The most common side effects reported with<unk>  are gastrointestinal complaints such as diarrhea and abdominal cramping. These adverse effects are analogous to the symptoms of opioid withdrawal, as the μ-opioid receptor blockade will increase gastrointestinal motility. The side effects of<unk>  by incidence are as follows: * Greater than 10%: difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea and/or vomiting, low energy, joint/muscle pain, and headache. * Less than 10%: loss of appetite, diarrhea, constipation, thirstiness, increased energy, feeling down, irritability, dizziness, skin rash, delayed ejaculation, erectile dysfunction, and chills. * A variety of other adverse events have also been reported with less than 1% incidence. Opioid withdrawal<unk>  should not be started until several (typically 7–10) days of abstinence from opioids have been achieved. This is due to the risk of acute opioid withdrawal if<unk>  is taken, as<unk>  will displace most opioids from their receptors. The time of abstinence may be shorter than 7 days, depending on the half-life of the specific opioid taken. Some physicians use a<unk> oxone challenge to determine whether an individual has any opioids remaining. The challenge involves giving a test dose of<unk> oxone and monitoring for opioid withdrawal. If withdrawal occurs,<unk>  should not be started. Aversive effects Whether<unk>  causes dysphoria, depression, anhedonia, or other aversive effects as side effects or not has been studied and reviewed. In early studies in normal and opioid-abstinent individuals, acute and short-term administration of<unk>  was reported to produce a variety of aversive effects including fatigue, loss of energy, sleepiness, mild dysphoria, depression, lightheadedness, faintness, mental confusion, nausea, gastrointestinal disturbances, sweating, and occasional feelings of unreality. However, these studies were small, often uncontrolled, and used subjective means of assessing side effects. Most subsequent longer-term studies of<unk>  for indications like alcohol or opioid dependence have not reported dysphoria or depression with<unk>  in most individuals. According to one source: :<unk>  itself produces little or no psychoactive effect in normal research volunteers even at high doses, which is remarkable given that the endogenous opioid system is important in normal hedonic functioning. Because endogenous opioids are involved in the brain reward system, it would be reasonable to hypothesize that<unk>  might produce anhedonic or dysphoric effects. Although some evidence from small, early trials suggested that patients with a history of opiate dependence might be susceptible to dysphoric effects in response to<unk>  (Crowley et al. 1985; Hollister et al. 1981), reports of such effects have been inconsistent. Most large clinical studies of recovering opioid-dependent individuals have not found<unk>  to have an adverse effect on mood (Greenstein et al. 1984; Malcolm et al. 1987; Miotto et al. 2002; Shufman et al. 1994). Some studies have actually found improvements in mood during the course of treatment with<unk>  (Miotto et al. 1997; Rawlins and Randall 1976). Hence, surprisingly,<unk>  seems to have minimal untoward influence in these areas at least with long-term therapy based on available evidence. It has been suggested that differences in findings between acute and longer-term studies of<unk>  treatment might be related to changes in the opioid system with chronic administration of<unk> . For example, marked upregulation of opioid receptors and supersensitivity to opioids have been observed with<unk>  in preclinical studies. Another possibility is that the central opioid system may have low endogenous tone in most individuals, becoming active only in the presence of exogenously administered opioid receptor agonists or with stimulation by endogenous opioids induced by pain or stress. A third possibility is that normal individuals may experience different side effects with<unk>  than people with addictive disease such as alcohol or opioid dependence, who may have altered opioid tone or responsiveness. It is notable in this regard that most studies of<unk>  have been in people with substance dependence.<unk>  may also initially produce opioid withdrawal-like symptoms in a small subset of people not dependent on opioids: : The side-effect profile of<unk> , at least on the recommended dose of 50 mg per day, is generally benign, although 5 to 10 percent of detoxified opioid addicts experience immediate, intolerable levels of withdrawal-like effects including agitation, anxiety, insomnia, light-headedness, sweating, dysphoria, and nausea. Most patients on<unk>  experience few or no symptoms after the first 1 to 2 weeks of treatment; for a substantial minority (20 to 30 percent) protracted discomfort is experienced. Persisting affective distress related to<unk>  may account for individuals on the drug who drop out of treatment.<unk>  has been reported to reduce feelings of social connection. Studies on whether<unk>  can decrease the pleasurable effects of listening to music are conflicting. Besides humans,<unk>  has been found to produce aversive effects in rodents as assessed by conditioned place aversion. Liver damage<unk>  has been reported to cause liver damage when given at doses higher than recommended. It carries an FDA boxed warning for this rare side effect. Due to these reports, some physicians may check liver function tests prior to starting<unk> , and periodically thereafter. Concerns for liver toxicity initially arose from a study of nonaddicted obese patients receiving 300 mg of<unk> . Subsequent studies have suggested limited or no toxicity in other patient populations and at typical recommended doses such as 50 to 100 mg/day.
Naltrexone
Normethadone
Isomethadone
Methadone
Buprenorphine
Guanfacine
Nabilone
Atomoxetine