Many complex factors influence the natural history of opioid addiction. Overall, the course is one of relapse and remission. Attempts to define opioid abusers as a group have been limited, because long-term contact with these frequently itinerant persons is difficult, and only a minority of opioid abusers can be studied effectively (i.e., those who elect to enter treatment). Given these obstacles to accurate understanding, some generalizations can still be made. The vast majority of active opioid abusers are between the ages of 20 and 50 years. Age at first use is usually in the teens or 20s. Race, ethnicity, and socioeconomic status variables are important. Though opioid addiction affects persons from all groups in the United States, black or Hispanic poor persons are overrep-resented. True iatrogenic opioid dependence rarely persists to become chronic, although the risk exists for those with chronic, painful medical or surgical problems. Although men and women seek treatment in roughly equal numbers, women who are mothers of dependent children may benefit from a more favorable prognosis.

Opioid addiction follows a relapsing and remitting course until middle age, when its relentless grip on the individual seems to abate slowly and spontaneously. Some experts have estimated 9 years as the average duration of active opioid addiction (Jaffe, 1989). Criminal activity, usually in support of addiction, is very common during periods of active use. In periods of remission, criminal activity drops off significantly. The overall death rate in opioid abusers is estimated to be as much as 20 times that of the general population. The proximate cause of death is usually overdose, use-related infections, suicide, homicide, or accidental death.

Significant psychiatric comorbidity has been observed; depression and personality disorder are the most frequent diagnoses. Polysubstance abuse is common in opioid addicts. Many are nicotine addicted, and many have serious alcohol-related problems as well. Benzodiazepine use is common and probably underestimated, because it may not be specifically assayed in urine specimens. Sporadic use of cocaine and other stimulants is common, as is the use of marijuana. A few opioid addicts also use hallucinogens or inhalants.

The medical complications of opioid abuse are many and diverse. They stem most commonly from (1) the failure to use aseptic techniques during injection, (2) the presence of particulate contaminants in the injected solution, and (3) the direct pharmacological actions of the drug. The consequences of infection are the most frequently encountered medical complications of opioid abuse. Skin abscesses, lymphadenopathy, osteomyelitis, septic emboli in the lungs, endocarditis, septicemia, glomerulonephritis, meningitis, and brain abscesses are encountered with regularity when "dirty needles" are used. A low-level immunodeficiency may exist in chronic opioid addicts, causing them to be more susceptible to infectious processes such as tuberculosis, syphilis, malaria, tetanus, and hepatitis (Senay, 1983). HIV infection may result from sharing needles with an infected individual. Risk of this complication is highest in the northeastern United States, where a survey of opioid addicts in methadone treatment programs showed seropositivity in 60% of those who reported sharing needles (Jaffe, 1989). Fortunately, the percentage drops dramatically in most other parts of the country, and aggressive efforts at education of both addicts and those who treat them in clinics and elsewhere have helped slow the spread of this deadly virus.

Addicts frequently inject opioid solutions contaminated with adulterants such as talc and starch; these substances are used to increase the bulk of the illicit powder, thus increasing profits for the drug dealer. Addicts mix the pow der with water, heat it, and use cotton or a cigarette filter to block the entry of undissolved particles as the solution is drawn into the syringe. As a result, fibers enter the venous bloodstream and lodge in the lungs, where conditions become favorable for the development over time of pulmonary thrombosis (emboli arise at distant sites), pulmonary hypertension, and right-side heart failure. Opioid abusers are at further risk of compromised pulmonary function if they use cigarettes and marijuana, as they often do. The antitussive effect of opioids also compromises pulmonary function, contributing to frequent pneumonia and other respiratory tract infections.

A number of lesions may occur in the central nervous system of those persons who have survived overdoses that featured anoxia and coma. The residual effects of such trauma include partial paralysis, parkinsonism, intellectual impairment, personality changes, peripheral neuropathy, acute transverse myelitis, and blindness.

Psychiatric comorbidity caused by opioid dependence occurs most frequently in the form of depression. When depression is observed during the recovery period, treatment with antidepressants and psychotherapy is indicated and frequently helpful if the individual is abstinent from illicit drug use. Dysphoria is common during with withdrawal interval, and is not helped by antidepressants, but rather by appropriate treatment of withdrawal symptoms.

The following disorders also are seen in association with opioid dependence:

1. Bipolar disorder.

2. Antisocial personality disorder.

3. Anxiety disorders.

4. Other personality disorders, including paranoid, schizoid, schizotypal, histrionic, narcissistic, borderline, dependent, obsessive-compulsive, and mixed.

5. Delirium and dementia (rare).

6. Schizophrenia (very rare).

Mood disorders may be diagnosable in many opioid addicts (Mirin, Weiss, Michael, & Griffin, 1989). Major depression is the most common mood disorder, diagnosed at almost 16% (Brooner, King, Kidorf, Schmidt, & Bigelow, 1997); it may have preceded the onset of drug abuse as chronic, episodic low-grade depression or dysthymia, and a full-blown major depressive episode may develop in the stressful and traumatic context of opioid addiction. Depression occurs more frequently in women than in men. Depression coexisting with opioid dependence is more strongly associated with a history of concomitant polydrug abuse. More attention is being paid to the complicating presence of attention-deficit/hyperactivity disorder (ADHD; King, Brooner, Kidorf, Stoller, & Mirsky, 1999).

Of the personality disorders, antisocial personality disorder is the most commonly diagnosed and can be seen in as many as 25% of opioid abusers seeking treatment; this is noted in men the vast majority of the time (Brooner et al., 1997). It is inaccurate to assume that drug-seeking behavior learned during years of addiction is responsible for the high percentage of antisocial personalities among opioid addicts. Antisocial personality disorder can be reliably diagnosed historically in most individuals at a young age, prior to the onset of opioid dependence. The relationship between opioid abuse and antisocial personality is complicated and appears to be influenced by a non-sex-linked genetic factor. When antisocial personality and opioid dependence are found together, the treatment course is frequently challenging, and the overall outcome is poor with regard to adequate length of time in treatment, relapse, criminal behavior during treatment, and ability to establish rapport with a therapist or counselor. The one exception appears to be the antisocial addict who also has a diagnosable depression. This group responds much better to treatment, on a par with the average opioid addict without significant psychiatric comorbidity (Woody, McLellan, Luborsky, & O'Brien, 1985).

Anxiety disorders, such as panic disorder, obsessive-compulsive disorder, generalized anxiety disorder, and phobia, are seen in approximately 10% of opioid addicts. Members of this group are typically somewhat younger in age and higher in socioeconomic status, and their drug use histories are not as extensive.

Delirium, dementia, and psychotic disorders such as schizophrenia, mania, and psychotic depression are not usually seen in opioid clinic populations. The presence of both a DSM-IV Axis I diagnosis (depression or an anxiety disorder) and an Axis II diagnosis (a personality disorder) in the same opioid-dependent individual is frequently observed; the proportion of such patients may approach 50% in clinic populations (Khantzian & Treece, 1985).

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