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Evidence summaries

Pharmacological Interventions for Clozapine-Induced Hypersalivation

There is insufficient evidence on the effect of pharmacological interventions for clozapine-induced hypersalivation. Level of evidence: "D"

A Cochrane review [Abstract] 1 included 15 studies with a total of 924 subjects. 14 studies were conducted in hospitals in China. Most frequently the primary outcome was the diameter of the wet patch on the pillow. Antimuscarinics (astemizole, diphenhydramine, propantheline, doxepin) were the most commonly evaluated drugs. For the outcome of 'no clinically important improvement' astemizole and diphenhydramine were more effective than placebo (astemizole: n=97, 2 RCTs, RR 0.61 CI 0.47 to 0.81 NNT 3 CI 2 to 5; diphenhydramine: n=131, 2 RCTs, RR 0.43 CI 0.31 to 0.58, NNT 2 CI 1.5 to 2.5), but the used doses of astemizole can cause toxicity. Data involving propantheline were heterogeneous, but both studies showed benefit over placebo. Adverse effects were poorly recorded. Of the other interventions, oryzanol (rice bran oil and rice embryo oil extract) showed benefit over the antimuscarinic doxepin in terms of 'no clinically important change' (n=104, 1 RCT, RR 0.45 CI 0.27 to 0.75, NNT 4 CI 2 to 7). The Chinese medicine suo quo wan (comprises spicebush root, Chinese yam and bitter cardamom) showed benefit over doxepin (n=70, 1 RCT, RR 'no clinically important change' 0.31 CI 0.16 to 0.59, NNT 3 CI 1.5 to 3.7).

Comment: The quality of evidence is downgraded by study quality (inadequate or unclear allocation concealment and lack of blinding) and by imprecise results (limited study size for each comparison).

    References

    • Syed R, Au K, Cahill C et al. Pharmacological interventions for clozapine-induced hypersalivation. Cochrane Database Syst Rev 2008;(3):CD005579. [PubMed].

Primary/Secondary Keywords