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Cyproheptadine is a non-selective serotonergic antagonist and antihistamine that has been reported to improve spasticity in SCI.

Table 17: Summary of Cyproheptadine Studies for Reducing Spasticity


Cyproheptadine performed favourably versus placebo in improving spasticity and walking in a small sample of chronic SCI patients (Wainberg et al. 1990, N=8).  Although the study design was randomized and placebo controlled, reductions in spasticity were only subjectively measured as subject reports of severity and frequency of involuntary movements.  Similarly, Barbeau et al. (1982) in a case series study involving 6 subjects confirmed this antispasmodic effect of cyproheptadine using subjective patient logs of clonus and spasms.  Norman et al. 1998 (N=12) corroborated the reduction in ankle clonus in a study of various drugs and gait in SCI.  Validated outcome measures (i.e. Ashworth and Pendulum tests) were used by Nance 1994 (N=25) in a pre/post-test study that provided statistically significant evidence supporting the use of cyproheptadine in treating SCI spasticity.

Primary reliance on subjective outcome measures, in RCT and non-RCT designs, with small sample sizes provides weak evidence in favour of cyproheptadine for the treatment of spasticity and walking.  Although spasticity was reduced when using cyproheptadine, it was found to be inferior to Baclofen.  Nevertheless, cyproheptadine as an adjunct treatment (along with baclofen and diazepam) was found to be useful in relieving spasticity and other complications of acute intrathecal baclofen withdrawal syndrome.


Limited level 1b evidence supports the use of cyproheptadine in the treatment of spasticity in chronic SCI patients, but results should be interpreted cautiously given the small sample sizes, reliance on non-validated subjective outcome measures and inferiority of cyproheptadine when compared to baclofen.

A single level 4 report supports the use of cyrpoheptadine (along with baclofen and diazepam) as an adjunct treatment of acute intrathecal baclofen withdrawal syndrome.

  • Cyproheptadine may be useful in treating SCI spasticity but requires additional confirmatory research.