Transdermal Clonidine Versus Chlordiazepoxide in Alcohol Withdrawal

What about clonidine for diarrhoea? A systematic review and meta-analysis of its effect in humans

“…The case reports [Mcarthur et al 1982;Sacerdote, 1986;Zimmermann et al 1986;Roof, 1987;Migliore et al 1988;Scholz et al 1991;Schworer et al 1995] are discussed narratively in a separate section below because of possible high placebo rates and are not included in the meta-analysis. The remaining 24 trials/case series included 10 studies with healthy volunteers (total sample size = 150 participants) [Schiller et al 1985;Baxter et al 1987;Pressman et al 1987;Baumer et al 1989;Gregersen et al 1989;Rubinoff et al 1989;Thollander et al 1997Thollander et al , 1999Mann and Shinkle, 1998;Viramontes et al 2001] and 14 studies (total sample size = 493 patients) with faecal incontinence, irritable bowel syndrome, diabetes, alcohol withdrawal, heroin withdrawal, ultra-rapid opioid detoxification, short bowel syndrome (high output ileostomy or high rectal output), intestinal transplant and cholera patients [Fedorak et al 1985;Bretzke, 1987;Gupta and Jha, 1988;Rabbani et al 1989;Baumgartner and Rowen, 1991;Morali et al 1991;Rovera et al 1997;Camilleri et al 2003Camilleri et al , 2009Mcdoniel et al 2004;Buchman et al 2006;Farzam and Najafi, 2009;Bharucha et al 2010Bharucha et al , 2014. Results regarding statistical analysis of these studies are described in the following.…”

“…Heterogeneity was still present in a similar magnitude (I 2 = 86%) as well as publication bias. When we included only the 10 studies with diagnoses that essentially constitute functional diarrhoea (diabetes, irritable bowel syndrome, faecal incontinence and withdrawal) [Fedorak et al 1985;Bretzke, 1987;Gupta and Jha, 1988;Baumgartner and Rowen, 1991;Morali et al 1991;Camilleri et al 2003Camilleri et al , 2009Farzam and Najafi, 2009;Bharucha et al 2010Bharucha et al , 2014, clonidine still had a significant strong effect on diarrhoea with a mean SMD of −1.04 (95% CI −1.54 to −0.53; see Figure 3C). Furthermore, when we included only the studies with sample size over 10 patients [Gupta and Jha, 1988;Baumgartner and Rowen, 1991;Morali et al 1991;Camilleri et al 2003Camilleri et al , 2009Farzam and Najafi, 2009;Bharucha et al 2010Bharucha et al , 2014, the mean SMD did not change much: −0.99 (95% CI −1.54 to −0.43; see Figure 3D).…”

“…The most prevalent side effect was dry mouth with a mean risk ratio of 12.3 (95% CI 2.5-61.2; I 2 = 0%) for clonidine versus placebo [Camilleri et al 2003;Bharucha et al 2014], appearing up to 100% of patients who had received clonidine [Bretzke, 1987;Rubinoff et al 1989;Baumgartner and Rowen, 1991;Thollander et al 1997Thollander et al , 1999Bharucha et al 2010Bharucha et al , 2014. Drowsiness, light-headedness and fatigue had mean risk ratios over 1 for clonidine versus placebo but with nonsignificant 95% CIs (2.37, 95% CI 0.80-7.00; 3.32, 95% CI 0.89-12.42; and 1.50, 95% CI 0.63-3.61, respectively; I 2 = 0% for all analyses) [Camilleri et al 2003; Bharucha [Fedorak et al 1985;Mcdoniel et al 2004;Buchman et al 2006] and 45% [Gupta and Jha, 1988] in patients who received clonidine but there was a general conception that this was a drop in systolic blood pressure up to 32.9 units with no symptomatology [Rubinoff et al 1989;Morali et al 1991]; however, a few cases of severe orthostatic hypotension [Rovera et al 1997] were described (Table 1).…”

A rational approach to the treatment of alcohol withdrawal in the ED

“…For example, delirium is a known adverse effect of β-blocker therapy; and one study showed an increase in delirium in AWS when propranolol was used in treatment [104,105]. Two medications in this class have shown some promise, but only as adjuncts: clonidine and dexmedetomidine [64,[106][107][108][109][110][111][112][113][114][115]. However, studies on these 2 medications, especially on the recently popular medication dexmedetomidine, have been small and limited to case reports or small case series; but there may be some promise for use of dexmedetomidine if used as an adjunct to standard therapy with benzodiazepines, phenobarbital, or propofol.…”

A randomized controlled study of additive use of dexmedetomidine to benzodiazepines for patients with alcohol withdrawal syndrome

“…Anticonvulsants, antipsychotics, ethanol, barbiturates and propofol have been used historically for this purpose [7,8], but the evidence base for these agents is weak or absent [6]. There have also been several studies of clonidine as adjunct treatment for AWS in the ICU, which significantly decreases AWS symptoms [9] and BZD doses [10], but is associated with greater risk of adverse events such as bradycardia and hypotension [10,11]. Downsides of clonidine include that it produces only a mild sedative effect, its significant hemodynamic impact and long duration of action (up to 12-16 h) [7].…”