Subdivisión de la función Foco

Several data from the literature define the relationship between depressive states and alcohol abuse, though controversy continues about the dynamics that link different kinds of depressive syndromes and alcohol-related problems. Most authors agree in considering heavy drinking as an equivalent, or a masked form, of depression [133]. Patients who con- tinue to drink, despite severe or advanced so- matic consequences, display a peculiar form of depression [133]. Alcoholism stems from de- pressive states, which are mostly of minor se- verity and a disguised kind [174]. Other stud- ies have described a significant association between bipolar disorders and alcohol abuse. According to Kraepelin, as many as 25% of bi- polar patients abused alcoholic drinks [88].

Several authors conclude that alcohol abuse mostly characterizes depressive states, and is resorted to as a way to elate mood and soothe pain, whereas alcohol use during states of mood elation is a sign of excitement and impulsiveness [20]. DSM also has suggested a close link between cyclothymia and alcohol abuse. Chronic depression too has been asso- ciated with alcohol abuse. It is not surprising, therefore, that alcohol use, which can stand as an addictive disease itself in some cases, is of- ten found combined with substance abuse in general. Studies in the literature have increas- ingly reported an association between heroin and alcohol abuse [5, 8, 13, 14, 25, 33, 61, 69, 87, 123, 144, 149]. Alcohol abuse seems to be

related to polyabuse, and mainly affects young addicts; among these, lifetime rates for alcohol- ism range between 10 and 75%. The National Drug Alcohol Collaborative Project (NDACP) reported a rate of 43% for combined alcohol- heroin use in a sample of over 1500 heroin addicts [25]. Heroin was the first substance to be abused in 99% of cases. Rounsaville re- ported a lifetime and index prevalence of alco- hol dependence of 13% and 34%, respectively [143]. Californian addicts have been reported to abuse alcohol at a rate of 53-75%, and 11% have been admitted to hospitals for alcohol- related somatic matters. Alcohol abuse occurs as often as 10-20% among street addicts, and up to 27% among methadone-maintained sub- jects [5, 61]. Some authors have tried to explain the increase in alcohol use during methadone treatment programmes, concluding that meth- adone-maintained addicts may abuse alcohol in order to counter the opioid-normalizing effect of methadone, and to go beyond the methadone-heightened opioid threshold [5, 61, 180]. When the correlation between alcohol use and heroin use among methadone-main- tained addicts was examined in a large sample of heroin addicts, it was pointed out that alco- hol use during methadone treatment seems to be the result of an automatic behavioural pat- tern, according to which alcohol use tends to rise as street-opiate use falls, and the reverse [5]. Furthermore, Rounsaville, who supports this theory, also reports that alcohol use is mostly found in addicts who had once abused alcohol, so displaying a relapse into a previous alcohol-related disorder [143].

On the basis of their clinical experience, Maremmani and Shinderman suggest that the use of alcohol, benzodiazepines and other types of drug in heroin addicts may be corre- lated with a condition of opiate dependence improperly compensated by street heroin or by substitution treatment dosages. Thus the search for an appropriate methadone dosage during methadone maintenance is crucial not only because it raises the retention rate for pa- tients within the treatment group, so allowing an improvement in social rehabilitation, but also because it lowers the risk of polydrug abuse [109, 110].

7.1 Psychopharmacotherapy of heroin addicts

with alcohol dependence

Alcohol undoubtedly has a negative influ- ence on the outcome of a methadone mainte- nance programme. It implies a more severe cognitive and behavioural disturbance, a high- er prevalence of psychiatric disorders, and a lower degree of compliance, which often con- ditions an operator towards a quicker, prema- ture tapering of methadone [40, 140]. Moreover, alcohol dependence has more serious somatic consequences (e.g. chronic hepatic failure), which can lead to premature death or may fa- vour overdosing accidents, due to interference with the methadone metabolism [55]. Since both addictions need to be treated at the same time, disulfiram was tried first on methadone- maintained patients, but, though the complete safety of the combination was ascertained [26, 93, 169], its efficacy is still controversial, as di- sulfiram is mostly equivalent to placebo [93]. The decrease in alcohol consumption appears to depend on a subject’s compliance with the combined treatment; this depends in its turn on the level of the subject’s awareness of the severity of the problem [93]. It is awkward to get addicted patients to take disulfiram daily: as an alternative, subcutaneous implantations can be resorted to, as long as patients consent; or else, methadone administration may be al- lowed, but only as long as compliance with di- sulfiram treatment is shown. Another strategy is not to provide patients with methadone if there is a positive result to the screening test for alcohol on the breath (revealing alcohol use during the previous 12 hours) or abnormally high alcohol blood levels. This procedure does not guarantee that patients will abstain from alcohol after their methadone has been admin- istered. Table 6 reports the feasible combina- tions of psychotropics with methadone, as ob- served by the PISA-SIA Group.

The combined use of methadone and di- sulfiram should be limited to the most severe cases, or at least to cases in which non-com- pliance has hampered the feasibility of other treatments. Apart from such cases, different pharmacotherapies, supportive approaches or

psychosocial treatment should be used. Naltrexone, though useful in pure alcohol- ics, is unsuitable for alcohol-dependent heroin addicts. During naltrexone treatment, in fact, substance abuse (like benzodiazepines and stimulants) has been reported to increase [97]. One possible explanation is the following: heroin is capable of inducing a strong craving, which reinforces heroin taking. Naltrexone blocks the heroin-induced reward, so leading craving to extinction, but at the same time, it ends up by intensifying the hypophoria caused by lack of opioid stimulation. Naltrexone- treated subjects may therefore resort to alcohol or BDZ to soothe late withdrawal symptoms and naltrexone-enhanced hypophoria

7.2 GHB for alcohol-dependent heroin ad-

dicts

GHB is a general anaesthetic drug which is no longer used for its original purpose. GHB has several pharmacological properties: at an- aesthetic dosages, it causes an increase in do- pamine levels in several cerebral areas, which follows a widespread inhibition of CNS neuro- nal activity. Lower dosages seem to selectively raise dopamine transmission in the mesence- phalic ventral tegmental area [46, 47, 78, 95, 171]. Some of GHB’s pharmacological prop- erties are particularly interesting: it binds to many different sites, none of them associated with GABA-A receptors, whereas, it does bind to GABA-B receptors; it substitutes for ethanol

in rats; moreover, it has been proved to de- crease ethanol consumption in alcoholics [50, 56, 101, 111]. Hence, GHB may be used in al- cohol-dependent heroin addicts, and be added on to methadone even when it is administered at high dosages, like those needed to control heroin use [105].

It is worth mentioning the case of a female heroin addict displaying alcohol dependence, who became stabilized on methadone when treated at the PISA-SIA Group. F.M. was a 31- year-old unemployed woman, with a 10-year history of heroin addiction, at that stage a poly- abuser and HIV-positive. She had been treated with 10 mg/day methadone at a Local Service, and was drunk with alcohol when first ob- served at the PISA-SIA Group Service. She was judged to be one of the most severe cases ever observed. After 24 days of treatment, she had cut down on her alcohol consumption by 70%, and her CGI score of 3 indicated a mild form of disease, so recording a major therapeutic gain combined with the absence of major side-ef- fects. She was given GHB at an average dose of 27 cc/day (min. 20, max. 30), together with methadone at an average dose of 27 mg/day (min. 10, max. 30) and clonazepam, on average 4.75 mg/day (min. 2, max. 9). Trimipramine, 100 mg, was also used in the evening to con- trol insomnia. During the subsequent phases of stabilization and maintenance, GHB dose was gradually increased up to 60 cc/day, to be maintained for at least one year. Maintenance lasted 7 years, until the patient passed away due to AIDS. At the time she died, she was re- ceiving methadone, 40 mg/day, while GHB, Table 6. Pharmacological interactions and dosages in methadone maintained alcoholics heroin addicts according to the experience of PISA-SIA Group

Dosages (mg/daily) Min Mean Max Methadone, stabilization dosage 240 310 380

GHB 10 27 30

Clonazepam 2 5 9

Trimipramine 50 70 100 §Use caution during the methadone induction phase. Re-evaluate methadone dosage if patient is already in treatment

previously given at 10 cc/day, had recently been tapered off.