Withdrawal from any opioid produces similar signs and symptoms. However, the severity and duration of withdrawal depends on the type of opioid taken. The symptoms of opioid withdrawal may develop within minutes or up to several days following reduction or stopping. Symptoms can include: extreme anxiety, nausea or vomiting, muscle aches, a runny nose, sneezing, diarrhea, and fever. Males may also experience spontaneous ejaculations whilst awake, and sweating.
Pathophysiology
Repeated dosages of opioids can quickly lead to tolerance and physical dependence. This is the marked decrease in opioid receptor sensitivity caused by long-term receptor stimulation triggering receptor desensitisation. Tolerance causes a decrease in opioid sensitivity, impairing the efficacy of endogenous opioid molecules that function in multiple brain regions. Opioids partially signal through the decrease in cellular cAMP. Cells with decreased cAMP adapt to regulate cAMP and increase production. In the tolerant, brain the sudden withdrawal of opioids coupled with the reduced sensitivity to inhibitory signals from the endogenous opioid systems can cause abnormally high levels of cAMP that may be responsible for withdrawal behaviours. Similar changes may also be responsible for the peripheral gastrointestinal effects such as diarrhea, as there is a reversal of the effect on gastrointestinal motility. Due to the difference in lipophilicity and mode of release between opioid analgesics, the severity and duration of withdrawal symptoms may differ. The followings are the general descriptions of duration of opioid withdrawal symptoms:
High intake for a long duration is associated with more severe level of withdrawal symptoms.
Short-acting or slow-released opioids result in more rapid onset and shorter duration of withdrawal symptoms.
Longer-acting opioids results in slower onset but longer duration of withdrawal symptoms.
Diagnosis
The diagnosis of opioid withdrawal requires recent use or exposure to opioids and symptoms consistent with the disorder. The severity of symptoms can be assessed by validated withdrawal scales, such as the Clinical Opiate Withdrawal Scale.
Treatment and management
Treatment for opioid withdrawal is based on underlying diagnostic features. A person with an acute opioid withdrawal but no underlying opioid use disorder can be managed by slowly reducing opioids and treatments aimed at the symptoms.
A major feature of opioid withdrawal is exacerbated noradrenaline release in the locus coeruleus, alpha 2 adrenergic agonists can be used to manage the symptoms of acute withdrawal. Lofexidine and clonidine are used for this purpose, both are considered to be equally effective, though clonidine has more side effects than lofexidine.
Withdrawal in opioid use disorder
The treatment of withdrawal in people with opioid use disorder additionally relies on symptomatic management in addition tapering with medications that replace typical opioids including buprenorphine and methadone. The principle of managing the syndrome is to allow the concentration of drugs in blood to fall to near zero and reverse physiological adaptation. This allows the body to adapt to the absence of drugs in order to reduce the withdrawal symptoms. The most commonly used strategy is to offer opioid drug users with long-acting opioid drugs and slowly taper the dose of the drug. Methadone and buprenorphine are often used in treating opioid withdrawal syndrome.
Dangerous or ineffective treatments
The cost and expense of opioid replacement treatments have led to some people trying treatments with limited evidence. At high doses, loperamide has been reported by some drug users to alleviate opioid withdrawal syndrome. The doses reported in the literature are associated with a strong risk of damage to the heart.
Neonatal opioid withdrawal
Many thousands of newborns each year are affected by being exposed to opioids during their prenatal development. Maternal use and abuse of opioids has become prolific. The use of opioids during pregnancy creates a dependency in the newborn who experiences withdrawal symptoms shown in clinical signs of opioid withdrawal. These signs are grouped as the neonatal opioid withdrawal syndrome, also known as the neonatal abstinence syndrome. The central nervous system, and the autonomic nervous system are affected. Common signs associated with the CNS are: high-pitched crying, reduced sleep, tremors, seizures, gastrointestinal dysfunction, and vomiting. Common ANS-associated signs include sweating, hyperthermia, yawning and sneezing, faster breathing rate, and nasal congestion.
