Methadone addiction

Gossop M Strang J (1991). A comparison of the withdrawal responses of heroin and methadone addicts during detoxification. British Journal of Psychiatry, 158, 697-9... 

Scott R (1990). The prevention of convulsions during benzodiazepine withdrawals. British Journal of General Practice, 40, 261 Seifert J, Metzner C, Paetzold W, Borsutzky M, Ohlmeier M, Passie T, Hauser U, Becker H, Wiese B, Emrich HM Schneider U (2005). Mood and affect during detoxification of opiate addicts a comparison of buprenorphine versus methadone. Addiction Biology, 10, 157-64... 

T.A. Slotkin, W.L. Whitmore, M. Salvaggio and F.J. Seidler, Perinatal methadone addiction affects brain synaptic development of biogenic amine systems in the rat, Life Sci., 24 (1979) 1223-1230. 

Three of the four subjects on the methadone study refused to continue with the experiments, an event which rarely happens at the U.S. Public Health Service laboratory in Lexmgton, Kentucky, after they had experienced the abstinence syndrome precipitated by iV-allylnormorphine. The acute syndrome precipitated by IV-allylnormorphine in methadone addicts contrasts strikingly with the mild changes which are observed after abrupt withdrawal of methadone. The subjects who refused to continue with the methadone study exhibited only lethargy, anorexia, and irritability during the first week after abrupt termination of methadone administration. N-Allylnormorphine failed to precipitate abstinence phenomena 3 days after completion of withdrawal of methadone by rapid reduction in the subject who continued with the study. 

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. 

More radical dissection of the morphine molecule was in progress concurrently with the work above. The chemistry of the series of analgesics that rely on an acyclic skeleton, the compounds related to methadone, is discussed earlier. Suffice it to say that this series of agents, with the possible exception of propoxyphene, seem to share abuse and addiction potential with their polycyclic counterparts. 

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. 

Detoxification of and temporary maintenance of narcotic addiction (methadone)... 

Two opioids are used in the treatment and management of opiate dependence levomethadyl and methadone. Levomethadyl is given in an opiate dependency clinic to maintain control over the delivery of the drug. Because of its potential for serious and life-threatening proarrhythmic effects, levomethadyl is reserved for use in the treatment of addicted patients who have no response to other treatments. Levomethadyl is not taken daily the drug is administered three times a week (Monday/Wednesday/Thursday or Tuesday/Thursday/ Saturday). Daily use of the usual dose will cause serious overdose. 

Methadone, a synthetic narcotic, may be used for the relief of pain, but it also is used in the detoxification and maintenance treatment of those addicted to narcotics. Detoxification involves withdrawing the patient from the narcotic while preventing withdrawal symptoms. 

Maintenance therapy is designed to reduce the patient s desire to return to the drug that caused addiction, as well as to prevent withdrawal symptoms. The dosses used vary with the patient, die length of time die individual has been addicted, and the averse amount of drug used each day. Fhtients enrolled in an outpatient methadone program for detoxification or maintenance therapy on methadone must continue to receive methadone when hospitalized. 

A protracted abstinence syndrome may follow the acute opioid withdrawal syndrome and last for many weeks (Martin et al. 1973). In one study ofher-oin addicts detoxified with methadone, withdrawal distress peaked at day 20,... 

The approval of buprenorphine for the office-based treatment of opioid dependence represents a major departure from the earlier methadone clinic system. Physicians with addiction specialist credentials or those who have completed 8 hours of approved training can become qualified to treat up to 30 patients in their private offices. Stable patients may be given prescriptions for up to a month of medication. The combination buprenorphine/naloxone tablet is expected to have minimal risk for diversion. When taken subhnguaUy, as prescribed, naloxone has minimal biologic activity and does not interfere with the buprenorphine dose. However, if an attempt is made to inject the drug, the addict will experience the full antagonist effect of the naloxone. 

It is anticipated that buprenorphine will be an acceptable treatment for younger addicts and for individuals with smaller habits and shorter histories of dependence, thus permitting earlier intervention in the course of the addiction. Clinical experience suggests that buprenorphine is less effective for individuals with larger opioid habits. Methadone or LAAM remains the preferred medication for those patients. 

The factors that correlate with treatment success do not clearly apply to success after detoxification from methadone maintenance. Correlates of successful detoxification include 1) less criminal behavior 2) more stable family 3) more stable employment 4) shorter drug history 5) long maintenance with lower dosage and 6) discharge status, with patient and staff consensus as opposed to unilateral discharge from treatment (Dole and Joseph 1978). In one study, addicts were followed an average of 2 years after detoxification (Stim-mel et al. 1977). Although only 28% of the total sample remained abstinent, 83% of those who had fully completed treatment remained abstinent. Another study of 105 patients detoxified after methadone maintenance treatment documented an 82% relapse rate within 12 months (Ball and Ross 1991). These... 

A 2.5-yeat follow-up study of opioid addicts in methadone maintenance treatment found that prevalence of cocaine use only shghtly declined and that... 

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

Bale RN, Zarconc VP, VanStone WW, et al Three therapeutic communities a prospective controlled study of narcotic addiction treatment process and two-year follow-up results. Arch Gen Psychiatry 41 185—191, 1984 Ball JC, Ross A The Effectiveness of Methadone Maintenance Treatment. New York, Springer-Verlag, 1991... 

Ball JC, Lange WR, Myers CP, et al Reducing the risk of AIDS through methadone maintenance treatment. J Health Soc Behav 29 214—226, 1988b Bare LA, Mansson E, Yang D Expression of two variants of the human mu opioid receptor mRNA in SK-N-SH cells and human brain. FEES Lett 354 213—216, 1994 Barr HL, Cohen A Abusers of alcohol and narcotics who are they Int J Addict 22 52 5— 541, 1987... 

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