Withdrawal symptoms from opiates

Individuals who are more heavily dependent on opiates clearly also require detoxification at various stages, and the remainder of the chapter discusses other forms of withdrawal treatment. As indicated in Chapter 1, community detoxification with methadone, as opposed to maintenance, is not well supported by evidence, but nevertheless this has been a standard treatment in the UK and other countries for many years. Meanwhile the almost certainly milder withdrawal symptoms from buprenorphine make this a more attractive proposition than methadone in detoxification, and the major impact made recently by this treatment will be examined. The last section discusses relapse prevention, focusing on counselling approaches and on the use of the opiate antagonist naltrexone, which we recommend after most detoxifications from opiates. 

A common strategy for treating chronic opiate addiction iavolves the substitution of methadone which can either be provided as maintenance therapy or tapered until abstinence is achieved. Naltrexone and buprenorphine [52485-79-7] have also been used ia this manner. The a2 adrenergic agonist clonidine [4205-90-7] provides some rehef from the symptoms of opiate withdrawal, probably the result of its mimicking the inhibitory effect of opiates on the activity of locus coerukus neurons. 

Chronic administration of opiates and alcohol leads to physical dependence a phenomenon, which is only weakly expressed following chronic administration of psychostimulants or other drugs of abuse. Physical dependence results from neuroadaptive intracellular changes to an altered pharmacological state. Abstinence from chronic opiate or alcohol use leads to a variety of physiological and psychological withdrawal symptoms based on these adaptations of the neuronal system. 

Substitution therapy with methadone or buprenorphine has been veiy successfiil in terms of harm reduction. Some opiate addicts might also benefit from naltrexone treatment. One idea is that patients should undergo rapid opiate detoxification with naltrexone under anaesthesia, which then allows fiuther naltrexone treatment to reduce the likelihood of relapse. However, the mode of action of rapid opiate detoxification is obscure. Moreover, it can be a dangerous procedure and some studies now indicate that this procedure can induce even more severe and long-lasting withdrawal symptoms as well as no improvement in relapse rates than a regular detoxification and psychosocial relapse prevention program. 

Potential side effects of naltrexone include anxiety, drowsiness, and nausea. In addition, it rarely causes a chemical hepatitis. For this reason, blood testing of liver enzymes should be conducted periodically. If any signs of naltrexone-induced hepatitis appear, it should be discontinued. Furthermore, patients should be advised that they must be totally abstinent from opiates for at least 2 weeks before using naltrexone or it can precipitate severe withdrawal symptoms. 

When beginning treatment for opiate dependence, it is imperative to assess the patient s long-term goals for treatment. The key variable is whether the patient desires to control his/her opiate nse or whether the patient wants to achieve total abstinence. In both cases, the first stage of treatment is detoxification. The endpoint of detoxification differs, however. Detoxification is complete in a patient desiring abstinence when (s)he is entirely tapered from the opiate. Conversely, detoxification is complete in a patient desiring maintenance therapy when the withdrawal symptoms have abated. 

Geriatric Considerations - Summary Diphenoxylate is an analog of meperidine and can cause opiate adverse effects. When discontinued, physical dependence and withdrawal symptoms can occur. Adverse GI effects such as constipation, nausea/vomit-ing, and abdominal pain may result from normal doses. Afropine is added to discourage abuse but can cause anticholinergic adverse effects in the older adult. The benefits of f his drug combination for older adulfs are limifed by fhe risk of adverse effects. 

As indicated, buprenorphine can offer a quicker option than methadone, with a three-day course reported to be effective for withdrawal from heroin (Cheskin et al. 1994). The side-effects of clonidine which render it unsuitable for community treatment can be manageable in the inpatient setting, although the drug is being superseded by lofexidine where that is available. Controlled studies have found clonidine and lofexidine to be equally effective in alleviating withdrawal symptoms in inpatient detoxification from heroin (Lin et al. 1997) and from methadone (Khan et al. 1997), with lofexidine resulting in less hypotension and fewer adverse effects. Another double-blind controlled study found lofexidine to be broadly as effective as a ten-day methadone detoxification in inpatient opiate withdrawal (Bearn et al. 1996). 

The next four drugs are what are referred to as "mixed agonists-antagonists". Although all can be abused, the potential is lower for the normal person because of the lowered potency. However, the addict will experience withdrawal symptoms either from the drug itself or if the drug is taken with heroin or morphine because of the competition for opiate receptors. 

Methadone is used for the treatment of narcotic withdrawal and dependence. It occupies the opioid receptor in the brain and is the stabilizing factor that permits addicts to change their behavior and to discontinue heroin use. Methadone suppresses narcotic withdrawal for between 24 and 36 hours, and because it is effective in eliminating withdrawal symptoms, it is used in detoxifying opiate addicts. Ultimately, the patient remains physically dependent on the opioid, but is freed from the uncontrolled, compulsive, and disruptive behavior seen in heroin addicts.42... 

Opioids are known to alter mood states. For example, opiates such as morphine produce euphoria and pain relief. Prolonged use of and withdrawal from opiates produce depressive-like symptoms as well. Based on the mood-altering effects of opiates, the role of endogenous opiates in psychiatric symptoms of various diseases has been studied. In addition, endogenous opioids are believed to play a role in neuronal circuitry responsible for reward and pleasure. Therefore, it is thought that perhaps the anhedonia observed in depressed patients is due to dysregulation of endogenous opioids in neuronal reward circuitry. 

These natural reward centers have developed over the course of evolution to reinforce useful behaviors (e.g., pleasure, sexual satisfaction, eating, and drinking). It is believed that drugs such as cocaine and amphetamine directly stimulate these centers, while opiates free the pathways from inhibitory control. Nicotine, on the other hand, reaches the brain in as little as 10-20 seconds, where it stimulates nicotine receptors to cause dopaminergic neurons to release large quantities of dopamine. After a few hours, dopamine levels decline, causing withdrawal symptoms to readily appear (e.g., anxiety, irritability, and inattentiveness). When cigarette smokers say they need a smoke to steady their nerves, what they really mean is that they have to contend with nicotine withdrawal. 

Clonidine [KLOE ni deen] is an a2 agonist that is used in essential hypertension to lower blood pressure because of its action in the CNS (see p. 189). It can be used to minimize the symptoms that accompany withdrawal from opiates or benzodiazepines. Clonidine acts centrally to produce inhibition of sympathetic vasomotor centers. Recently, an endogenous substance, agmantine, which appears to be the natural ligand at clonidine binding sites, has been identified. 

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