, Simkin, D, Ries, RK, Miller, SC, Fielin, DA. “Co-occurring psychiatric disorders in adolescents”. _Principles of Addiction Medicine._ 2009\. pp. 1473-81. 

Dupont, RL, Goldberger, BA, Gold, MS, Ries, RK, Miller, SC, Fielin, DA. “Clinical and legal considerations in drug testing”. _Principles of Addiction Medicine._ 2009\. pp. 1499-1511. 

Joffe, A, Ries, RK, Miller, SC, Fielin, DA. “Confidentiality in dealing with adolescents”. _Principles of Addiction Medicine._ 2009\. pp. 1465-67. 

Levy, S, Knight, JR, Ries, RK, Miller, SC, Fielin, DA. “Screening and brief intervention for adolescents”. _Principles of Addiction Medicine._ 2009\. pp. 1421-28. 

Newcomb, MD. “Psychosocial predictors and consequences of drug use: a developmental perspective within a prospective study”. _J Addict Disord._ vol. 16. 1997. pp. 51-89. 

Simkin, D, Ries, RK, Miller, SC, Fielin, DA. “Exposure to substances of abuse and neurobiology of addiction from a developmental perspective”. _Principles of Addiction Medicine._ 2009\. pp. 1391-1409. 

Simkin, D, Kessler, CL, Kraus, LJ. “Substance abuse in youth offenders”. _The Mental Health Needs of Young Offenders._ 2007\. pp. 146-179. 

Simkin, D, Grenoble, S. “Psychopharmacotherapies for adolescent substance use disorders”. _Psychiatr Clin North Am._ vol. 19. 2010. pp. 591-608. 

Wilford, BB, Ries, RK, Miller, SC, Fielin, DA. “Consent and confidentiality in addiction practice”. _Principles of Addiction Medicine._ 2009\. pp. 1491-94. 

Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved. 

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  * OVERVIEW: What every practitioner needs to know
  * Are you sure your patient has this condition? What are the typical findings for this condition?
    * What are the stages of substance abuse?
    * What do I need to know about consent and confidentiality when interviewing an adolescent for substance use?
    * How do I screen for substance use?
    * If a screen is positive, what interventions should I suggest?
    * What techniques would I use to gather information in a nonconfrontational way that would help me to know if the adolescent is ready for treatment?
    * How do I know whether the adolescent is motivated—what are the stages of motivation?
    * Can substance use mimic other psychiatric disorders?
    * What are the risks factors that can lead to substance use disorder?
    * What comorbid psychiatric disorders are more likely to be associated with substance abuse?


* What laboratory studies should you request to help confirm the diagnosis of substance use? How should these results be interpreted?
* Would imaging studies be helpful? If so, which ones?

  * If substance abuse disorder has been diagnosed or if a patient is intoxicated, what pharmacotherapies should be used?


* What are the possible outcomes of substance abuse?
* How can substance abuse be prevented?
* What is the evidence?