What are the common side-effects associated with opioid treatment, and how can they be managed? It is very important that GPs anticipate, recognise, and treat side-effects when patients are receiving opioids for pain. Common side-effects at the start of therapy or after dose escalation include somnolence, mental clouding, nausea, and constipation. Uncommon side-effects include fatigue, itching, adverse mood changes, dry mouth, loss of appetite, bloating, heartburn, urinary hesitancy, sweating, sexual dysfunction, headache, fluid retention, and sometimes significant weight gain. Although any side effect can persist, the most common long-term side effect is constipation. With overdose, opioids can cause serious respiratory depression, the risk of which is highest in the patient with limited or no ongoing opioid treatment. GPs should periodically enquire about side effects. If side effects are present and not well tolerated, treatment should be adjusted. This discussion assumes that the patient indicates that the opioid regimen does produce acceptable pain relief. The drug or how it is administered can be changed, or a specific treatment can be given for the side-effects. Typically, successful treatment depends on achieving and maintaining a favourable balance between analgesia and side-effects. Constipation is very common during opioid therapy, particularly among those patients who are predisposed (the elderly, patients taking other constipating drugs, patients with diseases that affect the gastrointestinal tract). Tolerance may not develop to opioid-induced constipation, and laxative therapy, attention to diet, and other bowel hygiene initiatives may be needed throughout the course of therapy. Somnolence and mental clouding are common when therapy is initiated or the dose is increased. Although these effects typically decline over time, some patients experience persistent impairment. The risk presumably is higher among those who are concurrently using other CNS depressants and those with diseases associated with encephalopathy. Nausea and vomiting may be treated with antiemetics such as phenothiazines, butyrophenones, or metoclopramide. When nausea is due to motion-related vestibular effects, a trial of an antihistamine, such as meclizine or scopolamine, should be considered. If opioid-induced gastroparesis is suspected (postprandial nausea, bloating, reflux symptoms), metoclopramide is a preferred drug because of its positive effects on gastrointestinal motility. To help manage nausea, it may be worthwhile to consider switching to a non-oral route of administration, at least for a time. Itching, which results at least in part from the release of histamines triggered by opioids, usually resolves within a few days. If itching persists, it may be treated with an antihistamine. Itching or skin reactions can occur with the use of transdermal patch systems. Please refer to the manufacturers’ instructions on recommendations should this problem arise. Respiratory depression is a rare adverse effect during chronic opioid treatment and will mainly occur in major overdose situations. Respiratory depression is possible if dose escalation occurs very quickly, beyond the ability of compensatory mechanisms to adjust; if some intercurrent cardiopulmonary event occurs (for example, pulmonary embolism or pneumonia), or if something happens to eliminate the source of the pain (for example, a nerve block). Except in rare circumstances, respiratory depression is preceded by somnolence and slowed breathing. Respiratory depression that occurs from some intercurrent cardiopulmonary event may be partially reversed by naloxone. Accordingly, a response to naloxone does not mean that the opioid was the primary problem. When patients develop respiratory depression in the setting of stable dosing, a prompt search for another cause usually is indicated, even if the patient improves with naloxone.