Impact of findings on practice stopping long-term use of benzodiazepine hypnotics is difficult users of a high daily dose might be more responsive to the effect of melatonin on the discontinuation of benzodiazepines investigators should take into account the difficulty of recruiting patients for studies on discontinuing the use of benzodiazepines Introduction 1 2 3 5 6 7 8 9 8 10 11 The administration of melatonin as a sleeping medication is a contradictory tool to help people discontinue use of BDs. Aim of the study Method Our study was designed as a randomized placebo-controlled discontinuation trial. We gathered data in nine general practices (2001–2004). The patients, their GPs and the principal investigator were blinded for the study medication. All practices were located in Maastricht, in the south of the Netherlands. 12 T 0 13 14 15 16 17 After returning the informed consent, patients were included for random allocation. T 0 18 T 1 T 2 T 3 T 1 T 3 Results 1 Fig. 1 Selection of patients and response/non-response; participants  Receiving the first questionnaire of these 124 patients, 22 did not respond, 56 decided not to participate and eight patients did not meet the inclusion criteria (six of whom had already stopped the BD use). At the end, only 38 participants (16 males and 22 females) were indicated to take part in the study. They were randomly allocated to melatonin or placebo. The participants compared to the non-participants were more often males (40% vs. 25%), and had a lower age (<50 years, 16% vs. 5%) and less elderly (>80 years, 5% vs. 18%). Of the total group, 76% were 60 years or older. 1 Table 1 Characteristics of the 38 participants, and for melatonin and placebo separately  n n n Gender Male 6 (30) 10 (56) 16 (42) Female 14 (70) 8 (44) 22 (58) Age in years <50 3 (15) 3 (17) 6 (16) 50–59 3 (15) 3 (17) 6 (16) 60–69 6 (30) 7 (39) 13 (34) 70−79 7 (35) 4 (22) 11 (29) ≥80 1 (5) 1 (5) 2 (5) Health insurance National health insurance 16 (80) 18 (100) 34 (90) Private insurance 4 (20) – 4 (10) Sleep quality Good 7 (35) 5 (28) 12 (32) Bad 11 (55) 11 (61) 22 (58)  2 missing 2 missing 4 missing Period of use of BD <1 year – – – 1−5 years 7 (35) 7 (39) 14 (37) 6−9 years 4 (20) 4 (22) 8 (21) ≥10 years 9 (45) 6 (34) 15 (39)   1 missing 1 missing Daily use of BD (PDD/DDD) ≤0.5 (low) 11 (55) 14 (78) 25 (66) 0.5–1.0 (moderate) 4 (20) – 4 (10) ≥1.0 (high) 5 (25) 4 (22) 9 (24) Smoking Yes 9 (45) 7 (39) 16 (42) No 10 (50) 11 (61) 21 (55)  1 missing  1 missing Alcohol use Yes 15 (75) 15 (83) 30 (79) No 5 (25) 3 (17) 8 (21) Body mass index (BMI) Normal 8 (40) 10 (56) 18 (47) BMI > 25 12 (60) 8 (44) 20 (53) Problematic BD use (subscale of Bendep-SRQ) Low 6 (30) 2 (11) 8 (21) Average 3 (15) 2 (11) 5 (13) High 11 (55) 13 (72) 23 (61)   1 missing 1 missing χ 2 Twenty-two participants had tried to stop BD use in the past, and 12 of them experienced a high level of withdrawal symptoms. 2 Table 2 Follow up after one year. Use of BD sleeping medication after the taper off and during follow up. Separate data for the melatonin and placebo group  T 1 T 2 T 3 *** T 3 n 12 10 8* 2 n 9 7 7* (1**) 1 Total 21 17 15 3 T 1 T 2 T 3 T 3 T 2 T 3 *** T 3 ® ® α 3 Table 3 Putative indicators of discontinuation of benzodiazepines (numbers and percentages)  Definite stoppers Non-stoppers Total Male 6 (38%) 10 (62%) 16 Female 9 (41%) 13 (59%) 22 Age <65 6 (33%) 12 (67%) 18 Age 65+ 9 (45%) 11 (55%) 20 Body mass index <25 6 (33%) 12 (67%) 18 Body mass index ≥25 9 (45%) 11 (55%) 20 Period of use <5 year 6 (43%) 8 (57%) 14 Period of use ≥5 year 8 (35%) 15 (65%) 23 (1 missing) PDD/DDD < 1.0 12 (41%) 17 (59%) 29 PDD/DDD ≥ 1.0 3 (33%) 6 (67%) 9 Awareness of problematic use, low 7 (29%) 17 (71%) 24 Awareness of problematic use, high 7 (54%) 6 (46%) 13 (1 missing) General health, low 6 (40%) 9 (60%) 15 General health, high 9 (41%) 13 (59%) 22 (1 missing) Sleeping quality, bad 8 (36%) 14 (64%) 22 Sleeping quality, good 6 (50%) 6 (50%) 12 (4 missing) χ 2 T 1 T 0 T 3 Discussion 10 11 19 20 3 5 21 n 1 21 In our trial, in contrast to that of Garfinkel et al., at the end only 9% still used melatonin. Four participants changed their use to a homeopathic or phytotherapeutic medication, which indicates a basic need to use something for their sleeping problem. Half of the patients who tried to stop by themselves before participating in our study, without taper off, suffered from withdrawal symptoms. In our trial this was 25%, showing the advantage of gradual tapering. We did not find a shift of addiction behavior, sleep quality or general health among stoppers of BD. Conclusions Our trial does not provide conclusive evidence that melatonin is helpful for BD discontinuation. The overall question about the effectiveness of intervention remains. Another trial, in contrast to the first trial, shows a negative result. One should consider that the results of all three trials are influenced by a possible selection bias or lack of power, due to the low number of participants. Further investigation is necessary, with special attention to the effect of the daily dose on stopping the use of BD. Finally one should take into account the difficulty of recruiting BD users for stop studies.