Relapse prevention trials

A second problem with relapse-prevention trials is related to research suggesting that the use of antidepressants might make people more vulnerable to relapse. Patients who are being treated... 

These continuation trials tell a very different story from that told by relapse-prevention trials. They show that there is little difference between antidepressant and placebo even when the clinical trial is extended over a longer period of time. Across the eight continuation trials that have been published, 79 per cent of patients on placebo and 93 per cent of patients on active medication remained well throughout the treatment period. In these long-term studies, placebo treatment was 95 per cent as effective as drug treatment. The authors of a meta-analysis of these trials concluded that the widely held - and probably erroneous - belief that the placebo response in depression is short-lived appears to be based largely on intuition and perhaps wishful thinking .17... 

Romano, S. (1999) A relapse prevention trial of bulimia nervosa using fluoxetine. Presented at the 152nd Annual Meeting of the American Psychiatric Association. Washington, DC, May 15-20,1999. 

Generally speaking, success of placebo-controlled relapse prevention trials depends on ... 

Irvine EJ, Zhou Q, Thompson AK. The short inflammatory bowel disease questionnaire A quality of life instrument for community physicians managing inflammatory bowel disease. CERPT investigators. Canadian Crohn s relapse prevention trial. Am J Gastroenterol 1996 91 1571— 1578. 

Kranzler HR, Del Boca F, Korner P, et ah Adverse effects limit the usefulness of flu-voxamine for the treatment of alcoholism.] Subst Abuse Treat 10 283-287, 1993 Kranzler HR, Burleson JA, Del Boca FK, et ah Buspirone treatment of anxious alcoholics a placebo-controlled trial. Arch Gen Psychiatry 31 720—731, 1994 Kranzler HR, Burleson JA, Korner P, et ah Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics. Am] Psychiatry 152 391-397, 1995 Kranzler HR, Burleson JA, Brown J, et al Fluoxetine treatment seems to reduce the beneficial effects of cognitive-behavioral therapy in type B alcoholics. Alcohol Clin Exp Res 20 1534-1341, 1996... 

Streeton C, Whelan G Naltrexone, a relapse prevention maintenance treatment of alcohol dependence a meta-analysis of randomized controlled trials. Alcohol Alcohol 36 544-552, 2001... 

More than 40 medications have been investigated but none have shown consistent efficacy for primary cocaine or amphetamine dependence. These medications include dopaminergic agonists, antidepressants, and more recently disulfiram, selegiline, and a cocaine vaccine (see Table 5—2 for summary). Studies have been relatively brief and have focused on abstinence initiation rather than on relapse prevention, but even these modest treatment goals have not been attained. The focus in the discussion that follows is on pharmacotherapies for cocaine dependence, because very few clinical trials have been completed with amphetamine-dependent patients. Furthermore, none of the studies of amphetamine dependence have shown results different from those described for cocaine dependence (Rawson et al. 2002b Srisurapanont et al. 2001). 

Taub, E., Steiner, S., Weingarten, E., and Walton, K., Effectiveness of broad spectrum approaches to relapse prevention in severe alcohlism A long term, randomized, controlled trial of Transcendental Meditation, EMG biofeedback and electronic eurotherapy. Special Issue Self-recovery Treating addictions using transcendental meditation and Maharishi Ayur-Veda. Alcoholism Treatment Quarterly 11 (1-2), 187-220, 1994. 

Nevertheless, some long-term efficacy trials have been conducted. These continuation studies are different from relapse-prevention or discontinuation trials in some very important ways. Instead of just looking at patients who have responded... 

Boening JA, Lesch OM, Spanagel R, et al. Pharmacological relapse prevention in alcohol dependence from animal models to clinical trials. Alcoholism 2001 25(5 Supplement ISBRA) 127S-131S. 

A critical review by Olver et al. (2001) on so-called third-generation antidepressants (venlafaxine, reboxetine, nefazodone, mirtazapine) covered 30 controlled therapeutic trials and a number of relapse prevention studies. Questions addressed were overall efficacy, speed of onset and safety but, according to this review, none of the third-generation antidepressants was specifically tested with respect to its potential effects on cognitive function in depressed patients. 

Kakko J, Svanborg KD, Kreek MJ Heilig M (2003). 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden a randomized, placebo-controlled trial. Lancet, 361, 662-8... 

Kranzier HR, Burleson JA, Korner P, et al. Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics. Am J Psychiatry 1995 152 391-397. 

Allsop, S., Saunders, W., and McNamee, B. (1987) Relapse Prevention Management with Problem Drinkers The Results of a Controlled Trial, Paper presented at the 7th International Conference on Alcohol Problems, Liverpool. 

Of the more recently introduced methods for smoking cessation, bupropion (an antidepressant with dopaminomimetic properties) has recently been introduced. Clinical trial data, in which the nicotine patch, bupropion at 300 mg, and a combination of the two drugs were compared with placebo treatment, have shown cessation of smoking rates of 36% for the patch, 49% for bupropion and 58% for the combined treatments following 7 weeks of treatment. The placebo response rate was 23%. All subjects received relapse prevention therapy. Thus bupropion appears to be a reasonably safe and effective treatment for nicotine dependence. It is however contraindicated in those subject to epilepsy its main side effects are dry mouth and insomnia. 

The least biased evidence on whether lithium and other mood stabilisers have antisuicidal properties comes from randomised controlled trials and this is negative. A large amount of data from studies of drug treatment of acute mania and relapse prevention found no difference in rates of suicide or suicide attempts between patients randomised to take mood stabilisers, including lithium, and those randomised to placebo (Storosum et al. 2005). 

Leucht S, Barnes TRE, Kissling W, Engel RR, Correll C, Kane JM. Relapse prevention in schizophrenia with new-generation antipsychotics a systematic review and exploratory meta-analysis of randomised, controlled trials. Am J Psychiatry 2003 160 1209-22. 

Substance abuse or relapse prevention, intended for a population considered to be a high liability risk, uncooperative with treatment trials, and requiring extensive records once marketed and... 

The relapse-preventing effects and safety profiles of balsalazide 1.5 g bd, balsalazide 3 g bd, and mesalazine 0.5 g tds have been studied in a multicenter, randomized, double-blind trial in 133 patients with ulcerative colitis in remission (7). High-dose balsalazide was significantly more effective in maintaining remission compared with the other two treatments. All three treatments were well tolerated. 

In an 18-month, double-blind, randomized, placebo-controlled trial in 318 patients, mesalazine 4 g/day did not significantly affect the postoperative course of Crohn s disease compared with placebo (11). There was some relapse-preventing effect in patients with isolated small bowel disease. The overall incidence of adverse effects was similar with mesalazine and placebo. Of the serious adverse effects reported, only one case of alopecia... 

Carroll, K. M. (1996). Relapse prevention as a psychosocial treatment A review of controlled clinical trials. Experimental and Clinical Psychopharmacolog, 4, 46-54. 

Wadden TA, Bartlett SJ, Foster GD, et al. Sertraline and relapse prevention training following treatment by very-low-calorie diet A controlled clinical trial. Obes Res 1995 3 549-557. 

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