Opioid dependence is a morbid addiction consisting in compulsive drug use, preoccupying drug-seeking behavior, progressive abandonment of alternative pleasures and interests, as well as persistent substance abuse despite abundant evidence of overtly detrimental consequences. Broadly speaking, opioid addiction is a cluster of behavioral, cognitive, and physiological episodes of unpredictable intensity and varying duration, where the use of opioid drugs takes an increasingly higher priority over other activities including those of daily living. The intake of opioids causes a strong sense of euphoria (“high”), but with chronic use tolerance develops, requiring higher doses of the drug of abuse to produce the desired effect.
Opioid dependence is characterized by acute withdrawal symptoms in case the abused drug is stopped or its dosage is reduced, which manifest themselves both psychologically (dysphoria, anxiety, paranoia, depression, insomnia) and physically (cramps, weakness, tachycardia, diarrhea, nausea, vomiting, perspiration, tremors, pain). Some rarer withdrawal symptoms, such as strokes, seizures, severe dehydration, as well as suicidal behavior, are life-threatening. Chronic users of opioids often take increasing doses of the abused substances to avoid or minimize the adverse effects of withdrawal, as opposed to regaining the gratifying sensation experienced at initial exposure. Opioid addiction as such is associated with a plethora of side effects affecting the gastrointestinal tract, mental status, peripheral nervous system, immunity, and endocrine balance. Opioid overdose can be fatal.
Opioids (or opiates) are narcotic alkaloids derived from the opium poppy; their synthetic or semi-synthetic analogs and derivatives belong to this category as well. Opioids are used medicinally for pain management, cough suppression, and the treatment of intractable diarrhea. Somewhat paradoxically, certain synthetic opioids are used in the therapy of opioid dependence. The medicinal use of opioids is relatively safe if supervised by healthcare professionals. It is important that opioids not be combined with other CNS depressants, such as antihistamines, benzodiazepines, barbiturates, and alcohol.
There are endogenous substances, called endorphins that resemble opioids in their analgesic and euphoric effects. They are produced in the hypothalamus and pituitary gland in response to strenuous exercise, pain, excitement, and physical intimacy. Endorphins have their physiological targets that bear so-called opioid receptors to which endorphins bind to realize their neurotransmitter effects. It is this mechanism of action that is hijacked by medicinal or recreational opioids. Archetypical opioid agonists, such as morphine, bind to opioid receptors and mimic the effects of endorphins: sedation, analgesia, and euphoria. Opioid antagonists, such as naloxone and naltrexone, bind to the opioid receptors, too, but with higher affinity than agonists, thereby preventing or reversing the effects of abused opiates.
Opioid dependence is a complex mental disorder requiring long-term treatment and care. The management of opioid addiction typically combines pharmacotherapy, counseling, and psychosocial rehabilitation aimed at societal reintegration and improved functioning. Although total abstinence is the primary goal, drug-free treatment is associated with high relapse rates. One approach to the pharmacotherapy of opioid dependence is the use of agonist maintenance, e.g. with methadone, which is considered anti-addictive. An alternative approach is therapy with naltrexone, which supports abstinence, produces no euphoria or sedation, and does not have any addictive potential. Naltrexone is an opioid receptor antagonist that works well in patients who have achieved abstinence during inpatient treatment or imprisonment, and who are at risk of relapsing upon discharge. Naltrexone cessation causes no withdrawal symptoms, since there is no underlying physical dependence. The availability of long-acting opioid antagonists significantly improves patient compliance.
PSI has recently completed a phase III study of a novel extended-release formulation of naltrexone in adult patients with opioid dependence. The study enrolled 250 patients in 11 months at as few as 13 centers, at an average rate of 1.7 patients/site/month. The key success factor was the excellent rapport of the project team, led by a seasoned manager who himself is a board-certified psychiatrist, with key opinion leaders. The study drug showed clinically meaningful and statistically significant improvement in the duration of abstinence, severity of cravings, and relapse rate. On the strength of the data from this study the product has been approved by the Food and Drug Administration for the treatment of opioid addiction.
