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. 2007 Oct 17;2007(4):CD005454. doi: 10.1002/14651858.CD005454.pub2

Vrethem 1997.

Methods Double blind placebo controlled crossover design, four weeks (one week dose titration then stable dose)
Three 3 week periods, one week washout, no carry over effect
Randomisation method not stated
Inclusion criteria:
 duration of symptoms at least six months
Participants Polyneuropathy (19 diabetic, 18 non‐diabetic). 37 participants (33 final number). Mean pain duration 48 months, 17 male and 19 female patients
Pain score for diabetics 5.0 (1.4) and for non‐diabetic 4.1 (1.9). Depression score for diabetic 2.8 (range 0 to18.0) and non‐diabetic 2.9 (range 0 to 22.5)
Interventions Amitriptyline dose escalation from 25 mg to 75 mg, or maprotiline from 25 mg to 75 mg, or placebo daily orally
Outcomes Pain patients reported, 5‐item global improvement, more than 20 % pain decrease
Comprehensive Psychopathological Rating Scale
Number of patients with improved sleep
On amitriptyline pain completely improved
 1/33, much improved 11/33, improved 10/33, no change 10/33,
 worse 1/33; on maprotiline completely improved 1/33, much improved 3/33, improved 10/33, no change 17/33,
 worse 2/33; on placebo completely improved 0/33, much improved 1/33, improved 7/33, no change 22/33, worse 3/33
Pain reduced at least 20% on amitriptyline 20/33, on maprotiline 15/33, on placebo 7/33
Depression score in diabetic patients on amitriptyline 1.2 (range 0‐12.5), on maprotiline 2.4 (range 0‐145), on placebo 2.3 (range 0‐12.5);
 in non‐diabetic patients on amitriptyline 1.1 (range 0‐10.5), on maprotiline 1.5 (range 0‐11.5), on placebo 1.6 (range 0‐11).
Sleep improved on amitriptyline
 11/33, on maprotiline 5/33, on placebo 4/33.
Notes Dropouts 7/37 (5 SE, 1 depression, 1 early drop out)
SE: 21/33 on amitriptyline, on 21/33 on maprotiline, 6/33 on placebo. Withdrawn due to SE 3 on amitriptyline (1 severe thirst, 1 urinary retention, 1 hyperglycaemia), 2 on maprotiline (1 sedation and vertigo, 1 urticaria)
QS = 4 (R1, DB2, W1)
Risk of bias
Bias Authors' judgement Support for judgement
Allocation concealment (selection bias) Unclear risk B ‐ Unclear