Family Practice Vol. 20, No. 4, 370-372
© Oxford University Press 2003
Mental health |
Predictors of relapse after discontinuation of long-term benzodiazepine use by minimal intervention: a 2-year follow-up study
a Department of Psychiatry, University Medical Centre St Radboud, Nijmegen,
b Department of Psychiatry and Institute for Research in Extramural Medicine, Vrije Universiteit Amsterdam,
c Department of Clinical Psychology and Personality, and
d Department of General Practice, University of Nijmegen and
e Department of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands.
Correspondence to Dr RC Oude Voshaar, MD, University Medical Centre St Radboud; Department of Psychiatry (hp 333), PO Box 9101, 6500 HB Nijmegen, The Netherlands; E-mail: r.oudevoshaar{at}psy.umcn.nl
Oude Voshaar R, Gorgels W, Mol A, van Balkom A, Breteler M, van de Lisdonk E, Mulder J and Zitman F. Predictors of relapse after discontinuation of long-term benzodiazepine use by minimal intervention: a 2-year follow-up study. Family Practice 2003; 20: 370–372.
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Abstract |
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Background. Long-term results of minimal intervention strategies to cut down benzodiazepine use are not available.
Objective. To evaluate the relapse rate over a two-year period and to search for predictors of relapse among patients who quit benzodiazepine use after receiving a discontinuation letter.
Methods. Baseline assessment and prospective monitoring of the medical records of 109 patients who quit long-term benzodiazepine use after a minimal intervention strategy in general practice.
Results. After 819 ± 100 days of follow-up, 53 (49%) patients had remained completely abstinent. Two independent predictors of relapse were identified by Cox regression analysis: use of more than 10 mg diazepam equivalent (RR = 2.4 [1.2 – 4.7]) and poor general health perception (RR = 0.98 [0.97 – 0.99]).
Conclusion. Short-term success rates after a minimal intervention were maintained well during long-term follow-up. High-dose users have the highest risk of relapse.
Keywords. Benzodiazepines, follow-up, general practice, minimal intervention.
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Introduction |
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About 20% of long-term benzodiazepine users in primary care successfully quit their benzodiazepine use in the short term with the aid of a minimal intervention, e.g. a letter containing advice to quit, an advisory consultation or an informational meeting.1–4 Long-term results, however, are not available.5
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Methods |
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Long-term benzodiazepine users (>3 months; n = 2964) were identified by means of a computerized search for benzodiazepine prescriptions at 30 general practices. Exclusion criteria were: current psychiatric treatment (n = 281), current treatment for drug or alcohol dependence (n = 82), medical history of psychosis (n = 80), epilepsy (n = 53), insufficient mastery of the Dutch language (n = 59) and terminal illnesses (n = 26). Furthermore, some people were excluded specifically at the GP’s request because of severe co-morbidity or for current psychosocial reasons (n = 379).
The remaining 2004 benzodiazepine users received a letter from their GP containing advice to quit gradually (=discontinuation letter). They were invited to the surgery in a second letter sent 3 months later. Informed consent to participate in the study was sought if they had been able to achieve complete abstinence since receiving the discontinuation letter.
The use of benzodiazepines and other prescribed drugs was monitored prospectively in the medical records for a mean (±SD) duration of 819 (±100) days. Benzodiazepine use relapse was defined as receiving a benzodiazepine prescription during follow-up. In addition, patients were assessed by self-report questionnaires directly after giving informed consent (baseline). We assessed the use of caffeine, nicotine and alcohol; psychological well being (GHQ-12, general health questionnaire), mood (POMS, profile of mood states);6 quality of life (MOS-SF-36: medical outcome studies short-form);7 and personality characteristics (Dutch shortened MMPI, Minnesota Multiphasic Personality Inventory).8
Predictors of relapse were analysed by means of Cox regression analysis, with time to relapse as the dependent variable, and the following independent variables: daily dosage (dichotomized at 10 mg diazepam equivalent), half-life (dichotomized at 24 h), potency (presence of a 4-aryl group), self-reported hypnotic or anxiolytic use, use of antidepressants (yes/no), use of pain medication (yes/no), and the variables measured at the baseline assessment. Variables with univariate risk ratios of P < 0.10 were entered into the multivariate Cox regression analysis using a backward elimination procedure.
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Results |
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Of the 2004 long-term users receiving the discontinuation letter, 1321/2004 (66%) visited their GP in order to evaluate the effect of the letter. Of those patients, 285/1321 (22%) had successfully stopped their use, and of the stoppers 109/285 (38%) gave informed consent. Participants (n = 109) and non-participants (n = 176) did not differ with respect to age (63 ± 4.3 years) and gender (69% female sex). However, participants had been using significantly higher benzodiazepine dosages before receiving the discontinuation letter (6.6 ± 4.3 versus 5.1 ± 4.5 mg diazepam equivalent, P < 0.01).
One patient was lost to follow-up from the medical records, which left 108 evaluable patients. In five patients, the duration of follow-up was limited to an average of 488 days (range 183–671) (two moved, three died).
After quitting benzodiazepine use, 53/108 (49%) patients remained completely abstinent during the 2-year follow-up, while 55/108 (51%) patients relapsed after a median period of abstinence of 243 days (P25 = 97 days, P75 = 459 days). Longitudinal monitoring of patients who relapsed showed intermittent benzodiazepine usage in 30/55 (55%) patients; 26 patients for periods of up to 30 days and four patients for periods between 30 and 90 days.
Four variables were related univariately to relapse: baseline benzodiazepine dosage, and three dimensions of the SF-36: general health perception, vitality and mental health. The multivariate Cox regression analyses (model: chi-square = 8.8. df = 2, P = 0.01) yielded two independent predictors: daily benzodiazepine dosage [relative risk (RR) 2.4 (1.2–4.7), P = 0.02] and general health perception (range 0–100) [RR 0.98 (0.97–0.99), P = 0.04] (Fig. 1
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The prescription of antidepressants remained stable (baseline and follow-up 19%), while the prescription of pain medication decreased from 44% at baseline to 36% at follow-up, for those patients who remain abstinent. Only one patient switched from benzodiazepine to another hypnotic treatment (zolpidem).
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Discussion |
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Half of the patients who had quit successfully in the short term remained abstinent for 2 years without any switches to the use of alternative drugs. Moreover, most patients who relapsed showed better usage patterns during follow-up compared with their baseline usage. These good long-term results contribute positively to the proposals of Russell and Lader9 and many others (e.g. Oude Voshaar et al.5) to use a minimal intervention strategy as a first step to cut down long-term benzodiazepine use.
The major limitation of our study was the low participation rate. However, our short-term evaluation 3 months after sending the letter revealed a success rate of 22% (285/1321). This is fairly comparable with the success rates reported by others and suggests that the patients who responded to this evaluation were representative of all patients who received the discontinuation letter.1 Some selection bias has obviously occurred, as participants in the follow-up study were using significantly higher dosages before receiving the letter compared with non-participants. However, as a lower dose level appeared to be the most important predictor of remaining benzodiazepine free, the present results can be considered conservative.
As we did not include a control group, we cannot compare our results with the natural course of benzodiazepine use. It is not likely that the success rate of 22% can be explained by the natural course of benzodiazepine use after a minimal intervention, because the mean duration of benzodiazepine use in our sample was 6.8 years. Moreover, our long-term success rate is substantially higher than the short-term success rate of 6% in the no intervention control group of the minimal intervention study of Cormack et al.1
The best predictor of relapse appeared to be high dosage use (>10 mg diazepam equivalent). Poor general health perception also predicted relapse, i.e. patients who perceived themselves as being less healthy were at greater risk of relapse. As the latter variable contributed only marginally to the model, we recommend closer monitoring only in high-dose users after they have quit of their own accord.
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Acknowledgments |
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The study was funded by the Dutch Health Care Insurance Council
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References |
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1 Cormack MA, Sweeney KG, Hughes-Jones H, Foot GA. Evaluation of an easy, cost-effective strategy for cutting benzodiazepine use in general practice. Br J Gen Pract 1994; 44: 5–8.[ISI][Medline]
2 O’Leary M. A novel approach to tackling the ‘benzodiazepine problem’ in general practice. Psychiatr Bull 1989; 13: 180–181.
3 Jones D. Weaning elderly patients off psychotropic drugs in general practice: a randomised controlled trial. Health Trends 1990; 22: 164–166.
4 Bashir K, King M, Ashworth M. Controlled evaluation of brief intervention by general practitioners to reduce chronic use of benzodiazepines. Br J Gen Pract 1994; 44: 408–412.[ISI][Medline]
5 Oude Voshaar RC, Gorgels WJMJ, Mol AJJ et al. Behandelmethoden om langdurig benzodiazepine gebruik te staken. Ned Tijdschr Geneeskd 2001; 145: 1347–1350.[Medline]
6 Wald FDM, Mellenbergh GJ. De verkorte versie van de Nederlandse vertaling van de Profile of Mood States (POMS). Ned Tijdschr Psychol 1990; 45: 86–90.
7 Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: 473–483.[ISI][Medline]
8 Luteijn F, Kok AR. NVM. Nederlands Verkorte MMPI [NVM: Dutch Shortened MMPI]. Luteijn F, Kok AR (eds). Swets and Zeitlinger; 1985
9 Russell J, Lader MH. Guidelines for the Prevention and Treatment of Benzodiazepine Dependence: On Behalf of the Substance Abuse Committee of the Mental Health Foundation. The Mental Health Foundation; 1993.
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