Research report
The long-term outcomes of heroin dependent-treatment-resistant patients with bipolar 1 comorbidity after admission to enhanced methadone maintenance

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Abstract

Objective

The aim of this study was to compare the long-term outcomes of treatment-resistant bipolar 1 heroin addicts with peers who were without DSM-IV axis I psychiatric comorbidity (dual diagnosis).

Method

104 Heroin-dependent patients (TRHD), who also met criteria for treatment resistance – 41 of them with DSM-IV-R criteria for Bipolar 1 Disorder (BIP1-TRHD) and 63 without DSM-IV-R axis I psychiatric comorbidity (NDD-TRHD) – were monitored prospectively (3 years on average, min. 0.5, max. 8) along a Methadone Maintenance Treatment Programme (MMTP).

Results

The rates for survival-in-treatment were 44% for NDD-TRHD patients and 58% for BIP1-TRHD patients (p=0.062). After 3 years of treatment such rates tended to become progressively more stable. BIP1-TRHD patients showed better outcome results than NDD-TRHD patients regarding CGI severity (p<0.001) and DSM-IV GAF (p<0.001). No differences were found regarding urinalyses for morphine between groups during the observational period. Bipolar 1 patients needed a higher methadone dosage in the stabilization phase, but this difference was not statistically significant.

Limitations

The observational nature of the protocol, the impossibility of evaluating a follow-up in the case of the patients who dropped out, and the multiple interference caused by interindividual variability, the clinical setting and the temporary use of adjunctive medications.

Conclusions

Contrary to expectations, treatment-resistant patients with bipolar 1 disorder psychiatric comorbidity showed a better long-term outcome than treatment-resistant patients without psychiatric comorbidity.

Introduction

Bipolar spectrum disorders and addiction often co-occur and constitute reciprocal risk factors (Bahorik et al., 2013, Hoblyn et al., 2009, Reif et al., 2011, Schneier et al., 2010) that we believe are best considered from a unified perspective (Maremmani et al., 2006). We studied the correlation between bipolar spectrum and heroin addiction at various levels. In our in-patient setting we found that a majority of our heroin addicts were affected by bipolar 1 disorder (Maremmani et al., 2000), whereas in our outpatient setting they obtained a diagnosis of bipolar 2 disorder (Maremmani et al., 1994). We found that depression and hostility as part of the bipolar spectrum – in the context of early-onset drug dependence, work and social-leisure problems – appear to be independently associated with suicidal ideation. (Maremmani et al., 2007a). We also found that subthreshold bipolarity, including hyperthymic and cyclothymic temperaments, seems to predispose patients to heroin addiction (Maremmani et al., 2009), but craving for the suppressed hypomania could, in its turn, lead to cocaine abuse, which eventually unmasks a frankly bipolar disorder – in some cases leading to mixed state, severe mania, or even to psychosis beyond mania (Maremmani et al., 2008). We also studied clinical presentations of substance abuse in bipolar heroin addicts at time of treatment entry. Besides one expected result – the prominent use of CNS stimulants during a depressive phase of bipolar patients – this study supports the hypothesis that mood elation is a pleasurable, rewarding experience that, in bipolar patients, can be started or prolonged by means of CNS stimulant drugs. Stimulant use was, therefore, more prevalent during the ‘up’ rather than the ‘down’ phase of the illness (Maremmani et al., 2012c). In conclusion, we are aware that the use of substances worsens the therapeutic outcome of bipolar patients (Camacho and Akiskal, 2005, Maj et al., 2003, Mazza et al., 2009, van Rossum et al., 2009). Agonist Opioid Treatment improves symptoms of psychopathology present in patients addicted to heroin (Maremmani et al., 2007b, Pani et al., 2000). In this perspective, we can assume that opiates // are an effective treatment in bipolar patients heroin addicts.

The aim of this study was to compare the long-term outcomes of treatment-resistant, heroin-dependent patients (HD) with bipolar 1 (BIP1-HD) ones, and patients without DSM-IV axis 1 psychiatric comorbidity (NDD-HD). We decided to evaluate whether comorbid psychopathology was able to influence methadone treatment outcomes in patients who had previously failed in first-line, low threshold treatment facilities, when those patients were included in a high-threshold, maintenance-oriented, high-dose methadone programme.

The hypothesis of the study was that DSM-IV bipolar 1 psychiatric comorbidity would not affect treatment outcomes if patients with comorbid disorders received higher, individualized doses of methadone and that a favourable outcome would be related to long-term ongoing treatment (retention).

To test this hypothesis, a group of treatment-resistant heroin addicts, with bipolar 1 or without DSM-IV axis I psychiatric comorbidity, were followed in a naturalistic approach for a minimum of 0.5 and a maximum of 8 years in the context of the maintenance high-threshold, high-dose Pisa methadone programme, using retention in treatment and rates of heroin use as the main end-point parameters.

Section snippets

Design of the study

A prospective cohort study was designed in order to evaluate treatment outcome (in terms of retention in treatment, substance use, clinical improvement and general social adjustment) of patients included in a methadone programme, in terms of its relationship to the presence of a bipolar 1 psychiatric comorbidity. Treatment-resistant, heroin-dependent patients (TRHD) were divided into two groups – those with bipolar 1 psychiatric comorbidity (BIP1-TRHD patients) and those without concomitant

Baseline evaluation (at the beginning of the treatment)

On the basis of DAH-RS-collected information, Table 1 reports the demographic, clinical and addiction history data of the sample at the beginning of treatment. BIP1-TRHD patients turned out to be different from NDD-TRHD patients in their educational level. The two groups did not differ significantly in the other demographic variables investigated (age, gender, marital status, work).

Moreover, BIP1-TRHD patients seemed to indicate a lower frequency for “daily or more” heroin intake and to have

Discussion

We examined treatment retention and outcomes for BIP1-TRHD and NDD-TRHD treatment-resistant, methadone-maintained patients. We observed that:

  •  BIP1-TRHD and NDD-TRHD patients differed at baseline in terms of their educational level, duration of their heroin addiction, level of heroin use, and age at first addiction treatment, but these differences did not appear to be related to the better retention or better outcome of the BIP1-TRHD patients.

  •  BIP1-TRHD patients were retained in treatment for

Conclusion

The main conclusions to be drawn from our results are:

  • (i)

    In the presence of problematic non-compliant patients with a bipolar 1 diagnosis, a flexible dosing regimen that permits the administration of higher doses may lead to higher retention rates. The relevance of the present data becomes clearer when we consider that between a third and a half of all opiate addicts suffer from additional mental disorders (Farrell et al., 1998, Rounsaville et al., 1981, Rounsaville et al., 1982).

  • (ii)

    Bipolar 1

Role of funding source

Authors states that this study was financed with internal funds.

No sponsor played a role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Conflict of interest

None of the authors have a conflict of interest.

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