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Benztropine Addition to the List Note: Commonly prescribed medication. Literature question Is benztropine effective and safe? Literature search Medline: Benztropine AND efficacy AND limit to (meta-analysis) Cochrane: Benztropine AND efficacy Soares-Weiser K, Mobsy C, and Holliday E. “Anticholinergic medication for neuroleptic-induced tardive dyskinesia (Review).” The Cochrane Library (2012). Implications for practice. Based on the currently available data, this systematic review can provide no reliable conclusions about the use of anticholinergics (benzhexol, benztropine, biperiden, orphenadrine, procyclidine, scopolamine or trihexylphenidyl) for the treatment of neuroleptic-induced TD. In addition, there is no evidence to support the suggestion that the withdrawal of these medications may benefit people with TD. In the absence of evidence one way or another, the clinician must balance the possible benefits against the potential adverse effects of the treatment. Katzenschlager R, Sampaio C, Costa J, and Lees A. “Anticholinergics for symptomatic management of Parkinson’s disease (Review).” The Cochrane Library (2009). Main results. Trial duration was between five and 20 weeks and drugs investigated were benzhexol (mean doses: 8 to 20 mg/d), orphenadrine (mean dose not reported), benztropine (mean dose not reported), bornaprine (8 to 8.25 mg/d), benapryzine (200 mg/d), and methixine (45 mg/d). Only one study involved two anticholinergic drugs. Outcome measures varied widely across studies and in many cases, the scales applied were the authors´ own and were not defined in detail. Incomplete reporting of methodology and results was frequent. The heterogeneous study designs as well as incomplete reporting precluded combined statistical analysis. Five studies used both tremor and other parkinsonian features as outcome measures. Outcome measures in these five studies were too different for a combined analysis and results varied widely, from a significant improvement in tremor only to significant improvement in other features but not in tremor. All studies except one (dealing with methixine) found a significant improvement from baseline on the anticholinergic drug in at least one outcome measure. The difference between placebo and active drug was reported in four studies and was found to be significant in all cases. No study failed to show superiority of the anticholinergic over placebo. The occurrence of neuropsychiatric and cognitive adverse events was reported in all but three studies (in 35 patients on active drug versus 13 on placebo). The most frequently reported reason for drop-outs from studies was in patients on placebo due to withdrawal from pre-trial anticholinergic treatment. Powney MJ, Adams CE, and Jones H. “Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation) (Review).” The Cochrane Library (2012). Adverse events In terms of movement disorders and the emergence of ataxia (1 RCT, n = 66, RR 0.44 CI 0.04 to 4.65), dystonia (1 RCT, n = 66, RR 3.54 CI 0.42 to 30.03), speech disorder (1 RCT,n = 66, RR 1.77 CI 0.35 to 9.01), rigidity (1 RCT, n = 66, RR 6.22 CI 0.33 to 115.91), tremor (1 RCT, n = 66, RR 1.77 CI 0.17 to 18.60) and the need for benztropine (1 RCT, n = 66, RR 1.99 CI 0.68 to 5.83). One study (n = 60) reported that significantly more participants experienced EPS in the haloperidol group compared with the lorazepam group (RR 15.00 CI 2.11 to 106.49, Analysis 13.7). Walshe M, Smith M, and Pennington L. “Interventions for drooling in children with cerebral palsy (Review).” The Cochrane Library (2012). Pharmaceutical Interventions. Both studies on pharmaceutical interventions (Camp-Bruno 1989; Mier 2000) compared intervention versus placebo. They differed in the medications given and outcome measures used. CampBruno 1989 examined reduction in salivary flow and found a statistically significant difference in salivary flow between participants (age range 4-44 years) on placebo and those taking benztropine (p<.001) immediately after intervention. Both studies examined the frequency and severity of drooling albeit using different outcome measures. Camp-Bruno 1989 defined a ’responder’ as those participants who obtained a mean TDS rating of less than 3. They also defined ’responsivity’ as a decrease of one baseline SD or greater. Mier 2000 defined an improvement of 4 points or greater in their 9 point scale as a standard for significant ’clinical improvement’. On the Teacher Drool Scale, Camp-Bruno 1989 found a statistically significant difference between both placebo and intervention in the frequency and severity of drooling immediately after intervention (p_0.001).Mier 2000 using an adaptation of Thomas-Stonell and Greenberg Scale also found a statistically significant difference between the placebo and intervention immediately after intervention (p<0.001). It is unknown how long the effects of these medications lasted in terms of reducing the quantity of saliva produced and reducing the frequency and severity of drooling. The adverse effects of benztropine reported were behavior changes such as irritability and listlessness. Medical side effects reported were insomnia, vomiting, dilated pupils, disorientation, facial flushing, ’glassy eyes’ , stomachache, and dry mouth. Three children of the 27 (11%) children in Camp-Bruno 1989 were excluded because of adverse reactions to benztropine. Eight of the 39 (20.5%) children inMier 2000 study dropped out because of the adverse side effects to glycopyrrolate. As with the trials on BoNT-A, it is difficult to determine whether all adverse effects reported were directly related to the medication.