• Jay M Meythaler, James F Roper, and Robert C Brunner.
• Department of Physical Medicine & Rehabilitation, University of Alabama School of Medicine and the University of Alabama Spain Rehabilitation Center, Birmingham 35249-7330, USA. Jmeythal@uab.edu
• Arch Phys Med Rehabil. 2003 May 1;84(5):638-42.

ObjectiveTo evaluate the efficacy of cyproheptadine in the management of acute intrathecal baclofen (ITB) withdrawal.DesignDescriptive case series.SettingUniversity hospital with a comprehensive in- and outpatient rehabilitation center.ParticipantsFour patients (3 with spinal cord injury, 1 with cerebral palsy) with implanted ITB infusion pumps for treatment of severe spasticity, who had ITB withdrawal syndrome because of interruption of ITB infusion.InterventionsPatients were treated with 4 to 8mg of cyproheptadine by mouth every 6 to 8 hours, 5 to 10mg of diazepam by mouth every 6 to 12 hours, 10 to 20mg of baclofen by mouth every 6 hours, and ITB boluses in some cases.Main Outcome MeasuresClinical signs and symptoms of ITB withdrawal of varying severity were assessed by vital signs (temperature, heart rate), physical examination (reflexes, tone, clonus), and patient report of symptoms (itching, nausea, headache, malaise).ResultsThe patients in our series improved significantly when the serotonin antagonist cyproheptadine was added to their regimens. Fever dropped at least 1.5 degrees C, and heart rate dropped from rates of 120 to 140 to less than 100bpm. Reflexes, tone, and myoclonus also decreased. Patients reported dramatic reduction in itching after cyproheptadine. These changes were associated temporally with cyproheptadine dosing.DiscussionAcute ITB withdrawal syndrome occurs frequently in cases of malfunctioning intrathecal infusion pumps or catheters. The syndrome commonly presents with pruritus and increased muscle tone. It can progress rapidly to high fever, altered mental status, seizures, profound muscle rigidity, rhabdomyolysis, brain injury, and death. Current therapy with oral baclofen and benzodiazepines is useful but has variable success, particularly in severe cases. We note that ITB withdrawal is similar to serotonergic syndromes, such as in overdoses of selective serotonin reuptake inhibitors or the popular drug of abuse 3,4-methylenedioxymethamphetamine (Ecstasy). We postulate that ITB withdrawal may be a form of serotonergic syndrome that occurs from loss of gamma-aminobutyric acid B receptor-mediated presynaptic inhibition of serotonin.ConclusionCyproheptadine may be a useful adjunct to baclofen and benzodiazepines in the management of acute ITB withdrawal syndrome.

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