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Letter
The long-term outcome of impulsive compulsive behaviours in Parkinson’s disease
  1. Pedro Melo Barbosa1,2,3,
  2. Atbin Djamshidian1,4,
  3. Sean S O'Sullivan5,
  4. Eduardo de Pablo-Fernandez1,2,3,
  5. Prasad Korlipara2,3,
  6. Huw R Morris2,3,
  7. Kailash P Bhatia2,3,
  8. Patricia Limousin2,3,
  9. Thomas Foltynie2,3,
  10. Andrew J Lees1,
  11. Thomas T Warner1,2,3
  1. 1 Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology, London, UK
  2. 2 Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
  3. 3 The National Hospital for Neurology and Neurosurgery, London UK
  4. 4 Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
  5. 5 Department of Neurology, Bon Secours Hospital, Cork, Ireland
  1. Correspondence to Dr Thomas T Warner, Reta Lila Weston Institute of Neurological Studies, Department of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, London WC1N1PJ, UK; t.warner{at}ucl.ac.uk

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Introduction

Impulsive compulsive behaviours (ICBs) such as dopamine dysregulation syndrome (DDS), pathological gambling, compulsive sexual behaviour, punding, compulsive shopping and binge eating are recognised complications of dopaminergic treatment that affect at least one in seven patients with Parkinson’s disease (PD).1 Only a few studies provide long-term data on ICBs although any firm conclusions are limited by restricted follow-up periods. We present long-term longitudinal data on 46 PD patients with ICBs with follow-up for a mean period of 8.2 years.

Methods

Patients with PD and ICBs who participated in previous research studies from 2007 to 2012 visit 1 (V1) were invited for re-assessment visit 2 (V2). Participants underwent a clinical interview and assessment with questionnaires and scales (detailed in online supplementary materials). The diagnosis of ICBs was based on screening questionnaires and confirmed with a structured interview. The study received ethics approval. Data was analysed in Statistical Package for Social Science 22 (SPSS 22). All variables were tested for normality and statistical tests chosen accordingly. A p value<0.05 was considered significant. Bonferroni correction was applied for comparison between visits and significance was considered to have been reached when p<0.025.

Supplementary data

Results

Of the 90 original participants, 46 were included. Eight declined to participate, five were lost to follow-up and 31 had died (see online supplementary figure 1). No cases of suicide or traumatic fatality were reported. Participants were followed up for 8.2 years (±2.6). Three patients had a biallelic parkin mutation. See table 1 for demographic and clinical details at each visit and online supplementary table 1 for results of the scales/questionnaires used at V2.

Table 1

Comparison between visits

Initial treatment of ICBs consisted of cessation of oral/transcutaneous dopamine agonists (DA) in 29 patients, reduction of DA dose in 13 and reduction of levodopa in 4. Seven patients (16.6%) developed dopamine agonist withdrawal syndrome (DAWS). Of the 46 patients, 19 (41.3%) improved completely and were asymptomatic at V2, 26 (56.5%) improved partially and 1 (2.2%) had no change of the addictive behaviour. No patients experienced worsening of ICBs over time. Five patients re-started DA. Details on the outcome of ICBs according to treatment can be seen in online supplementary figure 1.

Participants were divided into two groups based on the presence of ICBs at V2 and compared with to identify any factors associated with long-term remission (see online supplementary table 2). Patients with active ICBs at V2 scored higher in the Questionnaire for Impulsive-Compulsive disorders in Parkinson's disease rating scale (QUIP-RS), Hospital Anxiety and Depression Scale (HADS) total, HADS depression, unified Parkinson's disease rating scale (UPDRS) part I and Hoehn & Yahr scale. To assess if different ICBs were associated with different dopaminergic drugs, patients with DDS and/or punding (which are more associated with L-DOPA use) were compared with patients with other ICBs such as pathological gambling (which are more associated with the DA use). No differences were found (see online supplementary tables 3-5).

Discussion

Despite using different methodologies, all previous follow-up studies have reported improvement of ICBs after cessation/reduction of DA.2–4 Reduction of dopaminergic medication also led to improvement in all, but one of our patients. However, we found a lower remission rate (41.3%) than previously reported, despite achieving similar reduction in DA use to other reported studies. Continued use of DA as a consequence of DAWS, relapses of behavioural addictions following the necessary concomitant increase in L-DOPA dosage and the inclusion of more severe cases from a tertiary centre are possible explanations for the lower remission rate.

Compared with V1, fewer patients were using DA and more were using monoamine oxidase inhibitors (MAOi) and amantadine at V2. The increase in amantadine use is probably an attempt to control levodopa induced dyskinesias, a common comorbidity of ICBs.1 Although both these classes of drugs appear to be safer than DA in patients with ICBs, contradictory data has been published on the propensity of amantadine to induce ICBs and a few case reports of ICBs in patients receiving MAOi have also been published.1 More patients were also taking rotigotine and apomorphine at V2. Some studies have reported a lower proclivity of both these drugs to induce ICBs.1

The proportion of patients having multiple ICBs remained stable at V2, in agreement with a prospective 2-year study.5 However, we have found a higher prevalence of multiple ICBs than previously reported.1 The presence of ICBs was associated with depression and lower quality of life.1 ICBs at V2 were also associated with higher UPDRS part I scores and more advanced disease. The latter finding is in contradiction to published data showing that ICBs are not associated with disease severity.5 Patients with more advanced disease require higher doses of dopaminergic treatment and may, therefore, be at increased risk of recurrence of ICBs. A third of patients exhibited cognitive impairment at V2, supporting previous work suggesting ICBs are not a risk factor for PD dementia.5

A lower proportion of patients were using neuroleptic drugs at V2 compared with the findings of Sohtaoglu and colleagues.3 In their study, neuroleptics were used routinely if patients did not improve after initial treatment with reduction of DA. Deep brain stimulation (DBS) appears to be associated with low risk of ICBs, probably as a consequence of the reduction in dopaminergic treatment that usually follows the procedure. In our study, seven patients were still symptomatic after DBS, but none experienced worsening of ICBs.

Potential limitations of this study are that only half of the patients were available for re-assessment and there was no control group. The mortality rate found here is similar to what has been described among PD patients with similar age at disease onset. Diagnostic accuracy can also be a problem as patients and relatives commonly under-report ICBs.1 We believe the use of interviews aided by questionnaires at both visits contributed to accurate detections of ICBs.

Conclusion

In the longest follow-up study of ICBs in PD to date, we have found a lower rate of remission of ICBs than reported in previous studies with shorter follow-up periods. The most used treatment strategy was cessation of DA, but 40% of the patients were still receiving these drugs at follow-up. Even when reduction or discontinuation of DA was possible it did not guarantee long-term remission.

Acknowledgments

This paper presents independent research supported by the Reta Lila Weston Institute for Neurological Studies, Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility at the UCL Institute of Neurology and UCLH-National Hospital for Neurology and Neurosurgery, London, UK. Pedro Barbosa is supported by a grant from Brazilian Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

References

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Footnotes

  • Contributors PB: Conception, organisation and execution of the research project; statistical analysis design and execution; and writing of the first draft, review and final approval the manuscript. AD: Conception and organisation of the research project; design, review and critique of the statistical analysis; and review, critique and final approval of the manuscript. SOS: Conception and organisation of the research project; review and critique of the statistical analysis; and review, critique and final approval of the manuscript. EPF: Organisation of the research project; review and critique of the statistical analysis; and review, critique and final approval of the manuscript. PK: Review and critique of the statistical analysis and review, critique and final approval of the manuscript. HM: Review and critique of the statistical analysis and review, critique and final approval of the manuscript. KPB: Review and critique of the statistical analysis and review, critique and final approval of the manuscript. PL: Review and critique of the statistical analysis and review, critique and final approval of the manuscript. TF: Review and critique of the statistical analysis and review, critique and final approval of the manuscript. AJL: Review and critique of the statistical analysis and review, critique and final approval of the manuscript. TTW: Conception and organisation of the research project; design, review and critique of the statistical analysis; and review, critique and final approval of the manuscript.

  • Competing interests None declared.

  • Patient consent for publication Parental/guardian consent obtained

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Data sharing statement Data is available upon personal request.

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