Progress in Neuro-Psychopharmacology and Biological Psychiatry
Buprenorphine treatment outcome in dually diagnosed heroin dependent patients: A retrospective study
Introduction
A variety of studies has indicated the need of further research to determine if buprenorphine (BUP) treatment is more effective in particular settings or in particular subgroups of patients (Barnett et al., 2001). The hypothesis that a specific subtype of addicted individuals may be benefiting from BUP was also formulated by Fischer et al., 1999a, Fischer et al., 1999b but the pronostic factors able to characterize patients-subtypes and to predict BUP outcome are still unclear and confused.
Patients who dropped out from BUP treatment were reported to differ significantly from those who stayed, in terms of lower level of social integration and a higher level of psychopathological symptoms (Pani et al., 2000), without any apparent relationship between specific dual diagnoses and outcome measures.
The evidence of buprenorphine effectiveness in the pharmacological treatment of affective disorders was reported many years ago. A double blind investigation showed BUP to induce strong antidepressant effects in patients with endogenous depression (Emrich et al., 1983). Accordingly, depressive symptoms were found to decrease significantly in the heroin addicted patients who were depressed at intake to BUP treatment (Kosten et al., 1990).
Buprenorphine was re-tested as antidepressant in non-addicted individuals. In an open-label study, subjects with treatment-refractory, unipolar major depression showed clinical improvement in both subjective and objective measures of depression after BUP treatment (Bodkin et al., 1995).
The reports of Schottenfeld et al. (1998) indicate that a significantly better retention during BUP treatment for heroin addiction was associated with female gender with lifetime sedative dependence: the reason of a more positive outcome in these patients could be due to unrecognised depression that was repeatedly reported to be associated with benzodiazepines inappropriate treatment and dependence (Kupfer, 1999, Voyer et al., 2005, Valenstein et al., 2004), particularly among female patients (Sonnenberg et al., 2003).
In agreement with these evidence, our previous findings (Gerra et al., 2004), obtained in a 12-week observational study, indicated that BUP might obtain more successful results in the subgroup of patients affected by depression, both in terms of retention and opioid negative urines, in comparison with non-depressed individuals.
Although research has repeatedly suggested that buprenorphine may possess a specific antidepressant activity, contrasting data have been also reported in this field. Substitution treatment, with both buprenorphine and methadone, was found to improve depressive symptoms, with no differential benefit on depression for buprenorphine patients (Dean et al., 2004). Moreover, buprenorphine in association with desipramine was found to obtain a poor outcome in depressed opioid-dependent patients, casting doubts about its effectiveness in this subgroup of addicted individuals (Kosten et al., 2004).
For these reasons, in the present multi-centre retrospective study we decided to investigate the effectiveness of BUP maintenance treatment, in relationship with dual diagnosis, in a sample of heroin dependent outpatients.
Aim of the study was to evaluate whether or not comorbid psychopathologies were able to influence the endpoints of retention rate and reduction of illicit drug use during BUP treatment. The hypothesis was that BUP treatment outcome may be different in patients subgroups, not only in relationship with addiction severity or dose levels, but also with individual personality traits and comorbid psychiatric disorders. The mu-receptors agonist/kappa antagonist profile of buprenorphine could exert a specific action on the neurobiological changes underlying the psychiatric disorders that are commonly found in association with addictive behavior.
The study was conducted to determine retrospectively the responses of heroin dependent patients to BUP, in the first 12 months of a long-term treatment, measuring psychiatric diagnoses capacity to affect retention rates and positive urine rates.
Section snippets
Study population
Heroin-dependent subjects were selected from among patients participating in Milan, Caserta (Naples), Parma and Rome Addiction Services Programs (Servizi Tossicodipendenze—Ser.T) of the public health system during the period 2002–2003. Addiction Services in Italy provide outpatients treatment programs, with different therapeutic and rehabilitative strategies: methadone, BUP and naltrexone are administered in association with possible psychosocial intervention, such as psychotherapy, family
Demographic and clinical history data
As reported in Table 1, no significant differences in mean age, gender, daily heroin dose, years of heroin addiction history, other non-prescribed psychotropic drugs use (lifetime), interpersonal relationships quality, job performance, alcohol problems and previous METH and residential treatment rates were evidenced in the 5 subgroups. Antisocial patients (Group 3) had a significantly higher rate of legal problems, in comparison with all other groups (t = 2.9 p < 0.005; t = 2.6 p < 0.01; t = 3.1 p < 0.005;
Discussion
At this retrospective multi-centre evaluation, BUP maintenance treatment seems to obtain a better outcome, in terms of retention in treatment and negative urines, in depressed heroin dependent patients, in comparison with the other dually diagnosed patients and addicted individuals without psychiatric comorbidity. Alternatively, the subgroups of patients affected by cluster B personality disorders (antisocial and borderline) and schizophrenia appeared less responsive to BUP treatment.
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Conclusions
The present findings need to be interpreted with caution, because of the weakness of the design: the major limitation is the retrospective nature of the data and the lack of systematic and more periodic evaluation of the subjects. Although multivariate analysis excluded the interference of some variables, possible inter-individual and cultural variability, treatment variables, and other unmeasured confounds, may have reduced the strength and the validity of the study. The pronostic factors able
Acknowledgments
The study was performed with the support of the Federation of Public Addiction Services Professionals (Feder.Ser.D) and the funds of Addiction Research Centre of Parma. No private companies were included among the sources of financial support for the present study.
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