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

Table 22: Summary of Cyproheptadine Studies for Reducing Spasticity


Acute administration of cyproheptadine (5-HT antagonis) was found to decrease clinical measures of strength (LEMS) and spasticity/spasms (SCATS and modified Ashworth). (Thompson & Hornby 2013). Comfirming the modulatory effect of 5HT on both voluntary and involuntary force generation is the finding that SSRI administration increased strength and spasticity/spasms. (Thompson & Hornby 2013).

Cyproheptadine performed favourably versus placebo in improving spasticity and walking in a small sample of chronic SCI patients (Wainberg et al. 1990). Thompson and Hornby (2013) were unable to demonstrate that cyproheptadine improved walking but postulated that their patients in this small sample (n=12) may have subjectively opted to walk at slower more stable speeds. Although the study by Wainberg et al. (1990) 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 six subjects confirmed this antispasmodic effect of cyproheptadine using subjective patient logs of clonus and spasms. Norman et al. (1998) 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) in a pre-post 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.


There is level 1b evidence (from one RCT and one pre-post study; Thompson et al. 2013; Nance et al. 1994) that supports the use of cyproheptadine in the treatment of spasticity in patients with chronic SCI.

There is level 4 evidence (from one case series; Meythaler et al. 2003) supporting the use of cyproheptadine (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 trials using rigorous study design.