Dosing Tips

• Providing educational materials and counseling in combination with naltrexone treatment can increase the chances of success

• Individuals who abstain from alcohol for several days prior to initiating treatment with naltrexone may have greater reductions in the number of drinking days as well as number of heavy drinking days, and may also be more likely to abstain completely throughout treatment

• Long-acting naltrexone (injection) must be kept refrigerated

• For long-acting naltrexone (injection), the suspension should be administered immediately after mixing

• Adherence greatly enhanced and assured for 30 days at a time when administering by once monthly depot injection; oral treatment requires 30 decisions to comply in 30 days whereas long-acting injection requires only one decision every 30 days to comply

• Patients must be completely withdrawn and abstinent from opioids for 5 days (short-acting opioids) to 7 days (long-acting opioids) before starting naltrexone

Overdose

• Nausea, abdominal pain, sedation, dizziness, injection site reactions

Long-Term Use

• Has been studied in trials up to one year

Habit Forming

• No

How to Stop

• Taper not necessary

Pharmacokinetics

• Elimination half-life of oral naltrexone is approximately 13 hours

• Elimination half-life of naltrexone via injection is 5–10 days

Drug Interactions

• Is hepatically metabolized by dihydrodiol dehydrogenase and not by the CYP450 enzyme system, and thus is unlikely to be affected by drugs that induce or inhibit CYP450 enzymes

• Can block the effects of opioid-containing medications (e.g., some cough and cold remedies, antidiarrheal preparations, opioid analgesics)

• Concomitant administration with acamprosate may increase plasma levels of acamprosate, but this does not appear to be clinically significant and dose adjustment is not recommended

Other Warnings/Precautions

• Can cause hepatocellular injury when given in excessive doses

• To prevent withdrawal in patients dependent on opioids, patients must be opioid free for at least 7–10 days prior to initiating treatment

• Attempts by patients to overcome blockade of opioid receptors by taking large amounts of exogenous opioids could lead to opioid intoxication or even fatal overdose

• Individuals who have been previously treated with naltrexone should be warned that they may respond to lower doses of opioids than previously used, and thus previous doses may also lead to opioid intoxication

• Individuals receiving naltrexone who require pain management with opioid analgesia may need a higher dose than usual and may experience deeper and more prolonged respiratory depression; pain management with non-opioid or rapid acting opioid analgesics is recommended if possible

• Monitor patients for emergence of depressed mood or suicidality

• Use cautiously in individuals with known psychiatric illness

• Injection should be used cautiously in individuals with thrombocytopenia or any coagulation disorder

Do Not Use

• If patient is taking opioid analgesics

• If patient is currently dependent on opioids or is in acute opiate withdrawal

• If patient has failed the naloxone challenge test or has a positive urine screen for opioids

• If patient has acute hepatitis or liver failure

• If there is a proven allergy to naltrexone

• If there is a proven allergy to polylactideco-glycolide (PLG), arboxymethylcellulose, or any other components of the diluent (injection)

NALTREXONE: SPECIAL POPULATIONS

Renal Impairment

• Dose adjustment not generally necessary for mild impairment

• Not studied in moderate to severe renal impairment

Hepatic Impairment

• Has the potential to cause hepatocellular injury when given in excessive doses

• Dose adjustment not generally necessary for mild impairment

• Not studied in severe hepatic impairment

• Contraindicated in acute hepatitis or liver failure

Cardiac Impairment

• Limited available data

Elderly

• Safety and efficacy have not been established

• Some patients may tolerate lower doses better

Children and Adolescents

• Safety and efficacy have not been established

Pregnancy

• Risk Category C [some animal studies show adverse effects; no controlled studies in humans]

• Pregnant women needing to stop drinking may consider behavioral therapy before pharmacotherapy

• Not generally recommended for use during pregnancy, especially during first trimester

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or bottle feed

NALTREXONE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Individuals who are not ready to abstain completely from alcohol

• For binge drinkers

Potential Disadvantages

• Patients who “drink over” their treatment, including their long-acting injection

• Less effective in patients who are not abstinent at the time of treatment initation

Primary Target Symptoms

• Alcohol dependence

Pearls

• Not only increases total abstinence, but also can reduce days of heavy drinking

• May be a preferred treatment if the goal is reduced-risk drinking (i.e., 3–4 drinks per day in men, maximum 16 drinks per week; 2–3 drinks per day in women, maximum 12 drinks per week)

• Less effective in patients who are not abstinent at the time of treatment initiation

• Some patients complain of apathy or loss of pleasure with chronic treatment

• The combination of naltrexone and bupropion has demonstrated efficacy as treatment for obesity and is currently being evaluated in a long-term study to assess the cardiovascular health outcomes of this treatment

Suggested Reading

Anton RF, O’Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 2006;295(17):2003–17.

Johansson BA, Berglund M, Lindregn A. Efficacy of maintenance treatment with naltrexone for opioid dependence: a meta-analytical review. Addiction 2006;101(4):491–503.

Mannelli P, Peindl K, Masand PS, Patkar SS. Long-acting injectable naltrexone for the treatment of alcohol dependence. Expert Rev Neurother 2007;7(10):1265–77.

Rosner S, Leucht S, Lehert P, Soyka M. Acamprosate supports abstinence, naltrexone prevents excessive drinking: evidence from a meta-analysis with unreported outcomes. J Psychopharmacol 2008;22:11–23.

NEFAZODONE

NEFAZODONE: THERAPEUTICS

Brands

• Dutonin

see index for additional brand names

Generic?

Yes

Class

• SARI (serotonin 2 antagonist/reuptake inhibitor); antidepressant

Commonly Prescribed for

(bold for FDA approved)

• Depression

• Relapse prevention in MDD

• Panic disorder

• Posttraumatic stress disorder (PTSD)

How the Drug Works

• Blocks serotonin 2A receptors potently

• Blocks serotonin reuptake pump (serotonin transporter) and norepinephrine reuptake pump (norepinephrine transporter) less potently

How Long Until It Works

• Can improve insomnia and anxiety early after initiating dosing

• Onset of therapeutic actions usually not immediate, but often delayed 2-4 weeks

• If it is not working within 6-8 weeks for depression, it may require a dosage increase or it may not work at all

• May continue to work for many years to prevent relapse of symptoms

If It Works

• The goal of treatment is complete remission of current symptoms as well as prevention of future relapses

• Treatment most often reduces or even eliminates symptoms, but not a cure since symptoms can recur after medicine stopped

• Continue treatment until all symptoms are gone (remission)

• Once symptoms gone, continue treating for 1 year for the first episode of depression

• For second and subsequent episodes of depression, treatment may need to be indefinite

• Use in anxiety disorders may also need to be indefinite