Depression methadone

Methadone is a synthetic opioid, clinically available in the U.S. since 1947.8 It exists in the dextro- and levo-rotatory forms with the levo-isoform possessing approximately 8 to 50 times more pharmacological activity.27 34 Methadone acts on the CNS and cardiovascular system producing respiratory and circulatory depression. Methadone also produces miosis and increases the tone of smooth muscle in the lower gastrointestinal tract while decreasing the amplitude of contractions. It is used clinically for the treatment of severe pain and in maintenance programs for morphine and heroin addicts.34... 

A placebo-controlled study in 31 depressed methadone-maintained patients found that sertraline significantly increased the methadone plasma level/dose ratio by 26% while patients on placebo had a 16% decrease after 6 weeks treatment, but by 12 weeks ratios had shifted towards baseline values. Adverse effects were similar in both groups. A 31-year-old woman taking methadone 230 mg daily was found to have a prolonged QT interval after taking sertraline 50 mg daily was added to her medications, although she was asymptomatic. The QT interval returned to normal when the methadone and sertraline were stopped and her methadone was replaced with morphine. ... 

Dean AJ, Bell J, Mascord DJ, et al A randomized, controlled trial of fluoxetine in methadone maintenance patients with depressive symptoms. J Affect Disord 72 ... 

Kleber HD, Weissman MM, Rounsaville BJ, et al Imipramine as treatment for depression in addicts. Arch Gen Psychiatry 40 649-633, 1983 Kleber HD, Riordan CE, Rounsaville BJ, et al Clonidine in outpatient detoxification from methadone maintenance. Arch Gen Psychiatry 42 391-394, 1983 Kleber HD, Topazian M, Gaspari J, et al Clonidine and naltrexone in the outpatient treatment of heroin withdrawal. Am J Drug Alcohol Abuse 13 1-17, 1987 Kornetsky C. Brain stimulation reward, morphine-induced stereotypy, and sensitization implications for abuse. Neurosci Biobehav Rev 27 777-786, 2004 Kosten TR, Kleber HD Buprenorphine detoxification from opioid dependence a pilot study. Life Sci 42 633-641, 1988... 

Nestler EJ, Hyman SE, Malenka RC Molecular Neuropharmacology A Foundation for Clinical Neuroscience. New York, McGraw Hill, 2001 Novick DM, Pascarelli EE, Joseph H, et al Methadone maintenance patients in general medical practice a preliminary report. JAMA 259 3299—3302, 1988 Nunes EV, Quitkin EM, Donovan SJ, et al. Imipramine treatment of opiate-dependent patients with depressive disorders a placebo-controlled trial. Arch Gen Psychiatry 55 153-160, 1998... 

Wikler A Opioid Dependence Mechanisms and Treatment. New York, Plenum, 1980 Williams JT, Christie MJ, Manzoni O Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev 81 299—343, 2001 Woody GE, O Brien CR, Rickels K Depression and anxiety in heroin addicts a placebo-controlled study of doxepin in combination with methadone. Am J Psychiatry 132 447--i50, 1975... 

Schmitz JM, Averill P, Stotts AL, et al Fluoxetine treatment of cocaine-dependent patients with major depressive disorder. Drug Alcohol Depend 63 207-214,2001 Schottenfeld RS, Pakes JR, Oliveto A, et al Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse. Arch Gen Psychiatry 54 713-720, 1997... 

Depressants alcohol, barbiturates Opioids heroin, morphine, methadone... 

Codeine, hydrocodone, morphine, methadone, and oxycodone are substrates of the cytochrome P-450 isoenzyme CYP2D6.47 Inhibition of CYP2D6 results in decreased analgesia of codeine and hydrocodone due to decreased conversion to the active metabolites (e.g., morphine and hydromorphone, respectively) and increased effects of morphine, methadone, and oxycodone. Methadone is also a substrate of CYP3A4, and its metabolism is increased by phenytoin and decreased by cimetidine. CNS depressants may potentiate the sedative effects of opiates. 

Respiratory depression Accidental overdose with long-acting opioids (eg, methadone, levomethadyl) may result in prolonged respiratory depression. While nalmefene has a longer duration of action than naloxone in fully reversing doses, be aware that a recurrence of respiratory depression is possible. Observe patients until there is no reasonable risk of recurrent respiratory depression. 

For the complete or partial reversal of narcotic depression, including respiratory depression, induced by opioids including natural and synthetic narcotics, propoxyphene, methadone, nalbuphine, butorphanol, and pentazocine. Also indicated for the diagnosis of suspected acute opioid overdosage. 

Deaths, cardiac and resp have been reported during initiation and conversion of pain pts to methadone Tx from Tx w/ other opioids Uses Severe pain detox w/ maint of narcotic addiction Action Narcotic analgesic Dose Adults. 2.5-10 mg IM q3-8h or 5-15 mg PO q8h titrate as needed Feds. 0.7 mg/kg/24 h PO or IM -s- q8h T slowly to avoid resp depression X in renal impair Caution [B/D (prolonged use/high doses at term), + (w/ doses =/> 20 mg/24 h)], severe liver Dz Disp Tabs, inj SE Resp depression, sedation, constipation, urinary retention, T QT interval, arrhythmias Interactions T Effects W/ cimetidine, CNS depressants, protease inhibitors EtOH T effects OF anticoagulants, antihistamines, barbiturates, glutethimide, methocarbamol ... 

Propoxyphene (dextropropoxyphene Darvon) is structurally related to methadone but is much less potent as an analgesic. Compared with codeine, propoxyphene is approximately half as potent and is indicated for the treatment of mild pain. It is not antipyretic or antiinflammatory like aspirin and is less useful than aspirin in most cases of mild pain. Toxicity from propoxyphene, especially in combination with other sedatives, such as alcohol, has led to a decrease in its use. Death following ingestion of alcohol in combination with propoxyphene can occur rapidly (within 20 minutes to 1 hour). The drug is not indicated for those with histories of suicide or depressive illnesses. 

Another complication which can be expected in a methadone detoxification, seemingly more even than in other methods, is that of mood disturbances. In a comparison of methadone and buprenorphine withdrawal courses, actually in addition to carbamazepine, Seifert et al. (2005) found more tiredness, sensitivity in mood and depression in the (randomly assigned) methadone patients, which situation can lead to either tranquillizers or antidepressants being considered. 

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